The gut microbiome and nonalcoholic fatty liver disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139925/1/cld671.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139925/2/cld671_am.pd

Effect of lifetime alcohol consumption on the histological severity of non‐alcoholic fatty liver disease

Background & Aims Non‐alcoholic fatty liver disease ( NAFLD ) is defined based on recent alcohol consumption; however, remote or lifetime alcohol consumption is not taken into account. It is not known whether lifetime alcohol consumption contributes to the severity of disease in patients with NAFLD . To determine the effect of lifetime alcohol consumption on the histological severity in patients with NAFLD . Patients & Methods Adults >18 years of age with presumed NAFLD and alcohol consumption <40 g/week were enrolled. Lifetime alcohol consumption was determined using a questionnaire. Patients with a history of long‐term alcohol abuse or dependence were excluded. A liver biopsy was reviewed by a single pathologist in a blinded fashion. Demographic, clinical and histological findings were compared in those who had regular alcohol consumption and those who did not. Results A total of 77 patients had fatty liver on biopsy. Fifty‐two patients had a history of regular alcohol consumption. The median lifetime cumulative alcohol intake was 24 gram‐years. On multivariable analysis, increasing age ( OR 1.07, 95% CI 1.01–1.14) was associated with severe liver disease, whereas alcohol consumption of ≥24 gram‐years was associated with less severe disease ( OR 0.26, 95% CI 0.07–0.97, P  = 0.04). Patients who continued to consume alcohol or had been abstinent for ≤1 year had less severe disease. Conclusion Some degree of regular alcohol consumption over the course of a lifetime compared to minimal intake appears to have a protective effect on the histological severity of liver disease among patients with strictly defined NAFLD .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102218/1/liv12230.pd

Occult hepatitis B virus infection: A hidden menace?

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34784/1/510340128_ftp.pd

Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis

Aliment Pharmacol Ther 2010; 32: 1211–1221Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment.To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH.Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias.Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36–0.77, P  = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24–0.49, P  < 0.001) and ALT (WMD = 16.4, 95% CI 7.7–25.0, P  < 0.001), but not inflammation ( P  = 0.09) or fibrosis ( P  = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078–0.51, P  = 0.008). Metformin failed to improve any pooled outcome.Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79251/1/j.1365-2036.2010.04467.x.pd

Metabolic Syndrome Is Associated with Greater Histologic Severity, Higher Carbohydrate, and Lower Fat Diet in Patients with NAFLD

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73077/1/j.1572-0241.2006.00719.x.pd

CD73 (ecto‐5′‐nucleotidase) hepatocyte levels differ across mouse strains and contribute to mallory‐denk body formation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100334/1/hep26525.pd

Clinical and Histopathologic Features of Fluoroquinolone-Induced Liver Injury

Fluoroquinolone-induced liver injury is rare; no prospective studies of well-characterized case series have been published. We studied patients with fluoroquinolone-induced hepatoxicity, using data from the Drug-Induced Liver Injury Network (DILIN) to characterize injury patterns, outcomes, and associated features

NAFLD may be a common underlying liver disease in patients with hepatocellular Carcinoma in the United States

The incidence of hepatocellular carcinoma (HCC) in the United States is increasing, but the clinical characteristics of American patients with HCC have not been well described. The aims of this study were to determine the etiology of liver disease and short-term outcome among HCC patients presenting to a single center in the United States. One hundred five consecutive patients with HCC were studied; mean age was 59 years, 67% were men, and 76% were non-Hispanic white. The most common etiology of liver disease was hepatitis C (51%) and cryptogenic cirrhosis (29%). Half of the patients with cryptogenic cirrhosis had histologic or clinical features associated with nonalcoholic fatty liver disease (NAFLD). Fifty-three (50%) patients had HCC detected during surveillance (group I), whereas the remaining patients had symptomatic tumors (group II). Group I patients had smaller tumors ( P = 0.01), were more likely to be eligible for surgical treatment ( P = 0.005), and had a better medican survival compared with patients in group II ( P = 0.001). Patients with cryptogenic cirrhosis were less likely to have undergone HCC surveillance and had larger tumors at diagnosis. In conclusion, hepatitis C and cryptogenic liver disease are the most common etiologies of diseases in our patients with HCC. NAFLD accounted for at least 13% of the cases. Patients who underwent surveillance had smaller tumors and were more likely to be candidates for surgical or local ablative therapies. Because of the increasing incidence of NAFLD, further studies are needed to determine the risk of HCC in patients with NAFLD. (H EPATOLOGY 2002;36:1349-1354).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38413/1/1840360609_ftp.pd

A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C

Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score ≥ 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34794/1/510380230_ftp.pd

Intensive Interferon Therapy Does Not Increase Virological Response Rates in African Americans with Chronic Hepatitis C

To determine if an intensive regimen of daily, high-dose interferon would improve the initial response rates to therapy for hepatitis C genotype 1 among African American and Caucasian patients, we conducted a retrospective analysis of a treatment trial conducted between October 1995 and June 1997. Patients were randomized to 24 weeks of therapy with interferon −α- 2b at either 5 MU daily or 3 MU three times a week. On the standard interferon regimen (3 MU three times a week) African Americans and Caucasians had similar initial response rates. However, unlike Caucasians, African Americans did not have an increased initial virological response when treated with an intensive, daily dose regimen. Levels of HCV RNA decreased more slowly during the first 12 weeks of therapy among African Americans. Nelson-Aalen cumulative hazard estimates for the different race and dose combinations revealed that Caucasians who received daily interferon were most likely to have an initial response (logrank, P < 0.001).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44431/1/10620_2004_Article_458700.pd