-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The aim of the study is to evaluate recent trends in mortality, length of stay, costs, and charges for patients admitted to the US hospitals with the principal diagnosis of stroke. METHODS: This was a retrospective temporal trends study using data from the Nationwide Inpatient Sample from 2005 to 2009. RESULTS: During the study period, there were 2.7 million hospital admissions with the diagnosis of stroke in the United States (470,000 intracerebral hemorrhage, 130,000 subarachnoid hemorrhage, and 2.1 million ischemic strokes). In-hospital mortality decreased from 10.2% in 2005 to 9.0% in 2009 (26.0%-23.0%, 23.4%-23.1%, and 6.0%-5.1% for the stroke subtypes, respectively), the average length of stay decreased from 6.3 days to 5.9 days (5.6-5.2 days for ischemic stroke, remained the same for hemorrhagic stroke), and the average number of 1.3 ± 0.1 procedures per admission remained the same. The proportion of patients with major or extreme severity of illness increased from 39.2% to 47.0% (P < .0001). After adjustment for inflation, the average total charge per admission increased from $36,215 to $46,518 (P < .0001), whereas the average cost of treatment remained the same. Higher treatment cost is associated with lower in-hospital mortality after adjustment for demographic, hospital-related, and clinical confounders (odds ratio = .968 [.965-.970] per each extra $1000). CONCLUSIONS: Between 2005 and 2009, in-hospital mortality for patients hospitalized with stroke improved despite increasing severity of illness. At the same time, the average charge for hospitalization increased by 28% despite unchanged cost of treatment and shorter length of stay.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 03/2013;
-
[show abstract]
[hide abstract]
ABSTRACT: The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.
PLoS ONE 01/2013; 8(2):e56009. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIM: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and may be associated with increased mortality. Our aim was to determine whether anthropometric measures are independently associated with mortality in NAFLD. METHODS: The third National Health and Nutrition Examination Surveys (1988-1994) data was used. Extensive radiologic, serologic and clinical data were available. NAFLD was defined as moderate-to-severe hepatic steatosis on the hepatic ultrasound in the absence of any cause of chronic liver disease (e.g. hepatitis C virus RNA negative, hepatitis B-surface antigen negative, normal transferrin saturation and alcohol consumption <20 gram/day). Anthropometric measures [body mass index (kg/m(2)), waist, hip, arm, and thigh circumferences (cm), waist-to-hip ratio, percentage of body fat, and sum of skinfolds (mm)], laboratory measures and clinico-demographic data were analyzed. Statistical analyses were conducted with SUDAAN 10.0. RESULTS: A total of 10,565 adult participants were included [2,510 (weighted 21 %) with NAFLD and 8,055 non-NAFLD controls]. In multivariate analysis, NAFLD was independently associated with being Mexican-American (including Hispanic or other ethnicity), larger waist circumference (cm), type-2 diabetes, insulin resistance and hypertension. After about 14 years (median) of follow up, liver-specific mortality was independently associated with NAFLD and being White. CONCLUSIONS: Components of metabolic syndrome, and Mexican-American ethnicity are independently associated with NAFLD. Furthermore, NAFLD is an independent predictors of liver-specific mortality in men and Whites.
Digestive Diseases and Sciences 11/2012; · 2.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The presence of hepatic steatosis in individuals without a known cause of chronic liver disease, including excessive alcohol consumption, is the hallmark of nonalcoholic fatty liver disease (NAFLD). Although NAFLD is usually associated with obesity, nonobese patients can also present with NAFLD ("lean NAFLD"). Our objective was to determine factors independently associated with lean NAFLD in the United States population. For this purpose, we used data from National Health and Nutrition Examination Survey III (NHANES III) conducted between 1988 and 1994 with available hepatic ultrasound, clinico-demographic, and laboratory data. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by ultrasound), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in women), hepatitis B surface antigen(-), and hepatitis C antibody(-). Nonalcoholic steatohepatitis (NASH) was defined as having moderate-severe steatosis and elevated aminotransferases in the presence of type 2 diabetes or insulin resistance (IR). Logistic regression was used to identify independent predictors of lean NAFLD. As a result, of the 11,613 participants included in the study, 2185 (18.77% ± 0.76%) had NAFLD; of these, 307 (11.78% ± 1.03%) had NASH. Multivariate analysis showed that lean NAFLD was independently associated with younger age, female sex, and a decreased likelihood of having IR and hypercholesterolemia (p values < 0.05). Additionally, multivariate analysis showed that NASH was independently associated with being Hispanic, having a younger age, and having components of metabolic syndrome such as hypertension (p values < 0.05). Therefore, we conclude that lean individuals with NAFLD have a different clinical profile than overweight-obese individuals with NAFLD. Furthermore, patients with NASH are commonly Hispanic and have components of metabolic syndrome.
