ArticleLiterature Review

Epidemiology of fatty liver: An update

July 2014
World Journal of Gastroenterology 20(27):9050-9054

DOI:10.3748/wjg.v20.i27.9050

Source
PubMed

Authors:

Valerio Nobili

Bambino Gesu Children Hospital

Claudio Tiribelli

Italian Liver Foundation, Trieste, Italy

We provide a concise review of the main epidemiological literature on fatty liver (FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already available knowledge. We discuss the limitations inherent in the categorization of FL into non-alcoholic and alcoholic FL, the potential relevance of FL as an independent predictor of cardiometabolic disease, and recent research addressing the role of FL as an independent predictor of mortality. This review is organized as a series of answers to relevant questions about the epidemiology of FL.

Fatty liver and mortality: A cohort population study in South Italy

Article

Full-text available

Jun 2019

Objective Alcoholic fatty liver (AFLD) and non-alcoholic fatty liver (NAFLD) are two common conditions. However, if they can increase the risk of death is poorly explored. We therefore aimed to investigate the potential association between the presence and severity of liver steatosis and mortality in a large sample of older people. Design Prospective. Setting Community. Participants Women and men randomly sampled from the electoral rolls of the population of Castellana Grotte, a town in Southern Italy (Apulia region) between 2005 and 2006. Among 1942 initially contacted, 1708 (=87.9%) participated to the baseline survey (Multicentrica Colelitiasi III (MICOL III)). This specific study included 1445 older participants (mean age=65.2 years, females=44.2%). Exposure NAFLD or AFLD. Primary and secondary outcomes Mortality (all-cause and specific-cause). Results After a median of 12 years, 312 participants (=21.6%) died. After adjusting for nine potential confounders, the presence of steatosis was not associated with any increased risk of death in both NAFLD and AFLD. The severity of liver steatosis was not associated with any increased risk of mortality in NAFLD, while in AFLD, the presence of moderate steatosis significantly increased the risk of overall (HR=2.16; 95% CI 1.19 to 3.91) and cancer-specific (HR=3.54; 95% CI 1.16 to 10.87) death. Conclusions Liver steatosis is not associated with any increased risk of death in NAFLD, while moderate steatosis could be a risk factor for mortality (particularly due to cancer) in people affected by AFLD.

Updates on Quantitative MRI of Diffuse Liver Disease: A Narrative Review

Article

Full-text available

Dec 2022
BMRI

Diffuse liver diseases are highly prevalent conditions around the world, including pathological liver changes that occur when hepatocytes are damaged and liver function declines, often leading to a chronic condition. In the last years, Magnetic Resonance Imaging (MRI) is reaching an important role in the study of diffuse liver diseases moving from qualitative to quantitative assessment of liver parenchyma. In fact, this can allow noninvasive accurate and standardized assessment of diffuse liver diseases and can represent a concrete alternative to biopsy which represents the current reference standard. MRI approach already tested for other pathologies include diffusion-weighted imaging (DWI) and radiomics, able to quantify different aspects of diffuse liver disease. New emerging MRI quantitative methods include MR elastography (MRE) for the quantification of the hepatic stiffness in cirrhotic patients, dedicated gradient multiecho sequences for the assessment of hepatic fat storage, and iron overload. Thus, the aim of this review is to give an overview of the technical principles and clinical application of new quantitative MRI techniques for the evaluation of diffuse liver disease.

The Association of Pericardial Fat and Peri-Aortic Fat With Severity of Nonalcoholic Fatty Liver Disease

Preprint

Full-text available

Oct 2021

Background: Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. Methods: We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Result: Patients with moderate and mild NAFLD have greater volume of PCF (100.7±26.3vs. 77.1±21.3 vs. 61.7±21.6ml, P < 0.001) and TAT (11.2±4.1 vs. 7.6±2.6 vs. 5.5±2.6ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82-0.89 and 0.84-0.90). Conclusion: Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

Chronic Liver Diseases

Chapter

Nov 2020

Chronic liver disease is an umbrella term that encompasses a spectrum of diseases that affect the liver for at least a period of 6 months. Examples of this include primary sclerosing cholangitis, hepatic steatosis, and biliary cirrhosis. Unfortunately, the medical treatment for most of these diseases is either ineffective or simply nonexistent. As a result, there is high interest in finding chemical entities, including naturally occurring ones such as extracts from the milk thistle and the bioactive compound (+)-catechin, that can serve as a lead to the creation of a more effective treatment for such diseases. Furthermore, it has long been recognized that patients with a chronic liver disease are at a higher risk of malnutrition and therefore an appropriate nutritional regime is of utmost importance in improving the prognosis of this group of patients.

Modeling alcoholic liver disease in a human Liver-Chip

Preprint

Full-text available

Jul 2020

Fatty liver disease (FLD), is a major public health burden that affects up to 30% of people in Western countries and leads to progressive liver injury, comorbidities, and increased mortality. Key risk factors for developing FLD are obesity and alcohol consumption, both of which are growing in prevalence worldwide. There is an urgent need for human-relevant preclinical models to improve our understanding of FLD progression to steatohepatitis and for the development of sensitive noninvasive diagnostics and therapies. Alcohol-induced liver disease (ALD) represents an ideal case for modeling FDL as ethanol exposure is a comparatively simpler trigger for experimental induction of the pathology, as opposed to the complexity of modeling the diet- and life-style induced FLD. Further, despite their different root causes several common characteristics in disease progression and deterioration of liver function in the two disease entities, highlighting the potential of an ALD microphysiological model for broad application in translational research. Here, we leverage our recently reported human Liver-Chip for toxicity applications, to expand the capabilities of the platform for broad application in translational research. We report the first in vitro modeling of ALD that uses human relevant blood alcohol concentrations (BAC) and affords multimodal profiling of clinically relevant endpoints. Our ALD Liver-Chip recapitulates established FLD markers in response to ethanol in a concentration-dependent manner, including lipid accumulation and oxidative stress. Importantly, we show that the ALD Liver-Chip supports the study of secondary insults, as patients with advanced ALD often show high blood endotoxin levels due to alcohol-associated increased intestinal permeability and barrier dysfunction. Moreover, owing to new developments in the design, the ALD Liver-Chip enables the measurement of structural changes of the bile canaliculi (BC) network as a novel in vitro quantitative readout of alcoholic liver toxicity. In summary, we report the development of a human ALD Liver-Chip as a new platform for modeling the progression of alcohol-induced liver injury with direct translation to clinical research.

The effect of steatosis and fibrosis on blunt force vulnerability of the liver

Article

Full-text available

May 2020
INT J LEGAL MED

The aim of our study was to examine the possible effect of steatosis and fibrosis on the blunt force vulnerability of human liver tissue. 3.5 × 3.5 × 2-cm-sized liver tissue blocks were removed from 135 cadavers. All specimens underwent microscopical analysis. The tissue samples were put into a test stand, and a metal rod with a square-shaped head was pushed against the capsular surface. The force (Pmax) causing liver rupture was measured and registered with a Mecmesin AFG-500 force gauge. Six groups were formed according to the histological appearance of the liver tissue: intact (group 1), mild steatosis (group 2), moderate steatosis (group 3), severe steatosis (group 4), fibrosis (group 5), and cirrhosis (group 6). The average Pmax value was 34.1 N in intact liver samples (range from 18.1 to 60.8 N, SD ± 8.7), 45.1 N in mild steatosis (range from 24.2 to 79.8 N SD ± 12.6), 55.4 N in moderate steatosis (range from 28.9 to 92.5 N, SD ± 16.0), 57.6 N in severe steatosis (range from 39.8 to 71.5 N, SD ± 11.9), 63.7 N in fibrosis (range from 37.8 to 112.2 N, SD ± 19.5), and 87.1 N in the case of definite cirrhosis (range from 52.7 to 162.7 N, 30.3). The Pmax values were significantly higher in samples with visible structural change than in intact liver sample (p = 0.023, 0.001, 0.009, 0.0001, 0.0001 between group 1 and groups 2 to 6 respectively). Significant difference was found between mild steatosis (group 2) and cirrhosis (group 6) (p = 0.0001), but the difference between mild, moderate, and severe steatosis (groups 2, 3, and 4) was not significant. Our study demonstrated that contrary to what is expected as received wisdom dictates, the diseases of the parenchyma (steatosis and presence of fibrosis) positively correlate with the blunt force resistance of the liver tissue.

Article

Full-text available

Dec 2019

Differences in body fat distribution may be a reason for the sex-, age-, and ethnicity-related differences in the prevalence of fatty liver disease (FL). This study aimed to evaluate the sex- and age-related differences in the contribution of visceral (VAT) and subcutaneous (SAT) abdominal fat, measured by ultrasound, to fatty liver index (FLI) in a large sample of overweight and obese Caucasian adults, and to identify the VAT and SAT cut-off values predictive of high FL risk. A cross-sectional study on 8103 subjects was conducted. Anthropometrical measurements were taken and biochemical parameters measured. VAT and SAT were measured by ultrasonography. FLI was higher in men and increased with increasing age, VAT, and SAT. The sex*VAT, age*VAT, sex*SAT, and age*SAT interactions negatively contributed to FLI, indicating a lower VAT and SAT contribution to FLI in men and in the elderly for every 1 cm of increment. Because of this, sex- and age-specific cut-off values for VAT and SAT were estimated. In conclusion, abdominal adipose tissue depots are associated with FLI, but their contribution is sex- and age-dependent. Sex- and age-specific cut-off values of ultrasound-measured VAT and SAT are suggested, but they need to be validated in external populations.

Copeptin relates to a fatty liver and measures of obesity in a South African population with mixed ethnicities

Article

Full-text available

Aug 2019
ENDOCRINE

Purpose Elevated copeptin, a vasopressin marker, is linked to metabolic disease, and obese rats with low-vasopressin concentration had a decreased risk of liver steatosis. We here investigated the association between copeptin and nonalcoholic fatty liver disease (NAFLD) and possible differences in copeptin concentration between ethnicities. Methods In this cross-sectional study of 361 South Africans (n = 172 African black, 189 = Caucasian) with a mean age of 45 years and 45% men, plasma copeptin was measured and associated with NAFLD according to a validated fatty liver index accounting for measures of BMI, waist, triglycerides, and gamma-glutamyltransferase. Results There was no significant difference in copeptin concentrations between ethnicities after age and gender adjustment (p = 0.24). Increasing copeptin tertile levels were significantly associated with obesity, overweight, and abdominal obesity, respectively, after multivariate adjustment for age, gender, ethnicity, and high HOMA-IR (p = 0.02 for all). Individuals in the second and third copeptin tertile had an increased odds (95% CI) of NAFLD of 1.77 (1.04–3.02) and 2.97 (1.74–5.06), respectively, compared to the bottom tertile (p < 0.001). The association between increasing copeptin tertile and NAFLD remained significant after adjustment for age, gender, ethnicity, high HOMA-IR, self-reported current alcohol intake, and statin treatment (p = 0.01). Conclusions Elevated plasma copeptin is independently associated with NAFLD in a population with mixed ethnicities, pointing at the pharmacologically modifiable vasopressin system as a new mechanism behind NAFLD.

Involvement of G-Protein-Coupled Receptor 40 in the Inhibitory Effects of Docosahexaenoic Acid on SREBP1-Mediated Lipogenic Enzyme Expression in Primary Hepatocytes

Article

Full-text available

May 2019
INT J MOL SCI

Nonalcoholic fatty liver disease is a frequent liver malady, which can progress to cirrhosis, the end-stage liver disease if proper treatment is not applied. Omega-3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid, have been clinically proven to lower serum triglyceride levels. Various physiological activities of omega-3 fatty acids are due to their agonistic actions on G-protein-coupled receptor 40 (GPR40) and GPR120. Lipid droplets (LD) accumulation in hepatocytes confirmed that DHA treatment reduced the number of larger ( >10 μm2) LDs, as well as the total area of LDs. Moreover, DHA lowered protein and mRNA expression levels of lipogenic enzymes such as fatty acid synthase (FAS), acetyl-CoA carboxylase and stearoyl-CoA desaturase-1 (SCD-1) in primary hepatocytes incubated with liver X receptor (LXR) agonist T0901317 or high glucose and insulin. DHA also decreased protein expression of nuclear and precursor sterol response-element binding protein (SREBP)-1, a key lipogenesis transcription factor. We further found that exposure of murine primary hepatocytes to DHA for 12 h increased GPR40 and GPR120 mRNA levels. Specific agonists (Compound A for GPR120 and AMG-1638 for GPR40), hepatocytes from GPR120 knock-out mice and GPR40 selective antagonist (GW1100) were used to assess whether DHA’s antilipogenic effects are mediated through GPR120 or GPR40. Compound A did not decrease SREBP-1 and FAS protein expression in hepatocytes exposed to T0901317 or high glucose with insulin. Moreover, DHA downregulated lipogenesis enzyme expression in GPR120-null hepatocytes. In contrast, AMG-1638 lowered SREBP-1 and SCD-1 protein levels. Additionally, GW1100, a GPR40 antagonist, reversed the antilipogenic effects of DHA. Collectively, our data demonstrate that DHA downregulates the expression SREBP-1-mediated lipogenic enzymes via GPR40 in primary hepatocytes.

