Background
Non-alcoholic fatty liver disease (NAFLD) has been implicated as a possible cause of hepatocellular carcinoma (HCC) in several general review articles. We performed the first systematic review of the epidemiologic literature.
Methods
We searched PubMed for original reports published between 1/1992–12/2011 evaluating the association between NAFLD, non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) presumptively NASH-related and the risk of HCC. Studies were categorized as offering potential direct evidence (e.g., cohort studies) or indirect evidence (e.g., case-control or cross-sectional studies or case-series) of an association.
Results
A total of 17 cohort studies [3 population-based, 9 clinic-based (6 limited to cirrhotics), and 5 natural history], 18 case-control and cross-sectional studies, and 26 case-series were study-eligible. NAFLD or NASH cohorts with few or no cirrhosis cases demonstrated a minimal HCC risk (cumulative HCC mortality between 0%–3% for study periods up to two decades). Consistently increased risk was observed in NASH-cirrhosis cohorts (cumulative incidence between 2.4% over 7-years to 12.8% over 3-years). However, HCC risk was substantially lower in NASH-cirrhosis (NASH-C) cohorts than in HCV-related cirrhosis cohorts. The determinants of elevated risk among NASH-C cohorts were unclear as most studies were underpowered to perform multivariate analysis.
Conclusions
This systematic review shows that despite several limitations, the epidemiologic evidence supports an association between NAFLD or NASH and an increased HCC risk that seems to be predominantly limited to individuals with cirrhosis.