Medicine 10/2012; · 4.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The standard treatment for CH-C, pegylated interferon-α and ribavirin (PEG-IFN + RBV), is associated with depression. Recent studies have proposed a new role for cytokines in the pathogenesis of depression. We aimed to assess differential gene expression related to depression in CH-C patients treated with PEG-IFN + RBV. We included 67 CH-C patients being treated with PEG-IFN+RBV. Of the entire study cohort, 22% had pre-existing depression, while another 37% developed new depression in course of the treatment. Pretreatment blood samples were collected into PAXgene™ RNA tubes, the RNAs extracted from peripheral blood mononuclear cells (PBMCs) were used for one step RT-PCR to profile 160 mRNAs. Differentially expressed genes were separated into up- and down-regulated genes according to presence or absence of depression at baseline (pre-existing depression) or following the initiation of treatment (treatment-related depression). The mRNA expression profile associated with any depression and with treatment-related depression included four and six genes, respectively. Our data demonstrate a significant down-regulation of TGF-β1 and the shift of Th1-Th2 cytokine balance in the depression associated with IFN-based treatment of HCV infection. We propose that TGF-β1 plays an important role in the imbalance of Th1/Th2 in patients with CH-C and depression. With further validation, TGF-β1 and other components of Th1/Th2 regulation pathway may provide a future marker for CH-C patients predisposed to depression.
Brain and behavior. 09/2012; 2(5):525-31.
-
[show abstract]
[hide abstract]
ABSTRACT: Hepatic encephalopathy (HE) is a major complication of cirrhosis that causes substantial mortality and utilization of resources.
We analyzed 5 cycles of the Nationwide Inpatient Sample, conducted between 2005 and 2009, to determine national estimates of incidence, prevalence, inpatient mortality, severity of illness, and resource utilization for inpatients with HE.
The yearly inpatient incidence of HE ranged from 20,918 (2005) to 22,931 (2009) (P = .2226), comprising approximately 0.33% of all hospitalizations in the United States. Over the 5-year period of analysis, mortality of inpatients with HE remained relatively stable, at 14.13%-15.61% (P = .062); however, the proportion of patients with major and extreme severity of illness increased (P < .0001). The average length of inpatient stay increased from 8.1 to 8.5 days (P = .019). The average total inpatient charges increased from $46,663 to $63,108 per case (P < .0001). Furthermore, total national charges related to HE increased from $4676.7 million (2005) to $7244.7 million (2009). In multivariate analysis, independent predictors of inpatient mortality included the number of diagnoses per admission (odds ratio [OR] = 1.022; 95% confidence interval [CI], 1.016-1.029 per diagnosis), number of procedures per admission (OR = 1.192 per procedure; 95% CI, 1.177-1.208), and major or extreme severity of illness (OR = 3.16; 95% CI, 2.84-3.50). The most important predictors of cost, charge, and length of stay were admission to a large, urban hospital; use of Medicaid or Medicaid as the payer; major or extreme severity of illness; number of diagnoses at discharge; and procedures per admission (P < .05).
Resource utilization increased from 2005 to 2009 for patients discharged from US hospitals with the diagnosis of HE. The inpatient mortality rate, however, remained stable, despite a trend toward more severe disease.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2012; 10(9):1034-41.e1. · 5.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs) have common metabolic risk factors. Despite reports from clinical studies, the association between NAFLD, cardiovascular disease, and cardiovascular mortality are not clear at the population level.
We analyzed data from the National Health and Nutrition Examination Survey III, conducted from 1988 to 1994, and compared hepatic ultrasound and mortality data. Participants were classified into those with NAFLD (moderate or severe hepatic steatosis, based on ultrasound analysis, without any evidence of other liver disease; n = 2492) and those without (absence of NAFLD or any other chronic liver diseases: controls). The prevalence of CVD was compared between subjects with and without NAFLD. Additional comparisons were made between NAFLD patients who had increased levels of liver enzymes and those who had normal levels. Independent predictors of CVD and cardiovascular mortality also were studied.
During the follow-up period (median, 171 mo), 12.21% of the National Health and Nutrition Examination Survey III participants died; cardiovascular mortality was 3.76%. Regardless of whether levels of liver enzymes were increased or not, individuals with NAFLD were older, predominantly male, more likely to be Hispanic, and less likely to be African American than controls. They also had a higher prevalence of all components of metabolic syndrome and CVD. Regardless of levels of liver enzymes, NAFLD was associated independently with CVD, after adjusting for major demographic, clinical, and metabolic confounders (odds ratio, 1.23; 95% confidence interval, 1.04-1.44). The independent association of NAFLD with cardiovascular mortality was not statistically significant.
NAFLD is associated independently with an increased risk of CVD. However, NAFLD did not increase cardiovascular mortality over a 14-year period.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2012; 10(6):646-50. · 5.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients.
Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort.
The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype.
IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV.
Journal of Translational Medicine 01/2012; 10:25. · 3.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States. African Americans are known to have a higher prevalence of HCV and lower response to anti-HCV therapy.
The aim of this study is to assess the differences in the prevalence of chronic HCV infection in according to patients' ethnic background.
We used the recent National Health and Nutrition Examination Survey with extensive clinical and laboratory data. Active HCV infection was defined as having HCV-positive antibody with detectable HCV RNA by polymerase chain reaction. HCV clearance was defined as HCV-positive antibody with negative HCV RNA. Clinico-demographic data were compared between anti-HCV positive individuals with or without HCV clearance. The stratum-specific χ test for independence was used. Logistic regression was used to identify independent predictors of HCV clearance. P-values ≤0.05 were considered statistically significant. All analyses were run using SAS 9.1 and SUDAAN 10.0.
The cohort included 14,750 adults (age 47.6 ± 0.75 y, 64% white, 21% African American, 10% Hispanics, and 63% male). Of these, 1.32 ± 0.11% were anti-HCV positive with 75.94 ± 4.72% having active HCV viremia. The only parameter significantly different between those who did or did not clear HCV was the proportion of African Americans: 8.0 ± 3.7% versus 24.9 ± 5.0%, P=0.0163. Indeed, the rate of HCV clearance was lowest among African Americans (9.3 ± 3.5%) as compared with both whites (27.2 ± 6.5%) and Hispanics 31.2 ± 9.1% (P<0.05). In multivariate analysis, the only independent predictor of active HCV infection was African American race: odds ratio (95% confidence interval)=3.80 (1.31-11.06), P=0.0151.
African Americans not only have lower response to anti-HCV therapy but also are less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV.
Journal of clinical gastroenterology 12/2011; 46(8):e62-5. · 2.21 Impact Factor
-
Michael Estep,
Massih Abawi,
Mohammed Jarrar,
Lei Wang, Maria Stepanova,
Hazem Elariny,
Amir Moazez,
Zachary Goodman,
Vikas Chandhoke,
Ancha Baranova,
Zobair M Younossi
[show abstract]
[hide abstract]
ABSTRACT: Three protein products of ghrelin gene (acylated ghrelin, des-acylated ghrelin, and obestatin) are involved in appetite stimulation and suppression. Additionally, there is some evidence suggesting their involvement in metabolic and inflammatory pathways which may be implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the relationships of ghrelin gene products in patients with NAFLD.
