Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study

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• 作者：Jian Sun¹ ; ^&dagger ; ; Hong Ma² ; ^&dagger ; ; Qing Xie³ ; Yao Xie⁴ ; Yongtao Sun⁵ ; Hao Wang⁶ ; Guangfeng Shi⁷ ; Mobin Wan⁸ ; Junqi Niu⁹ ; Qin Ning¹⁰ ; Yanyan Yu¹¹ ; Huijuan Zhou³ ; Jun Cheng⁴ ; Wenzhen Kang⁵ ; Yi Xie¹² ; Rong Fan¹ ; Lai Wei⁶ ; Hui Zhuang¹³ ; Jidong Jia² ; Jinlin Hou¹ ; ^{jlhousmu@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ADV ; adefovir ; AEs ; adverse events ; ALT ; alanine aminotransferase ; BMI ; body mass index ; CHB ; chronic hepatitis B ; EOF ; end of follow-up ; EOT ; end of treatment ; ETV ; entecavir ; HBV ; hepatitis B virus ; HBeAg ; hepatitis B e antigen ; HBeAb ; hepatitis B e antibody ; HBsAb ; hepatitis B surface antibody ; HBsAg ; hepatitis B surface antigen ; ITT ; intention to treat ; NAs ; nucleot(s)ide analogs ; PEIU ; Paul Ehrlich international units ; PegIFN ; pegylated interferon ; RGT ; response-guided therapy ; ULN ; upper l
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：4
• 页码：674-682
• 全文大小：848 K

文摘

Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B.

Methods

In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180 μg/week) for 24 weeks. Early responders (HBsAg <1500 IU/ml and HBV DNA <10⁵ copies/ml at week 24) received PegIFN for a further 24 weeks (arm A), while non-early responders were randomized to PegIFN for another 24 weeks (arm B), another 72 weeks (arm C) or PegIFN for another 72 weeks plus adefovir for 36 weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF).

Results

For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (−0.71 vs. −0.67 log₁₀ IU/ml, P = 0.407). The rate of HBeAg seroconversion with HBV DNA <2000 IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500 IU/ml or HBV DNA <10⁵ copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000 IU/ml at EOF respectively.

Conclusions

Patients with HBsAg <1500 IU/ml or HBV DNA <10⁵ copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48 weeks PegIFN monotherapy.

Lay summary

Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48 weeks did not show convincing benefit. Patients who achieved HBsAg <1500 IU/ml or HBV DNA <10⁵ copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment.

Clinical Trial Number: NCT01086085.