Liver Research Unit, Linkou Medical Center, Chang Gung Memorial Hospital; College of Medicine, Chang Gung University.
The optimal duration of nucelos(t)ide analoge (Nuc) treatment in hepatitis B e antigen (HBeAg) negative patients with chronic hepatitis B virus (HBV) infection is unknown. Asian Pacific Association for the Study of the Liver (APASL) guidelines recommend that treatment can be discontinued if undetectable HBV-DNA has been documented on three occasions ≥ 6 months apart. This study aimed to test this stopping rule in HBeAg-negative chronic hepatitis B (CHB) patients treated with Entecavir (ETV). Ninety-five patients (39 cirrhotics) were treated with ETV for a median of 721 (395-1762) days before stopping therapy and were then monitored with serum HBV DNA and alanine aminotransferase (ALT) at least every 3 months. Within 1-year after stopping ETV therapy, "clinical relapse" (an episode of ALT elevation >2× upper limit of normal plus HBV-DNA>2000IU/mL) occurred in 43 (45.3%) of the 95 patients. Of the 39 cirrhotic patients, 17 (43.6%) relapsed and one (2.6%) developed decompensation. The median duration till relapse was 230 days (74.4% > 6 months). Logistic regression analysis showed that baseline HBV-DNA ≤2×105 IU/mL was the only significant independent factor for sustained response. The 1-year relapse rate was 29% in patients with a baseline HBV DNA ≤2×105 IU/mL vs 53% in those with HBV DNA >2×105 IU/mL (p=0.027). For the later, consolidation therapy > 64 weeks reduced relapse rate to 33.3% in non-cirrhotic patients. Conclusion: With an overall 1-year relapse rate of 45% and 29% in those with a baseline serum HBV DNA ≤2×105 IU/mL, the APASL stopping rule for HBeAg-negative CHB patients with proper off-therapy monitoring is adequate even in cirrhotic patients. Consolidation therapy > 64 weeks seems more appropriate for those with higher baseline HBV DNA.