Treatment cessation in noncirrhotic, e-antigen negative chronic hepatitis B is safe and effective following prolonged anti-viral suppression with nucleosides/nucleotides

Abstract

Background: The treatment of HBeAg-negative chronic hepatitis B (CHB) is considered to be open-ended, with no guidelines for treatment cessation.

Aim: To evaluate biochemical and virological relapse requiring retreatment in noncirrhotic HBeAg-negative CHB in patients who stopped treatment following a period of prolonged viral suppression with nucleotides/nucleosides.

Methods: We performed a single-centre retrospective chart review of patients with HBeAg-negative CHB who maintained viral suppression for 4-5 years on anti-viral treatment, and thus subsequently stopped treatment. The primary end point of composite relapse was defined by an increase in HBV DNA >2000 IU/mL, ALT elevation above 1.25 × normal or doubling of ALT from cessation, and re-initiation of anti-viral therapy.

Results: We identified 33 patients with HBeAg-negative CHB who stopped treatment following viral suppression. Mean treatment duration was 5.28 ± 2.73 years. Patients were treated with lamivudine (3), adefovir (14), entecavir (4), and tenofovir (12). Eleven (33%) patients met the primary end point of composite relapse. For individual end points, 21 (63%) patients had a viral relapse, 16 (48%) had a biochemical relapse, and 16 (48%) restarted treatment, leaving 17 (52%) patients who remained treatment-free over a median 36 months of follow-up. Lower pre-treatment ALT and detectable HBV DNA within the first month after treatment discontinuation were associated with increased rates of composite relapse (HR 1.01; P = 0.022 for ALT and HR 1.01; P = 0.038 for HBV DNA).

Conclusion: Patients with noncirrhotic HBeAg-negative CHB can stop treatment after greater than 4-5 years of suppressive therapy with nucleosides/nucleotides with more than 50% remaining treatment-free.