Impact of the PNPLA3 genotype on the risk of hepatocellular carcinoma after hepatitis C virus eradication.

Abstract

Almost all chronic hepatitis C (CHC) patients can achieve sustained virological response (SVR) with direct-acting antivirals. However, the development of hepatocellular carcinoma (HCC), even after the achievement of SVR, continues to be a serious problem. The aim of this study was to assess the association between host genetic factors and de novo HCC after SVR. This single-center, retrospective study consisted of 442 consecutive CHC patients without a history of HCC who achieved SVR through interferon (IFN)-based and IFN-free therapy. Predictive factors associated with the development of HCC were determined by the Cox proportional hazards model. The single-nucleotide polymorphism (SNP) genotyping data of 223 patients were available for analysis. Of the seven SNPs analyzed in this study, only the patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 GG genotype was significantly, positively associated with the development of de novo HCC after adjusting for age, sex, and fibrosis status (adjusted hazard ratio [aHR] 5.66, p = 0.003). In multivariable analysis, age (aHR 1.05, p = 0.007), advanced fibrosis (aHR 2.69, p = 0.019), α-fetoprotein at post-12 weeks of treatment ≥7.0 ng/ml (aHR 3.85, p = 0.001), and PNPLA3 GG genotype (aHR 3.02, p = 0.004) were extracted as independent predictors of the development of de novo HCC. In conclusion, the PNPLA3 genotype was independently associated with the de novo HCC of CHC patients who achieved SVR. Such detailed knowledge of host genetic factors will be useful for HCC surveillance after HCV elimination.

• Authors: Azusa Ohta, Eiichi Ogawa, Masayuki Murata, Yuji Matsumoto, Sho Yamasaki, Hiroaki Ikezaki, Norihiro Furusyo
• Journal: Journal of medical virology (J Med Virol) Vol. 94 Issue 10 Pg. 5007-5014 (10 2022) ISSN: 1096-9071 [Electronic] United States
• PMID: 35652276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley Periodicals LLC.

Chemical References

• Antiviral Agents
• Membrane Proteins
• Acyltransferases
• Lipase
• adiponutrin, human
• Phospholipases A2, Calcium-Independent

Topics

• Acyltransferases (genetics)
• Antiviral Agents (therapeutic use)
• Carcinoma, Hepatocellular (genetics, virology)
• Fibrosis
• Genotype
• Hepacivirus (genetics)
• Hepatitis C (complications)
• Hepatitis C, Chronic (complications, drug therapy, pathology)
• Humans
• Lipase (genetics, therapeutic use)
• Liver Neoplasms (epidemiology, genetics, pathology)
• Membrane Proteins (genetics)
• Phospholipases A2, Calcium-Independent (genetics)
• Retrospective Studies
• Sustained Virologic Response