Entecavir in the treatment of chronic hepatitis B virus infection
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
Entecavir (Baraclude) is an orally administered cyclopentyl guanosine analogue that has been approved for treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevation in serum aminotransferases or histologically active disease. Approval was based upon the results of three phase 3 trials involving a total of 1633 patients ages 16 and older who had chronic HBV infection, persistently elevated serum ALT levels (≥1.3x the upper limit of normal), and chronic inflammation on liver biopsy. Entecavir has also been studied in patients who were refractory to lamivudine and in HBV/HIV coinfected patients.
This topic review will discuss the treatment of chronic hepatitis B with entecavir. A general approach to patients with hepatitis B (including other treatment options) is presented separately. (See "Hepatitis B virus: Overview of management" and "Combination therapy for chronic hepatitis B virus infection" and "Efficacy of tenofovir disoproxil fumarate in the treatment of adults with chronic HBV infection who do not have HIV infection".)
THE EFFICACY OF ENTECAVIR IN DIFFERENT PATIENT POPULATIONS
HBeAg-positive chronic hepatitis — Treatment with entecavir achieves hepatitis B e antigen (HBeAg) seroconversion in about 20 percent of patients with HBeAg-positive hepatitis B virus (HBV) who have not previously been treated with nucleoside(tide) analogues [1-6]. In addition, one-year treatment is associated with a 5 to 7 log(10) reduction in mean HBV DNA levels and corresponding improvement in liver histology. The rate of virologic resistance is around 1 percent with up to five years of follow-up.
Versus lamivudine — A multinational trial included 715 patients with HBeAg-positive chronic HBV who were randomly assigned to entecavir (0.5 mg daily) or lamivudine (100 mg daily) for 48 weeks . Patients were eligible if they had HBV DNA levels ≥3 mEq/mL (approximately 600,000 international units/mL), a serum ALT ≥1.3 times the upper limit of normal, compensated liver disease, and had no or <12 weeks of nucleoside(t)e therapy for HBV previously.
At week 48, HBeAg seroconversion was observed in 21 percent of the entecavir group and 18 percent of the lamivudine group (table 1 and table 2). Serum HBV DNA decreased from baseline by an average of 6.86 log(10) compared with 5.39 log(10) in the lamivudine group. Suppression of HBV DNA to less than 0.7 mEq/mL (approximately 140,000 international units/mL) and normalization of serum ALT were observed significantly more often in the entecavir group (91 versus 65 percent and 78 versus 70 percent, respectively). Serum HBV DNA was undetectable by PCR assay in 67 percent of the entecavir group compared with 36 percent in the lamivudine group.
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- Qiu YW, Huang LH, Yang WL, et al. Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients. Int J Infect Dis 2016; 43:43.
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- THE EFFICACY OF ENTECAVIR IN DIFFERENT PATIENT POPULATIONS
- HBeAg-positive chronic hepatitis
- - Versus lamivudine
- - Versus adefovir
- - Versus tenofovir
- HBeAg-negative chronic hepatitis
- Patients previously treated with lamivudine
- Patients previously treated with adefovir
- HIV coinfected patients
- Severe exacerbation
- Decompensated cirrhosis
- Patients with minimally elevated ALT levels
- VIROLOGIC RESPONSE TO THERAPY
- OPTIMAL DURATION OF THERAPY
- RISK OF RELAPSE AFTER DISCONTINUING ENTECAVIR
- SUMMARY AND RECOMMENDATIONS