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Weight loss: Cornerstone in the treatment of non-alcoholic fatty liver disease
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide, mostly due to the dramatic increase in obesity rates. This disease presents mainly as simple liver steatosis, whereas 10-20% of patients exhibit an inflammatory phenotype referred to as non-alcoholic steatohepatitis (NASH). Advanced liver disease affects a smaller group of patients including fibrosis, cirrhosis and hepatocellular carcinoma. Higher age, extensive overweight, and number of features of the metabolic syndrome are associated with NAFLD severity. In most cases, NAFLD is associated with insulin resistance and insulin resistance is therefore a major target for all NAFLD treatment modalities. Various treatments into this direction, such as the use of thiazolidinediones have recently failed and did not lead to an improvement in liver histology parameters. Successful weight loss either achieved via bariatric surgery or subsequent to lifestyle modification/behavior therapy, however, has been demonstrated to improve both metabolic parameters and liver histology including inflammatory changes. The first recently reported randomized controlled trial in NASH patients testing the effects of weight loss showed that a one year period of lifestyle adjustment resulted in a 7-10% weight loss with significant histological improvement of liver disease. Orlistat, the only available obesity drug treatment on the market, failed to improve insulin resistance or histopathology in NAFLD. Therefore, new weight-loss inducing agents are eagerly awaited to increase the percentage of obese people to benefit from weight reduction.
... Weight loss in patients with NASH and T2D is of great interest, as relatively small amounts of weight loss reduce fatty liver, and improve insulin resistance and dyslipidemia [3][4][5][6]13,14 . Most studies are devoted to pharmacological or surgical weight loss methods, but they have a lot of adverse effects [2][3][4][15][16][17] . ...
... The results confirm and extend similar previous studies 7, 13,18 . A weight loss higher than 10% was associated with histological improvement, regression of nonalcoholic fatty liver diseases and amelioration of fibrosis 16,19 . ...
... Weight loss in patients with NASH and T2D is of great interest, as relatively small amounts of weight loss reduce fatty liver, and improve insulin resistance and dyslipidemia [3][4][5][6]13,14 . Most studies are devoted to pharmacological or surgical weight loss methods, but they have a lot of adverse effects [2][3][4][15][16][17] . ...
... The results confirm and extend similar previous studies 7, 13,18 . A weight loss higher than 10% was associated with histological improvement, regression of nonalcoholic fatty liver diseases and amelioration of fibrosis 16,19 . ...
Objective:
To evaluate the effectiveness of the fast weight loss method on liver steatosis, fibrosis, inflammation, glycemic and lipids features and body composition in patients with severe Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes (T2D).
Methods:
A 24-week open prospective randomised controlled clinical trial including 80 adult patients (aged 40-65 years) was performed. The patients after randomisation were divided in two groups: Main group followed the fast weight loss method; Control group received conventional drug treatment. The fast weight loss method included calorie restriction, salt intake, walking and sexual self-restraint. The conventional drug therapy included Vitamin E, Orlistat, Pioglitazone hydrochloride, Atorvastatin, Lisinopril, benzodiazepines and anti-inflammatory agents. Primary endpoints: ultrasound and histology suggestive of steatohepatitis, hepatic enzymes, weight loss, 2-hour oral glucose tolerance test, HbA1c. Secondary endpoints: blood pressure, lipids.
Results:
83% patients completed the study. In Main weight lost 7-16 kg (10-20% from baseline) for 8-10 weeks. In Main weight lost due to reduction of fat mass only. Main vs. Controls showed higher decrease in fat mass from baseline (P < 0.001). Ultrasound imaging and liver histological scoring system evidenced significant improvement on liver steatosis/fibrosis in Main (P < 0.001). In Main vs. Controls weight lost at 24 weeks led to positive laboratory changes in ALT, AST, 2-hour OGTT, HbA1c, HOMA-IR, BP, cholesterol, triglycerides, bilirubin total, blood hemoglobin (P = 0.01). The fast weight loss in the patients adequately led to decrease in symptomatic drugs up to complete abolition.
Conclusions:
The study showed benefits of the fast weight loss method improving in steatosis/fibrosis, biochemical/metabolic outcomes in patients with severe NASH and T2D.
... Inulin-type fructans have shown their ability to improve blood lipids and steatosis in various rodent models fed with high-fat or high-sugar diets [10][11][12]. Several modes of action have been proposed to explain the potential interest of prebiotic compounds in the prevention and management of NAFLD, including the improvement of plasma glucose and lipid control as well as direct effects on weight management [13][14][15] which can benefit patients. ...
... Finally, the steatosis level measured by histopathological scoring revealed the ability of α-GOS treatment to normalize this feature. This effect was not mediated by weight loss and the subsequent normalization of metabolic status [13] as we primarily hypothesized. Current NAFLD management is based on lifestyle modifications that aim to reduce body weight [8] and can include hypolipidemic therapy when appropriate [36,37], suggesting that the improvement of the plasma lipid profile may be one of the factors responsible for the normalization of liver parameters with α-GOS treatment. ...
Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide and is linked to the development of metabolic syndrome and obesity. As alpha-galacto-oligosaccharides (α-GOS) from legumes have been shown to reduce body weight and hyperphagia in overweight adults, it was hypothesized that they would exert benefits on the development of metabolic syndrome and associated NAFLD in a rodent model. C57Bl/6J mice were fed a high-fat diet until they developed metabolic syndrome and were then orally treated either with α-GOS at a physiological dose (2.2 g/kg BW/d) or the vehicle over 7 weeks. α-GOS induced a reduction in food intake, but without affecting body weight during the first week of treatment, when compared to the vehicle. Fasting glycaemia was improved after 4 weeks of treatment with α-GOS, whereas insulin sensitivity (assessed with HOMA-IR) was unaffected at the end of the experiment. Plasma non-esterified fatty acids, low-density lipoprotein (LDL) and total cholesterol were lowered by α-GOS while high-density lipoprotein (HDL) and triglycerides levels remained unaffected. α-GOS markedly improved liver steatosis as well as free fatty acid and triglyceride accumulation in the liver. α-GOS improved plasma lipids and prevented NAFLD development through mechanisms which are independent of body weight management and glycemic control.
... That makes interpretation of such studies difficult and weakens the available evidence. Lastly, certain treatments studied, such as lifestyle modification (diet and exercise), may be proven to be effective but they are quite challenging to implement, difficult to sustain in a non-research setting and hence nonrealistic [10,11]. Future investigations should aim at preventing NASH, understanding its pathophysiology and targeting key components of the pathogenetic process. ...
... Diet and/or exercise: Despite adequate evidence supporting the effect of weight loss (achieved either by diet or exercise) in decreasing the hepatic triglyceride content of patients with NAFLD, there are few data on the role of such interventions for the management of NASH [11,20]. Weight loss of 5-10% from baseline has repeatedly been shown to decrease hepatic steatosis by approximately 50% but its effect on inflammation or fibrosis has not been adequately studied [21,22]. ...
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Nonalcoholic steatohepatitis (NASH) reflects severe liver disease within the NAFLD spectrum and can progress to end-stage liver disease. Within this manuscript we review the available evidence for the treatment of NASH as well as the newer therapeutic agents that are currently being investigated.
... Weight loss is the strongest predictor for histological improvement in NASH, with a minimum of 10% weight loss leading to regression of fibrosis and resolution of NASH. 7,8 Lifestyle and dietary modifications have been the cornerstone of treatment for NASH thus far. Unfortunately, less than half of the patients are able to meet the goal of weight loss with intensive lifestyle modifications, even in controlled clinical trial settings. ...
Obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD) as well as advanced forms of the disease such as steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. While lifestyle and diet modifications have been the cornerstone of treatment for NASH thus far, they are only effective for less than half of the patients. New endoscopic bariatric therapies (EBT) have already proved to be safe and effective for the treatment of obesity and type 2 diabetes mellitus, and may provide an intermediate, less invasive and cost-effective option for patients with NASH. In this review, we aim to describe the data and evidence as well as outline future areas of development for endobariatric therapies for treatment of NASH. In conclusion, EBTs present an effective and safe therapeutic modality for use in the growing pandemic of obesity related liver disease and should be further investigated with large scale trials in this patient population.
... It was considered irreversible in the past, but the current studies showed that fibrosis [4][5][6], and even cirrhosis [7,8] in some series, could be reversible diseases. Our study aimed to compare the degree of hepatic fibrosis in overweight patients with CHC before and after weight loss achieved by diet and exercise, as it is considered the standard treatment for steatosis [9,10]. ...
... 27 Although lifestyle modifications such as weight loss, dietary management and exercise have been shown to be helpful, they are difficult to adopt for a long time. 28 Therapeutic failure is therefore not uncommon due to the inability to sustain weight loss for a long period. There is therefore a need to develop drugs that will target strategic points in the pathophysiology of NAFLD.A summary of the drugs that can be used in NAFLD is summarized in TABLE 1 and 2. ...
Insulin resistance refers to the reduced physiological effects of insulin on various tissues. Insulin resistance has been implicated in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), which is a spectrum of diseases ranging from hepatic steatosis on one end to steatohepatitis, liver cirrhosis and hepatocellular carcinoma on the other end. In most parts of the developed world, it is now the most commoncause of chronic liver disease and the most commonindication for liver transplantation. A similar findingis emerging in the developing world due to the rising prevalence of obesity and widespread adoption of Western lifestyles. Despite these epidemiological data, there are no universally approved medications for the treatment of NAFLD. The pathophysiological mechanisms of NAFLD essentially include adipose tissue insulin resistance, hepatic insulin resistance, inflammation and fibrosis. At the subcellular level, mitochondrial dysfunction, oxidative changes and endoplasmic reticulum dysfunction have been documented. Several drugs have been tested in vitro and in animal studies to target these pathophysiological mechanisms. Some are presently going through clinical trials, while others have already gone through clinical trials with variable results. Other potential target sites of drug development for the treatment of NAFLD are based on the complex pathophysiology of the disease. Insulin resistance plays an important role in the development of NAFLD. There are potential targets in the pathophysiology of NAFLD that can be explored in the development of medications for the disease.
... Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in humans [1]. is disease is characterized by excessive hepatic fat accumulation due to significant ethanol depletion and viral infection [2,3]. In Western countries, the prevalence of NAFLD is between 17% and 33% and significantly increases to 80% in obese individuals [4]. ...
Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The Hugan Qingzhi formula (HGQZ) has been proven effective in treating NAFLD through clinical and pharmacological mechanism studies. A screening study of the chemical components was carried out to better control the quality of this formula. Current research has combined biological activity assessment with chemical analysis to screen and identify the bioactive compounds in HGQZ for use as potential quality markers (Q-markers) to control the quality of this herbal product. The HGQZ extracted by three different solvents was evaluated in a free fatty acid-induced hepatic steatosis LO2 cell model. Simultaneously, the twelve major chemical constituents of these extracts were quantitatively measured by ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS). Extraction with 50% ethanol showed the most potent lipid-lowering effect in steatosis LO2 cells and the highest extraction rate of major chemical constituents. Correlation analysis was used to establish the relationship between the biological activities and chemical characteristics of these extracts. The results showed that the contents of typhaneoside, hyperoside, isoquercitrin, isorhamnetin-3-O-neohesperidoside, notoginsenoside R1, and alisol B 23-acetate were positively correlated to the lipid-lowering effect. The subsequent bioassay confirmed that typhaneoside, isoquercitrin, and alisol B 23-acetate played the role of reducing the lipid effect. In conclusion, 50% of ethanol extraction produced the most active extract of HGQZ. Typhaneoside, isoquercitrin, and alisol B 23-acetate could be considered potential Q-markers for the quality control of HGQZ.
... Perspectives and signi cance Page 7/12 These data con rms an independent and equal association between ALT and BMI in both sexes [30]. The sex-speci c variations in ALT levels seem to be unrelated to CVD-related risk factors and is largely unexplained. ...
Background
High and low levels of serum alanine aminotransferase (ALT) are associated with cardiovascular diseases (CVD) especially in elderly but the roles of sex and age are unexplained. This study investigated sex- and age-related variation of serum ALT and associations between ALT and CVD risk factors in men and women in a Caucasian population.
Methods
This study used cross-sectional data from Tromsø 6 in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years). Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT.
Results
Abnormal ALT was detected in 113 (4.4%) men and 188 (6.6%) women. ALT correlated negatively with age in men (r = -0.231, p < 0.001) and positively in women (r = 0.124, p < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60–64 years were found. Age was independently associated with ALT in men only [OR 1.05 (95% CI 1.04, 1.07), p < 0.001] and body mass index (BMI) was independently associated with ALT in both sexes.
Conclusion
The relationship between age and ALT was opposite directed in men compared to women, and linearly and independently in men only. Neither BMI as the strongest associated CVD risk factor in both sexes nor other risk components could explain this. Separate sex-analyses should be used in studies investigating the role of ALT as a disease marker.
... 8 Diet modification and weight loss are considered as important components of the main line of NAFLD treatment. 9,10 For centuries, garlic (Allium sativum L.) has been known as a herbal medicine and is still used as a traditional medicine in various cultures. 11 https://doi.org/10.1016/j.ctim.2020.102428 ...
Background
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Insulin resistance, oxidative stress, and obesity are major contributors to NAFLD pathogenesis. The effects of garlic powder supplementation on these risk factors in patients with NAFLD was investigated.
Methods
In this 12-wk, randomized controlled clinical trial, ninety patients with NAFLD were randomly assigned to two groups. The treatment group received four tablets of garlic (each coated tablet contained 400 mg garlic powder) daily and the control group received four tablets of placebo (each coated tablet contained 400 mg starch).
Results
A significant decrease was seen in the treatment group compared to the control group in waist circumference (P = 0.001), body fat percent (P < 0.001), serum concentration of fasting blood sugar (P = 0.01), insulin (P < 0.001), homeostatic model assessment for insulin resistance (P < 0.001), and malondialdehyde (P < 0.001), as well as significant increase in skeletal muscle mass (P = 0.002), serum concentration of superoxide dismutase (P < 0.001), and total antioxidant capacity (P < 0.001).
Conclusion
Garlic powder supplementation improved risk factors of NAFLD. Further studies are needed to determine the effects of garlic on hepatic features in patients with NAFLD. The study protocol was registered at Iranian clinical trials website under code IRCT20170206032417N4.
... Yaşam tarzı ve beslenmenin NAYKH üzerine etkisi ise son yıllarda obezite bağlamında ele alınmaktadır. Çeşitli çalışmalar NAYKH ile obezite ilişkisini ve kilo kaybının önemini göstermiştir [7]. Kilo kaybı temel olarak diyet modifikasyonu ve egzersize bağlıdır [8]. ...
