면역 관용기 만성 B형간염 환자의 간세포암 및 사망 발생의 위험성

Abstract

Objective: High serum hepatitis B virus (HBV) DNA levels are associated with high risks of hepatocellular carcinoma (HCC) and cirrhosis in chronic hepatitis B (CHB) patients. Although the immune-tolerant (IT) phase is characterized 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 CHB patients 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 analogs. 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 (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.54-4.18) and death/transplantation (HR, 3.38; 95% CI, 1.85-6.16) than the IA group; which was consistently identified through inverse probability treatment weighting, propensity score-matched, and competing risks analyses. Conclusions: Untreated IT phase CHB patients 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.