We included 75 morbidly obese patients with biopsy-proven NAFLD (41 with histologic non-alcoholic steatohepatitis (NASH)) with clinical and laboratory data as well as frozen serum samples from the time of liver biopsy. Fasting serum was assayed for obestatin as well as acylated and des-acyl-ghrelin concentrations using ELISA. Bio-Plex inflammatory cytokine assays were used to profile expression of 17 inflammatory mediators, including IL-6, IL-7, IL-8, G-CSF, CCL2, and MIP-1β.
Patients with NASH had twofold higher concentration of des-acyl-ghrelin than patients with non-NASH (2.58 vs. 1.24 pg/ml, P < 0.02). Ghrelin concentrations in NASH patients with fibrosis stage ≥2 were almost double the concentration of NASH patients with fibrosis stage <2 (8.73 vs. 4.22 pg/ml, P < 0.04). Obestatin levels also increased with the fibrosis stage (2.54 vs. 3.46 pg/ml, P < 0.03). NAFLD patients with higher fibrosis stage had lower IL-7 concentrations (16.89 vs. 10.68 pg/ml, P = 0.014). Obestatin levels at baseline significantly correlated with rate of weight loss after bariatric surgery at various time points.
This study suggests that products of the GHRL gene may be important for the pathogenesis of NASH and fibrosis. Additional confirmatory studies are needed.
Obesity Surgery 07/2011; 21(11):1750-7. · 3.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Professional societies recommend hepatitis A and hepatitis B immunization for individuals with chronic liver disease (CLD), but the degree of implementation is unknown. Data were obtained from the National Health and Nutrition Examination Surveys (NHANES) conducted in 1999-2008. For the entire study population and for those with CLD and diabetes, we determined the rates and independent predictors of history of hepatitis A and hepatitis B (HepA and HepB) vaccinations, of their effectiveness, and of seroprevalence of hepatitis A antibody and anti-HB surface antibody. In total, 24,871 participants from NHANES were included: 14,886 (1999-2004) and 9,985 (2005-2008). Of these individuals, 14.0% had CLD and 8.6% had diabetes. During the study period, HepA vaccination in CLD increased from 13.3% ± 1.0% to 20.0% ± 1.5%, HepB vaccination increased from 23.4% ± 1.2% to 32.1% ± 1.5%. Of subtypes of CLD, HepA vaccination rates increased only in nonalcoholic fatty liver disease (NAFLD), whereas HepB vaccination increased for patients with hepatitis C and nonalcoholic fatty liver disease. In the diabetic cohort, HepA vaccination rates increased from 9.3% ± 1.1% to 15.4% ± 1.7% and HepB rates increased from 15.2% ± 1.5% to 22.4% ± 1.7%. All changes were similar to those observed in the general population. The quality measure (QM) for HepA in the general population decreased from 44.4% ± 1.2% in 1999-2004 to 41.7% ± 1.9% in 2005-2008, and similar changes were noted for all subcohorts. On the other hand, QM for HepB increased from 31.7% ± 0.9% to 40.7% ± 1.0% in the population, whereas no changes in QM were noted in any diagnostic cohort except for NAFLD. CONCLUSIONS: Although vaccination rates in CLD and diabetic cohorts are increasing, they remain low. Given the public health implications of acute hepatitis A and hepatitis B in patients with CLD, better implementation of the vaccination recommendations for these populations is warranted.
Hepatology 07/2011; 54(4):1167-78. · 11.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis.
This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables.
Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated.
Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65-M30 (necrosis) [AUC: 0.81, 95% CI, 0.70-0.89, 300 p value <9E 301 (-06)]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68-0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70-0.89; p value, 0.000062].
This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.
Obesity Surgery 04/2011; 21(4):431-9. · 3.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic liver diseases (CLDs) are major causes of morbidity and mortality worldwide. We assessed changes in the prevalence of different types of CLD in the United States.
National Health and Nutrition Examination Surveys conducted between 1988 and 2008 were used to estimate changes in the prevalence and predictors of CLDs. Serologic and clinical data were used to establish the diagnoses of CLDs in 39,500 adults. Statistical analyses were conducted with SUDAAN 10.0 (SAS Institute, Inc, Cary, NC).