The effect of DASH diet on atherogenic indices, pro-oxidant-antioxidant balance, and liver steatosis in obese adults with non-alcoholic fatty liver disease: A double-blind controlled randomized clinical trial

Article

Full-text available

Apr 2023

Background: The present clinical trial aimed to examine whether adherence to Dietary Approaches to Stop Hypertension (DASH) diet could improve lipid profile, the Pro-oxidant-antioxidant balance (PAB) as well as liver function in obese adults with non-alcoholic fatty liver disease (NAFLD). Methods: Sixty two patients with NAFLD were equally allocated into either DASH or low-calorie diet (LCD) group for 8 weeks. The primary and secondary outcomes were determined before and after the trial. Results: Forty patients completed the trial. Significant within group differences were found in dietary saturated fat, selenium, vitamins A and E as well as body weight and body mass index (BMI) and waist circumference (WC) after the intervention (P<0.05). DASH diet showed greater significant change in systolic and diastolic blood pressure without significant differences between the groups after 8 weeks. Apart from serum high-density lipoprotein cholesterol (HDL-C) and triglyceride/HDL-C, greater reductions were found not only in serum lipids and atherogenic indices (P<0.05) but also in serum aspartate aminotransferase (AST), AST to platelet ratio index (APRI) and lipid accumulation product (LAP) in DASH group in comparison to control group (P=0.008, P=0.019 and P=0.003, respectively). Nevertheless, there was not any difference in PAB level between the groups. Furthermore, adherence to DASH diet was more effective in alleviating liver steatosis compared with usual LCD (P=0.012). Conclusion: Adherence to DASH diet appears to be more effective in improving obesity, atherogenic and liver steatosis biomarkers but not oxidative stress (OS) than usual LCD.

Role of p53 suppression in the pathogenesis of hepatocellular carcinoma

Article

Full-text available

Jun 2023

In the world, hepatocellular carcinoma (HCC) is among the top 10 most prevalent malignancies. HCC formation has indeed been linked to numerous etiological factors, including alcohol usage, hepatitis viruses and liver cirrhosis. Among the most prevalent defects in a wide range of tumours, notably HCC, is the silencing of the p53 tumour suppressor gene. The control of the cell cycle and the preservation of gene function are both critically important functions of p53. In order to pinpoint the core mechanisms of HCC and find more efficient treatments, molecular research employing HCC tissues has been the main focus. Stimulated p53 triggers necessary reactions that achieve cell cycle arrest, genetic stability, DNA repair and the elimination of DNA-damaged cells' responses to biological stressors (like oncogenes or DNA damage). To the contrary hand, the oncogene protein of the murine double minute 2 (MDM2) is a significant biological inhibitor of p53. MDM2 causes p53 protein degradation, which in turn adversely controls p53 function. Despite carrying wt-p53, the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway. High p53 in-vivo expression might have two clinical impacts on HCC: (1) Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways; and (2) Exogenous p53 makes HCC susceptible to various anticancer drugs. This review describes the functions and primary mechanisms of p53 in pathological mechanism, chemoresistance and therapeutic mechanisms of HCC.

Approaches in the Nutritional Management of Non Alcoholic Fatty Liver Disease

Article

Mar 2023

Nonalcoholic fatty liver disease (NAFLD) is at the upward thrust global Representing a public fitness issue. Its coexistence with weight problems and Different metabolic changes is relatively frequent. Therefore, present day remedy Interventions for NAFLD are especially centered on modern weight reduction Thru modulation of normal calorie consumption without or with precise Macronutrient adjustments. Furthermore, different applicable dietary Interventions are constructed on meals choice and time-restrained eating. Since Each approach would possibly carry unique results, selecting the top of the line Eating regimen remedy for a affected person is a complex task, due to the fact NAFLD is a multifactorial complicated disease. Importantly, a few elements want To be considered, consisting of nutrition-primarily based totally proof in phrases Of hepatic morphophysiological enhancements in addition to adherence of the Affected person to the meal plan and adaptableness of their cultural context. Thus, The cause of this evaluate is to discover and evaluate the subtleties and nuances Of the maximum applicable scientific exercise recommendations and the dietary Techniques for the control of NAFLD with a unique interest to tangible results And long-time period adherence

The effect of DASH diet on glycemic response, meta-inflammation and serum LPS in obese patients with NAFLD: a double-blind controlled randomized clinical trial

Article

Full-text available

Feb 2023
NUTR METAB

Background As dietary approaches to stop hypertension (DASH) dietary pattern has been shown to be effective in hypertension and obesity, the present study investigated the effects of following DASH diet on glycemic, meta-inflammation, lipopolysaccharides (LPS) and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD). Methods In this double-blind controlled randomized clinical trial, 40 obese patients with NAFLD were randomly allocated into either “DASH diet” (n = 20) or calorie-restricted diet as "Control” (n = 20) group for 8 weeks. Anthropometric measures, blood pressure, glycemic response, liver enzymes, toll-like reseptor-4 (TLR-4) and monocyte chemoattractant protein (MCP-1) and LPS as well as Dixon's DASH diet index were assessed at baseline and after 8 weeks. Results After 8 weeks, although all obesity indices decreased significantly in both groups, the reduction in all anthropometric measures were significantly greater in DASH vs control group, after adjusting for baseline values and weight change. Fasting glucose level decreased in both group, however, no inter-group significant difference was found at the end of study. Nevertheless, serum levels of hemoglobin A1c (HbA1c), TLR-4, MCP-1 and LPS as well as aspartate aminotransferase (AST) decreased significantly in DASH group, after adjusting for baseline values and weight change (p < 0.001, p = 0.004, p = 0.027, p = 0.011, and p = 0.008, respectively). The estimated number needed to treats (NNTs) for one and two grade reductions in NAFLD severity following DASH diet were 2.5 and 6.67, respectively. Conclusion Adherence to DASH diet could significantly improve weight, glycemia, inflammation and liver function in obese patients with NAFLD.

GAMBARAN PERLEMAKAN HATI NON-ALKOHOLIK DI RSUP SANGLAH DENPASAR PERIODE TAHUN 2017-2018

Article

Full-text available

Feb 2019

ABSTRAK Perlemakan hati (fatty liver, disingkat FL) merupakan penyakit yang paling sering terjadi di negara-negara barat. Diabetes Melitus (DM) adalah penyakit metabolik kronis yang terjadi akibat gangguan fungsi pankreas dalam menghasilkan insulin atau tubuh tidak dapat menggunakan insulin (resistensi insulin). Resistensi insulin yang disebabkan oleh T2DM juga dapat menjadi penyebab dari NAFLD ini. Selain itu, pasien T2DM juga berpotensi mengidap fibrosis dan sirosis, akibat perkembangan penyakit NAFLD. Studi ini adalah studi deskriptif potong lintang (cross-sectional). Sampel yang digunakan adalah seluruh populasi terjangkau yang diambil dari rekam medis. Data kemudian diolah menggunakan analisis deskriptif. Hasil penelitian diperoleh 13 sampel dengan reratausia 49,62 tahun (SD ± 9,57) dan penderita terbanyak pada kelompok umur 50-59 tahun. Didapatkan 8 penderita dengan indeks massa tubuh (IMT) berlebih (IMT ≥23) (61,5%), dan 5 orang dengan IMT tidak berlebih (<23) (38,5%). Selain itu, hanya 2 penderita (15,4%) yang menderita diabetes melitus dan NAFLD, dan 11 orang sisanya (84,6%) tidak menderita diabetes melitus. Berdasarkan hasil penelitian yang sudah dilakukan disimpulkan bahwa jumlah penderita NAFLD pada RSUP Sanglah periode 2017-2018 sebanyak 13 kasus, dengan rerata usia 49,62 tahun (± SB 9,57), 61,5% dengan IMT berlebih (≥23), dan 15,4% menderita diabetes melitus. ABSTRACT Fatty liver (FL) is the most common disease in western countries. Diabetes Mellitus (DM) is a chronic metabolic disease that caused by pancreas inability to produce insulin, or inability to use insulin adequately (insulin resistant). This condition can develop into NAFLD. Untreated NAFLD may results to fibrosis and cirrhosis. This study is a cross-sectional descriptive study, where the samples are obtained from all accessible population from medical record. The samples are then analyzed with desctiptive analysis. In this study, there were found 13 subjects with an average of 49.62 years (SD 9.57). Most of them are within 50-59 age group. 8 subjects have overweight BMI (23) (61.5%), while the rest 5 subjects have non-overweight BMI (<23). Moreover, only 2 subjects (15.4%) that have diabetes mellitus, as opposed to the other 11 subjects (84.6%) that did not have diabetes. From the study, we can conclude that there were 13 NAFLD patients in RSUP Sanglah in 2017-2018 with an average of 49.62 years old (SD 9.57). 61.5% of the subjects have overweight BMI (23) and 15.4% have diabetes mellitus.

Hyperuricemia as a predictor of non-alcoholic fatty liver disease

Article

Jun 2022

Non-alcoholic fatty liver disease (NAFLD) is currently a widespread disease among the adult population and, being a component of the metabolic syndrome (MS), is often associated with obesity, insulin resistance (IR), type 2 diabetes mellitus (DM2), cardiovascular diseases (CVD). Many authors in scientiﬁc studies have found that hyperuricemia (HU) can be considered as a predictor of non-alcoholic fatty liver disease (NAFLD), as well as other diseases associated with metabolic syndrome (MS).

Dietary patterns in adult patients with Non-Alcoholic Fatty Liver Disease in Iraq

Article

Full-text available

Feb 2022

Objectives: The aim of this study was to assess the dietary patterns of Iraqi patients with non-alcoholic fatty liver disease (NAFLD) and compare it with controls. Subjects and methods: A case control study, that included 88 Iraqi patients, aged between 18 and 70 years, of the 88 patients, 46 Iraqi patients were having NAFLD (identified as cases), and 42 patients were free of liver disease and they were considered as controls. The assessment of the dietary intake during the last 6 months was done through utilizing Food frequency questionnaire. NAFLD was diagnosed by using ultrasonography showing specific changes of that disease together with no excessive drinking of alcoholic beverages. Results: There were statistically significant higher rates of daily consumption of processed meats (p-value 0.03), pasta (p-value 0.010) and soft drinks (p-value 0.023) regarding daily portion of most western food items in comparison between patients with NAFLD and control group. And there were statistically significant higher rates of daily consumption of corn oil (p-value 0.027) and soft drinks (p-value 0.023) in the traditional Iraqi food items in comparison between patients with NAFLD and control group. Regarding body weight (p-value 0.003), BMI (p-value 0.033) and waist circumference (p-value <0.001), they were significantly higher among cases with NAFLD. Conclusion: The current study has found that the western diet patterns in particular processed meat, pasta and soft drinks were associated with a higher risk for NAFLD in Iraqi adults.

Adherence to lifestyle modification in patients with nonalcoholic fatty liver disease

Article

Full-text available

Jan 2022

Nonalcoholic fatty liver disease (NAFLD) makes a major impact on morbidity and mortality among the workingage population in developed countries. In the lack of effective pharmacological methods, the leading role in treatment of NAFLD belongs to lifestyle modification, consistent and gradual weight loss, and its maintenance. The qualitative and quantitative structure of the diet, intensity of physical activity, and most importantly, regularity and consistency of implementation of lifestyle modification activities are the key to successful management of patients with NAFLD. To date, there are very few studies on adherence to lifestyle modification activities in this group of patients, which is mainly due to a deficiency of methodological tools. The questionnaire “QAA-25” recommended by the Russian Scientific Medical Society of Therapists for quantitative assessment of adherence to treatment allows to assess both adherence to therapy in general and adherence to its individual components (adherence to drug therapy, adherence to medical counseling, and adherence to lifestyle modification), which requires further study taking into account features of therapeutic strategies in treating NAFLD.

