Complex Association of Virus- and Host-Related Factors with Hepatocellular Carcinoma Rate following Hepatitis C Virus Clearance.

Abstract

Little is known about the effects of virus- and host-related factors on hepatocarcinogenesis in patients who show viral clearance after HCV RNA eradication by direct-acting antivirals (DAAs). The subjects of this retrospective study were 1,922 patients with HCV genotype 1 (HCV-1)- or HCV-2-related chronic liver disease who showed a sustained virological response (SVR; defined as negative results for HCV RNA at 12 weeks after the cessation of all-oral DAAs). All patients were confirmed to be hepatocellular carcinoma (HCC) free before and during DAAs. HCC was diagnosed in 43 patients during the follow-up, with an incidence rate per 1,000 person years of 9.44. The cumulative HCC rates were 1.2, 2.0, and 3.1% at the end of 1, 2, and 3 years, respectively. The annual rate of HCC during the first 3 years was 1.0%. The incidence rate was significantly higher in patients infected with the HCV-1b core amino acid (aa) 70 mutant than in those infected with HCV-2a/2b, and the rate in patients infected with the HCV-1b core aa 70 wild type tended to be higher than that in patients infected with HCV-2a/2b. The rate in patients infected with the HCV-1b NS5A aa 93 mutant was significantly higher than that in patients infected with HCV-2a/2b. However, the rate was not different between patients infected with the IL28B rs8099917 TT genotype and patients infected with the non-TT genotype. Multivariate analysis identified a Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+M2BP) cutoff index (COI) of ≥2.5 and infection with the HCV-1b core aa 70 mutant subgroup to be pretreatment predictors of posttreatment HCC. The same analysis identified an alpha-fetoprotein concentration of ≥5 μg/liter and an WFA+M2BP COI of ≥1.0 to be predictors of HCC at 24 weeks after the end of antiviral therapy. We conclude that both virus- and host-related factors seem to influence the development of HCC after HCV RNA eradication.

• Authors: Norio Akuta, Fumitaka Suzuki, Hitomi Sezaki, Masahiro Kobayashi, Shunichiro Fujiyama, Yusuke Kawamura, Tetsuya Hosaka, Mariko Kobayashi, Satoshi Saitoh, Yoshiyuki Suzuki, Yasuji Arase, Kenji Ikeda, Hiromitsu Kumada
• Journal: Journal of clinical microbiology (J Clin Microbiol) Vol. 57 Issue 1 (01 2019) ISSN: 1098-660X [Electronic] United States
• PMID: 30381417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Microbiology.

Chemical References

• Antiviral Agents
• RNA, Viral
• Viral Core Proteins
• Viral Nonstructural Proteins
• NS-5 protein, hepatitis C virus

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (therapeutic use)
• Carcinoma, Hepatocellular (blood, epidemiology, etiology, virology)
• Female
• Genotype
• Hepacivirus (drug effects, genetics, pathogenicity)
• Hepatitis C, Chronic (complications, drug therapy, epidemiology, virology)
• Host Microbial Interactions
• Humans
• Liver Neoplasms (blood, epidemiology, etiology, virology)
• Male
• Middle Aged
• RNA, Viral (blood, drug effects)
• Retrospective Studies
• Risk Factors
• Viral Core Proteins (genetics)
• Viral Nonstructural Proteins (genetics)
• Young Adult