The prevalence rates for CLD were 11.78% (1988-1994), 15.66% (1999-2004), and 14.78% (2005-2008). During the same period, the prevalence of hepatitis B virus infection (0.36%, 0.33%, and 0.34%), hepatitis C virus (1.95%, 1.97%, and 1.68%), and alcoholic liver disease (1.38%, 2.21%, and 2.05%) remained generally stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) increased from 5.51% to 9.84% to 11.01%. From 1988 to 1994, NAFLD accounted for 46.8% of CLD cases; from 1994 to 2004 its prevalence increased to 62.84%, and then to 75.1% from 2005 to 2008. During these time periods, steady increases were observed in obesity (21.74%, 30.02%, and 33.22%), visceral obesity (35.18%, 48.16%, and 51.43%), type II diabetes (5.55%, 7.88%, and 9.11%), insulin resistance (23.29%, 32.50%, and 35.00%), and hypertension (22.68%, 33.11%, and 34.08%). A multivariate analysis showed that during all time periods, obesity was an independent predictor of NAFLD.
National Health and Nutrition Examination Surveys data collected from 1988 to 2008 show that the prevalence of major causes of CLD remained stable, except for NAFLD, which increased steadily, along with the prevalence of metabolic conditions. Given the increasing rates of obesity, NAFLD prevalence is expected to contribute substantially to the burden of CLD in the United States.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2011; 9(6):524-530.e1; quiz e60. · 5.64 Impact Factor
-
Gut 02/2011; · 10.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Since the initial description of nonalcoholic steatohepatitis (NASH), several sets of pathologic criteria for its diagnosis have been proposed. However, their interprotocol agreement and ability to predict long-term liver-related mortality (LRM) have not been demonstrated. In this study, we examined patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) for whom liver biopsy slides and clinical and mortality data were available. Liver biopsy samples were evaluated for a number of pathologic features and were classified according to the presence or absence of NASH by (1) the original criteria for NAFLD subtypes, (2) the nonalcoholic fatty liver disease activity score (NAS), (3) the Brunt criteria, and (4) the current study's criteria. All NASH diagnostic criteria and individual pathologic features were tested for agreement and for their independent associations with LRM, which were determined with a Cox proportional hazards model. Two hundred fifty-seven NAFLD patients with complete data were included. The diagnoses of NASH by the original NAFLD subtypes and by the current study's definition of NASH were in almost perfect agreement (κ = 0.896). However, their agreement was moderate with NAS (κ = 0.470 and κ = 0.511, respectively) and only fair to moderate with the Brunt criteria (κ = 0.365 and κ = 0.441, respectively). Furthermore, the agreement of the Brunt criteria with NAS was relatively poor (κ = 0.178). During the follow-up (median = 146 months), 31% of the patients died (9% were LRM). After we controlled for confounders, a diagnosis of NASH by the original criteria for NAFLD subtypes [adjusted hazard ratio = 9.94 (95% confidence interval = 1.28-77.08)] demonstrated the best independent association with LRM. Among the individual pathologic features, advanced fibrosis showed the best independent association with LRM [adjusted hazard ratio = 5.68 (95% confidence interval = 1.50-21.45)]. CONCLUSION: The original criteria for NAFLD subtypes and the current study's criteria for NASH were in almost perfect agreement, but their level of agreement with the NAS and Brunt criteria was lower. A diagnosis of NASH by the original criteria for NAFLD subtypes demonstrated the best predictability for LRM in NAFLD patients.
