Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population.

METHODS: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion.

RESULTS: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1-3), the median necroinflammatory grade was 1 (1-3), and the median fibrosis stage was 2 (0-4). The median level of red cell folate was 526 ng/ml (range 99-708); the normal level was 268-616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60+/-25 vs. 54+/-29, P=0.5 and 86+/-29 vs. 83+/-42, P=0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients.

CONCLUSION: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient.