title: Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review.
abstract: OBJECTIVE
  Nonalcoholic fatty liver disease (NAFLD) has been implicated as a cause of hepatocellular carcinoma (HCC). We performed a systematic review of epidemiology studies to confirm the association between these disorders.
  
  
  METHODS
  We searched PubMed for original reports published from January 1992 to December 2011 that evaluated the association between NAFLD, nonalcoholic steatohepatitis (NASH), cryptogenic cirrhosis presumed to be NASH-related, and the risk of HCC. Studies were categorized as offering potential direct evidence (eg, cohort studies) or indirect evidence (eg, case-control, cross-sectional, or case-series studies) for an association. We analyzed data from a total of 17 cohort studies (3 population based, 9 clinic based [6 limited to patients with cirrhosis], and 5 natural history), 18 case-control and cross-sectional studies, and 26 case series.
  
  
  RESULTS
  NAFLD or NASH cohorts with few or no cases of cirrhosis cases had a minimal risk for HCC (cumulative HCC mortality of 0%-3% for study periods up to 20 y). Cohorts with NASH and cirrhosis had a consistently higher risk (cumulative incidence ranging from 2.4% over 7 y to 12.8% over 3 y). However, the risk for HCC was substantially lower in these cohorts than for cohorts with hepatitis C-related cirrhosis. Factors that increased risk among cohorts with NASH and cirrhosis could not be determined, because most studies were not sufficiently powered for multivariate analysis.
  
  
  CONCLUSIONS
  This systematic review shows that despite several limitations, there is epidemiologic evidence to support an association between NAFLD or NASH and an increased risk of HCC; risk seems to be limited to individuals with cirrhosis.
authors.affiliation: Clinical Epidemiology and Outcomes Program, Houston Veteran Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veteran Affairs Medical Center, Houston, TX, USA. dwhite1@bcm.edu
authors.forename: Donna L
authors.initials: DL
authors.lastname: White
authors.forename: Fasiha
authors.initials: F
authors.lastname: Kanwal
authors.forename: Hashem B
authors.initials: HB
authors.lastname: El-Serag
mesh_terms: D005234:Fatty Liver / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D065626:Non-alcoholic Fatty Liver Disease; D018570:Risk Assessment