Head‐to‐Head Comparison of Long‐Term HCC Risk of Antivirals‐Treated Versus Untreated Low‐Level Viremia in HBV‐Compensated Cirrhosis

ABSTRACT Background Among patients with hepatitis B virus (HBV)‐infected compensated cirrhosis and low‐level viremia, there are limited data for comparative outcomes between those treated with oral nucleos(t)ide analogs versus those not. We conducted a large, multi‐ethnic, multi‐center study to examine the impact of antiviral treatment (AVT) on long‐term hepatocellular carcinoma (HCC) risk for compensated cirrhosis and low‐level viremia. Methods Patients with compensated cirrhosis and low‐level viremia (serum HBV‐DNA 20–2000 IU/mL) at baseline or before AVT were screened for eligibility from 19 hospitals in South Korea, Singapore, and Japan. The primary outcome was HCC development, compared between those receiving AVT versus those untreated throughout follow‐up. Results Among 848 patients (mean age 55.7 years and 66.9% male), AVT ( n  = 233) was associated with significantly lower annual HCC incidence compared to non‐AVT ( n  = 615); 1.72/100 versus 2.99/100 person‐years (PY), respectively ( p  = 0.033). Multivariable Cox‐regression analyses determined that AVT was associated with significantly lower HCC risk, compared to non‐AVT (adjusted HR [HR] 0.514, 95% confidence interval [CI] 0.271–0.976; p  = 0.042). In a landmark analysis, HCC incidence was similar between two groups until 18 months, but after this landmark, the treated group had the significantly lower HCC risk compared to untreated group ( p  = 0.012). Furthermore, propensity score‐matching analysis consistently showed that AVT was associated with significantly lower HCC risk, compared to non‐AVT; the annual HCC incidence of 1.45/100 PYs versus 2.73/100 PY, respectively ( p  = 0.043). Conclusions Patients with compensated cirrhosis and low‐level viremia may benefit from long‐term AVT, highlighting appropriate amendment of reimbursement guidelines.