Z Amaç: Çağımızda yaşam tarzı düzensizliklerinin bir sonucu olarak çeşitli klinik bozukluklar ortaya çıkmaktadır. Non-alkolik yağlı karaciğer hastalığı (NAYKH) bu klinik bozukluklar arasında adından sıkça söz ettirmektedir. Çalışmanın amacı, NAYKH tanısı konulan hastalarda B12 vitamin değerlerini incelemektir. Materyal Metot: Retrospektif olarak yapılan bu çalışmada, NAYKH tanısı konulan hastalara ait veriler hastane bilgi yönetim sistemi (HBYS) üzerinden alındı. Çalışmaya dahil edilme kriterlerine uyan tüm hastalar NAYKH açısından gruplandırıldı. Bu hastaların 227'si erkek iken, 454'ü kadın idi. Hastaların NAYKH tanıları, ultrasonografik (USG) görüntüleme sonuçlarına göre, radyoloji uzman doktorları tarafından konuldu. NAYKH tanısı konulmayan hastalar "Grade 0" olarak belirlendi. NAYKH tanısı konulan hastalar için gruplar, "hafif Grade I", "orta Grade II" ve "ileri derece Grade III" şeklinde oluşturulmuştur. Tüm hastaların B12 vitamin değerleri gruplara göre ayrı ayrı tespit edildi. B12 test parametresi, Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi (SÜEAH) biyokimya laboratuvarında Architect i2000 cihazında analiz edildi. İstatistik çalışmaları "IBM SPSS for Windows ver. 20.0 software" programı kullanılarak yapıldı. Verilerin istatistiksel değerlendirilmesinde tanımlayıcı istatistikler hesaplanarak, tek yönlü varyans analizi, mann-Whitney U, ki-kare ve student t testi ile gruplar arasındaki farklılık incelendi. İstatistiksel anlamlılık düzeyi p<0,05 olarak kabul edildi. Bulgular: Çalışmada, kriterlerimize uyan 681 hastanın B12 vitamini laboratuvar değerleri. Hastane Bilgi Yönetim Sistemi (HBYS) üzerinden, geriye dönük olarak incelendi. Erkek hastaların B12 değerleri ortalama olarak 325,6±190.12 (pq/mL) iken, kadın hastalarda bu değer 328,13±186,92 (pq/mL) olarak tespit edildi. Karaciğer yağlanması ve B12 değerleri birlikte incelendiğinde, en yüksek B12 değeri Grade 0'da (299 pq/mL), en düşük B12 değeri ise Grade III'te (199 pq/mL) tespit edildi. Bu durumun istatistiksel olarak anlamlı olduğu görüldü (p<0.05). Sonuç: NAYKH dereceleri ile B12 vitamini değerleri arasında ilişki olduğu görülmüştür. Ancak bu ilişki, beslenme alışkanlıklarını da içeren yaşam tarzı araştırmaları ile daha net olarak ortaya konulmaya muhtaç görülmektedir. Anahtar Kelimeler: Non-alkolik, yağlı karaciğer, grade, b12 vitamini Journal of Halal Life Medicine الحالل الحياة طب مجلة Helal Yaşam Tıbbı Dergisi https://dergipark.org.tr/hlm
... 1. By achieving weight loss: Weight loss is the key in the treatment of NAFLD [36]. Seven to ten percent of weight loss by lifestyle modification has been shown to improve hepatic steatosis and steatohepatitis [37]. ...
... NAFLD is today recognized as the most frequent liver disease worldwide, and, together with the increase of obesity, its incidence is also expected to further increase [42]. There is a close connection between NAFLD and the metabolic syndrome, and in regard to NAFLD prevention and therapy, it is important to note that improvement of individual components of the metabolic syndrome (e.g., body weight reduction, improvement of diabetes, or correction of dyslipidemia) also have a beneficial effect on NAFLD [43]. ...
Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome. The bone morphogenetic protein-8B (BMP8B) has been shown to be expressed in brown adipose tissues and the hypothalamus and to affect thermogenesis and susceptibility to diet-induced obesity. Here, we aimed to analyze BMP8B expression in NAFLD and to gain insight into BMP8B effects on pathophysiological steps of NAFLD progression. BMP8B mRNA and protein expression were dose-dependently induced in primary human hepatocytes in vitro upon incubation with fatty acids. Furthermore, hepatic BMP8B expression was significantly increased in a murine NAFLD model and in NAFLD patients compared with controls. Incubation with recombinant BMP8B further enhanced the fatty acid-induced cellular lipid accumulation as well as NFκB activation and pro-inflammatory gene expression in hepatocytes, while siRNA-mediated BMP8B depletion ameliorated these fatty acid-induced effects. Analysis of the expression of key factors of hepatocellular lipid transport and metabolisms indicated that BMP8B effects on fatty acid uptake as well as de novo lipogenesis contributed to hepatocellular accumulation of fatty acids leading to increased storage in the form of triglycerides and enhanced combustion by beta oxidation. In conclusion, our data indicate that BMP8B enhances different pathophysiological steps of NAFLD progression and suggest BMP8B as a promising prognostic marker and therapeutic target for NAFLD and, potentially, also for other chronic liver diseases.
... Importantly, we have previously shown that feeding this WTD to mice caused pathological changes in the liver that closely mimic liver pathology observed in patients with NAFLD [26,35]. Today, this chronic liver disease is considered to be the hepatic manifestation of the metabolic syndrome, and it has been shown that improvement of individual components of the metabolic syndrome such as reduction of body weight or correction of insulin resistance or dyslipidemia has beneficial effects on NAFLD, too [46]. Previous studies have shown that IAAs have a beneficial effect on body fat mass, elevated blood glucose levels, elevated triglycerides associated with insulin resistance as well as hepatic steatosis in rodents fed with high-fat or atherogenic diets as well as genetic models of obesity and diabetes [9-13, 18, 24, 47, 48]. ...
Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome. Iso-alpha acids (IAAs), hop-derived bitter compounds in beer, have been shown to beneficially affect different components of the metabolic syndrome such as insulin resistance and dyslipidemia. However, IAAs have not yet been studied in the context of chronic liver disease. Here we analyzed the effect of IAA on the pathogenesis of NAFLD. Once, we applied IAA to mice in combination with a NAFLD-inducing Western-type diet (WTD), and observed that IAA significantly inhibited WTD-induced body weight gain, glucose intolerance, and hepatic steatosis. Fitting to this, IAA dose-dependently inhibited cellular lipid accumulation in primary human hepatocytes (PHH) in vitro. Reduced expression of PPAR-gamma and key enzymes of lipid synthesis as well as increased expression of PPAR-alpha, indicative for increased lipid combustion, were identified as underlying mechanisms of reduced hepatocellular steatosis in vitro and in vivo. Analysis of hepatic HMOX1 expression indicated reduced oxidative stress in IAA-treated mice, which was paralleled by reduced activation of the JNK pathway and pro-inflammatory gene expression and immune cell infiltration. Furthermore, IAA reduced hepatic stellate cell (HSC) activation and pro-fibrogenic gene expression. Similarly, IAA also dose-dependently reduced oxidative stress and JNK activation in steatotic PHH, inhibited HSC activation, and reduced proliferation and pro-fibrogenic gene expression in already activated HSC in vitro. In conclusion, IAAs inhibit different pathophysiological steps of disease progression in NAFLD. Together with previous studies, which demonstrated the safety of even long-term application of IAA in humans, our data suggest IAA as promising therapeutic agent for the prevention and treatment of (non)alcoholic (fatty) liver disease.
... Importantly, we have previously shown that feeding this WTD to mice caused pathological changes in the liver that closely mimic liver pathology observed in patients with NAFLD [26,35]. Today, this chronic liver disease is considered to be the hepatic manifestation of the metabolic syndrome, and it has been shown that improvement of individual components of the metabolic syndrome such as reduction of body weight or correction of insulin resistance or dyslipidemia has beneficial effects on NAFLD, too [46]. Previous studies have shown that IAAs have a beneficial effect on body fat mass, elevated blood glucose levels, elevated triglycerides associated with insulin resistance as well as hepatic steatosis in rodents fed with high-fat or atherogenic diets as well as genetic models of obesity and diabetes [9-13, 18, 24, 47, 48]. ...
... Rapid weight loss can cause portal inflammation and fibrosis [10]. About 7-10% of weight loss over one year by lifestyle changes has been associated with histological improvement in simple steatosis and NASH [11]. Another study showed vigorous and moderate exercises were equally effective in reducing hepatic triglyceride content largely through weight loss [12]. ...
... Dietary intervention and exercise are traditionally considered the cornerstone of NAFLD treatment 70,71 . The efficacy of this approach is limited, however, by patient compliance. ...