Fatty Liver Index as a Simple and Useful Predictor for 10-year Cardiovascular Disease Risks Determined by Framingham Risk Score in the General Korean Population

Article

Full-text available

Jun 2021
J GASTROINTEST LIVER

Background and aims: The fatty liver index (FLI) is a simple and non-invasive method for the diagnosis of fatty liver disease with an increased risk of cardiovascular disease (CVD) as well as liver-related mortality. We examined the association between FLI and 10-year CVD risk as determined by the Framingham risk score. Methods: This cross-sectional study included 7,240 individuals aged 30 to 69 years who underwent a health examination between 2015 and 2017. The FLI was calculated using an algorithm based on triglyceride, γ-glutamyltransferase, body mass index (BMI), and waist circumference. Multiple linear and logistic regression analyses were performed to assess independent relationships between the FLI and Framingham risk score after adjusting for confounding variables. Results: The overall prevalence of fatty liver disease among study participants as assessed by an FLI ≥ 60 was 19.7%. Compared with non-hepatic steatosis (FLI < 30), the odds ratio (95% confidence interval) for a high Framingham 10-year CVD risk ≥ 10% in individuals with hepatic steatosis (FLI ≥ 60) was 2.56 (1.97-3.33) after adjusting for age, gender, fasting plasma glucose, high-density and low-density lipoprotein cholesterol, blood pressure, C-reactive protein, regular exercise, alcohol-drinking, and current smoking. Conclusions: The FLI was positively and independently associated with a Framingham 10-year CVD risk in the general Korean population. Our findings suggest that the FLI, a simple, useful, and economical index, may be an indicator of CVD events.

Hepatic Energy Metabolism Underlying Differential Lipidomic Responses to High-Carbohydrate and High-Fat Diets in Male Wistar Rats

Article

Full-text available

Jun 2021

Background Low-carbohydrate diets are suggested to exert metabolic benefits by reducing circulating triacylglycerol (TG) concentrations, possibly by enhancing mitochondrial activity. Objective We aimed to elucidate mechanisms by which dietary carbohydrate and fat differentially affect hepatic and circulating TG, and how these mechanisms relate to fatty acid composition. Methods Six-week-old, ∼300 g male Wistar rats were fed a high-carbohydrate, low-fat [HC; 61.3% of energy (E%) carbohydrate] or a low-carbohydrate, high-fat (HF; 63.5 E% fat) diet for 4 wk. Parameters of lipid metabolism and mitochondrial function were measured in plasma and liver, with fatty acid composition (GC), high-energy phosphates (HPLC), carnitine metabolites (HPLC-MS/MS), and hepatic gene expression (qPCR) as main outcomes. Results In HC-fed rats, plasma TG was double and hepatic TG 27% of that in HF-fed rats. The proportion of oleic acid (18:1n–9) was 60% higher after HF vs. HC feeding while the proportion of palmitoleic acid (16:1n–7) and vaccenic acid (18:1n–7), and estimated activities of stearoyl-CoA desaturase, SCD-16 (16:1n–7/16:0), and de novo lipogenesis (16:0/18:2n–6) were 1.5–7.5-fold in HC vs. HF-fed rats. Accordingly, hepatic expression of fatty acid synthase (Fasn) and acetyl-CoA carboxylase (Acaca/Acc) was strongly upregulated after HC feeding, accompanied with 8-fold higher FAS activity and doubled ACC activity. There were no differences in expression of liver-specific biomarkers of mitochondrial biogenesis and activity (Cytc, Tfam, Cpt1, Cpt2, Ucp2, Hmgcs2); concentrations of ATP, AMP, and energy charge; plasma carnitine/acylcarnitine metabolites; or peroxisomal fatty acid oxidation. Conclusions In male Wistar rats, dietary carbohydrate was converted into specific fatty acids via hepatic lipogenesis, contributing to higher plasma TG and total fatty acids compared with high-fat feeding. In contrast, the high-fat, low-carbohydrate feeding increased hepatic fatty acid content, without affecting hepatic mitochondrial fatty acid oxidation.

Investigating pharmacological mechanisms of andrographolide on non-alcoholic steatohepatitis (NASH): A bioinformatics approach of network pharmacology

Article

Full-text available

May 2021

Objective To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases. Methods The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein-protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms. Results The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of de novo fatty acids synthesis, anti-inflammation and anti-oxidation. Conclusion This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.

Combined Metabolic Activators Decrease Liver Steatosis by Activating Mitochondrial Metabolism in a Golden Syrian Hamster Study

Article

Jan 2021

Calcium to magnesium intake ratio and non-alcoholic fatty liver disease development: a case-control study

Article

Full-text available

Mar 2021
BMC Endocr Disord

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Adoption of sedentary life style and westernized diet are shown to be associated with development of NAFLD. Since previous studies suggested that calcium (Ca) to magnesium (Mg) ratio intake is associated with some chronic diseases including dyslipidemia and insulin resistance, we designed this study to find any possible association between this ratio and NAFLD development. Methods The NAFLD was diagnosed using Fibroscan according to a CAP cut-off value of 263 dB/m. Dietary intakes of one hundred and ninety-six patients with incident NAFLD diagnosis, and eight hundred and three controls without NAFLD were assessed using a valid food frequency questionnaire (FFQ). Dietary nutrients were calculated using Nutritionist IV software. Results Age of the study population (57 % female) was 43.2 ± 14.1 years. In addition, energy-adjusted daily calcium to magnesium intake ratio was 2.34 ± 0.57 and 2.73 ± 0.69 for control and case groups, respectively. In the multivariable-adjusted model, after adjustment for potential confounding variables; including, age, gender, BMI, alcohol consumption, smoking, diabetes, physical activity, energy, dietary fiber, carbohydrate, fat, and protein intakes, participants in the third (Q3) and fourth (Q4) quartile of Ca/Mg ratio intake had a greater development of incidental NAFLD compared to the lowest quartile (Q1) [(OR = 2.86; 95 % CI: 1.20–6.81), (P-value = 0.017) and (OR = 5.97; 95 % CI: 2.54–14.01), (P-value

Combined Metabolic Activators decrease liver steatosis by activating mitochondrial metabolism in a Golden Syrian hamster study

Preprint

Full-text available

Feb 2021

The prevalence of non-alcohol fatty liver disease (NAFLD), defined as the liver's excessive fat accumulation, continues to increase dramatically. We have recently revealed the molecular mechanism underlying NAFLD using in-depth multi-omics profiling and identified that combined metabolic activators (CMA) could be administered to decrease the amount of hepatic steatosis (HS) in mouse model and NAFLD patients based on systems analysis. Here, we investigated the effects of a CMA including L-carnitine, N-acetyl-l-cysteine, nicotinamide riboside and betaine on a Golden Syrian hamster NAFLD model fed with HFD, and found that HS was decreased with the administration of CMA. To explore the mechanisms involved in the clearance HS, we generated liver transcriptomics data before and after CMA administration, and integrated these data using liver-specific genome-scale metabolic model of liver tissue. We systemically determined the molecular changes after the supplementation of CMAs and found that it activates mitochondria in the liver tissue by modulating the global fatty acid, amino acids, antioxidant and folate metabolism.

Relationship Between Serum Uric Acid Levels and Non-alcoholic Fatty Liver Disease in the Non-Obese Chinese Population: A Secondary Analysis Based on A Cross-Sectional Study

Preprint

Full-text available

Jan 2021

Background: Non-alcoholic fatty liver disease (NAFLD) is linked to some metabolic disorders. Herein, we explored the relationship of levels of serum uric acid （SUA）with NAFLD in a population of non-obese Chinese. Methods: This was a cross-sectional study that involved 183,903 Chinese men and women with an average age of 40.98 years who underwent physical examinations at a health screening center at Wenzhou People’s Hospital. We defined NAFLD by ultrasound detection of steatosis. We employed univariate analysis along with multivariate Cox proportional hazards analyses to investigate the relationship of SUA level with NAFLD. Moreover, we employed the receiver operating characteristic curve to establish the SUA cutoffs of estimating NAFLD. Results: Overall, 25,501 participants (13.9%) had NAFLD. The NAFLD ORs were 1.47 (95% CI 1.35 to 1.59), 2.01 (95% CI 1.85 to 2.18) and 2.77 (95% CI 2.55 to 3.02) compared with Q1.AUC values for SUA ratios was 0.728. The optimal SUA level cut-off value for identification of NAFLD was 287.5, with a specificity and a sensitivity of 60.7% and 73.9%, respectively. Conclusion: High Serum uric acid levels shows positive correlation with NAFLD. SUA constitutes a cheap, simple, non-invasive, as well as a beneficial biomarker that could be utilized to forecast NAFLD in the non-obese Chinese population.

Nutritional Approaches for the Management of Nonalcoholic Fatty Liver Disease: An Evidence-Based Review

Article

Full-text available

Dec 2020

Nonalcoholic fatty liver disease (NAFLD) is on the rise worldwide representing a public health issue. Its coexistence with obesity and other metabolic alterations is highly frequent. Therefore, current therapy interventions for NAFLD are mainly focused on progressive weight loss through modulation of overall calorie intake with or without specific macronutrient adjustments. Furthermore, other relevant nutritional interventions are built on food selection and time-restricted eating. Since every strategy might bring different results, choosing the optimal diet therapy for a patient is a complicated task, because NAFLD is a multifactorial complex disease. Importantly, some factors need to be considered, such as nutrition-based evidence in terms of hepatic morphophysiological improvements as well as adherence of the patient to the meal plan and adaptability in their cultural context. Thus, the purpose of this review is to explore and compare the subtleties and nuances of the most relevant clinical practice guidelines and the nutritional approaches for the management of NAFLD with a special attention to tangible outcomes and long-term adherence.

Liver Regeneration after Hepatectomy and Partial Liver Transplantation

Article

Full-text available

Nov 2020
INT J MOL SCI

The liver is a unique organ with an abundant regenerative capacity. Therefore, partial hepatectomy (PHx) or partial liver transplantation (PLTx) can be safely performed. Liver regeneration involves a complex network of numerous hepatotropic factors, cytokines, pathways, and transcriptional factors. Compared with liver regeneration after a viral-or drug-induced liver injury, that of post-PHx or-PLTx has several distinct features, such as hemodynamic changes in portal venous flow or pressure, tissue ischemia/hypoxia, and hemostasis/platelet activation. Although some of these changes also occur during liver regeneration after a viral-or drug-induced liver injury, they are more abrupt and drastic following PHx or PLTx, and can thus be the main trigger and driving force of liver regeneration. In this review, we first provide an overview of the molecular biology of liver regeneration post-PHx and-PLTx. Subsequently, we summarize some clinical conditions that negatively, or sometimes positively, interfere with liver regeneration after PHx or PLTx, such as marginal livers including aged or fatty liver and the influence of immunosuppression.

Liver fat quantification: where do we stand?

Article

Full-text available

Nov 2020

Excessive intracellular accumulation of triglycerides in the liver, or hepatic steatosis, is a highly prevalent condition affecting approximately one billion people worldwide. In the absence of secondary cause, the term nonalcoholic fatty liver disease (NAFLD) is used. Hepatic steatosis may progress into nonalcoholic steatohepatitis, the more aggressive form of NAFLD, associated with hepatic complications such as fibrosis, liver failure and hepatocellular carcinoma. Hepatic steatosis is associated with metabolic syndrome, cardiovascular disease and represents an independent risk factor for type 2 diabetes, cardiovascular disease and malignancy. Percutaneous liver biopsy is the current reference standard for NAFLD assessment; however, it is an invasive procedure associated with complications and suffers from high sampling variability, impractical for clinical routine and drug efficiency studies. Therefore, noninvasive imaging methods are increasingly used for the diagnosis and monitoring of NAFLD. Among the methods quantifying liver fat, chemical-shift-encoded MRI (CSE-MRI)-based proton density fat-fraction (PDFF) has shown the most promise. MRI-PDFF is increasingly accepted as quantitative imaging biomarker of liver fat that is transforming daily clinical practice and influencing the development of new treatments for NAFLD. Furthermore, CT is an important imaging method for detection of incidental steatosis, and the practical advantages of quantitative ultrasound hold great promise for the future. Understanding the disease burden of NAFLD and the role of imaging may initiate important interventions aimed at avoiding the hepatic and extrahepatic complications of NAFLD. This article reviews clinical burden of NAFLD, and the role of noninvasive imaging techniques for quantification of liver fat.

