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 "Overview of the management of hepatitis B and case examples" 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 HBeAg seroconversion in about 20 percent of patients with HBeAg positive HBV who have not previously been treated with nucleoside(tide) analogues [1-5]. 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 virological 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 int. unit/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 int. unit/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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- Ridruejo E, Marciano S, Galdame O, et al. Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir. J Viral Hepat 2014; 21:590.
- Jeng WJ, Sheen IS, Chen YC, et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology 2013; 58:1888.
- THE EFFICACY OF ENTECAVIR IN DIFFERENT PATIENT POPULATIONS
- HBeAg-positive chronic hepatitis
- - Versus lamivudine
- - Versus adefovir
- HBeAg-negative chronic hepatitis
- Lamivudine refractory HBV
- Adefovir refractory HBV
- HIV coinfected patients
- Severe exacerbation
- Decompensated cirrhosis
- Patients with low ALT levels
- RESPONSE TO THERAPY
- OPTIMAL DURATION OF THERAPY
- Risk of relapse after discontinuing entecavir
- SUMMARY AND RECOMMENDATIONS