Clinical Epidemiology and Outcomes Program, Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Health Services Research, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. Electronic address: firstname.lastname@example.org.
Nonalcoholic fatty liver disease (NAFLD) has been implicated as a possible cause of hepatocellular carcinoma (HCC) in several general review articles. We performed a systematic review of the epidemiologic literature.
We searched PubMed for original reports published between January 1992 and December 2011 that evaluated the association between NAFLD, nonalcoholic steatohepatitis (NASH), and cryptogenic cirrhosis (CC) presumptively NASH-related and the risk of HCC. Studies were categorized as offering potential direct evidence (eg, cohort studies) or indirect evidence (eg, case-control or cross-sectional studies or case series) of an association.
A total of 17 cohort studies (3 population-based, 9 clinic-based [6 limited to cirrhotic patients], 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% and 3% for study periods up to 2 decades). Consistently increased risk was observed in NASH-cirrhosis cohorts (cumulative incidence between 2.4% during 7 years to 12.8% during 3 years). However, HCC risk was substantially lower in NASH-cirrhosis cohorts than in hepatitis C virus-related cirrhosis cohorts. The determinants of elevated risk among NASH-cirrhosis cohorts were unclear because most studies were underpowered to perform multivariate analysis.
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.