Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis B vs Chronic Hepatitis C After Achievement of Virologic Response

G.-A. Kim;


J Viral Hepat. 2017;24(11):990-997. 

In This Article

Abstract and Introduction


It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow-up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30–3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg-interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.


Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer mortality in the world, accounting for more than 600 000 deaths each year.[1] HCC has been the fastest rising cause of cancer-related deaths in developed countries during the past two decades and is expected to increase further in the next decade.[2,3] Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the most frequent causes of HCC.[2–4] Worldwide, it is estimated that 400 millions and 170 millions people are chronically infected with HBV and HCV, respectively, and approximately 54% and 31% of HCC cases are attributed to HBV and HCV infections.[5,6]

The ultimate goal of treating chronic hepatitis B (CHB) or chronic hepatitis C (CHC) is an improvement in patients' survival by preventing, or at least reducing, the development of cirrhosis, liver failure and HCC. Despite remarkable advances in the antiviral treatments for HBV and HCV during the last two decades, sparse data are available on whether the incidence of HCC is decreasing.[1–3] In fact, a recent systematic review demonstrated that HBV and HCV still are the predominant causes of HCC.[4] A possible explanation would be that some precedent risk factors that are not amenable to antiviral therapy might contribute to the development of HCC. Furthermore, few data are available to determine on whether achieving a virologic response (VR) by treatment of CHB modifies the risk of HCC differently compared with achieving a sustained virologic response (SVR) by treatment of CHC.

The primary aim of this cohort study was to compare the risk of HCC between patients with CHB and CHC who achieved VR and SVR, respectively. In addition, we sought to identify the factors that modify the risk of HCC between patient groups.