Effect of combination treatment based on interferon and nucleos(t)ide analogues on functional cure of chronic hepatitis
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ARTICLE
Effect of combination treatment based on interferon and nucleos(t) ide analogues on functional cure of chronic hepatitis B: a systematic review and meta‑analysis Jiaye Liu1,2 · Tingyan Wang3 · Wei Zhang2,4 · Yongqian Cheng2 · Qing He1 · Fu‑Sheng Wang2 Received: 6 July 2020 / Accepted: 5 October 2020 © Asian Pacific Association for the Study of the Liver 2020
Abstract Background Priority of antiviral treatment for patients with chronic hepatitis B (CHB) is to increase the probability of functional cure. We aimed to synthesize evidence regarding the efficacy of different combination strategies of antiviral treatment based on interferon (IFN) and nucleos(t)ide analogues (NAs) in adults with CHB. Methods PubMed, Web of Science and Embase databases were searched from inception to May 26, 2019. Three types of combination strategies were studied: initial combination (IFN or NAs monotherapy as control), add-on (I: IFN add-on NAs vs. NAs; II: NAs add-on IFN vs. IFN), switch-to (I: IFN switch-to NAs vs. IFN; II: NAs switch-to IFN vs. NAs). Results Compared to NAs monotherapy, initial combination strategy improved the probability of HBeAg loss (RR: 1.62, 95% CI 1.33–1.97) and HBsAg loss (RR: 15.59, 95% CI 3.22–75.49), while compared to IFN monotherapy, no higher rates in the loss of HBsAg or HBeAg for initial combination. Compared to NAs monotherapy, IFN add-on NAs strategy had a higher rate of HBsAg loss (RR: 4.52, 95% CI 1.95–10.47), while compared to IFN monotherapy, NAs add-on IFN had a similar outcome. Compared to NAs monotherapy, NAs switch-to IFN strategy improved HBsAg loss (RR: 12.15, 95% CI 3.99–37.01); while compared to IFN monotherapy, IFN switch-to NAs had no improved rate of HBsAg clearance but higher rates in undetectable HBV DNA, and HBeAg loss. Conclusion IFN add-on NAs, or NAs switched to IFN could significantly improve the probability of HBsAg loss compared to NAs monotherapy. Keywords Chronic hepatitis B · Interferon · Nucleos(t)ide analogues · Combination treatment strategies · HBsAg loss Jiaye Liu, Tingyan Wang, and Wei Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12072-020-10099-x) contains supplementary material, which is available to authorized users. * Fu‑Sheng Wang [email protected] 1
Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen 518112, Guangdong, China
2
Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
3
Nuffield Department of Medicine, University of Oxford, Oxford, UK
4
Diagnosis and Treatment Center for Liver Disease, The 960Th Hospital of Chinese PLA Joint Logistics Support Force, Tai’an 271000, Shandong, China
Abbreviations ADV Adefovir ALT Alanine transaminase cccDNA Covalently closed circular DNA CHB Chronic hepatitis B CIs Confidence intervals ETV Entecavir HBeAg Hepatitis B e antigen HBV Hepatitis B vi
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