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J Clin Microbiol. 2019 Jan 2;57(1). pii: e01463-18. doi: 10.1128/JCM.01463-18. Print 2019 Jan.

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

Author information

1
Department of Hepatology, Toranomon Hospital, Tokyo, Japan akuta-gi@umin.ac.jp.
2
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
3
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
4
Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan.

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.

KEYWORDS:

HCV; IL-28B; NS5A; WFA+M2BP; core; direct-acting antivirals; hepatocellular carcinoma; mutant; sustained virological response; wild

PMID:
30381417
PMCID:
PMC6322466
[Available on 2019-07-02]
DOI:
10.1128/JCM.01463-18

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