Aims and background
Nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are two major causes of liver disease worldwide. Epidemiological and clinical data have clearly demonstrated that NAFLD and its associated metabolic abnormalities are a risk factor for HCC. Traditionally, the mechanisms whereby NAFLD acts as a risk for HCC are believed to include replicative senescence of steatotic hepatocytes and compensatory hyperplasia of progenitor cells as a reaction to chronic hepatic injury. Recent years have witnessed significant advances in our understanding of the mechanisms underlying the link between NAFLD and HCC.
Methods
In the present review, we provide an update on the pathophysiological pathways linking NAFLD and its associated metabolic derangements to malignant hepatic transformation, with a special focus on insulin resistance, adipokines, inflammation, and angiogenesis. We will also discuss the potential therapeutic implications that such molecular links carry.
Results
Although treating NAFLD could reduce the risk of malignant hepatic transformation, no long-term studies focusing on this issue have been conducted thus far. Insulin resistance, inflammation as well as derangements in adipokines and angiogenic factors associated with NAFLD are closely intertwined with the risk of developing HCC.
Conclusions
Traditional therapeutic approaches in NAFLD including metformin and statins may theoretically reduce the risk of HCC by acting on common pathophysiological pathways shared by NAFLD and HCC.
... At present there is no effective therapy for NAFLD and the treatment options are mainly directed towards lifestyle modifi cation in the form of diet modifi cation, weight loss and exercise as these factors improve obesity and insulin sensitivity. However, patient's adherence to life style modifi cation and compliance falls with time [96][97][98]. Liver transplantation is the only option left for NASH patients with cirrhosis. ...
p> Background : Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of fatty liver, characterized by the accumulation of fat in the hepatocytes in the absence of alcohol consumption. The spectrum of this disease ranges from steatosis to hepatitis and fi nally cirrhosis and hepatocellular carcinoma. NAFLD pathogenesis is not completely understood but various risk factors like obesity, insulin resistance, and metabolic syndromes have been identifi ed. With the rapid increase in obesity and diabetes during the past decade, the incidence of NAFLD is on the rise and is predicted to become the most common indication for liver transplantation in the future.
Context of the study: The treatment option for NAFLD is limited and mainly focuses on risk factor modifi cation like dietary changes and exercise. A major shortcoming of this approach is the lack of adherence and non-compliance over time. Other therapeutic options are available but are limited in number and have questionable effi cacy and safety profi les. Thus, new target-oriented therapies are needed.
Results : One such option is using agonists of the farnesoid X receptor (FXR) which are nuclear receptors abundantly expressed in the liver and shown to play a key role in various metabolic pathways such as bile acid, cholesterol, lipid and glucose metabolism.
Main focus and conclusions : In this review, we mainly discuss the role of FXR in the pathophysiology of NAFLD and how it can be a useful treatment target for such patients.</p
... Our study was aimed to compare the degree of hepatic fibrosis in overweight patients with CHC before and after weight loss achieved by diet and exercise, which is considered as the standard treatment of steatosis [9,10]. ...
... Nonalcoholic fatty liver disease (NAFLD), currently the most frequent chronic liver disease in humankind, is characterized with accumulation of hepatic fat with no other causes for the liver disease such as viral infection and significant ethanol consumption (Musso et al., 2010;Tiniakos et al., 2010;Angulo, 2005;Tilg and Moschen, 2010). NAFLD includes a spectrum of the liver disorders in a range from steatosis to cirrhosis, steatohepatitis, as well as to hepatocellular carcinoma (Masterjohn and Bruno, 2012). ...
... However, the shortcoming of this approach is the lack of adherence and non-compliance with time [139] . Various studies have shown the benefit of weight loss in NAFLD [140] . Dietary modification also plays a key role since a carbohydrate-rich diet, especially with high fructose, is the major cause of obesity, insulin resistance and NAFLD development [141] . ...
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease. Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available. The treatment for ALD remains as it was 50 years ago: abstinence, nutritional support and corticosteroids (or pentoxifylline as an alternative if steroids are contraindicated). As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. However, the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination therapy towards multiple targets would eventually be required. In this review, we delineate the treatment options in ALD and NAFLD, including various new targeted therapies that are currently under investigation. We hope that soon we will be having an effective multi-therapeutic regimen for each disease.
... Weight loss and lifestyle modification still assume the cornerstone of management. 11 Thus if the appropriate cut offs of anthropometric obesity markers to predict the presence of fatty liver can be determined in Asian Indians, therapeutic goals for obesity reduction can be set too. The metabolic and anthropometric profile of Indians is quite different from the Western population. ...
Background and aims:
With the rising prevalence of obesity and metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder in both developed and developing nations. Several studies on NAFLD have described waist circumference, a surrogate marker of visceral fat accumulation and waist height ratio as a better screening tool for NAFLD and metabolic syndrome than body mass index (BMI). We conducted this study to assess simple abdominal obesity indices as a predictor of NAFLD and determine the appropriate cut-off levels with reference to NAFLD.
Methods:
1000 subjects with NAFLD detected ultrasonographically and 360 controls attending a Gastroenterology Clinic at Cuttack, Odisha were included in the study and subjected to detailed anthropometric measurements. The abdominal anthropometric cut offs were determined using ROC analysis. Statistical analysis was performed by using SPSS software version 16.
Results:
All receiver operating curve (ROC) curves of waist circumference, waist-height ratio and BMI were significantly above the diagonal line. There were no significant differences in the area under the curve values among these abdominal obesity indices in each gender. The appropriate cut-off point of waist circumference in screening for NAFLD was 89 cm for men and 84 cm for women and the optimal cut-off point of waist-height ratio was 0.53 for men and 0.57 for women and the cut-off point of waist to hip ratio was 0.94 for men and 0.87 for women with very good sensitivity and specificity.
Conclusions:
The simple anthropometric parameters, such as BMI, waist circumference, waist-hip ratio and waist-height ratio are useful for predicting NAFLD in Indian adults. The anthropometry cut offs would be very useful in setting target points of life style modification and weight reduction. Besides, our study also clearly demonstrated that a simple assessment of BMI is as efficacious as other anthropometry parameters in predicting NAFLD.
... One popular theory is that 'two hits' are involved [15]. The first 'hit' involves the development of hepatic steatosis (fatty liver), with IR being a major risk factor in the net retention of lipids within hepatic liver cells [16][17][18]. The second 'hit' is the progression of steatosis to NASH and fibrosis/cirrhosis and involves inflammatory mechanisms. ...
Nonalcoholic fatty liver disease (NAFLD) results from excessive fat accumulation in the liver in the absence of excessive alcohol consumption. Insulin resistance (IR) is proposed to be an underlying pathogenic factor in the development and progression of disease. There are currently no proven pharmacotherapies and weight loss is the only prescribed treatment despite a lack of evidence to support a specific diet or lifestyle therapy. The aim of this review is to evaluate the efficacy of dietary lifestyle interventions on IR measured by Homeostasis model assessment in patients with NAFLD. A systematic electronic search of Medline, Scopus, The Cochrane Library, CINAHL and PubMed databases (1999-2015) was performed by two independent reviewers. Randomized control trials evaluating the efficacy of diet and lifestyle interventions on IR in adults diagnosed with NAFLD were included. A total of 6441 articles were identified; eight randomized control trials fulfilled the inclusion criteria. Three studies involved dietary interventions and five incorporated diet and exercise. The majority of intervention groups resulted in significant reductions in IR, with no significant changes observed in the control groups. Lifestyle interventions compared with controls reduced IR measured by homeostasis model assessment. All diet and diet and lifestyle intervention trials were efficient in reducing IR in participants with NAFLD. A lack of literature and variation across interventions warrants the need for extensive research to establish firm dietary lifestyle recommendations.
... Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance (IR), hepatic steatosis and frequently type 2 diabetes and is a major public health problem in industrialized countries affecting up to 20-30% of individuals [1]. NAFLD represents a multi-hit process in which the accumulation of triglycerides increases the susceptibility to inflammatory damage, with subsequent onset of oxidative stress, mitochondrial dysfunction, endotoxemia, and endoplasmic reticulum stress [2][3][4]. The excessive fatty acid oxidation and mitochondrial dysfunction, with production of reactive oxygen species (ROS), represent important features for NAFLD progression toward nonalcoholic steatohepatitis (NASH) [5]. ...
... Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance (IR), hepatic steatosis and frequently type 2 diabetes and is a major public health problem in industrialized countries affecting up to 20-30% of individuals [1]. NAFLD represents a multi-hit process in which the accumulation of triglycerides increases the susceptibility to inflammatory damage, with subsequent onset of oxidative stress, mitochondrial dysfunction, endotoxemia, and endoplasmic reticulum stress [2][3][4]. The excessive fatty acid oxidation and mitochondrial dysfunction, with production of reactive oxygen species (ROS), represent important features for NAFLD progression toward nonalcoholic steatohepatitis (NASH) [5]. ...
Scope:
Virgin olive oil is an essential component of the Mediterranean diet. Its anti-oxidant and anti-inflammatory properties are mainly linked to phenolic contents. This study aims to evaluate the beneficial effects of a polyphenol-rich virgin olive oil (HPCOO) or olive oil without polyphenols (WPOO) in rats fed high-fat diet (HFD).
Methods and results:
Male Sprague-Dawley rats were divided into 4 groups based on the different types of diet: 1) Standard diet (STD); 2) HFD; 3) HFD containing WPOO and 4) HFD containing HPCOO. HPCOO and WPOO induced a significant improvement of HFD-induced impaired glucose homeostasis (by hyperglycemia, altered oral glucose tolerance and HOMA-IR) and inflammatory status modulating pro- and anti-inflammatory cytokines (TNF-α, IL-1 and IL-10) and adipokines. Moreover, HPCOO and less extensively WPOO, limited HFD-induced liver oxidative and nitrosative stress and increased hepatic fatty acid oxidation. To study mitochondrial performance, oxidative capacity and energy efficiency were also evaluated in isolated liver mitochondria. HPCOO, but not WPOO, reduced H2 O2 release and aconitase activity by decreasing degree of coupling which plays a major role in the control of mitochondrial ROS emission.
Conclusion:
Polyphenol-rich virgin olive oil limits HFD-induced insulin resistance, inflammation and hepatic oxidative stress, preventing non alcoholic fatty liver disease progression. This article is protected by copyright. All rights reserved.
... Изучается эффективность множества медикаментозных препаратов, однако ни один из них не обладает доказанной долгосрочной эффективностью. Единственными доказанным эффективным и общепризнанным методом лечения НАЖБП остаётся изменение образа жизни, включающее диетические ограничения и повышение физической активности; также целесообразен контроль имеющихся метаболических нарушений [31]. ...
Article is devoted to the role of body overweight in development of non-alcoholic steatohepatitis. Authors provide information about adipokines, peroxisome proliferator-activated receptors, proinflammatory cytokines in pathogenesis of nonalcoholic steatohepatitis. Authors analyze and describe special features of clinical picture and diagnostics, and also prophylaxis and treatment ways (changes in lifestyle, decrease of weight, possibility of metformin, thiazolidinedione, statins, essential phospholipids, vitamin E, ursodeoxycholic acid and probiotics treatment).
... Nonalcoholic fatty liver disease (NAFLD) is one of the common liver diseases (1) strongly linked to lifestyle habits (2). The prevalence of NAFLD in the general population of Western countries is 20% -30%, whereas, it is 6.3% -33% worldwide (3). ...
... A report on testing the effects of weight loss on this disease entity showed that a 1-year period of lifestyle adjustment resulted in a 7-10% weight loss with significant histological improvement of liver disease. [63] Given the pivotal role that insulin resistance is considered to play in the pathogenesis of NAFLD, the potential role of insulin sensitizers such as biguanides, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase four inhibitors cannot be overlooked. Of the insulin sensitizers, metformin is the one that is widely studied as regarding its role in the management of NAFLD. ...
Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of fat >5% of liver weight is increasingly becoming an important cause of chronic liver disease. This article tries to chronicle advances that have occurred in the understanding of the pathogenesis, pathology as well as the management of this disease. We have done a Medline search on published work on the subject and reviewed major conference proceedings in the preceding years. The Pathogenesis involves a multi-hit process in which increased accumulation of triglycerides in face of insulin resistance results in increased susceptibility to inflammatory damage mediated by increased expression of inflammatory cytokines and adipokines, oxidative stress and mitochondrial dysfunction, endoplasmic reticulum stress and gut derived endotoxemia. An interplay of multiple metabolic genetic expression and environmental factors however determine which patient with NAFLD will progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. The minimum criteria for diagnosis of NASH are steatosis, ballooning and lobular inflammation; fibrosis is not required. The NASH Clinical Research Network (CRN), histological scoring system is used to grade and stage the disease for standardization. The management of NAFLD consists of treating liver disease as well as associated metabolic co-morbidities such as obesity, hyperlipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM). Patient education is important as their insight and commitment is pivotal, and lifestyle modification is thefirst line of treatment. Improvement in liver histology in non-diabetic NASH patients has been reported with use of Vitamin E. Other liver-related therapies under investigations include pentoxyfiylins, Caspar inhibitors, Resveratrol as well as probiotics. The prognosis (both overall and liver-related mortality) for simple steatosis is not different from that of the general population however.
... Diet and exercise (30 min of aerobic exercise 4 times a week, i.e., moderate physical activity) are the preferred methods of weight loss. There are many studies showing the benefit of weight loss in NAFLD [39] . Five percent to 10% of body weight loss can reduce a significant amount of liver fat and improve steatohepatitis. ...
There is worldwide epidemic of non-alcoholic fatty liver disease (NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.
... Several studies have demonstrated the beneficial impacts of dietary interventions in treating obesity, insulin resistance, and NAFLD and that specific macronutrients might benefit NAFLD independent of weight loss. [3][4][5][6][7][8] This review summarizes the evidence for the macronutrient effects including carbohydrates, lipids, and proteins in the management of patients with NAFLD. ...
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and a serious health burden worldwide which increases risk of cirrhosis, type 2 diabetes mellitus (T2DM), and cardiovascular complications. Current epidemics of obesity, unhealthy dietary patterns, and sedentary lifestyles, all contribute to the high prevalence of NAFLD. Dietary patterns and nutrients are important contributors to the development, progression, and treatment of NAFLD. A healthy diet is beneficial for all NAFLD patients beyond weight reduction. Generally, hypercaloric diets, especially rich in trans/saturated fat and cholesterol, high consumption of red and processed meat, and fructose-sweetened beverages seem to increase the risk of progression toward nonalcoholic steatohepatitis (NASH), whereas reducing caloric intake and high-glycemic index (GI) foods, increasing consumption of monounsaturated fatty acids, omega-3 fatty acids, fibers, and specific protein sources such as fish and poultry have preventive and therapeutic effects. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation. In this review, the evidence linking macronutrients to NAFLD are discussed.
... Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Moreover, lifestyle modifications, such as diet and physical exercise, may be proven to be effective, but they are challenging to implement [10,11] . ...
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules.
... The diet of children with NAFLD is characterized by over consumption of fructose, soft drinks, meat, saturated fat, and cholesterol, and low consumption of fiber, fish, omega 3 fats, and vitamin E [25]. So far, weight loss, though hard to achieve, is still the biggest and best-known treatment [26]. Recent advances have been focused on dietary fructose, antioxidants, omega-3 fatty acids, and pre-/pro-biotics. ...
With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.
... Several studies have demonstrated the beneficial impacts of dietary interventions in treating obesity, insulin resistance, and NAFLD and that specific macronutrients might benefit NAFLD independent of weight loss. [3][4][5][6][7][8] This review summarizes the evidence for the macronutrient effects including carbohydrates, lipids, and proteins in the management of patients with NAFLD. ...