Hepatology 02/2011; 53(6):1874-82. · 11.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Only half of chronic hepatitis C (CH-C) patients treated with pegylated interferon and ribavirin (PEG-IFN+RBV) achieve sustained virologic response) SVR. In addition to known factors, we postulated that activation of key protein signaling networks in the peripheral blood mononuclear cells (PBMCs) may contribute to SVR due to inherent patient-specific basal immune cell signaling architecture. In this study, we included 92 patients with CH-C. PBMCs were collected while patients were not receiving treatment and used for phosphoprotein-based network profiling. Patients received a full course of PEG-IFN+RBV with overall SVR of 55%. From PBMC, protein lysates were extracted and then used for Reverse Phase Protein Microarray (RPMA) analysis, which quantitatively measured the levels of cytokines and activation levels of 25 key protein signaling molecules involved in immune cell regulation and interferon alpha signaling. Regression models for predicting SVR were generated by stepwise bidirectional selection. Both clinical-laboratory and RPMA parameters were used as predictor variables. Model accuracies were estimated using 10-fold cross-validation. Our results show that by comparing patients who achieved SVR to those who did not, phosphorylation levels of 6 proteins [AKT(T308), JAK1(Y1022/1023), p70 S6 Kinase (S371), PKC zeta/lambda(T410/403), TYK2(Y1054/1055), ZAP-70(Y319)/Syk(Y352)] and overall levels of 6 unmodified proteins [IL2, IL10, IL4, IL5, TNF-alpha, CD5L] were significantly different (P < 0.05). For SVR, the model based on a combination of clinical and proteome parameters was developed, with an AUC = 0.914, sensitivity of 92.16%, and specificity of 85.0%. This model included the following parameters: viral genotype, previous treatment status, BMI, phosphorylated states of STAT2, AKT, LCK, and TYK2 kinases as well as steady state levels of IL4, IL5, and TNF-alpha. In conclusion, SVR could be predicted by a combination of clinical, cytokine, and protein signaling activation profiles. Signaling events elucidated in the study may shed some light into molecular mechanisms of response to anti-HCV treatment.
Journal of Proteome Research 02/2011; 10(2):774-9. · 5.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The pathogenic mechanisms of hepatic steatosis in hepatitis C (HCV) remain unclear. Aim: To assess the potential role of cytokines and adipokines in HCV-related steatosis and fibrosis.
We profiled several adipokines, cytokines, and related soluble molecules in 99 HCV patients and analyzed their potential associations with hepatic steatosis and fibrosis.
Serum leptin and IL-1RA were significantly higher in HCV genotype 1 as compared to genotype 3. On the other hand, serum resistin, IL-8, IL-1B and sIL-6R, were significantly higher in HCV genotype 3. No differences were observed for adiponectin, visfatin, IL-6 and TNF-α. Regardless of HCV genotype, steatosis could be predicted by a combination of IL-8, IL-6, and sIL-6R/IL-6. When analysis was repeated for each of the genotypes, the reliability of models improved. Regardless of HCV genotype, moderate to severe fibrosis (Metavir score >F2), was predicted by IL-8 and resistin levels.
Analysis of adipocytokines associated with steatosis supports the hypothesis that steatogenic pathways differ in HCV genotype 3 from those infected with non-genotype 3 infections.
Digestion 01/2011; 83(1-2):32-40. · 2.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Successful treatment with antiviral therapy could potentially reduce morbidity and mortality in patients with hepatitis C virus (HCV) infection. However, at the population level, these benefits may be offset by a limited number of patients who have access to antiviral treatment. Using data from the National Health and Nutrition Examination Survey conducted in 2005-2008, we analyzed the health insurance status and treatment candidacy of HCV-positive (HCV+) individuals. A total of 10,582 subjects were examined; of those, 1.16% had detectable HCV RNA and were defined as HCV+. The HCV+ patients were less likely to be insured than HCV-negative individuals (61.2% versus 81.2%; P = 0.004). Among those with health insurance, HCV+ patients were less likely to have private insurance, whereas the coverage by Medicare/Medicaid and other government-sponsored plans was similar to the rest of the population. In multivariate analysis, HCV infection was an independent predictor of being uninsured even after adjustment for demographic disparity of the HCV+ cohort (odds ratio, 0.43; 95% confidence interval, 0.24-0.78). Of all HCV+ patients, 66.7% were eligible for anti-HCV treatment. However, only 54.3% of HCV+ treatment candidates had any type of insurance coverage. Finally, only 36.3% of HCV+ patients were potentially eligible for treatment and had health insurance. CONCLUSION: A high proportion of HCV+ patients are currently uninsured, and many have publicly funded health insurance. Among those who could be candidates for treatment, the rate of insurance coverage is even lower. These findings can have important implications for health insurance coverage of these patients under the new health care reform legislation in the United States.
