Extrahepatic Malignancies in Nonalcoholic Fatty Liver Disease

Malignancy is the second most common cause of death in individuals with nonalcoholic fatty liver disease (NAFLD). Understanding unique characteristics of malignancy risk beyond hepatocellular carcinoma in NAFLD has significant implications in counseling and personalized preventative measures in this high-risk population. Herein, we systematically review the literature reporting extra-hepatic malignancies in NAFLD and discuss the key biological mechanisms underpinning the association between excess adiposity and cancer risk.

Several studies have shown significant associations between NAFLD and extrahepatic malignancies. The strongest association was found with cancers of the gastrointestinal tract and hormone-sensitive cancers. Recent data support sex-specific differences in cancer risk increase in NAFLD: colorectal cancer in men and uterine cancer in women. The risk of cancer development is higher in NAFLD than obesity alone.

A growing body of observational evidence over the last decade supports the association between NAFLD and extrahepatic malignancies. This association requires further studies, ideally designed to include more detailed measures of body fat deposition beyond BMI in well-characterized, large cohorts of NAFLD patients, to determine if screening policies should be individualized in this group.