The effect of hepatic steatosis and fibrosis on liver weight and dimensions

Article

Full-text available

Aug 2020
Leg Med

The liver is the most commonly injured abdominal organ, accounting for around half of abdominal organ injuries. The emergence of liver injury is determined by the injury mechanism, force, and tissue vulnerability. The vulnerability of the liver depends on the strength of the capsule and parenchyma, as well as the weight and dimensions of the liver. The common hepatic diseases, like steatosis, fibrosis, and cirrhosis, can change the organ weight and dimensions, but their exact correlation is not well known. This study was designed to evaluate the correlation between liver diseases, weight, and dimensions. The liver weight, horizontal, vertical, and antero-posterior length were measured obtained by 213 forensic autopsies. The recorded data were compared with body height, age, and liver histology. Body height positively correlated with liver weight (R²=0.252), but the correlation was much stronger in the case of livers without structural disease (R²=0.450). The liver size seems to significantly decrease with age (R²=0.081), but the effect is mostly due to structural alterations that are proven by histology. The comparison of the liver weight in various histological groups clearly indicated that steatosis increases the liver size, but fibrosis does not (if no steatosis is present at the same time). In general, liver dimensions increase proportionally to the liver weight. However, hepatic steatosis causes disproportional enlargement: it does not have a significant effect on the horizontal dimension and has only a minor effect on the vertical dimension. Steatosis affects disproportionally the dimensions with a strange tendency to expand liver anteroposteriorly.

Lipophagy Impairment Is Associated With Disease Progression in NAFLD

Article

Full-text available

Jul 2020

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is associated with aging and features of metabolic syndrome. Lipotoxicity and oxidative stress are consequent to dysregulation of lipid metabolism and lipid accumulation, leading to hepatocyte injury and inflammation. Lipophagy consists in selective degradation of intracellular lipid droplets by lysosome and mounting evidence suggests that lipophagy is dysregulated in NAFLD. Here we demonstrate lipophagy impairment in experimental models of NAFLD and in a NAFLD patient cohort by histomorphological and molecular analysis. High fat diet-fed C57BL/6J male mice and high-fat/high-glucose cultured Huh7 cells showed accumulation of both p62/SQSTM1 and LC3-II protein. In 59 NAFLD patients, lipid droplet-loaded lysosomes/lipolysosomes and p62/SQSTM1 clusters correlated with NAFLD activity score (NAS) and with NAS and fibrosis stage, respectively, and levels of expression of lysosomal genes, as well as autophagy-related genes, correlated with NAS and fibrosis stage. An increased amount of lipid droplets, lipolysosomes and autophagosomes was found in subjects with NAFLD compared to healthy subjects at ultrastructural level. In conclusion, here we observed that NAFLD is characterized by histological, ultrastructural and molecular features of altered autophagy that is associated with an impaired lipid degradation. Impaired autophagy is associated with features of advanced disease. Lipopolysosomes, as individuated with light microscopy, should be further assessed as markers of disease severity in NAFLD patients.

Higher Serum Uric Acid Level Predicts Non-alcoholic Fatty Liver Disease: A 4-Year Prospective Cohort Study

Article

Full-text available

Apr 2020

Background: Non-alcoholic fatty liver disease (NAFLD) has become a serious disease affecting people's health in the world. This article studies the causal relationship between NAFLD and serum uric acid (SUA) levels. Methods: During the 4 years of follow-up in a fixed cohort that was established in 2014, 2,832 follow-up subjects without NAFLD were finally included in this study. The study population was divided into four groups according to baseline SUA levels. Cox hazard regression model and Kaplan–Meier survival curves analysis were used to predict risk factors of NAFLD. The receiver operating characteristic curve analyses were used to determine SUA cutoffs for predicting NAFLD. Results: The cumulative prevalence rates of NAFLD were 33.97% (962/2,832), 38.93% (758/1,947) in males and 23.05% (204/885) in females. The results showed that males had a higher incidence of NAFLD (χ2 = 68.412, P = 0.000). The Cox regression analysis disclosed that the hazard ratios of NAFLD [95% confidence interval (CI)] were 1.431 (95% CI, 1.123~1.823), 1.610 (95% CI, 1.262–2.054), and 1.666 (95% CI, 1.287–2.157) across the second to the fourth quartile of SUA adjusted for other confounders. The SUA cutoffs, sensitivity, specificity, and area under the curve (AUC) (95% CI) were ≥288.5 μmol/L, 75.5, 46.5%, 0.637(0.616–0.658), respectively, for total; ≥319.5 μmol/L, 65.8%, 48.4%, 0.590 (0.564–0.615), respectively, for males; and ≥287.5 μmol/L, 51.0%, 75.6%, 0.662 (0.619–0.704), respectively, for females. Kaplan–Meier survival curves revealed that individuals with higher SUA level had an increased risk of NAFLD in comparison to lower SUA level (P = 0.000). Conclusion: Serum uric acid is positively correlated with NAFLD, and elevated SUA level can be used as an independent predictor for NAFLD.

Analysis Of Risk Factors For Nonalcoholic Fatty-Liver Disease In Hepatitis B Virus Infection: A Case–Control Study

Article

Full-text available

Oct 2019

Background: Nonalcoholic fatty-liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although NAFLD has been studied extensively, potential risk factors for NAFLD among chronic hepatitis B (CHB) patients and their comparison with healthy individuals have remained understudied in Iran. As such, we examined the association between HBV infection and the development of NAFLD in two groups. Methods: A case-control study was done on 376 CHB patients and 447 healthy subjects randomly selected from Birjand, South Khorasan province, Iran. We used logistic regression to estimate adjusted ORs with 95% CIs for incidence of NAFLD. Potential risk factors for NAFLD were evaluated while adjusting for age, sex, marital status, and educational level. Also, χ2 was used to compare demographic characteristics between the two groups. Results: A total of 373 CHB patients (mean age 40.1±12.9 years) versus 447 individuals in the control group (mean age 39.8±13.9 years) were included in this study (p=0.337). Liver characteristics were found to be significantly different in CHB and healthy groups (p<0.05). According to the results obtained from logistic regression, the adjusted OR (95% CI) for NAFLD incidence of comparing HBsAg-positive to HBsAg-negative participants was 0.62 (0.45-0.84). Conclusion: The results suggested that HBsAg seropositivity was associated with lower risk of developing NAFLD. This study also revealed that mild cases of fatty liver in carriers of hepatitis B are more common than in healthy subjects. However, moderate and severe cases of this condition are more common in healthy people than in hepatitis B carriers.

Relationships between Metabolic Comorbidities and Occurrence, Severity, and Outcomes in Patients with Acute Pancreatitis: A Narrative Review

Article

Full-text available

Oct 2019
BMRI

Background . The population of patients with acute pancreatitis treated by the staff at our department of gastroenterology includes those with mild and self-limited disease ranging to those with severe and fatal disease. Early diagnosis and accurate prediction of the severity and outcome of this disease, which is commonly seen by our department, is important for a successful outcome. Metabolic comorbidities (e.g., diabetes mellitus, fatty liver, obesity, and metabolic syndrome) are relevant to the severity and progression of many diseases. The objective of this review was to examine clinical relationships between metabolic comorbidities and occurrence, severity, and outcome of acute pancreatitis.

Automated Liver Fat Quantification at Nonenhanced Abdominal CT for Population-based Steatosis Assessment

Article

Sep 2019

Background Nonalcoholic fatty liver disease and its consequences are a growing public health concern requiring cross-sectional imaging for noninvasive diagnosis and quantification of liver fat. Purpose To investigate a deep learning-based automated liver fat quantification tool at nonenhanced CT for establishing the prevalence of steatosis in a large screening cohort. Materials and Methods In this retrospective study, a fully automated liver segmentation algorithm was applied to noncontrast abdominal CT examinations from consecutive asymptomatic adults by using three-dimensional convolutional neural networks, including a subcohort with follow-up scans. Automated volume-based liver attenuation was analyzed, including conversion to CT fat fraction, and compared with manual measurement in a large subset of scans. Results A total of 11 669 CT scans in 9552 adults (mean age ± standard deviation, 57.2 years ± 7.9; 5314 women and 4238 men; median body mass index [BMI], 27.8 kg/m2) were evaluated, including 2117 follow-up scans in 1862 adults (mean age, 59.2 years; 971 women and 891 men; mean interval, 5.5 years). Algorithm failure occurred in seven scans. Mean CT liver attenuation was 55 HU ± 10, corresponding to CT fat fraction of 6.4% (slightly fattier in men than in women [7.4% ± 6.0 vs 5.8% ± 5.7%; P < .001]). Mean liver Hounsfield unit varied little by age (<4 HU difference among all age groups) and only weak correlation was seen with BMI (r2 = 0.14). By category, 47.9% (5584 of 11 669) had negligible or no liver fat (CT fat fraction <5%), 42.4% (4948 of 11 669) had mild steatosis (CT fat fraction of 5%-14%), 8.8% (1025 of 11 669) had moderate steatosis (CT fat fraction of 14%-28%), and 1% (112 of 11 669) had severe steatosis (CT fat fraction >28%). Excellent agreement was seen between automated and manual measurements, with a mean difference of 2.7 HU (median, 3 HU) and r2 of 0.92. Among the subcohort with longitudinal follow-up, mean change was only -3 HU ± 9, but 43.3% (806 of 1861) of patients changed steatosis category between first and last scans. Conclusion This fully automated CT-based liver fat quantification tool allows for population-based assessment of hepatic steatosis and nonalcoholic fatty liver disease, with objective data that match well with manual measurement. The prevalence of at least mild steatosis was greater than 50% in this asymptomatic screening cohort. © RSNA, 2019.

Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease

Article

Full-text available

Jul 2019
DIGEST LIVER DIS

Background & aims: Although antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers. Methods: Cross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis ≥ F1-F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ). Results: Overall, 789 subjects were included (52.6% men, age 58.83 ± 6.58 years), 714 had reliable FibroMax. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43-0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30-0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47-0.99, P = 0.045; OR = 0.57, 0.38-0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest. Conclusion: Vitamin E and C intake may be protective from NAFLD-related liver damage.

Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: a meta-analysis

Article

Mar 2019

Objectives The aim of this meta-analysis was to evaluate the diagnostic accuracy of hepatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for the assessment of liver steatosis (LS) with histology as reference standard. Methods A systematic literature search was performed to identify pertinent studies. Quality analyses were conducted by Quality Assessment of Diagnostic Accuracy Studies-2. Diagnostic data were extracted and inconsistency index was calculated for LS≥G1, LS≥G2, and LS=G3, respectively. The area under summary receiver operating characteristic curve (AUC) served as the indicator of diagnostic accuracy. The pooled sensitivity and specificity were calculated if threshold effect was absent. Results Thirteen studies containing 1100 subjects were included. There was significant threshold effect for LS≥G1. The AUCs for LS≥G1, LS≥G2, and LS=G3 were 0.98 (95% confidence interval (CI) 0.76, 1.00), 0.91 (95% CI 0.89, 0.94), and 0.92 (95% CI 0.89, 0.94), respectively. The pooled sensitivities for LS≥G2 and LS=G3 were 0.83 (95% CI 0.75, 0.88) and 0.79 (95% CI 0.63, 0.90), respectively; the pooled specificities for LS≥G2 and LS=G3 were 0.89 (95% CI 0.84, 0.92) and 0.89 (95% CI 0.84, 0.92), respectively. Conclusions MRI-PDFF has high diagnostic accuracy at detecting and grading LS with histology as reference standard, suggesting that MRI-PDFF is able to provide an accurate quantification of LS in clinical trials and patient care. Key Point • MRI-PDFF is able to provide an accurate quantification of LS in clinical trials and patient care.