Hepatology 12/2010; 53(3):737-45. · 11.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Both non-alcoholic steatohepatitis (NASH) and polycystic ovary syndrome (PCOS) are associated with metabolic syndrome (MS) and insulin resistance (IR). Except for a few case reports, there are no systematic assessments of NASH in PCOS patients.
To determine the prevalence of NASH and independent factors associated with NASH in a cohort of patients with documented PCOS.
Patients with established diagnosis of PCOS and matched controls (matched for gender, age, and body mass index (BMI)) were included in the study. Causes of other liver diseases were systematically excluded by clinical and laboratory tests. Excessive alcohol use was defined as alcohol consumption of greater than 10 g/day. All liver biopsies were read by a single pathologist blinded to the clinical data. Histologic NASH was defined as steatosis with lobular inflammation and ballooning degeneration of hepatocytes with or without Mallory-Denk bodies or pericellular fibrosis. Univariate and multivariate analyses with logistic regression were performed to compare PCOS to matched controls.
Sixty-six patients were included in the study (34 PCOS and 32 matched controls). Of PCOS patients, 73% had a liver biopsy while 78% of the matched controls had a liver biopsy. In comparing PCOS patients to the matched controls, clinical (BMI, waist circumference, type 2 diabetes, MS, or its components, any alcohol consumption in the prior year, ethnic background, age, gender, etc.) and laboratory data (aminotransferases, ferritin, glucose, etc.) were not significantly different (p > 0.05). However, PCOS patients tended to have more histologic NASH on their liver biopsies (44.0% vs. 20.8%, p = 0.08). Independent predictors of histologic NASH in PCOS patients were elevated aspartate aminotransferase (AST), high triglycerides and small amounts of alcohol consumption (p = 0.019, 10-fold cross-validated AUC = 0.80, 95% CI = 0.56-0.94). Although about half of PCOS patients did not report any alcohol consumption, 50% did report rare alcohol use. In fact, PCOS patients with histologic NASH tended to report higher alcohol consumption per week than PCOS without NASH (3.80 ± 6.16 vs. 1.11 ± 1.87 g/week, p = 0.1). Nevertheless, these amounts of alcohol consumption were quite minimal.
Despite similar clinical and laboratory profiles to the matched controls, PCOS patients seem to have more histologic NASH. Although alcohol consumption was rare for both PCOS and controls, even rare alcohol consumption in PCOS patients was independently associated with histologic NASH.
Scandinavian journal of gastroenterology 11/2010; 46(4):479-84. · 2.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic liver disease (CLD) is a major cause of mortality and morbidity worldwide. The aim of this study was to assess the overall and liver-related mortality and their predictors in patients with CLD using population data.
The Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality data were utilised. Participants from NHANES III (1988-1994) and their mortality status were updated by the Center for Disease Control (CDC) as of 31 December 2006. In this study, the aetiology of CLD was based on available serological tests and clinical data. Each diagnostic cohort was compared with a cohort without liver disease using stratum-specific χ(2). The Cox proportional hazard model was used for analysis, and HRs adjusted for all major confounders; overall mortality and cause-specific mortality were calculated for each type of liver disease. All analyses were run using SAS-callable SUDAAN 10.0 functions using remote access to the CDC Research Data Center server with restricted use linked mortality data.
The study cohort included 15 866 NHANES III participants with complete clinical, demographic, laboratory and mortality follow-up data. Of these, 235 subjects had alcohol-related liver disease (ALD), 66 had chronic hepatitis B (CH-B), 264 had chronic hepatitis C (CH-C), 991 were presumed to have non-alcoholic fatty liver disease (NAFLD) and 505 had other liver disease. Additionally, 13 004 subjects without evidence of liver disease served as controls. The analysis shows that type II diabetes (DM) and/or insulin resistance (IR) are independent predictors of overall mortality in CH-B, NAFLD and ALD (p <0.05). Additionally, DM, IR, obesity and metabolic syndrome could be independent predictors of liver-related mortality in CH-C, NAFLD and ALD.
Components of metabolic syndrome are associated with overall and liver-related mortality in subjects with CLD.
Gut 10/2010; 59(10):1410-5. · 10.11 Impact Factor
