Science of Nonalcoholic Fatty Liver Disease in Anti-Aging Medicine 2011

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease caused primarily by obesity, and its incidence among Japanese adults is rapidly rising at 10-40%. Most NAFLD presents as simple steatosis, but some are nonalcoholic steatohepatitis (NASH) progressing to hepatic cirrhosis or hepatocellular carcinoma. NAFLD is diagnosed by the following three features; (1) alcohol non-consumers (“non-drinkers”), (2) steatosis, and (3) exclusion of liver disease caused by other factors, with non-drinkers including light consumers of alcohol in amounts not engendering alcoholic liver disease. Dietary treatment is the basis of therapy, but evidence concerning exercise therapy has accumulated recently, and its mechanisms have been explained. Dehydroepiandrosterone (DHEA) is an androgenic intermediate metabolite produced by the adrenals and known as an Anti-Aging hormone with an improving effect on insulin resistance, an antioxidant effect, and an antifibrotic effect. Serum dehydroepiandrosterone sulfate (DHEA-s) has been shown to present low levels in advanced stages of NAFLD and diminished DHEA may contribute to progression of NAFLD. Growth hormone (GH) plays a crucial role not only in childhood growth but also in adult metabolic regulation, and adult GH deficiency (GHD) leads to increased visceral fat, dyslipidemia, and decreased QOL. Complicating NAFLD/NASH is a frequent occurrence in adult GHD and is improved by GH replacement therapy. On this basis, aging is an important risk factor for progression of NASH, which suggests a need for discussion of NASH and NAFLD from the perspective of Anti-Aging Medicine.