title: A Better Antiviral Efficacy Found in Nucleos(t)ide Analog (NA) Combinations with Interferon Therapy than NA Monotherapy for HBeAg Positive Chronic Hepatitis B: A Meta-Analysis.
abstract: BACKGROUND
  The clinical efficacy of nucleos(t)ide analogues (NAs) combined with interferon (IFN) therapy vs. NAs monotherapy for chronic hepatitis B (CHB) remains inconclusive. The aim of this meta-analysis was to determine whether the NAs plus IFN regimen offers synergistic efficacy that justifies the cost and burden of such a combination therapy in CHB patients.
  
  
  METHODS
  Related publications covering the period of 1966 to July 2014 were identified through searching MEDLINE, EMBASE, Cochrane library, Chinese Biomedical Literature Database, WANFANG, and CNKI database. A total of 17 studies were enrolled, including 6 in English and 11 in Chinese. Then, we established a final list of studies for the meta-analysis by systematically grading the quality and eligibility of the identified individual studies. We used hepatitis B antigen (HBeAg) loss, HBV-DNA undetectable rate, HBeAg seroconversion, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, and histological score at the end of treatment for efficacy evaluation. A quantitative meta-analysis (Review Manager, Version 5.1.0) was performed to assess the differences between NAs and IFN combination therapy and NAs monotherapy.
  
  
  RESULTS
  Our analysis demonstrated that HBeAg loss (RR = 1.73, 95% CI = 1.32-2.26, p < 0.001), HBV-DNA undetectable rate (RR = 1.58, 95% CI = 1.22-2.04, p < 0.001), HBeAg seroconversion (RR = 1.68, 95% CI = 1.36-2.07, p < 0.001), and HBsAg loss (RR = 2.51, 95% CI = 1.32-4.75, p < 0.001) in the combination therapy group were significantly higher than those in the monotherapy group. However, there were no significant differences in HBsAg seroconversion (RR = 4.25, 95% CI = 0.62-29.13, p = 0.14), sustained virological response rates, and biochemical response rates observed between the two groups. The results showed that the combination therapy group had more improved HBV histology than the NAs monotherapy group (RR = 1.14, 95% CI = 0.93-1.39, p = 0.22).
  
  
  CONCLUSIONS
  NAs and IFN or Peg-IFN combination therapy had a better efficacy in terms of HBeAg loss, HBV-DNA undetectable rate, HBeAg seroconversion, and HBsAg loss, compared to the NA monotherapy group at the end of treatment; however, there was no significant difference in HBsAg seroconversion between the two regimens.
authors: Clinical Epidemiology and Evidence-based Medicine Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing 100050, China. vivi_0306@126.com.|National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. vivi_0306@126.com.
authors: Wei
authors: W
authors: Wei
authors: National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. qinmeiw@163.com.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. qinmeiw@163.com.
authors: Qinmei
authors: Q
authors: Wu
authors: National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. zhoujialing11@126.com.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. zhoujialing11@126.com.
authors: Jialing
authors: J
authors: Zhou
authors: Clinical Epidemiology and Evidence-based Medicine Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing 100050, China. vivi_0306@126.com.|National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. vivi_0306@126.com.
authors: Yuanyuan
authors: Y
authors: Kong
authors: Clinical Epidemiology and Evidence-based Medicine Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing 100050, China. youhong30@sina.com.|National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. youhong30@sina.com.|Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China. youhong30@sina.com.
authors: Hong
authors: H
authors: You
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D009705:Nucleosides / Q000627:therapeutic use*; D009711:Nucleotides / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D009711:Nucleotides; D007372:Interferons
keywords: antiviral; chronic hepatitis B; combination therapy; interferon; nucleos(t)ide analogues