Clin Mol Hepatol.  2024 Jul;30(3):326-344. 10.3350/cmh.2024.0155.

Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication

Affiliations
  • 1Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 2College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 3Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 4Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University and Academia Sinica, Kaohsiung, Taiwan
  • 5Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
  • 6School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan

Abstract

Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

Keyword

HCV; HCC; SVR; Genetic; Epigenetic; Surveillance
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