Cholestatic liver injury associated with dietary supplements: a report of five cases in active duty service members.

The use of dietary supplements (DS) is common in the active duty population, often without physician knowledge or approval. DS have been associated with drug-induced liver injury, with rare cases resulting in liver failure or death. We report five cases of transient drug-induced liver injury temporally associated with the use of a total of six DS in active duty service members. All patients presented with elevated serum bilirubin and liver-associated enzymes: three patients had a cholestatic liver enzyme pattern, one had a hepatocellular pattern, and one had a mixed pattern. In all cases, percutaneous needle core biopsies of the liver were obtained and demonstrated a cholestatic pattern of injury with variable periportal fibrosis. Causality was considered highly probable for three cases, probable for one case, and possible for one case. Hepatotoxicity has been previously associated with four of the supplements in our cases. For the two remaining supplements, C4 Extreme and Animal Stak, we are unaware of any previous reports of hepatotoxicity. Health care professionals, in particular military physicians, should be aware of the potential risk of these supplements and be prepared to discuss these risks with their patients.

Ribavirin analogs.

Ribavirin is ineffective against hepatitis C virus as mono-therapy but is critical in attaining both early virologic response and sustained virologic response when combined with pegylated interferon. Ribavirin has significant dose-limiting toxicities, the most important of which is hemolytic anemia. Taribavirin is a ribavirin pro-drug, which targets the liver and has less incidence of anemia, and it may be a promising alternative to ribavirin in the future.

The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n »10) or group B (n» 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and 0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.