This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nonalcoholic steatohepatitis (NASH) is an increasingly recognized clinic pathological condition that may progress to end-stage liver disease. No effective medical therapy is currently available for patients with NASH. Betaine is a normal component of the metabolic cycle of methionine and has been shown to increase S-adenosylmethionine levels (SAM). SAM converts phosphatidyl-ethanolamine to phophatidylcholine which is an important constituent of lipoproteins involved in the transport of fat from the liver, hence preventing the infiltration of fat into the liver and subsequent liver damage. By increasing SAM levels, betaine protects against fat accumulation within hepatocytes. Prevention of steatosis arrests mitochondria reactive oxygen species production and decreases lipid peroxidation, which in turn blocks progress along the continuum from steatosis to steatohepatitis to advanced fibrosis that occurs in patients with NASH. In an open label pilot study conducted by our group, we have previously shown that betaine significantly improves or normalizes abnormal liver test results, as well as liver histological damage in patients with NASH.
The aim of the current study is to determine the efficacy and safety of betaine in a randomized, double-blind, placebo controlled trial. A total of 46patients with NASH will be randomized to treatment with betaine (Cystadane ) 20 g/d or an identical placebo for 12 months. The primary end-point will be changes in degree of steatosis, necroinflammatory activity and fibrosis on liver biopsy, whereas secondary end-points will be changes in liver test results and health related quality of life.
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