Entecavir treatment for chronic hepatitis B: Adaptation is not needed for the majority of naïve patients with a partial virological response

Abstract

Entecavir (ETV) is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients. The aim of this study was to investigate the long term efficacy and safety of ETV in NA-naïve CHB patients, particularly in those with detectable hepatitis B virus (HBV) DNA after 48 weeks, in whom treatment adaptation is suggested by current guidelines. In a multicenter cohort study, we investigated 333 CHB patients treated with entecavir monotherapy. The NA-naïve population consisted of 243 patients, whereas 90 were NA-experienced. Virological response (VR) (HBV DNA <80 IU/ mL) was achieved in 48%, 76%, and 90% of hepatitis B e antigen (HBeAg)-positive and in 89%, 98%, and 99% of HBeAg-negative NA-naïve patients at weeks 48, 96, and 144, respectively. Thirty-six of 175 (21%) NA-naïve patients with at least 48 weeks of follow-up had a detectable load at week 48 (partial virological response [PVR]). Twenty-nine (81%) patients with PVR reached VR during prolonged ETV monotherapy, and none of them developed ETV-resistance. Among 22 patients with HBV DNA <1,000 IU/mL at week 48, VR was achieved in 21 (95%) patients, compared with eight of 14 (57%) patients with HBV DNA !1,000 IU/mL. Continuous HBV DNA decline was observed in most patients without VR during follow-up, and in three patients adherence was suboptimal according to the treating physician. ETV was safe and did not affect renal function or cause lactic acidosis. Conclusion: ETV monotherapy can be continued in NA-naïve patients with detectable HBV DNA at week 48, particularly in those with a low viral load because long-term ETV leads to a virological response in the vast majority of patients. (HEPATOLOGY 2011;54:443-451) C urrent treatment guidelines consider nucleos(-t)ide analogues (NAs) and pegylated interferon as first-line treatment for chronic hepatitis B (CHB). The ultimate goal of treatment is prevention of cirrhosis, hepatic decompensation, and hepatocellular carcinoma.1 Entecavir (ETV) is a cyclopentyl guanosine analogue that has shown superior biochemical, virological, and histological efficacy compared with lamivudine (LAM) in large phase III trials.2,3 Moreover, genotypic resistance to ETV is rare in NA-naïve

Prolonged Entecavir Therapy Is Not Effective for HBeAg Seroconversion in Treatment-Naive Chronic Hepatitis B Patients with a Partial Virological Response

“…About 84% of the patients with PVR achieved VR through prolonged therapy without adaptation. These results were consistent with previous ETV therapy studies (15,16). Our results support previous studies suggesting that continuous ETV therapy is an effective and promising choice (15,16).…”

Resistance mutations of hepatitis B virus in entecavir‐refractory patients

“…Because these NAs share a common target for the viral reverse transcriptase (RT), resistance mutations to these reagents have been reported only in RT domains. Among these NAs, ETV is one of the most potent anti‐HBV reagents; it has a very low resistance rate in treatment‐naive patients7, 8, 9, 10, 11 and has long been used as a first‐line reagent. To date, a limited number of ETV‐resistant mutations have been reported.…”

Current Concepts on Management of Chronic Hepatitis B

“…In the VIRGIL multicenter study including 243 consecutive NA-naïve patients receiving ETV monotherapy, the cumulative probability of achieving a virological response at week 144 was 90% in HBeAg-positive patients and 99% in HBeAg-negative patients [47]. In this cohort, 81% of patients with partial virological response at 48 weeks reached a virological response during prolonged ETV monotherapy and no patient developed ETV resistance.…”