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and a serious health burden worldwide which increases risk of cirrhosis, type 2 diabetes mellitus (T2DM), and cardiovascular complications. Current epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle, all, contribute to the high prevalence of NAFLD. Dietary patterns and nutrients are important contributors to the development, progression, and treatment of NAFLD. A healthy diet is beneficial for all NAFLD patients beyond weight reduction. Generally, hypercaloric diet, especially rich in trans/saturated fat and cholesterol, high consumption of red and processed meat, and fructose-sweetened beverages seem to increase risk of progression toward non-alcoholic steatohepatitis (NASH), whereas reducing caloric intake and high-glycemic index (GI) foods, increasing consumption of monounsaturated fatty acids, omega-3 fatty acids, fibers, and specific protein sources such as fish and poultry have preventive and therapeutic effects. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation. In this review, the evidence linking macronutrients to NAFLD will be discussed.
... As a possible intervention, weight loss by diet and exercise could be a safe option, and has been shown to dose-dependently improve histological disease activity in non-alcoholic steatohepatitis associated with obesity. 25,26 In terms of the impact of being underweight, several previous studies have also reported that being underweight was associated with a poor outcome after allogeneic HSCT. 4,27,28 Navarro et al. 4 has reported that OS in AML patients with BMI at transplant o 18 was inferior to that in patients with a normal BMI in patients who received stem cells from related donors, but not in the unrelated donor group. ...
To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ⩾18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m(2), Underweight, n=1791; 18.5⩽BMI<25, Normal, n=8444; 25⩽BMI<30, Overweight, n=1591; BMI⩾30, Obese, n=224. The median age was 45 years (range, 18-77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM.Bone Marrow Transplantation advance online publication, 11 August 2014; doi:10.1038/bmt.2014.178.
A fatty liver plays a significant role in human health. Biblical verses related to fatty liver are explored from a contemporary perspective, evaluating its mechanisms, etiology, the various diseases associated with it, and management strategies for this condition. This research concludes that, in order to provide appropriate treatment for patients suffering from fatty liver, it is important to understand the historical context of this condition.
Key messages
• Liver disease is now the second leading cause of years of working life lost in Europe, after only ischaemic heart disease
• The clinical focus in patients with liver disease is oriented towards cirrhosis and its complications, whereas early and reversible disease stages are frequently disregarded and overlooked
• The dissociation between primary and secondary care and the considerable heterogeneity across clinical pathways and inconsistent models of care cause delays in diagnosis of both rare and common liver diseases
• Stigma has a major impact on liver diseases in Europe, leading to discrimination, reduction in health-care seeking behaviour, and reduced allocation of resources, which all result in poor clinical outcomes
• Europe has the highest level of alcohol consumption in the world, which, together with ultra-processed food consumption and high prevalence of obesity, are the major drivers of liver-related morbidity and mortality
• A scarcity of consistent and efficient screening and vaccination programmes for viral hepatitis combined with the high costs of drugs due to variable European reimbursement systems result in reduced access to treatment and delays in elimination programmes
• COVID-19, alongside imposing delays in diagnostic pathways of liver diseases, has brought overlapping metabolic risk factors and social inequities into the spotlight as crucial barriers to liver health for the next generation of Europeans
• Liver diseases are generally avoidable or treatable if measures for prevention and early detection are properly implemented; achieving this would reduce premature morbidity and mortality, saving the lives of almost 300 000 people across Europe each year
A obra intitulada “Tecnologias aplicadas nas ciências da saúde vol. 2”, publicada pela Brazilian Journals, apresenta um conjunto de vinte e sete capítulos que visa abordar diversas áreas do conhecimento da área da saúde. Logo, os artigos apresentados neste volume abordam: alterações da resposta imune em pacientes com obesidade; tumor de células granulares em língua: relato de caso; análise dos fatores de risco relacionados ao comportamento suicida em crianças e adolescentes; o processo de trabalho em saúde e a educação permanente: desafios e possibilidades; rizotomia dorsal seletiva cervical no tratamento de paralisia cerebral espástica em crianças: uma revisão; análise do perfil epidemiológico de crianças expostas ao HIV no Estado de Sergipe entre os anos de 2008-2019, entre outros. Dessa forma, agradecemos aos autores por todo esforço e dedicação que contribuíram para a construção dessa obra, e esperamos que este livro possa colaborar para a discussão e entendimento de temas relevantes para a área de educação, orientando docentes, estudantes, gestores e pesquisadores à reflexão sobre os assuntos aqui apresentados.
Non-alcoholic fatty liver disease (NAFLD), which affects over 20% of the adult population, is the most common liver disease worldwide and can progress to inflammatory hepatitis, cirrhosis and liver cancer. The need to alleviate NAFLD is imperative, but there are limited pharmacological therapies available. Based on previous reports that piceatannol, a stilbenoid metabolite of resveratrol, exhibits anti-obesity, antioxidant and anti-inflammatory effects, the goal of this study was to determine the efficacy of piceatannol on prevention and/or treatment of NAFLD. The results showed that piceatannol significantly decreased fat accumulation and suppressed lipogenesis and fatty acids (FAs) uptake by decreasing sterol regulatory element-binding protein 1 (SREBP1) and cluster of differentiation 36 (CD36) in steatosis-induced HepG2 hepatocytes. Piceatannol treatment also promoted FAs β-oxidation by increasing farnesoid X receptor (FXR), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase I α (CPT1α) under steatosis conditions. Moreover, piceatannol significantly suppressed FA-induced oxidative stress and inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal–regulated kinases 1/2 (ERK1/2). Overall, it is suggested that piceatannol reduced fat accumulation in steatosis-induced HepG2 cells by suppressing lipogenesis (SREBP1 and ACC) and FA uptake (CD36), and promoting FAs oxidation (FXR, PPARα and CPT1α).
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and type 2 diabetes. This study aimed to investigate the effects of green coffee extract (GCE) on glycemic indexes, leptin levels, and obesity values in patients with NAFLD. This double-blind, randomized, controlled clinical trial was conducted on 48 patients with NAFLD aged 20–60 years and body mass index (BMI) of 25–35 kg/m². Subjects were randomly assigned to receive a daily dose of 400 mg GCE (2 × 300 mg; n = 24) or placebo (n = 24) for eight weeks. Fasting blood samples, anthropometric measurements, and dietary intake data was collected for all patients at baseline and at the end of the study. GCE supplementation significantly reduced fasting blood glucose (mean difference (MD) = −11.50 and 95 % confidence interval (CI) = −19.59 to −3.42), homeostatic model assessment for insulin resistance (MD = −0.97 and 95 % CI = −1.84 to −0.11), weight (MD = −1.73 and 95 % CI = −2.44 to −1.01), BMI (MD = −0.57 and 95 % CI = −0.84 to −0.29), and waist circumference (MD = −3.69 and 95 % CI = −5.85 to −1.54) in the intervention group compared to the control group. Serum leptin levels decreased significantly in GCE group compared to the baseline values (P = 0.022). No significant changes were observed in serum insulin concentration and waist to hip ratio in any of the groups. In conclusion, GCE supplementation improved glycemic parameters and obesity values and may be useful in the management of NAFLD complications.
Introduction
Ten percent of cirrhotic patients are known to have a high risk of postoperative complications. Ninety percent of bariatric patients suffer from non-alcoholic fatty liver disease (NAFLD), and 50% of them may develop non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis. The aim of this study was to assess whether the presence of cirrhosis at the time of bariatric surgery is associated with an increased rate and severity of short- and long-term cirrhotic complications.
