Controlling oxidative stress in non-alcoholic steatohepatitis (NASH)

Non-alcoholic steatohepatitis (NASH) is a severe form of non- alcoholic fatty liver disease (NAFLD), in which most patients exhibit non-progressive non-alcoholic fatty liver (NAFL) representing simple steatosis of the liver. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level, and induces hepatic steatosis, inflammation and fibrosis. Among these factors, oxidative stress is considered a key contributor to the progression from NAFL to NASH. Although several clinical trials have shown that anti-oxidative therapy with vitamin E can effectively control the effects of hepatitis in the short term, the long-term effects remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to demonstrate benefits. This might be attributed to the non-selective anti-oxidant properties or excessive anti- oxidative effects of these drugs. Molecular hydrogen has recently been identified as an effective antioxidant that specifically reduces cytotoxic reactive oxygen species (ROS). Several diseases associated with oxidative stress, such as ischemia reperfusion injury of brain or heart, Parkinson's disease, post-chemotherapeutic renal injury, or transplant rejection, are responsive to hydrogen. The progress of NASH and transition of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water in mouse models. Long-term clinical intervention is required to control this complex lifestyle-related disease.