Hepatocellular carcinoma and other complications of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in Japan: A structured literature review article.

BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured literature review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. METHODS An English and Japanese structured literature search was conducted in Pubmed, Embase and ICHUSHI, identifying 6,553 studies, 34 of which met pre-defined inclusion criteria. RESULTS HCC was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4): 10.5%-20.0%. While NASH results in less HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 vs. 0.0% in NASH F0/2 over 7.7 years. NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls and with slightly higher rates of gastric cancer than HCV patients. CONCLUSION HCC is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.