Risk Factor Analysis Between Newly Screened and Established Hepatitis C in GI and Hepatology Clinics.

BACKGROUND: Several studies show inconsistencies in the rate of hepatitis C virus (HCV) detection among baby boomers (born 1945-1965). We conducted a cross-sectional HCV screening followed by a case-controlled comparison of the newly screened population with established HCV subjects. METHOD: Enrollment was offered to subjects aged 40-75 at our gastroenterology and hepatology clinics. Demographic data and potential risk factors were obtained, and HCV antibody test was offered to those who had never been screened and compared with a group with established HCV. Logistic regression analysis and Fisher's exact test were performed. RESULTS: Six hundred and seventy-five patients were offered participation, of whom 128 declined while 50 consented to participate but did not perform the HCV antibody test. Of 497 enrolled subjects, 252 patients had HCV, while 245 subjects (188 patients among "baby boomer") underwent screening for HCV. There were more females (62.4 vs. 41.7%) and immigrants (34.7 vs. 22.2%) among the newly screened group. Among the screened population, five patients had HCV antibody (2.04%), and two of them had positive viral load (0.82%) of whom only one fell in the baby boomer category (0.53%). Compared to HCV group, screened group had significantly lower-risk factors, such as IV drug use (1.22 vs. 43.3%), intranasal cocaine use (14.3 vs. 49.6%), and blood transfusion (18.8 vs. 32.5%). CONCLUSION: We found a slightly lower but similar prevalence of HCV antibody when screening based on birth cohort as compared to larger baby boomer studies. Future studies evaluating addition of other screening strategies or possibly universal screening may be needed.

Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study.

BACKGROUND & AIMS: Noninvasive surrogate end points of long-term outcomes of patients with primary biliary cirrhosis (PBC) are needed to monitor disease progression and evaluate potential treatments. We performed a meta-analysis of individual patient data from cohort studies to evaluate whether patients' levels of alkaline phosphatase and bilirubin correlate with their outcomes and can be used as surrogate end points. METHODS: We performed a meta-analysis of data from 4845 patients included in 15 North American and European long-term follow-up cohort studies. Levels of alkaline phosphatase and bilirubin were analyzed in different settings and subpopulations at different time points relative to the clinical end point (liver transplantation or death). RESULTS: Of the 4845 patients, 1118 reached a clinical end point. The median follow-up period was 7.3 years; 77% survived for 10 years after study enrollment. Levels of alkaline phosphatase and bilirubin measured at study enrollment (baseline) and each year for 5 years were strongly associated with clinical outcomes (lower levels were associated with longer transplant-free survival). At 1 year after study enrollment, levels of alkaline phosphatase that were 2.0 times the upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other thresholds. Of patients with alkaline phosphatase levels ≤ 2.0 times the ULN, 84% survived for 10 years compared with 62% of those with levels >2.0 times the ULN (P < .0001). Absolute levels of alkaline phosphatase 1 year after study enrollment predicted patient outcomes better than percentage change in level. One year after study enrollment, a bilirubin level 1.0 times the ULN best predicted patient transplant-free survival (C statistic, 0.79). Of patients with bilirubin levels ≤ 1.0 times the ULN, 86% survived for 10 years after study enrollment compared with 41% of those with levels >1.0 times the ULN (P < .0001). Combining levels of alkaline phosphatase and bilirubin increased the ability to predict patient survival times. We confirmed the predictive value of alkaline phosphatase and bilirubin levels in multiple subgroups, such as patients who had not received treatment with ursodeoxycholic acid, and at different time points after study enrollment. CONCLUSIONS: Levels of alkaline phosphatase and bilirubin can predict outcomes (liver transplantation or death) of patients with PBC and might be used as surrogate end points in therapy trials.

The Metabolic Syndrome and Its Influence on Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) and the metabolic syndrome (MetS) are highly prevalent in the Western population. Their pathogenesis is closely linked to insulin resistance, which serves as a therapeutic target for the management of these conditions. This review article reviews the research supporting the influence of MetS on NASH and includes studies supporting their similar epidemiology, pathogenesis, and treatment.

