Author(s)

Ayako Suzuki

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Background: Mitochondrial dysfunction plays a pivotal role in the progression of nonalcoholic steatohepatitis (NASH). L-alanine was shown to restore ATP content and protect the liver in various liver injury models. Aim: To assess the safety and therapeutic effects of long-term administration of L-alanine in patients with NASH, we conducted a pilot trial. Methods: Patients with NASH were enrolled and treated with 6 - 18 g/day L-alanine for 12 months and monitored for serum aminotransferases and renal function. Liver histology was obtained at baseline and 12 months. Changes in serum aminotransferase were assessed by differences from entry and rate of change per month using all available measures. Changes in liver histology were assessed by differences in Brunt scores of steatosis, lobular inflammation, and fibrosis. Results: Nine patients were enrolled and six completed the treatment. The reasons of the study withdrawal were nausea (n = 1), planned bariatric surgery (n = 1), and un-specified reason (n = 1). One participant experienced exacerbation of pre-existing renal failure that required hospitalization, although the medication was safely resumed after 2-week cessation and treatment was completed. Serum alanine aminotransferase (ALT) (?24.8 ± 32.1 IU/L vs.0, p = 0.11) and aspartate aminotransferase (AST) (?8 ± 16.2 1IU/L vs. 0, p = 0.28) were improved in 4 and 3 of the 6 completed participants, while rate of ALT and AST change per month showed improvement over time (negative slope) in 5 and 4 of the 6. Liver histology did not change significantly. Conclusion: The 12-month administration of L-alanine seems to be safe, but did not show significant therapeutic effects on serum aminotransferase or liver histology in patients with NASH, along with less than ideal tolerability.

Nonalcoholic Steatohepatitis, Treatment, Hepatic ATP

A. Suzuki, "A Pilot Study: No Therapeutic Effect of L-Alanine in Patients with Nonalcoholic Steatohepatitis," Food and Nutrition Sciences, Vol. 1 No. 2, 2010, pp. 67-73. doi: 10.4236/fns.2010.12011.