Risk factors of hepatocellular carcinoma development in non-cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection

J Gastroenterol Hepatol. 2015 Jul;30(7):1183-9. doi: 10.1111/jgh.12915.


Background and aim: Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, that is eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV-infected patients who achieved SVR.

Methods: The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon-based antiviral therapy for HCV. Patients maintained regular follow-up every 6 months for HCC surveillance. The FIB-4 index and aspartate aminotransferase to platelet count ratio index were calculated based on laboratory data at the time that SVR was documented (SVR24).

Results: Patients continued follow-up visits for 1.0-22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at 5 years and 4.3% at 10 years. The use of peginterferon or ribavirin for treatment and a history of antiviral therapy prior to the course when SVR was achieved were not associated with the incidence of HCC after SVR. The presence of diabetes mellitus (risk ratio 2.08; P = 0.0451) and FIB-4 index calculated at the time of SVR24 (risk ratio 1.73; P = 0.0198) were associated with a higher likelihood of HCC after SVR by multivariate analysis.

Conclusions: Patients with diabetes mellitus and patients with the elevation of FIB-4 index at SVR24 are at higher risk of HCC after SVR. Surveillance for HCC should be continued in this patient subpopulation.

Keywords: antiviral therapy; chronic hepatitis C; hepatocellular carcinoma; risk factors; sustained virologic response.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / etiology*
  • Diabetes Complications / complications
  • Female
  • Follow-Up Studies
  • Forecasting
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Incidence
  • Interferon-alpha / therapeutic use
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Risk Factors
  • Time Factors


  • Antiviral Agents
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a