Effect of soy milk consumption on glycemic status, blood pressure, fibrinogen and malondialdehyde in patients with non-alcoholic fatty liver disease: a randomized controlled trial

Article

Feb 2019
COMPLEMENT THER MED

Objective: Diet plays a critical role in the management of non-alcoholic fatty liver disease (NAFLD). Studies on the NAFLD's experimental models have reported that soy had positive effects on the improvement of metabolic parameters. However, there is a lack of clinical trials regarding the efficacy of whole soy foods. Therefore, this study was conducted to determine the effect of soy milk on some of the metabolic characteristics in patients with NAFLD. Methods: Sixty-sex patients diagnosed with NAFLD were included in this randomized, parallel, controlled trial and were randomly assigned to either the soy milk or control group. Both groups received a 500-deficit calorie diet plan. Also, patients in the soy milk group consumed 240 ml/day soy milk for 8 weeks. Fasting blood sugar (FBS), serum insulin, HOMA-IR, HOMA-β%, and QUICKI as well as serum malondialdehyde (MDA), plasma fibrinogen, and blood pressure (BP) were measured at the beginning and end of the study. Results: After 8-weeks of intervention, soy milk group had a greater significant reduction in serum insulin(-3.44 ± 5.02 vs. -1.09 ± 3.77 μIU/ml, P = 0.04), HOMA-IR (-0.45±0.64 vs -0.14 ± 0.47, P = 0.03), systolic (-3.81±4.15 vs -1.48±2.93 mmHg, P = 0.01) and diastolic (-2.39±2.80 vs. -0.94±2.76 mmHg, P = 0.04) BP, and also, a significant increase in QUICKI (0.02± 0.032 vs. 0.008±0.018, P = 0.04) compared to the control group. While, changes in the FBS, HOMA-β%, fibrinogen, and MDA were not significantly different between the study groups. Conclusion: A low-calorie diet containing soy milk had beneficial effects on serum insulin, HOMA-IR, QUICKI, and BP in patients with NAFLD.

Automated Assessment of T2-Weighted MRI to Differentiate Malignant and Benign Primary Solid Liver Lesions in Noncirrhotic Livers Using Radiomics

Article

Aug 2023
ACAD RADIOL

Rationale and objectives: Distinguishing malignant from benign liver lesions based on magnetic resonance imaging (MRI) is an important but often challenging task, especially in noncirrhotic livers. We developed and externally validated a radiomics model to quantitatively assess T2-weighted MRI to distinguish the most common malignant and benign primary solid liver lesions in noncirrhotic livers. Materials and methods: Data sets were retrospectively collected from three tertiary referral centers (A, B, and C) between 2002 and 2018. Patients with malignant (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) and benign (hepatocellular adenoma and focal nodular hyperplasia) lesions were included. A radiomics model based on T2-weighted MRI was developed in data set A using a combination of machine learning approaches. The model was internally evaluated on data set A through cross-validation, externally validated on data sets B and C, and compared to visual scoring of two experienced abdominal radiologists on data set C. Results: The overall data set included 486 patients (A: 187, B: 98, and C: 201). The radiomics model had a mean area under the curve (AUC) of 0.78 upon internal validation on data set A and a similar AUC in external validation (B: 0.74 and C: 0.76). In data set C, the two radiologists showed moderate agreement (Cohen's κ: 0.61) and achieved AUCs of 0.86 and 0.82. Conclusion: Our T2-weighted MRI radiomics model shows potential for distinguishing malignant from benign primary solid liver lesions. External validation indicated that the model is generalizable despite substantial MRI acquisition protocol differences. Pending further optimization and generalization, this model may aid radiologists in improving the diagnostic workup of patients with liver lesions.

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy

Article

Oct 2021

Background Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. Methods Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. Results Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: -405; ∆AST NAIC: 617, ∆AST DMAT: -380). UR and UL had similar expression of ferroptosis regulators RPL8,HO-1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO-1 and HIFα in DMAT (HO-1 NAIC: 6.93, HO-1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin-7) differences were noted. Conclusion PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.

Simplified Guide to MR Elastography in Early Detection of Hepatic Fibrosis with Case Reports: The New Norm in Assessing Liver Health

Article

Full-text available

Oct 2021

The current unhealthy diets and sedentary lifestyle have led to increase in the prevalence of diabetes and metabolic syndrome globally. Fatty liver is a common occurrence in metabolic syndrome. The liver health is often ignored due to delayed warning signs. Fatty changes of the liver is one of the common findings in ultrasonography. Ultrasound does not detect fibrosis except when cirrhosis is developed. Early stages of fibrosis are asymptomatic with no significant laboratory or preliminary imaging findings. With fibrosis, the elasticity of the liver is reduced and becomes stiffer. Over the years, many techniques have developed to assess the stiffness of the liver, starting from palpation, ultrasonography, and recently developed magnetic resonance elastography (MRE). In this article, we have tried to simplify the concepts of MRE to detect fibrosis and present few case reports. The basic steps involved in generating elastograms and interpretation with some insight on how to incorporate it into the clinical workflow are discussed. MRE is superior to various other available techniques and even offers certain advantages over biopsy. MRE is FDA approved for liver fibrosis since 2009, yet it is hardly used in the Indian setting. MRE is a safe and noninvasive technique to evaluate a large volume of the liver and can be a new norm for the evaluation of fatty liver. Magnetic resonance imaging (MRI)-based elastography techniques hold an exciting future in providing mechanical properties of tissues in various organs like spleen, brain, kidney, and heart.

Evaluation of fatty liver disease using ultrasound in a semi-urban population in Jos, North Central Nigeria

Article

Full-text available

Jul 2021

Background: Fat liver is one of the most common abnormalities of the liver depicted on ultrasound and whose impact has not been fully evaluated in Nigeria. Ultrasound scan is an imaging modality that is cheap and readily available and comes in handy in evaluating this disease. Aim of the current study was to determine the relationship of Fatty liver with age, gender, alcohol consumption and body habitus.Methods: This is a hospital-based cross-sectional study involving 316 subjects diagnosed with fatty liver on ultrasound scan. A structured questionnaire was administered to each subject to ascertain their age, sex, and alcohol intake. The weight and height of all subjects were also measured and the body mass index (BMI) was calculated.Results: The study comprises 151 (47.8%) males and 165 (52.2%) females respectively. A good number of the participants 232 (73.4%) were between the age of 30-59 years. The majority of the participants had of 30 kg/m2 and above. Majority of the participants 225 (71.2%) do not consume alcohol. The study showed a positive but weak correlation between increasing BMI and fatty liver span. The study revealed that most participants with liver span <15.9 cm (57.1%) or ≥16 cm (75.5%) have BMI ≥30 kg/m2.Conclusions: This study showed fatty liver is common in all ages and gender but commoner in the middle age groups with strong relationship between increasing body weight and fatty liver, but a weak relationship with regards to the span of the liver.

Modeling alcohol-associated liver disease in a human Liver-Chip

Article

Full-text available

Jul 2021

Alcohol-associated liver disease (ALD) is a global health issue and leads to progressive liver injury, comorbidities, and increased mortality. Human-relevant preclinical models of ALD are urgently needed. Here, we leverage a triculture human Liver-Chip with biomimetic hepatic sinusoids and bile canaliculi to model ALD employing human-relevant blood alcohol concentrations (BACs) and multimodal profiling of clinically relevant endpoints. Our Liver-Chip recapitulates established ALD markers in response to 48 h of exposure to ethanol, including lipid accumulation and oxidative stress, in a concentration-dependent manner and supports the study of secondary insults, such as high blood endotoxin levels. We show that remodeling of the bile canalicular network can provide an in vitro quantitative readout of alcoholic liver toxicity. In summary, we report the development of a human ALD Liver-Chip as a powerful platform for modeling alcohol-induced liver injury with the potential for direct translation to clinical research and evaluation of patient-specific responses.

Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis

Article

Apr 2021

Objectives: To investigate associations between histology and hepatic mechanical properties measured using multiparametric magnetic resonance elastography (MRE) in adults with known or suspected nonalcoholic fatty liver disease (NAFLD) without histologic fibrosis. Methods: This was a retrospective analysis of 88 adults who underwent 3T MR exams including hepatic MRE and MR imaging to estimate proton density fat fraction (MRI-PDFF) within 180 days of liver biopsy. Associations between MRE mechanical properties (mean shear stiffness (|G*|) by 2D and 3D MRE, and storage modulus (G'), loss modulus (G″), wave attenuation (α), and damping ratio (ζ) by 3D MRE) and histologic, demographic and anthropometric data were assessed. Results: In univariate analyses, patients with lobular inflammation grade ≥ 2 had higher 2D |G*| and 3D G″ than those with grade ≤ 1 (p = 0.04). |G*| (both 2D and 3D), G', and G″ increased with age (rho = 0.25 to 0.31; p ≤ 0.03). In multivariable regression analyses, the association between inflammation grade ≥ 2 remained significant for 2D |G*| (p = 0.01) but not for 3D G″ (p = 0.06); age, sex, or BMI did not affect the MRE-inflammation relationship (p > 0.20). Conclusions: 2D |G*| and 3D G″ were weakly associated with moderate or severe lobular inflammation in patients with known or suspected NAFLD without fibrosis. With further validation and refinement, these properties might become useful biomarkers of inflammation. Age adjustment may help MRE interpretation, at least in patients with early-stage disease. Key points: • Moderate to severe lobular inflammation was associated with hepatic elevated shear stiffness and elevated loss modulus (p =0.04) in patients with known or suspected NAFLD without liver fibrosis; this suggests that with further technical refinement these MRE-assessed mechanical properties may permit detection of inflammation before the onset of fibrosis in NAFLD. • Increasing age is associated with higher hepatic shear stiffness, and storage and loss moduli (rho = 0.25 to 0.31; p ≤ 0.03); this suggests that age adjustment may help interpret MRE results, at least in patients with early-stage NAFLD.

Serum uric acid is positively associated with the prevalence of nonalcoholic fatty liver in non-obese type 2 diabetes patients in a Chinese population

Article

Feb 2021
J DIABETES COMPLICAT

Aims To investigate whether SUA is independently associated with NAFLD in non-obese type 2 diabetic patients in a Chinese population. Methods A cross-sectional study was carried out among 400 non-obese type 2 diabetic inpatients. Patients were stratified according to SUA levels and presence/absence of NAFLD. The clinical and laboratory features were collected retrospectively. Multivariate logistic regression analysis was conducted to estimate odds ratios of SUA for NAFLD. Results The levels of SUA were significantly higher in patients with NAFLD than those without NAFLD. SUA was positively associated with the risk factors of NAFLD such as BMI, serum insulin and lipids. The odds of NAFLD were increasingly higher from the second to the fourth quartile of SUA as compared to the lowest quartile. After adjustment for age, gender, BMI and other metabolic components, the odds of NAFLD remained significantly increased for quartile 4. Conclusions SUA levels are strongly and independently associated with the prevalence of NAFLD. SUA may be used as an useful predictor to stratify the higher risks for NAFLD of non-obese type 2 diabetes patients.

Contrast-Enhanced Ultrasound (CEUS) quantification assessment of focal fatty variations in liver parenchyma

Article

Sep 2020

Objectives: The purpose of this study was to quantify contrast-enhanced ultrasound enhancement of focal fatty sparing (FFS) and focal fatty infiltration (FFI) and compare it with adjacent liver parenchyma. Methods: This was a retrospective observational study yielding 42 cases in the last 4 years. Inclusion criteria were a focal liver lesion, adequate video availability, and an established diagnosis of FFS or FFI based on clinical or imaging follow-up or a second modality. Contrast-enhanced ultrasound examinations were performed with a standard low-mechanical index technique. Commercially available software calculated quantitative parameters for a focal liver lesion and a reference area of liver parenchyma, producing relative indices. Results: In total, 42 patients were analyzed (19 male) with a median age of 18 (interquartile range, 42) years and a median lesion diameter of 30 (interquartile range, 16) mm. The cohort included 26 with FFS and 16 with FFI. Subjectively assessed, 27% of FFS and 25% of FFI were hypoenhancing in the arterial phase, and 73% of FFS and 75% of FFI were isoenhancing. In the venous and delayed phases, all lesions were isoenhancing. The peak enhancement (P = .001), wash-in area under the curve (P < .01), wash-in rate (P = .023), and wash-in perfusion index (P = .001) were significantly lower in FFS compared with adjacent parenchyma but not the mean transit time. In the FFI subgroup, no significant difference was detected. Comparing relative parameters, only the wash-in rate was significantly (P = .049) lower in FFS than FFI. The mean follow-up was 2.8 years. Conclusions: Focal fatty sparing shows significantly lower and slower enhancement than the liver parenchyma, whereas FFI enhances identically. Focal fatty sparing had a significantly slower enhancement than FFI.

