Impact of circulating miR-122 for histological features and hepatocellular carcinoma of nonalcoholic fatty liver disease in Japan

Relationships between circulating microRNA-122 (miR-122) and histological features of nonalcoholic fatty liver disease (NAFLD) are unclear. The impact of serum miR-122 levels for histological features and hepatocellular carcinoma (HCC) was investigated in 305 Japanese patients with histological proven NAFLD. Twenty-three patients were with HCC at the time of diagnosis of NAFLD, and four patients developed HCC during the follow-up. The cross-sectional or longitudinal evaluations were performed to investigate the impact for HCC. Serum miR-122 levels (calibrated relative to the median levels of patients) partly affected severity of steatosis, ballooning, lobular inflammation, and stage. Multivariate analysis identified HCC and/or histological components of NASH as morphological factors that independently influenced serum miR-122 levels at the diagnosis of NAFLD. There was a strong correlation between serum miR-122 levels and AST, ALT levels. In cross-sectional evaluation, serum miR-122 levels of patients without HCC were significantly higher than those with HCC in patients of stage 3 but not stage 4. In longitudinal evaluation of one patient with follow-up time of 25 years, from the diagnosis of NAFLD until HCC, serum miR-122 levels had already tended to decrease before the progression of fibrosis stage. HCC and/or histological components of NASH affected serum miR-122 levels, independently. In longitudinal evaluation of HCC patients, serum miR-122 levels had already tended to decrease before the progression of fibrosis stage. Further prospective studies are needed to investigate the impact of serum miR-122 for histological features and hepatocarcinogenesis of NAFLD.