Methods
A cohort of 110 bariatric patients, between May 2003 and February 2018, who had undergone liver biopsy at the time of bariatric surgery were reassessed for histological outcome and divided into two groups based on the presence (C, n = 26) or absence (NC, n = 84) of cirrhosis. The NC group consisted of NASH (n = 49), NAFLD (n = 24) and non-NAFLD (n = 11) liver histology. Medical notes were retrospectively assessed for patient characteristics, development of 30-day postoperative complications, severity of complications (Clavien-Dindo (CD) classification) and length of stay. The C group was further assessed for long-term cirrhosis-related outcomes.
Results
The C group was older (52 years vs 43 years) and had lower BMI (46 kg/m² vs 52 kg/m²) and weight (126 kg vs 145 kg) compared to the NC group (p < 0.05). The C group had significantly higher overall complication rate (10/26 vs 14/84, p < 0.05) and severity of complications (CD class ≥ III, 12% vs 7%, p < 0.05) when compared to the NC group. The length of stay was similar between the two groups (5 days vs 4 days). The C group had significant improvement in model end-stage liver disease scores (7 vs 6, p < 0.01) with median follow-up of 4.5 years (range 2–11 years). There were no long-term cirrhosis-related complications or mortality in our studied cohort (0/26).
Conclusion
Bariatric surgery in cirrhotic patients has a higher risk of immediate postoperative complications. Long-term cirrhosis-related complications or mortality was not increased in this small cohort. Preoperative identification of liver cirrhosis may be useful for risk stratification, optimisation and informed consent. Bariatric surgery in well-compensated cirrhotic patients may be used as an aid to improve long-term outcome.
Non‐alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Recently, some novel compounds have been investigated for the prevention and treatment of NAFLD. Oleoylethanolamide (OEA), an endogenous PPAR‐α agonist, has exhibited a plethora of pharmacological properties for the treatment of obesity and other obesity‐associated metabolic complications. This systematic review was performed with a focus on the effects of OEA on the risk factors for NAFLD. PubMed, Scopus, Embase, ProQuest, and Google Scholar databases were searched up to December 2018 using relevant keywords. All articles written in English evaluating the effects of OEA on the risk factors for NAFLD were eligible for the review. The evidence reviewed in this article illustrates that OEA regulates multiple biological processes associated with NAFLD, including lipid metabolism, inflammation, oxidative stress, and energy homeostasis through different mechanisms. In summary, many beneficial effects of OEA have led to the understanding that OEA may be an effective therapeutic strategy for the management of NAFLD. Although a wide range of studies have demonstrated the most useful effects of OEA on NAFLD and the associated risk factors, further clinical trials, from both in vivo studies and in vitro experiments, are warranted to verify these outcomes.
In the present meta-analysis, the efficacy and safety of orlistat in the treatment of non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) were evaluated. PubMed, Embase, the Cochrane Library, Web of Science, and Wan Fang data were searched for controlled trials of orlistat in patients with NAFLD or NASH, published before August 2017. Three randomized controlled trials and four single-arm trials were included. The involved participants with NAFLD or NASH (330 patients) were analyzed for clinical outcomes including alteration in hepatic histological variables and biomarkers of liver function. Improvements were observed in levels of alanine aminotransferase [standard mean difference (SMD)=-1.41; P=0.01], aspartate aminotransferase (SMD=-2.06; P=0.0005), γ-glutamyl transpeptidase (SMD=-1.91; P=0.05), glucose [mean difference (MD)=-0.51; P=0.01], triglycerides (MD=-0.93; P=0.01), homeostasis model assessment of insulin resistance index (MD=-1.05; P=0.04) and body mass index (MD=-1.97; P=0.02), but not in liver fibrosis score (SMD=-0.14; P=0.71). On sub-analyses of the different patient groups, no significant differences were observed in patients with NASH. Taken together, these findings demonstrate that orlistat could serve as a therapeutic drug to improve biochemical indicators of liver damage, but not as first-choice drug for the management of NAFLD or NASH; thus suggesting a novel palliative drug only for the treatment of NAFLD.
Liver carcinogenesis in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is a subject of intense research nowadays, since NAFLD is the most common chronic liver disease, affecting a great percentage of the population worldwide, while hepatocellular carcinoma (HCC), which represents the most common primary liver malignancy, is the third leading cause of cancer-related mortality. The underlying pathogenic pathways of both NAFLD and HCC are not completely understood, but there is growing evidence that they share many common pathophysiologic mechanisms and risk factors. Due to lack of solid evidence, though, the ultimate goal of designing effective diagnostic tools, treatment options and screening policies remain unmet for the time being. This review article aims to present recent data available regarding pathogenesis, diagnosis and management of HCC and NAFLD, as well as to highlight the importance of the development of HCC in the setting of NAFLD and NASH.
Objective: To investigate the preventive effects of rosiglitazone on nonalcoholic steatohepatitis (NASH) rats and to explore the potential mechanisms in modulating peroxisome proliferator-activated receptor gamma (PPARγ), nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2) expression. Methods: Thirty male SD rats were assigned into the normal group (n=10), the model group (n=10), rosiglitazone prevention group [n=10, simultaneously 4mg/(kg·d) gavage daily at beginning]. Liver appearance, liver index, and histological changes were assessed. Serum tumor necrosis factor-α. (TNF-α.) and prostaglandin E2(PGE2) were determined using enzyme-linked immunosorbent assay. The expressions of PPARγ, NF-κB, and COX-2 in liver were determined using immunohistochemical methods. The mRNA and protein expressions of COX-2 were disclosed by real-time polymerase chain reaction and Western blot analysis. Results: Compared with the normal group, the liver index significantly increased in model group (3.92±0.72 vs. 5.71±1.05, P=0.004). HE and Masson staining showed significantly increased steatosis, inflammation, and fibrosis. The serum levels of TNF-α, PGE2 in high-fat-diet-fed rats were significantly increased (11.72±2.47 vs. 29.39±5.32, P=0.002; 236.60±24.90 vs. 288.24±17.17, P=0.004). Immunohistochemistry showed NF-kB and COX-2 in livers were significantly elevated, but PPARγ was decreased in nonalcoholic steatohepatitis rats. Real-time polymerase chain reaction and Western blot found mRNA and protein expressions of COX-2 were increased in the model group (0.57±0.08 vs. 2.83±0.24, P=0.0007; 0.38±0.03 vs. 1.00±0.03, P=0.004). Compared with the model group, the expressions of PPAR7 significantly increased and the expressions of NF-κB and COX-2 significantly decreased (mRNA: 2.83±0.24 vs. 0.46±0.11, P=0.002; protein: 1.00±0.03 vs. 0.62±0.02, P=0.006) in the rosiglita-zone prevention group. Conclusion: By inhibiting NF-κB and COX-2 expressions, rosiglitazone can reduce insulin resistance and then prevent the occurrence and development of nonalcoholic steatohepatitis.
Surgically induced weight loss improves nonalcoholic fatty liver disease (NAFLD) in morbidly obese Caucasian patients. Similar data are lacking from India.
To compare the histologic features of NAFLD in morbidly obese Indian patients before and 6 months after bariatric surgery. Histologic changes were also separately assessed according to the type of bariatric intervention.
Teaching institution, India; private practice.
All patients undergoing bariatric surgery from July 2012 to July 2013 underwent a routine liver biopsy at the time of bariatric surgery. If the biopsy specimen indicated NAFLD, patients were asked to undergo a second biopsy after 6 months. Baseline anthropometry, clinical data, biochemistry, and pathology were recorded and repeated at follow-up.
Eighty-eight of 134 index biopsy specimens indicated NAFLD. Thirty patients had paired liver biopsies. Steatosis was present in all, 14 had lobular inflammation, 10 had ballooning degeneration, and 14 had fibrosis. Mean time between the biopsies was 7.1 months (range 6-8 months). At the second biopsy, steatosis had resolution in 19 and improvement in 11, lobular inflammation had resolution in 12 and improvement in 2, ballooning had resolution in 9 and improvement in 1 and fibrosis had resolution in 11 and improvement in 3 (P<0.05 for all). Improvement was greater among those who underwent a sleeve gastrectomy in comparison to a Roux-en-Y gastric bypass, although this difference was not statistically significant. None had worsening of liver histologic results.
