Metabolic Risk Factors in Hepatocellular Carcinoma

Context.—The common risk factors for hepatocellular carcinoma (HCC) include persistent viral infection with either hepatitis B or C virus, alcohol abuse, hemochromatosis, and metabolic syndrome. Steatohepatitic (SH) HCC has been recently recognized as a special morphologic variant of HCC associated with metabolic risk factors. Objective.—To assess the SH pattern in HCC cases of various etiologies in Indian patients and to further correlate this morphology with the presence of metabolic risk factors. Design.—A total of 101 cases of HCC with various etiologies in explanted livers from adults were included in the study. Morphologic examination was performed to identify SH lesions within the tumor and in the nontumorous liver parenchyma. Correlation of nontumor and tumor SH morphology with clinically identifiable metabolic risk factors and with non-SH type of HCC was performed. Results.—The SH variant of HCC was identified in 19 livers (18.8%). Most SH-HCC cases were associated with metabolic risk factors such as obesity, diabetes, hypertension, and hyperlipidemias. Comparison of SH-HCC with non–SH-HCC was statistically significant in terms of presence of metabolic risk factors. Conclusions.—Steatohepatitic morphology in HCC is frequent in nonalcoholic fatty liver disease–associated cirrhosis (P = .009) and is significantly associated with metabolic risk factors (P = .03). By recognizing SH pattern, one may predict associated metabolic diseases and determine the prognosis both in pretransplant and posttransplant patients.

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Determinants of Hepatocellular Carcinoma in the United States: Differences in Risk Factor and Genetic Susceptibility by Race/Ethnicity

10.48091/lkml8578 ◽

2021 ◽

pp. 18-33

Author(s):

Mehwish Rafique ◽

Dana Kristjansson

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Liver Disease ◽

Genetic Analysis ◽

Genetic Susceptibility ◽

The United States ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Alcoholic Fatty Liver ◽

Race Ethnicity

Background: Hepatocellular carcinoma (HCC) is one of the few cancers with an increasing incidence and mortality worldwide. This study aims to determine the contribution of known risk factors for HCC by race and ethnicity. Methods: Data on race, ethnicity, age, and gender were obtained from National Health and Nutrition Examination Survey (NHANES). Population attributable fractions (PAFs) of risk factors were estimated using non-invasive scoring measures of Hepatitis B and C virus infection, excessive alcohol use, smoking, diabetes and emerging metabolic risk factors [non-alcoholic steatohepatitis advanced cirrhosis (NASH) and non-alcoholic fatty liver disease-advanced fibrosis (NAFLD-fib)] over a 10-year period, 1999-2002 and 2009-2012. Genetic analysis was performed using DisGenet platform by attaining the top enriched genes strongly related to HCC. Furthermore, cytoscape network was used to form a gene-disease network association. Results: NASH-cirrhosis increased in the overall population and among all race and ethnic groups. Both liver fat accumulation and ALT levels vary among different populations; however, Hispanics have the highest prevalence of NAFLD and elevated ALT levels. Non-Hispanic (NH) blacks and Hispanics had a 3 to 4 times higher PAF for HCC than whites attributed due to chronic liver diseases, including NASH-cirrhosis and NAFLD-fib. Our genetic analysis demonstrated that PNPLA3 polymorphism is strongly associated with NAFLD-fib, which appears to represent susceptibility to liver disease among the Hispanic community. Conclusion: Hispanics and NH blacks are at a disproportionately higher risk for HCC in part due to the higher prevalence of liver disease comorbidities, including NASH-cirrhosis and NAFLD-fib. Compared to NH whites, Hispanics and NH blacks have a higher baseline risk for liver cancer due to non-metabolic factors, which may include a genetic susceptibility. Metabolic risk factors have increased and are now contributing to nearly half of HCC cases in the US.

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