Non-Alcoholic Fatty Liver Disease and Hepatocellular Cancer: A Systematic Review

By D. White, F. Kanwal, H. B. EL‐SERAG. Clinical Gastroenterology and Hepatology, 2012

722 citations recorded by the source corpus.

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.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Hepatology

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Citations in the corpus

Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases (2019, background): “(43) An association between NAFLD and HCC is well established.(12) In a study comparing the incidence of HCC among patients with HCV infection and NAFLD,(44) 315 patients with cirrhosis secondary to HCV and 195 with cirrhosis attributed to NAFLD were followed for a median of 3.”
Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. (2014, background): “lower rate of HCC development among NASH patients has been reported in several additional studies.(10-17) Despite the low incidence of HCC among NASH patients, the overall increasing prevalence of NAFLD will undoubtedly lead to increased prevalence of NASH and a subsequent increased prevalence of NA”
Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases (2018, background): “(43) An association between NAFLD and HCC is well established.(12) In a study comparing the incidence of HCC among patients with HCV infection and NAFLD,(44) 315 patients with cirrhosis secondary to HCV and 195 with cirrhosis attributed to NAFLD were followed for a median of 3.”
Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes. (2014, background): “In recent years, obesity leading to metabolic syndrome, steatosis, and steatohepatitis has attracted increased attention because of increased HCC incidence in Western countries (White et al., 2012).”
Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009 (2015, background): “Z 1723 highly effective second-generation direct antiviral agents for treatment of HCV.1,4 Although most cases of HCC occur in the setting of advanced fibrosis or cirrhosis, there are some suggestions that patients with NAFLD without cirrhosis may develop HCC.5 One study estimated that the yearly cu”
Obesity and cancer risk: Emerging biological mechanisms and perspectives. (2019, background): “Disruption of circadian rhythms may be associated with HCC due to metabolic and obesityrelated factors.”
Early Detection, Curative Treatment, and Survival Rates for Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis: A Meta-analysis (2014, background): “For example, patients with HCV cirrhosis have a higher risk of HCC than those with alcohol-induced cirrhosis or NASH [75,76].”
Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease (2017, background): “Most liver-related outcomes occur once cirrhosis has developed with the exception of HCC that can occur even in the absence of cirrhosis (7).”
Epidemiology of Hepatocellular Carcinoma in the United States: Where Are We? Where Do We Go? (2014, background): “Although there are several mechanisms for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD-NASH)-related HCC conceivably in the presence of mild or no fibrosis,(7) there are no systematic studies to confirm or quantify this contention.(8) Indirect measures of severity of hepatic ”