Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance

Oncotarget. 2017 Jul 4;8(27):43925-43933. doi: 10.18632/oncotarget.14937.

Abstract

Background/aims: Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethods: A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis.

Results: Nineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15).

Conclusions: Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.

Keywords: HCC; HCV; spontaneous clearance; treatment.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Biomarkers
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / etiology*
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Hepacivirus*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / virology*
  • Humans
  • Incidence
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / etiology
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Risk Factors
  • Sustained Virologic Response

Substances

  • Antiviral Agents
  • Biomarkers