L-ALANINE IN NASH

Nonalcoholic steatohepatitis (NASH) is one stage of nonalcoholic fatty liver disease, which has been increasingly recognized as the obese population increases. Approximately 20% of patients with NASH are thought to develop severe fibrosis. Several therapeutic approaches have shown preliminary efficacy in patients with NASH; however, none of them has shown efficacy in randomized placebo-controlled trials. The treatment of NASH has not yet been established.

Oxidative stress is thought to play a pivotal role in the disease progression and one of the promising targets to prevent the development of fibrosis in NASH. L-alanine is a glycogenic amino acid and also used as a substrate of ATP synthesis. A series of recent animal studies showed potential therapeutic effects of L-alanine on hepatocytes by protecting from various cellular injuries through restoring ATP content and, probably, reducing production of reactive oxygen species. The hepatoprotective effect was preliminarily shown in humans by the experimental administration of L-alanine to cirrhotic patients.

In this pilot trial in patients with NASH we will work to assess the therapeutic efficacy of L-alanine in improving biological and histological findings by administrating 6-18g/day L-alanine for one year. We will also assess the safety and toxicity profile of long-term administration of L-alanine. Furthermore, this study will be conducted in collaboration with basic laboratory evaluations to permit the assessment of the level of gene expression related to mitochondrial function and anti-oxidative systems in the liver, and how the expression levels of the target genes may be changed by the treatment. Thus, this study will provide us with significant information about future therapy in patients with NASH.