Рrospects for the use of “dry” carbon dioxide baths in patients with chronic viral hepatitis c with concomitant non-alcoholic fatty liver disease (literature review and own research)

Article

Full-text available

Jun 2020

Anna IZHA

The paper analyzes modern views on the etiology, epidemiology, pathogenesis, methods of treating patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease (NAFLD), discusses the possibility of using "dry" carbon dioxide baths (DCDB) in this category of patients. Our research was conducted to study the effectiveness of the integrated use of antiviral therapy (AVT) and DCDB procedures in patients with chronic hepatitis C with concomitant NAFLD. The authors of the study were the first to suggest using of DCDB in this category of patients. Based on the results obtained, for the first time, ideas about the specificity of the DCDBʹs effect on the clinical course of the underlying and concomitant diseases, on the functional state of the liver, the dynamics of lipid metabolism, and ultrasonographic parameters of the liver were detailed. It is concluded that DCDB can be successfully used in the complex treatment of patients with chronic hepatitis C with concomitant NAFLD.

Prognostic Analysis of Acute Pancreatitis with Fatty Liver

Article

Jan 2020

The Role of Bone Morphogenetic Protein Signaling in Non-Alcoholic Fatty Liver Disease

Article

Full-text available

Jun 2020

Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two BMP inhibitors reduced hepatic triglyceride content in diabetic (db/db) mice. BMP inhibitor-induced decrease in hepatic triglyceride levels was associated with decreased mRNA encoding Dgat2, an enzyme integral to triglyceride synthesis. Treatment of hepatoma cells with BMP2 induced DGAT2 expression and activity via intracellular SMAD signaling. In humans we identified a rare missense single nucleotide polymorphism in the BMP type 1 receptor ALK6 (rs34970181;R371Q) associated with a 2.1-fold increase in the prevalence of NAFLD. In vitro analyses revealed R371Q:ALK6 is a previously unknown constitutively active receptor. These data show that BMP signaling is an important determinant of NAFLD in a murine model and is associated with NAFLD in humans.

Causes of liver steatosis influence the severity of ischemia reperfusion injury and survival after liver transplantation in rats

Article

Jun 2020

Liver steatosis is a leading cause of graft disposal in liver transplantation; however, the degree of steatosis has been so far the almost single factor determining whether the grafts is acceptable or not. We investigated how the cause of liver steatosis affects graft function in rat orthotopic liver transplantation (OLT). OLT was performed using two types of steatotic liver grafts; the fasting and hyper alimentation (FHA) and methionine and choline deficient diet (MCDD) models. The FHA and 4‐week MCDD feeding (MCDD4wk) groups showed similar liver triglyceride levels without signs of steatohepatitis; therefore, the two groups were compared in the following experiment. With 6‐hour cold storage, 7‐days survival rate after OLT was far worse in the FHA than the MCDD4wk group (0% vs. 100%, P = 0.002). With 1‐hour cold storage, the FHA group showed higher aspartate and alanine aminotransferase levels and histological injury score in zone 1 and 2 at 24 hours after reperfusion than the Normal liver and MCDD4wk groups. Intrahepatic microcirculation and tissue ATP level were significantly lower in the FHA group after reperfusion. Hepatocyte necrosis, sinusoidal endothelial cell injury and abnormal swelling of mitochondria were also found in the FHA group after reperfusion. Tissue malondialdehyde levels were higher in the MCDD4wk group before and after reperfusion; however, the grafts upregulated several antioxidant enzymes soon after reperfusion. Conclusion: Even though the degree of steatosis was equivalent, the two liver steatosis models possessed quite unique basal characteristics and showed completely different response against ischemia reperfusion injury and survival after transplantation. Our results demonstrated that the degree of fat accumulation is not a single determinant for the fate of steatotic liver graft.

Dietary Patterns Are Associated with Likelihood of Hepatic Steatosis among US Adults

Article

Apr 2020

Background and aims Non‐alcoholic fatty liver disease (NAFLD) is a rapidly growing public health problem. In this study, we explored the association between dietary patterns (DPs) and fatty liver and liver function tests. Methods This was a cross‐sectional study using data from the US community‐based National Health and Nutrition Examination Survey (NHANES). Participants with data on dietary intake, blood pressure and status for diabetes mellitus were analyzed. DPs were determined by principal components analysis (PCA). Analysis of covariance (ANCOVA) and logistic regression models accounted for the survey design and sample weights. Results Of the 20643 eligible participants, 45.7% had prevalent fatty liver. Three DPs collectively explained 50.8% of variance in dietary nutrients consumption. The first DP was representative of a diet containing high levels of saturated and mono‐unsaturated fatty acids; the second DP comprised vitamins and trace elements; and the third DP was mainly representative of polyunsaturated fatty acids. In adjusted multivariable regression models, participants in the top quarter of the second DP had 34% lower odds of prevalent fatty liver [odds ratio 0.66 (95% confidence interval [CI] 0.43‐0.71)], while those in the quarter of the first DP subject had 86% higher odds [1.86 (95% CI: 1.42‐2.95)] of prevalent fatty liver, relative to participants in the bottom quarter of each of the DPs. Conclusion Our findings suggest that a diet with high load of vitamins, minerals and fiber content is associated with lower NAFLD prevalence.

Association of fatty liver disease with mortality outcomes in an Eastern Finland male cohort

Article

Full-text available

May 2019

Objective Fatty liver disease (FLD) has been associated with extrahepatic morbidity outcomes. However, reports on the association of FLD, assessed using fatty liver index (FLI), with mortality outcomes have been inconsistent. Our objective was to examine the effect of metabolic factors (blood pressure, insulin, fasting glucose, lipoproteins) on the associations of FLI with mortality outcomes among middle-aged men. Study design Prospective cohort study. Methods Our subjects were 1893 men at baseline from 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Multivariable Cox regression models were used to analyse the association of baseline FLI, with the HRs for all-cause, disease, cardiovascular, non-cardiovascular and cancer mortality outcomes. Results The mean FLI in the FLI categories were 16.2 in the low and reference category (FLI<30), 43.4 in the intermediate FLI category (FLI=30–<60) and 77.5 in the high FLI (FLD) category (FLI≥60). Over an average follow-up of 20 years, 848 disease deaths were recorded through Finnish national cause of death register. In models adjusted for constitutional, lifestyle and inflammatory factors, for the high (FLI≥60) vs low (FLI<30) FLI category, the HRs (95% CI) for mortality outcomes were 1.50 (1.26–1.78) for all-cause mortality; 1.56 (1.31–2.86) for disease mortality; 1.51 (1.18–1.94) for cardiovascular disease (CVD) mortality; 1.42 (1.12–1.80) for non-CVD mortality and 1.45 (1.02–2.07) for cancer mortality. With further adjustment for metabolic factors, the HRs were 1.25 (1.01–1.53) for all-cause mortality; 1.26 (1.02–1.56) for disease mortality; 1.06 (0.78–1.43) for CVD mortality; 1.46 (1.09–1.94) for non-CVD mortality and 1.49 (0.97–2.29) for cancer mortality. Conclusion High FLI (FLD) is associated with increased risks of mortality outcomes. The FLI-CVD mortality association can be largely explained by metabolic factors. Persons with FLD should be monitored for metabolic deterioration and extrahepatic morbidity to improve their prognoses.

Evidence and Recommendations for Imaging Liver Fat in Children, Based on Systematic Review

Article

Full-text available

Sep 2013

& Aims: Fatty liver is a common problem in children, and increases their risk for cirrhosis, diabetes, and cardiovascular disease. Liver biopsy is the clinical standard for diagnosing and grading fatty liver. However, non-invasive imaging modalities are needed to assess liver fat in children. We performed a systematic review of studies that evaluated imaging of liver fat in children. We searched PubMed for original research articles in peer-reviewed journals from January 1,1982 through December 31, 2012 using the key words "imaging liver fat." Studies included those in English, and those performed in children from birth to 18 y of age. To be eligible for inclusion, studies were required to measure hepatic steatosis via an imaging modality and a quantitative comparator as the reference standard. We analyzed 9 studies comprising 610 children; 4 studies assessed ultrasonography and 5 assessed magnetic resonance imaging (MRI). Ultrasonography was used in the diagnosis of fatty liver with positive predictive values of 47-62%. There was not a consistent relationship between ultrasound steatosis score and the reference measurement of hepatic steatosis. Liver fat as measurements by MRI or by spectroscopy varied with the methodologies used. Liver fat measurements by MRI correlated with results from histologic analyses, but sample size did not allow for assessment of diagnostic accuracy. Available evidence does not support the use of ultrasonography for the diagnosis or grading of fatty liver in children. Although MRI is a promising approach, the data are insufficient to make evidence-based recommendations regarding its use in children for assessment of hepatic steatosis.

Resolution of Fatty Liver and Risk of Incident Diabetes

Article

Full-text available

Jul 2013
J CLIN ENDOCR METAB

Context: Fatty liver is associated with an increased risk of type 2 diabetes, but whether an increased risk remains in people in whom fatty liver resolves over time is not known. Objective: The objective of the study was to assess the risk of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened over 5 years. Design and methods: A total of 13,218 people without diabetes at baseline from a Korean occupational cohort were examined at baseline and after 5 years, using a retrospective study design. Fatty liver status was assessed at baseline and follow-up as absent, mild, or moderate/severe using standard ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for incident diabetes at follow-up were estimated after controlling for multiple potential confounders. Results: Two hundred thirty-four people developed incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640, and progressed from mild to moderate/severe in 324 people. Resolution of fatty liver was not associated with a risk of incident diabetes [aOR 0.95 (95% CIs 0.46, 1.96), P = .89]. Development of new fatty liver was associated with incident diabetes [aOR 2.49 (95% CI 1.49, 4.14), P < .001]. In individuals in whom severity of fatty liver worsened over 5 years (from mild to moderate/severe), there was a marked increase in the risk of incident diabetes [aOR 6.13 (2.56, 95% CI 14.68) P < .001 (compared with the risk in people with resolution of fatty liver)]. Conclusion: Change in fatty liver status over time is associated with markedly variable risks of incident diabetes.

Prevalence of Nonalcoholic Fatty Liver Disease in the United States: The Third National Health and Nutrition Examination Survey, 1988-1994

Article

Full-text available

May 2013

Previous estimates of the prevalence of nonalcoholic fatty liver disease (NAFLD) in the US population relied on measures of liver enzymes, potentially underestimating the burden of this disease. We used ultrasonography data from 12,454 adults who participated in the Third National Health and Nutrition Examination Survey, conducted in the United States from 1988 to 1994. We defined NAFLD as the presence of hepatic steatosis on ultrasonography in the absence of elevated alcohol consumption. In the US population, the rates of prevalence of hepatic steatosis and NAFLD were 21.4% and 19.0%, respectively, corresponding to estimates of 32.5 (95% confidence interval: 29.9, 35.0) million adults with hepatic steatosis and 28.8 (95% confidence interval: 26.6, 31.2) million adults with NAFLD nationwide. After adjustment for age, income, education, body mass index (weight (kg)/height (m)(2)), and diabetes status, NAFLD was more common in Mexican Americans (24.1%) compared with non-Hispanic whites (17.8%) and non-Hispanic blacks (13.5%) (P = 0.001) and in men (20.2%) compared with women (15.8%) (P < 0.001). Hepatic steatosis and NAFLD were also independently associated with diabetes, with insulin resistance among people without diabetes, with dyslipidemia, and with obesity. Our results extend previous national estimates of the prevalence of NAFLD in the US population and highlight the burden of this disease. Men, Mexican Americans, and people with diabetes and obesity are the most affected groups.

Pediatric non alcoholic fatty liver disease: Old and new concepts on development, progression, metabolic insight and potential treatment targets

Article

Full-text available

Mar 2013
BMC Pediatr

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. NAFLD has emerged to be extremely prevalent, and predicted by obesity and male gender. It is defined by hepatic fat infiltration >5% hepatocytes, in the absence of other causes of liver pathology. It includes a spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to various degrees of necrotic inflammation and fibrosis (non-alcoholic steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with severe metabolic impairments, determining an increased risk of developing the metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Both genetic and environmental factors seem to be involved in the development and progression of the disease, but its physiopathology is not yet entirely clear. In view of this mounting epidemic phenomenon involving the youth, the study of NAFLD should be a priority for all health care systems. This review provides an overview of current and new clinical-histological concepts of pediatric NAFLD, going through possible implications into patho-physiolocical and therapeutic perspectives.

Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis

Article

Full-text available

Mar 2013
NAT REV GASTRO HEPAT

NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mellitus and abdominal obesity. As lifestyles have become increasingly sedentary and dietary patterns have changed, the worldwide prevalence of NAFLD has increased dramatically and is projected to be the principal aetiology for liver transplantation within the next decade. Importantly, a growing body of clinical and epidemiological evidence suggests that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing both cardiovascular disease and type 2 diabetes mellitus. This article reviews the evidence that suggests NAFLD is a multisystem disease and the factors that might determine interindividual variation in the development and progression of its major hepatic and extrahepatic manifestations (principally type 2 diabetes mellitus and cardiovascular disease).

Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

Article

Full-text available

Jul 2012
WORLD J GASTROENTERO

Henry Völzke

Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term "non-alcoholic" fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and "non-alcoholic" fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and "non-alcoholic" fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and "non-alcoholic" fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level.

Nutrition and physical activity in NAFLD: An overview of the epidemiological evidence

Article

Full-text available

Aug 2011
WORLD J GASTROENTERO

Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. The efficacy and safety profile of pharmacotherapy in the treatment of NAFLD remains uncertain and obesity is strongly associated with hepatic steatosis; therefore, the first line of treatment is lifestyle modification. The usual management of NAFLD includes gradual weight reduction and increased physical activity (PA) leading to an improvement in serum liver enzymes, reduced hepatic fatty infiltration, and, in some cases, a reduced degree of hepatic inflammation and fibrosis. Nutrition has been demonstrated to be associated with NAFLD and Non-alcoholic steatohepatitis (NASH) in both animals and humans, and thus serves as a major route of prevention and treatment. However, most human studies are observational and retrospective, allowing limited inference about causal associations. Large prospective studies and clinical trials are now needed to establish a causal relationship. Based on available data, patients should optimally achieve a 5%-10% weight reduction. Setting realistic goals is essential for long-term successful lifestyle modification and more effort must be devoted to informing NAFLD patients of the health benefits of even a modest weight reduction. Furthermore, all NAFLD patients, whether obese or of normal weight, should be informed that a healthy diet has benefits beyond weight reduction. They should be advised to reduce saturated/trans fat and increase polyunsaturated fat, with special emphasize on omega-3 fatty acids. They should reduce added sugar to its minimum, try to avoid soft drinks containing sugar, including fruit juices that contain a lot of fructose, and increase their fiber intake. For the heavy meat eaters, especially those of red and processed meats, less meat and increased fish intake should be recommended. Minimizing fast food intake will also help maintain a healthy diet. PA should be integrated into behavioral therapy in NAFLD, as even small gains in PA and fitness may have significant health benefits. Potentially therapeutic dietary supplements are vitamin E and vitamin D, but both warrant further research. Unbalanced nutrition is not only strongly associated with NAFLD, but is also a risk factor that a large portion of the population is exposed to. Therefore, it is important to identify dietary patterns that will serve as modifiable risk factors for the prevention of NAFLD and its complications.

Touching some firm ground in the epidemiology of NASH

Article

Full-text available

Aug 2011

ASH and NASH

Article

Full-text available

Jul 2011
DIGEST DIS

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) have a similar pathogenesis and histopathology but a different etiology and epidemiology. NASH and ASH are advanced stages of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). NAFLD is characterized by excessive fat accumulation in the liver (steatosis), without any other evident causes of chronic liver diseases (viral, autoimmune, genetic, etc.), and with an alcohol consumption ≤20-30 g/day. On the contrary, AFLD is defined as the presence of steatosis and alcohol consumption >20-30 g/day. The most common phenotypic manifestations of primary NAFLD/NASH are overweight/obesity, visceral adiposity, type 2 diabetes, hypertriglyceridemia and hypertension. The prevalence of NAFLD in the general population in Western countries is estimated to be 25-30%. The prevalence and incidence of NASH and ASH are not known because of the impossibility of performing liver biopsy in the general population. Up to 90% of alcoholics have fatty liver, and 5-15% of these subjects will develop cirrhosis over 20 years. The risk of cirrhosis increases to 30-40% in those who continue to drink alcohol. About 10-35% of alcoholics exhibit changes on liver biopsy consistent with alcoholic hepatitis. Natural histories of NASH and ASH are not completely defined, even if patients with NASH have a reduced life expectancy due to liver-related death and cardiovascular diseases. The best treatment of AFLD/ASH is to stop drinking, and the most effective first-line therapeutic option for NAFLD/NASH is non-pharmacologic lifestyle interventions through a multidisciplinary approach including weight loss, dietary changes, physical exercise, and cognitive-behavior therapy.

Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort

Article

Full-text available

May 2011

Non-alcoholic fatty liver disease (NAFLD) is a common cause of abnormal LFTs in primary care, but there are no data defining its contribution nor reporting the range of NAFLD severity in this setting. This study seeks to calculate the range of disease severity of NAFLD in a primary care setting. Adult patients with incidental abnormal LFTs, in the absence of a previous history, or current symptoms/signs of liver disease were prospectively recruited from eight primary care practices in Birmingham. NAFLD was diagnosed as fatty liver on ultrasound, negative serological liver aetiology screen, and alcohol consumption ≤30 and ≤20 g/day in males and females, respectively. The NAFLD Fibrosis Score (NFS) was calculated to determine the presence or absence of advanced liver fibrosis in subjects identified with NAFLD. Data from 1118 adult patients were analysed. The cause of abnormal LFTs was identified in 55% (614/1118) of subjects, with NAFLD (26.4%; 295/1118) and alcohol excess (25.3%; 282/1118) accounting for the majority. A high NFS (>0.676) suggesting the presence of advanced liver fibrosis was found in 7.6% of NAFLD subjects, whereas 57.2% of NAFLD patients had a low NFS (<-1.455) allowing advanced fibrosis to be confidently excluded. NAFLD is the commonest cause of incidental LFT abnormalities in primary care (26.4%), of whom 7.6% have advanced fibrosis as calculated by the NFS. This study is the first of its kind to highlight the burden of NAFLD in primary care and provide data on disease severity in this setting.

Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease

Article

Full-text available

May 2011
GUT

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is associated with cardiovascular risk. The aim of this study was to determine the role of fatty liver in predicting coronary artery disease and clinical outcomes in patients undergoing coronary angiogram. This was a prospective cohort study carried out in a University hospital. Consecutive patients who underwent coronary angiogram had ultrasound screening for fatty liver. Significant cardiovascular disease was defined as ≥50% stenosis in at least one coronary artery. The primary outcome was a composite end point comprising cardiovascular deaths, non-fatal myocardial infarction and the need for further coronary intervention during prospective follow-up. Among 612 recruited patients, 356 (58.2%) had fatty liver by ultrasonography, 318 (52.0%) had elevated serum alanine aminotransferase and 465 (76.0%) had significant coronary artery disease. Coronary artery disease occurred in 84.6% of patients with fatty liver and 64.1% of those without fatty liver (p<0.001). After adjusting for demographic and metabolic factors, fatty liver (adjusted OR 2.31; 95% CI 1.46 to 3.64) and alanine aminotransferase level (adjusted OR 1.01; 95% CI 1.00 to 1.02) remained independently associated with coronary artery disease. At a mean follow-up of 87±22 weeks, 30 (10.0%) patients with fatty liver and 18 (11.0%) patients without fatty liver reached the composite clinical end point (p=0.79). In patients with clinical indications for coronary angiogram, fatty liver is associated with coronary artery disease independently of other metabolic factors. However, fatty liver cannot predict cardiovascular mortality and morbidity in patients with established coronary artery disease.

Nine-year incident diabetes is predicted by fatty liver indices: The French D.E.S.I.R. study

Article

Full-text available

Jun 2010
BMC GASTROENTEROL

Fatty liver is known to be linked with insulin resistance, alcohol intake, diabetes and obesity. Biopsy and even scan-assessed fatty liver are not always feasible in clinical practice. This report evaluates the predictive ability of two recently published markers of fatty liver: the Fatty Liver Index (FLI) and the NAFLD fatty liver score (NAFLD-FLS), for 9-year incident diabetes, in the French general-population cohort: Data from an Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R). At baseline, there were 1861 men and 1950 women, non-diabetic, aged 30 to 65 years. Over the follow-up, 203 incident diabetes cases (140 men, 63 women) were identified by diabetes-treatment or fasting plasma glucose > or = 7.0 mmol/l. The FLI includes: BMI, waist circumference, triglycerides and gamma glutamyl transferase, and the NAFLD-FLS: the metabolic syndrome, diabetes, insulin, alanine aminotransferase, and asparate aminotransferase. Logistic regression was used to determine the odds ratios for incident diabetes associated with categories of the fatty liver indices. In comparison to those with a FLI < 20, the age-adjusted odds ratio (95% confidence interval) for diabetes for a FLI > or = 70 was 9.33 (5.05-17.25) for men and 36.72 (17.12-78.76) for women; these were attenuated to 3.43 (1.61-7.28) and 11.05 (4.09 29.81), after adjusting on baseline glucose, insulin, hypertension, alcohol intake, physical activity, smoking and family antecedents of diabetes; odds ratios increased to 4.71 (1.68-13.16) and 22.77 (6.78-76.44) in those without an excessive alcohol intake. The NAFLD-FLS also predicted incident diabetes, but with odds ratios much lower in women, similar in men. These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes. Physicians should screen for diabetes in patients with fatty liver.

A position statement on NAFLD/NASH based on the EASL 2009 special conference

Article

Full-text available

Aug 2010

Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest)

Article

Full-text available

Apr 2010
BMC GASTROENTEROL

FibroTest and elastography have been validated as biomarkers of liver fibrosis in the most frequent chronic liver diseases and in the fibrosis screening of patients with diabetes. One challenge was to use them for estimating the prevalence of fibrosis, identifying independent risk factors and to propose screening strategies in the general population. We prospectively studied 7,463 consecutive subjects aged 40 years or older. Subjects with presumed advanced fibrosis (FibroTest greater than 0.48) were re-investigated in a tertiary center. The sample characteristics were similar to those of the French population. FibroTest was interpretable in 99.6%. The prevalence of presumed fibrosis was 2.8%, (209/7,463), including cirrhosis in 0.3% (25/7,463); 105/209 (50%) subjects with presumed fibrosis accepted re-investigation. Fibrosis was confirmed in 50, still suspected in 27, indeterminate in 25 and not confirmed with false positive FibroTest or false negative elastography in 3 subjects. False negative rate of FibroTest estimated using elastography was 0.4% (3/766). The attributable causes for confirmed fibrosis were both alcoholic and nonalcoholic fatty liver disease (NAFLD) in 66%, NAFLD in 13%, alcohol in 9%, HCV in 6%, and other in 6%. Factors independently associated (all P < 0.003) with confirmed fibrosis were age, male gender, waist circumference, HCV antibody and alcohol consumption estimated using carbohydrate-deficient transferrin, enabling efficient screening-oriented strategies to be compared and proposed. Biomarkers have permitted to estimate prevalence of advanced fibrosis around 2.8% in a general population aged 40 years or older, and several risk factors which may be used for the validation of selective or non-selective screening strategies.

The metabolic syndrome: Useful concept or clinical tool? Report of a WHO Expert Consultation

Article

Full-text available

Dec 2009
DIABETOLOGIA

This article presents the conclusions of a WHO Expert Consultation that evaluated the utility of the 'metabolic syndrome' concept in relation to four key areas: pathophysiology, epidemiology, clinical work and public health. The metabolic syndrome is a concept that focuses attention on complex multifactorial health problems. While it may be considered useful as an educational concept, it has limited practical utility as a diagnostic or management tool. Further efforts to redefine it are inappropriate in the light of current knowledge and understanding, and there is limited utility in epidemiological studies in which different definitions of the metabolic syndrome are compared. Metabolic syndrome is a pre-morbid condition rather than a clinical diagnosis, and should thus exclude individuals with established diabetes or known cardiovascular disease (CVD). Future research should focus on: (1) further elucidation of common metabolic pathways underlying the development of diabetes and CVD, including those clustering within the metabolic syndrome; (2) early-life determinants of metabolic risk; (3) developing and evaluating context-specific strategies for identifying and reducing CVD and diabetes risk, based on available resources; and (4) developing and evaluating population-based prevention strategies.

MR Spectroscopy of the Liver: Principles and Clinical Applications1

Article

Full-text available

Oct 2009
RADIOGRAPHICS

Aliya Qayyum

Magnetic resonance (MR) spectroscopy allows the demonstration of relative tissue metabolite concentrations along a two- or three-dimensional spectrum based on the chemical shift phenomenon. An MR spectrum is a plot of the signal intensity and frequency of a chemical or metabolite within a given voxel. At proton MR spectroscopy, the frequency at which a chemical or compound occurs depends on the configuration of the protons within the structure of that chemical. At in vivo proton MR spectroscopy, the frequency location of water is used as the standard of reference to identify a chemical. The frequency shift or location of chemicals relative to that of water allows generation of qualitative and quantitative information about the chemicals that occur within tissues, forming the basis of tissue characterization by MR spectroscopy. MR spectroscopy also may be used to quantify liver fat by measuring lipid peaks and to diagnose malignancy, usually by measuring the choline peak. Interpretation of MR spectroscopic data requires specialized postprocessing software and is subject to technical limitations including low signal-to-noise ratio, masking of metabolite peaks by dominant water and lipid peaks, partial-volume averaging from other tissue within the voxel, and phase and frequency shifts from motion. MR spectroscopy of the liver is an evolving technology with potential for improving the diagnostic accuracy of tissue characterization when spectra are interpreted in conjunction with MR images.

Alcohol and Nutrition as Risk Factors for Chronic Liver Disease

Chapter

Jul 2013

The liver is the largest gland of the human body and plays a central role in the metabolism of nutrients. Hundreds of biochemical reactions take place in the liver, explaining its susceptibility to metabolic stressors. However, the natural history of metabolic liver disease has started to be unraveled only recently. For instance, it is now known that nonalcoholic fatty liver disease (NAFLD), which has long been considered a benign and nonspecific response of the liver to different inflammatory and metabolic factors, can progress to fibrosis and cirrhosis when associated with necroinflammation [1–3]. The burden of NAFLD goes in parallel with the burden of obesity and type 2 diabetes, so that NAFLD is currently considered the hepatic manifestation of the metabolic syndrome [1–3]. More importantly, NAFLD is emerging as an independent predictor of cardiometabolic disease and liver-related and general mortality [3–8]. As shown in Fig. 38.1, fatty liver (FL) may progress to fibrosis and cirrhosis both in alcoholic liver disease (ALD; left panel) and in nonalcoholic liver disease (NALD; right panel). Fibrosis leading to cirrhosis can accompany any chronic liver disease (CLD) associated with hepatobiliary distortion and/or inflammation [9, 10]. The main causes of fibrosis, cirrhosis, and hepatocarcinoma (HCC) worldwide are presently hepatitis B (HBV) and C (HCV) virus infections [11, 12]. Alcohol consumption is another important cause of CLD at present but may be a less important risk factor in coming years. Indeed, the great burden of CLD in forthcoming years is expected to come from NAFLD and especially from its progressive form known as nonalcoholic steatohepatitis (NASH) [1].

Prevalence of and risk factors for nonalcoholic fatty liver disease: Te Dionysos nutrition and liver study

Article

Jan 2005

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

Article

Aug 2012
GASTROENTEROLOGY

Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy

Article

Jan 2000

Stefano Bellentani

Background: Although hepatic steatosis is seen with increasing frequency in clinical practice, its prevalence and risk factors are unknown. Objective: To investigate the prevalence of and risk factors for hepatic steatosis, such as alcohol consumption and obesity. Design: Cross-sectional, observational study. Setting: Participants in the Dionysos Study. Patients: 257 participants assigned to one of four categories (67 controls, 66 obese persons, 69 heavy drinkers, and 55 obese heavy drinkers). Measurements: Ethanol intake, assessed by a validated questionnaire and expressed as daily (g/d) and lifetime (kg) consumption, and body mass, expressed as body mass index. Biochemical tests of liver and metabolic function and hepatic ultrasonography were done. Results: The prevalence of steatosis was increased in heavy drinkers (46.4% [95% Cl, 34% to 59%]) and obese persons (75.8% [CI, 63% to 85%]) compared with controls (16.4% [Cl, 8% to 25%]). Steatosis was found in 94.5% (Cl, 85% to 99%) of obese heavy drinkers. Compared with controls, the risk for steatosis was higher by 2.8-fold (Cl, 1.4-fold to 7.1-fold) in heavy drinkers, 4.6-fold (Cl, 2.5-fold to 11.0-fold) in obese persons, and 5.8-fold (Cl, 3.2-fold to 12.3-fold) in persons who were obese and drank heavily. In heavy drinkers, obesity increased the risk for steatosis by twofold (Cl, 1.5-fold to 3.0-fold) (P < 0.001), but heavy drinking was associated with only a 1.3-fold (Cl, 1.02-fold to 1.6-fold) increase in risk in obese persons (P = 0.0053). Elevated alanine aminotransferase and triglyceride levels are the most reliable markers of steatosis. Conclusions: Steatosis is frequently encountered in healthy persons and is almost always present in obese persons who drink more than 60 g of alcohol per day. Steatosis is more strongly associated with obesity than with heavy drinking, suggesting a greater role of overweight than alcohol consumption in accumulation of fat in the liver.

Epidemiology of alcoholic and nonalcoholic fatty liver disease in China

Article

Aug 2013
J GASTROEN HEPATOL

Jian-Gao Fan

graphic The prevalence of patients presenting with fatty liver disease ( FLD ) in C hina has approximately doubled over the past two decades. At present, FLD , which is typically diagnosed by imaging, is highly prevalent (∼27% urban population) in C hina and is mainly related to obesity and metabolic syndrome ( MetS ). However, the percentage of alcoholic liver disease (ALD) among patients with chronic liver diseases in clinic is increasing as well, and a synergetic effect exists between heavy alcohol drinking and obesity in ALD . Prevalence figures reveal regional variations, with a median prevalence of ALD and nonalcoholic FLD ( NAFLD ) of 4.5% and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although the prevalence increases to 68.2% among obese children. With the increasing pandemic of obesity and MetS in the general population, C hina is likely to harbor an increasing reservoir of patients with FLD . The risk factors for FLD resemble to those of C aucasian counterparts, but the ethnic‐specific definitions of obesity and MetS are more useful in assessment of C hinese people. Therefore, FLD / NAFLD has become a most common chronic liver disease in C hina. Public health interventions are needed to halt the worldwide trend of obesity and alcohol abuse to ameliorate liver injury and to improve metabolic health.

The danger of dichotomizing continuous variables: A visualization

Article

Jun 2013
Teach Stat

Oliver Kuss

Four rather different scatterplots of two variables X and Y are given, which, after dichotomizing X and Y, result in identical fourfold-tables misleadingly showing no association.

External Validation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in a Population-Based Study.

Article

Jan 2013

BACKGROUND & AIMS: We aimed to validate the fatty liver index (FLI), an algorithm based on waist circumference, body mass index (BMI), and levels of triglyceride and g-glutamyltransferase. We calculated its ability to identify fatty liver disease from any cause or non-alcoholic fatty liver disease (NAFLD) in large population of Caucasian elderly persons. METHODS: We collected ultrasonography and FLI data from participants of the Rotterdam Study from February 2009 to February 2012; 2652 subjects (mean age, 76.3±6.0 y) were interviewed and received a clinical examination that included an abdominal ultrasound, analysis of blood samples during fasting, and anthropometric assessment. The ability of the FLI to detect (non-alcoholic) fatty liver was assessed using area under the receiver operator characteristic (AUROC) curve analysis. RESULTS: FLI score was associated with NAFLD in multivariable analysis (odds ratio, 1.05; 95% confidence interval [CI], 1.04-1.05;P <.001). FLI identified patients with NAFLD with an AUROC curve of 0.813 (95% CI, 0.797-0.830) and those with fatty liver from any cause with an AUROC curve of 0.807 (95% CI, 0.792-0.823). CONCLUSION: The FLI (an algorithm based on waist circumference, BMI, and levels of triglyceride and g-glutamyltransferase) accurately identifies NAFLD, confirmed via ultrasonography, in a large, Caucasian, elderly population.

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

Article

Jan 2013
WORLD J GASTROENTERO

To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease (NAFLD). Cross-sectional study of subjects from the general population, a subgroup from the First Israeli National Health Survey, without excessive alcohol consumption or viral hepatitis. All subjects underwent anthropometric measurements and fasting blood tests. Evaluation of liver fat was performed using four noninvasive methods: the SteatoTest; the fatty liver index (FLI); regular abdominal ultrasound (AUS); and the hepatorenal ultrasound index (HRI). Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods: the HRI, the ratio between the median brightness level of the liver and right kidney cortex; and the SteatoTest, a biochemical surrogate marker of liver steatosis. The FLI is calculated by an algorithm based on triglycerides, body mass index, γ-glutamyl-transpeptidase and waist circumference, that has been validated only vs AUS. FLI < 30 rules out and FLI ≥ 60 rules in fatty liver. Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests. The prevalence rate of NAFLD was 31.1% according to AUS. The FLI was very strongly correlated with SteatoTest (r = 0.91, P < 0.001) and to a lesser but significant degree with HRI (r = 0.55, P < 0.001). HRI and SteatoTest were significantly correlated (r = 0.52, P < 0.001). The κ between diagnosis of fatty liver by SteatoTest (≥ S2) and by FLI (≥ 60) was 0.74, which represented good agreement. The sensitivity of FLI vs SteatoTest was 85.5%, specificity 92.6%, positive predictive value (PPV) 74.7%, and negative predictive value (NPV) 96.1%. Most subjects (84.2%) with FLI < 60 had S0 and none had S3-S4. The κ between diagnosis of fatty liver by HRI (≥ 1.5) and by FLI (≥ 60) was 0.43, which represented only moderate agreement. The sensitivity of FLI vs HRI was 56.3%, specificity 86.5%, PPV 57.0%, and NPV 86.1%. The diagnostic accuracy of FLI for steatosis > 5%, as predicted by SteatoTest, yielded an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI: 0.95-0.98). The diagnostic accuracy of FLI for steatosis > 5%, as predicted by HRI, yielded an AUROC of 0.82 (95% CI: 0.77-0.87). The κ between diagnosis of fatty liver by AUS and by FLI (≥ 60) was 0.48 for the entire sample. However, after exclusion of all subjects with an intermediate FLI score of 30-60, the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65, representing good agreement. Excluding all the subjects with an intermediate FLI score, the sensitivity of FLI was 80.3% and the specificity 87.3%. Only 8.5% of those with FLI < 30 had fatty liver on AUS, but 27.8% of those with FLI ≥ 60 had normal liver on AUS. FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI. However, if intermediate values are excluded FLI has high diagnostic value vs AUS.

Perspective: Nonalcoholic fatty liver disease and cardiovascular risk

Article

Feb 2013
CURR OPIN LIPIDOL

Nonalcoholic fatty liver disease (NAFLD) has emerged as a clear risk factor for cardiovascular risk. Through its association with metabolic syndrome including insulin resistance and type 2 diabetes, NAFLD certainly has strong indirect associations with cardiovascular risk. Recent population studies have strengthened the association with prevalent coronary heart disease. Investigative cardiology has shown that NAFLD is also associated with markers of subclinical atherosclerosis, such as diminished endothelial function and carotid artery intima-media thickening. Though causality between NAFLD and cardiovascular disease can only be tested in a clinical trial, these recent findings do emphasize the need to develop strategies including nutritional that may prevent NAFLD.

Non-Alcoholic Fatty Liver Disease as an Independent Manifestation of the Metabolic Syndrome: Results of a U.S. National Survey in Three Ethnic Groups.

Article

Jan 2013
J GASTROEN HEPATOL

The metabolic syndrome (MetS) and each of its components are strongly associated with non-alcoholic fatty liver disease (NAFLD). This has led many investigators to suggest that NAFLD is an independent component of the MetS. We formally tested this hypothesis using confirmatory factor analysis, which allows comparison of different models, with or without including NAFLD as a component of the MetS. We analyzed data from 3846 subjects of the Third National Health and Nutrition Examination Survey (1988–1994). NAFLD was defined by increased liver fat measured by ultrasonography. MetS by Adult Treatment Panel III criteria was present in 20.5%, and 30.2% had NAFLD, defined as mild, moderate, or severe ultrasonographic steatosis. Using confirmatory factor analysis, a basic model representing the MetS using its currently accepted components (glucose, waist, triglyceride/high-density lipoprotein ratio, and mean arterial pressure) showed excellent goodness-of-fit statistics. Addition of NAFLD to the model as a fifth independent variable decreased model fit, suggesting that NAFLD is not an additional independent component of the MetS. Analysis by ethnicity showed that addition of NAFLD decreased model fit in Whites but resulted in minor improvements in non-Hispanic Blacks and Mexican Americans. The MetS is strongly associated with NAFLD. However, we found no evidence that NAFLD is an independent component or manifestation of the MetS. Interestingly, ethnic differences might be important in this relationship and require further study.

Epidemiology of fatty liver: An update

Abstract

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