Addition of nucleoside analogues to peg-IFN alpha-2a enhances virological response in chronic hepatitis B patients without early response to peg-IFN alpha-2a: a randomized controlled trial

作者：Xu, Yan; Wang, Xu; Liu, Zhenhua; Zhou, Changyu; Qi, Wenqian; Jiao, Jian; Yu, Fan; Guo, Honghua; Zhao, Ping; Wang, Jiangbin^*

来源：BMC Gastroenterology, 2017, 17(1): 102.

DOI：10.1186/s12876-017-0657-y

• Chronic hepatitis B
• Interferon
• Nucleoside analog
• Virological response
• Combination therapy

Background: Current treatments for chronic hepatitis B (CHB) include pegylated interferon alpha (PEG-IFN-alpha) which is an immune modulator, and nucleos(t) ide analogs (NAs) which directly inhibit HBV DNA polymerase. With the limited efficacy of PEG-IFN-alpha and prolonged treatment periods associated with NAs, there is an urgent need for novel therapeutic strategies, especially for patients with a poor early response to anti-viral therapy.
Methods: In this study, 178 patients with chronic hepatitis B (n = 131) and compensated (n = 47) HBV-induced cirrhosis were enrolled, 120 patients with HBeAg (+). All the patients were treated for 12 weeks with PEG-IFN-alpha. Among them, a total of 138 patients with a poor virological response after 12 weeks were treated for an additional 48 weeks with Peg-IFN alpha-2a (control) (n = 43), with Peg-IFN alpha-2a + entecavir (ETV) (n = 49), or Peg-IFN alpha-2a + adefovir dipivoxil (ADV) (n = 46), and were followed for 48 weeks after therapy. Early virological response was defined as undetectable HBV DNA after anti-viral therapy for 12 weeks. Sustained virological response (SVR) was defined as no change in therapeutic effectiveness after 6 months follow-up, and no recurrence. Therapeutic efficacy was determined by evaluating HBV DNA levels, serum and liver HBsAg levels, liver function tests and liver histology.
Results: Patients in the Peg-IFN alpha-2a + ETV and Peg-IFN alpha-2a + ADV groups showed a significantly greater decrease in HBV DNA levels over time, and a significantly higher SVR compared to patients receiving Peg-INF alpha-2a monotherapy (both P values < 0.05). Although patients receiving combination therapy had a significantly higher change in serum HBsAg levels compared to the monotherapy group, there was no significant difference in liver HBsAg levels between the three treatment groups.
Conclusion: This study demonstrated that in patients with a poor virological response after 12 weeks of treatment with Peg-IFN alpha-2a alone, addition of ADV or ETV significantly reduced HBV DNA levels, serum HBsAg levels, and increased SVR. Individualization of anti-viral therapy would ensure that only patients who do not respond to Peg-IFN alpha-2a would receive combination therapy. Our data have important implications for the treatment of CHB patients who fail to show an early response to Peg-IFN alpha-2a monotherapy.

• 出版日期2017-8-30
• 单位吉林大学