Article

Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study.

Gut (Impact Factor: 13.32). 05/2014; DOI: 10.1136/gutjnl-2014-307237
Source: PubMed

ABSTRACT The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated.
Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥2 years with undetectable HBV DNA levels on ≥3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000 IU/mL).
184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11 000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37-1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (±0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=-0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p>0.05).
Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.

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    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 antiviral 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 1.25x 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.
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