A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical Treatment for NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world with prevalence of 20-33%. NAFLD comprises a pathological spectrum. Nonalcoholic fatty liver (NAFL) is at one end and consists of simple hepatic steatosis. On the contrary, nonalcoholic steatohepatitis (NASH) consists of steatosis, inflammation, and ballooning degeneration and can progress to cirrhosis. Despite the rising incidence, definitive treatment for NAFLD, specifically NASH, has not yet been established. Lifestyle modification with dietary changes combined with regular aerobic exercise, along with multidisciplinary approach including cognitive behavior therapy, has been shown to be an effective therapeutic option, even without a significant weight loss. Pioglitazone and vitamin E have shown to be most effective in NASH patients. Surgery and weight loss medication are effective means of weight loss but can potentially worsen NASH related fibrosis. Other agents such as n-3 polyunsaturated fatty acids, probiotics, and pentoxifylline along with herbal agent such as milk thistle as well as daily intake of coffee have shown potential benefits, but further well organized studies are definitely warranted. This review focuses on the available evidence on pharmaceutical and nonpharmaceutical therapy in the treatment and the prevention of NAFLD, primarily NASH.

Association between metabolic syndrome and liver histology among NAFLD patients without diabetes.

BACKGROUND: Metabolic syndrome (MetS) and obesity are associated with non-alcoholic fatty liver disease (NAFLD). The aim of this observational study was to examine the relationship of MetS and a diagnosis of non-alcoholic steatohepatitis (NASH) in patients without diabetes in the NASH Clinical Research Network (CRN). METHODS: Clinical, demographic, histological, laboratory and anthropometric data were collected on 356 adult patients without diabetes with NAFLD. Obesity was defined as body mass index ≥30.0. MetS was determined using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATPIII) 2001 criteria to include 3 or more of the following: increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, hypertension and elevated fasting blood glucose. RESULTS: Most patients were obese (71%) and had MetS (67%). Obesity was more prevalent among patients with MetS (80% vs 52%; p≤0.001). Markers of insulin resistance such as homoeostasis model assessment of insulin resistance (6.5 vs 4.9, p≤0.001) were higher among those with MetS compared with those without MetS. Histologically, patients without MetS had higher hepatocellular (p=0.04) and reticuloendothelial system iron (p=0.04). Patients with MetS were more likely to have severe hepatic steatosis (p=0.04) and chronic portal inflammation (p=0.01). On multiple logistic regression analysis, patients with definite NASH were almost 2.5 times more likely to have MetS than those without definite NASH (OR=2.41, p=0.01). CONCLUSIONS: MetS is common in patients without diabetes with NAFLD and is associated with greater insulin resistance, hepatic steatosis and portal inflammation. While patients without MetS have greater iron overload, patients with MetS may have an increased propensity to have NASH. Therefore, presence of MetS in patients without diabetes with NAFLD may serve as a potential criterion for liver biopsy. TRIAL REGISTRATION NUMBER: NCT00063622; Pre-results.

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease.

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease (NAFLD) in patients with and without type 2 diabetes mellitus (T2DM) using updated nonalcoholic steatohepatitis clinical research network (NASH-CRN) grading system. METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2DM. This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author. The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison. The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist. The updated criteria for type 2 diabetes have been utilized for analysis. Background data of patients with NASH and NAFLD has been included. The mean differences were compared using χ(2) and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis. RESULTS: Patients with NAFLD and T2DM were significantly older (49.9 vs 43.0, P < 0.01), predominantly female (71.4 vs 56.3, P < 0.02), had higher rate of metabolic syndrome (88.7 vs 36.4, P < 0.01), had significantly higher aspartate transaminase (AST)/alanine transaminase (ALT) ratio (0.94 vs 0.78, P < 0.01) and Fib-4 index (1.65 vs 1.06, P < 0.01) as markers of NASH, showed higher mean NAFLD activity score (3.5 vs 3.0, P = 0.03) and higher mean fibrosis score (1.2 vs 0.52, P < 0.01) compared to patients with NAFLD without T2DM. Furthermore, advanced fibrosis (32.5 vs 12.0, P < 0.01) and ballooning (27.3 vs 13.3, P < 0.01) was significantly higher among patients with NAFLD and T2DM compared to patients with NAFLD without T2DM. On multivariate analysis, T2DM was independently associated with NASH (OR = 3.27, 95%CI: 1.43-7.50, P < 0.01) and advanced fibrosis (OR = 3.45, 95%CI: 1.53-7.77, P < 0.01) in all patients with NAFLD. There was a higher rate of T2DM (38.1 vs 19.4, P < 0.01) and cirrhosis (8.3 vs 0.0, P = 0.01) along with significantly higher mean Bilirubin (0.71 vs 0.56, P = 0.01) and AST (54.2 vs 38.3, P < 0.01) and ALT (78.7 vs 57.0, P = 0.01) level among patients with NASH when compared to patients with steatosis alone. The mean platelet count (247 vs 283, P < 0.01) and high-density lipoprotein cholesterol level (42.7 vs 48.1, P = 0.01) was lower among patients with NASH compared to patients with steatosis. CONCLUSION: Patients with NAFLD and T2DM tend to have more advanced stages of NAFLD, particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2DM.

Metal storage disorders: Wilson disease and hemochromatosis.

Hereditary hemochromatosis and Wilson disease are autosomal recessive storage disorders of iron and copper overload, respectively. These metals are involved in multiple redox reactions, and their abnormal accumulation can cause significant injury in the liver and other organs. Over the last few decades clinicians have developed a much better understanding of these metals and their mechanism of action. Moreover, sophisticated molecular genetic testing techniques that make diagnostic testing less invasive are now available. This article updates and discusses the pathogenesis, diagnosis, and management of these metal storage disorders.

Diagnosis and treatment of hereditary hemochromatosis: an update.

Hereditary hemochromatosis is an inherited iron overload disorder caused by inappropriately low hepcidin secretion leading to increased duodenal absorption of dietary iron, most commonly in C282Y homozygous individuals. This can result in elevated serum ferritin, iron deposition in various organs and ultimately end-organ damage, although there is incomplete biochemical and clinical penetrance and variable phenotypic expression of the HFE mutation in hereditary hemochromatosis. An elevated SF >1000 mg/l [corrected] is associated with an increased risk of cirrhosis and mortality in C282Y homozygotes.Conversely, a SF <1000 µg/l is associated with a very low likelihood of cirrhosis, making liver biopsy unnecessary among C282Y homozygotes in the absence of concomitant risk factors for liver disease. Phlebotomy remains the mainstay of treatment and new treatments being studied include erythrocytapheresis and 'mini-hepcidins'. Iron overload is being recognized to play a carcinogenic role in hepatocellular carcinoma and other cancers, possibly supporting iron depletion in these patients.

Prevalence of Helicobacter pylori infection in bariatric patients: a histologic assessment.

BACKGROUND: Studies on rates of Helicobacter pylori (HP) infection in morbidly obese patients awaiting bariatric surgery are conflicting because of small sample size and variability in diagnostic testing. The objective of this study was to determine the rate of biopsy-proven active HP infection in morbidly obese patients undergoing bariatric surgery. METHODS: Retrospective analysis was done on all morbidly obese patients who underwent bariatric surgery between 2001 and 2009. All patients underwent preoperative upper endoscopy with biopsy to evaluate HP status. All endoscopies and surgeries were performed by a single endoscopist and surgeon, respectively. Data were analyzed with Student t test, Pearson χ(2) test, and logistic regression for multivariate analysis. RESULTS: The 611 patients included 79 males (12.9%) and 532 females (87.1%). Mean age was 39.9 ± 10.7 years, and mean body mass index (BMI) was 47.8 ± 6.4 kg/m(2). The overall HP infection rate was 23.7%. Rate of infection did not differ between gender (22.8% in males, 23.9% in females; P = .479) or BMI (48.6 ± 6.5 kg/m(2) in HP-positive patients, 47.5 ± 6.4 kg/m(2) in HP-negative patients; P = .087). Patients with HP were older compared with those without infection (41.2 versus 38.7 years; P =.016). Hispanics had a higher prevalence of HP (OR 2.35; P = .023). CONCLUSION: Increasing BMI is not an independent risk factor for active HP infection within the morbidly obese patient population. Need for invasive testing to detect HP infection in these patients should be re-evaluated. Other methods of detecting active HP infection should be considered as an alternative to invasive or serologic testing.