Higher incidence of hepatocellular carcinoma in suppressed hepatitis B cirrhosis compared to cured hepatitis C cirrhosis.

Abstract

/Aims: Direct-acting antiviral agents (DAA) effectively cure chronic hepatitis C (CHC) whereas curative therapy for chronic hepatitis B (CHB) is rare. We aimed to compare HCC incidence between suppressed CHB versus cured CHC patients with cirrhosis. We analyzed 5773 cirrhosis patients from 43 centers in 9 countries: 1877 with treated and suppressed CHB and 3896 with DAA-cured CHC using inverse probability treatment weight (IPTW) and competing risk analysis via Fine and Gray method. After IPTW (on age, sex, ethnicity, study location, albumin, total bilirubin, creatinine, platelet, tobacco use, alcohol use, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, steatotic liver disease, obesity, and follow-up years), two study groups became similar in relevant characteristics. The 5-year cumulative HCC incidence was significantly higher in suppressed CHB compared to cured CHC (18.1% vs. 7.4%, P<0.001) with consistent findings in subgroups by sex and MELD (all P<0.021), fast CHB responders (time from treatment to viral suppression <1 year) (P<0.001), and CHB suppressed for <2 years (P<0.001), but not among CHB suppressed for ≥2 years whose HCC incidence was similar to those of cured CHC (P=0.954). On multivariable analysis, CHB suppression <2 years as compared to cured CHC (subdistribution hazard ratio (sHR) 20.92, P<0.001) and total bilirubin (sHR 0.71, P=0.04) were associated with higher HCC risk. HCC risk remains high in both treated and suppressed CHB cirrhosis and cured CHC cirrhosis. However, with prolonged CHB suppression, risk of HCC can be reduced, highlighting benefits of early treatment and viral suppression in patients with CHB.