Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

• Published in: World journal of gastroenterology : WJG Vol. 18; no. 43; pp. 6277 - 6283
• Main Authors: Song, Myeong Jun, Song, Do Seon, Kim, Hee Yeon, Yoo, Sun Hong, Bae, Si Hyun, Choi, Jong Young, Yoon, Seung Kew, Paik, Yong-Han, Lee, June Sung, Lee, Hyun Woong, Kim, Hyung Joon
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 21-11-2012
• Subjects: Adult; Antiviral Agents - administration & dosage; Biomarkers - blood; Brief; DNA, Viral - blood; DNA水平; Drug Administration Schedule; Female; HBeAg; Hepatitis B e Antigens - blood; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B, Chronic - diagnosis; Hepatitis B, Chronic - drug therapy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Viral Load; 乙型肝炎病毒; 反应; 慢性乙型肝炎; 抗病毒治疗; 耐久性; 阳性; Recurrence; Durability; Hepatitis B e antigen positive; Consolidation; Chronic hepatitis B; Seroconversion
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v18.i43.6277

AIM：To evaluate the durability in hepatitis B e antigen （HBeAg） positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS：A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus （HBV） DNA 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows：（1） achievement of virological response; and （2） duration of consolidation therapy （≥ 6 mo）. After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS：During the median follow-up period of 18.2 mo （range：5.1-47.5 mo） after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo （range：1.2-10.9 mo）. Of the 48 patients with HBeAg positive chronic hepatitis, 20 （41.6%） showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo （range：4.3-27.1 mo）. The mean age of the virological recurrence group was older than that of the non-recurrence group （46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022）. Age （ 40 years） and the duration of consolidation treatment （≥ 15 mo） were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk （RR） 0.31, 95% CI （0.096-0.998） and P = 0.005, RR 11.29, 95% CI （2.054-65.12）, respectively]. Patients with age （≤ 40 years） who received consolidation treatment （≥ 15 mo） significantly showed durability in HBeAg positive chronic hepatitis B patients （P = 0.014）. These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION：Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment （≥ 15 mo） in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.