High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B

Abstract

Objective: High serum HBV DNA levels are associated with high risks of hepatocellular carcinoma (HCC) and cirrhosis in patients with chronic hepatitis B (CHB). Although the immune-tolerant (IT) phase is characterised by high circulating HBV DNA levels, it remains unknown whether antiviral treatment reduces risks of HCC and mortality. Design: This historical cohort study included HBeAg-positive patients with CHB with high HBV DNA levels (≥20 000 IU/mL) and no evidence of cirrhosis at a tertiary referral hospital in Korea from 2000 to 2013. The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues. Results: The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses. Conclusions: Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients.