The association between steatosis and diabetes with hepatocellular carcinoma in non-genotype 3 chronic hepatitis C patients

Liver Int. 2018 Jun;38(6):1064-1073. doi: 10.1111/liv.13633. Epub 2017 Dec 12.

Abstract

Background & aims: Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown.

Methods: A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis.

Results: Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12-3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3-5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44-7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients.

Conclusions: Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.

Keywords: chronic hepatitis C; diabetes mellitus; genotype 3; hepatocellular carcinoma; steatosis; sustained virological response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / complications*
  • Carcinoma, Hepatocellular / virology
  • Diabetes Complications / virology*
  • Diabetes Mellitus / virology
  • Fatty Liver / complications*
  • Fatty Liver / virology
  • Female
  • Genotype
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons / therapeutic use
  • Kaplan-Meier Estimate
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Risk Factors
  • Sustained Virologic Response
  • Taiwan / epidemiology

Substances

  • Antiviral Agents
  • Ribavirin
  • Interferons