Surgically induced weight loss significantly and rapidly improves liver histology in morbidly obese Indians with NAFLD.
Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
Objective
Resveratrol (RSV) regulates NAD bioavailability and sirtuin-related metabolism, which relates to aging, metabolic syndrome and non-alcoholic fatty liver disease. The purpose of this study was to investigate the effects of resveratrol on hepatic metaflammation in a rodent model of high-fat (HF) diet-induced obesity (DIO).
Materials/Methods
DIO was induced in a subset of mice given a HF diet (45% kcal fat). After 6 weeks of HF diet feeding, RSV was delivered via an osmotic pump for 4 weeks. The experimental groups were as follows: 1) lean control fed with a standard diet, 2) HF diet-induced obese control, and 3) HF_RSV (8 mg/kg/day). After 4 weeks of each treatment, blood and liver tissues were collected and the indices of glucose control, serum and liver triglyceride (TG), sirtuin pathway, inflammation, and NOD-like receptor family, pryin domain containing 3 (NLRP3) inflammasome were analyzed.
Results
Body weight and food intake were not altered by administering resveratrol. Glucose control was impaired, and serum and liver TG levels were increased by the HF diet. Hepatic inflammation was aggravated in mice fed with the HF diet, as shown by the increased levels of the pro-inflammatory markers interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha in the liver. However, resveratrol administration significantly improved glucose control, and serum and liver TG contents. Also, resveratrol treatment reduced the levels of the pro-inflammatory markers. These improvements were accompanied by alterations in sirtuin pathway and NLRP3 inflammasome activation.
Conclusions
These results demonstrate that resveratrol ameliorates hepatic metaflammation, accompanied by alterations in NLRP3 inflammasome.
Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required. We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life with limited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twin-pregnant sheep were fed diets meeting 100% (NORM) or 50% (LOW) of energy and protein requirements during the last trimester. Twin offspring were fed either a normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood; only females), resulting in four groups: NORM-CONV, LOW-CONV, NORM-HCHF and LOW-HCHF. At the age of 6 months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance) and adrenalin challenges. At 6 months of age, postnatal HCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutrition was found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lack of or the opposite response compared with the controls) in 2-year-old adults. In conclusion, a HCHF diet interfered with β-cell function, whereas maternal undernutrition did not lead to any changes in the LOW offspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.
This study was aimed at finding out whether weight reduction alone can improve liver function in obese patients with fatty liver. We did a longitudinal, clinical intervention study on weight reduction by behavior modification, diet and exercise. The study subjects were 25 patients referred to an obesity clinic in whom obesity is the sole factor causing abnormal liver function and fatty liver. Patients were weighed about one year later. We compared the degree of improvement in hepatic function between Group I that showed weight reduction and Group II that showed no-weight reduction. Group I (13) showed dramatic improvement in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, nearly all down to within normal levels. AST showed statistically significant improvement from 74 +/- 36 IU/l to 25 +/- 7 IU/l. ALT also showed statistically significant improvement from 109 +/- 67 IU/l to 30 +/- 14 IU/l. Group II (12) showed higher AST and ALT levels on follow-up visit than initial visit. AST showed statistically significant elevation from 43 +/- 11 IU/l to 59 +/- 23 IU/l. ALT also showed statistically significant elevation from 64 +/- 21 IU/l to 97 +/- 33 IU/l. If we can rule the other causes of hepatic abnormalities in obese patients with fatty liver, we suggest these patients would benefit by weight reduction.
Nonalcoholic steatohepatitis (NASH) is the most common histological finding in morbidly obese patients undergoing liver biopsy. Biliopancreatic diversion has been widely used for the treatment of morbid obesity and hepatic steatosis, and very few cases of liver impairment as a complication of this operation have been reported.
During the last 9 years, 470 morbidly obese patients were operated by means of a biliopancreatic diversion with duodenal switch ( BPD-DS), and 93 of them were performed laparoscopically.
10 cases of clinical hepatic impairment occurred after the BPD-DS. The clinical course of these patients ranged from transient subclinical alterations of liver function tests to severe cases of jaundice and one death from liver failure.
Randomized prospective studies with standardization of BPD-DS are needed, to know the real incidence of hepatic impairment and the proper treatment for this condition. Careful follow-up and correction of possible malnutrition should be addressed to avoid hepatic impairment and/or progression of liver disease.
NAFLD and alcoholic liver disease affect a substantial proportion of the population worldwide. Although presence and amount of steatosis can be determined with a good level of accuracy using noninvasive imaging techniques, currently, there is no available noninvasive tests to distinguish between simple steatosis from steatohepatitis or to stage fibrosis that had demonstrated to be simple, reproducible, and valid in patients who have NAFLD or alcoholic liver disease. Liver biopsy remains a useful tool to confirm the diagnosis and exclude other liver disease and remains the only investigation able to provide prognostic information by staging and grading these diseases. Noninvasive serum markers offer considerable promise in their ability to stage liver fibrosis. Routine liver tests may detect occult cirrhosis but are insensitive at predicting lesser stages of fibrosis. Several serum markers of collagen synthesis and degradation are not validated sufficiently and are not available in most medical centers to replace liver biopsy. These markers currently may assist in stratifying patients who are more likely to have advanced fibrosis and, therefore, may benefit from proceeding with liver biopsy. It is likely the more complex models, which include multiple serum markers, will be more accurate at predicting fibrosis. These currently have limited ability at predicting the full range of liver fibrosis, generally having the greatest diagnostic accuracy at predicting advanced fibrosis or absent fibrosis but not in-between. Measuring liver stiffness with different imaging techniques holds promise, but further carefully designed studies are necessary before they can be recommended in clinical practice.
15 consecutive persons aged under 50 with an overweight exceeding 75% were examined clinically, biochemically and with liver biopsy after gastric bypass (7 patients) or gastroplasty (8 patients). After 1 year the occurrence of steatosis had fallen from 73 to 40% which, together with a marked decrease in individual gradings of fatty changes, represented a significant regression of the steatosis. Likewise, discrete inflammatory and granulomatous changes largely disappeared. In no case was fibrosis present. Serum alkaline phosphatases preoperatively increased above normal range in 20% but their mean level was significantly reduced after 12 months of weight loss. Other liver function tests remained normal and stable. In contrast to published experience with jejunoileal bypass operations liver steatosis associated with morbid obesity seems to be morphologically and biochemically reversed together with the weight reduction obtained by gastroplasty or gastric bypass.
Nonalcoholic steatohepatitis is now recognized as a common chronic liver disorder. Up to 16% of affected patients may progress to cirrhosis. The incidence and prevalence of this disease are noted to be increasing, in parallel with the nationwide increase in obesity and diabetes. Treatment options for these patients remain quite limited, however. Weight reduction has been advocated, but there are little data to support this practice, as most patients are unable to comply with the proper dietary modifications. We report three obese patients with biopsy-proven nonalcoholic steatohepatitis treated for 6-12 months with a weight reduction medication, orlistat, who lost between 22-42 lb, and had significant clinical and histopathological improvement on follow-up.
Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of fat-induced liver injury, ranging from relatively benign steatosis to cirrhosis and liver failure. The presence of obesity and insulin resistance is strongly associated with non-alcoholic fatty liver and confers on it a greater risk of histologically advanced disease. There is a growing concern in the medical profession as the prevalence of this disease continues to rise in parallel with the rise in obesity and the metabolic syndrome. Treatment options are limited and dietary weight loss is often advised. Low fat diets are difficult to adhere to and recent studies have shown the potential of low carbohydrate diets for weight loss and improving insulin resistance. Thus far, no study has evaluated the effect of low carbohydrate diets on NAFLD. Future studies will be required to address this question and others with regards to the nutritional adequacy and long-term side effects of these diets.