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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

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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.

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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 virus

HCC:

Hepatocellular carcinoma

HBsAg:

Hepatitis B surface antigen

LAM:

Lamivudine

LdT:

Telbivudine

NAs:

Nucleos(t)ide analogues

NRSI:

Nonrandomized studies of interventions

Peg-IFN:

Pegylated interferon

Q1:

Quartile 1

Q3:

Quartile 3

RCTs:

Randomized controlled trials

ROBINS-I:

Risk of Bias in Non-randomized Studies of Interventions

RR:

Risk ratio

TDF:

Tenofovir disoproxil fumarate

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Funding

This work was supported by the grants from National Natural Science Foundation of China (No.81803299), Natural Science Foundation of Shandong Province, China (No.ZR2019PH046), China Postdoctoral Science Foundation (2019M660840), and Sanming Project of Medicine in Shenzhen (No.SZSM201612014).

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Author notes

  1. Jiaye Liu, Tingyan Wang, and Wei Zhang contributed equally to this work.

Authors and Affiliations

  1. Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, 518112, Guangdong, China

    Jiaye Liu & Qing He

  2. Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

    Jiaye Liu, Wei Zhang, Yongqian Cheng & Fu-Sheng Wang

  3. Nuffield Department of Medicine, University of Oxford, Oxford, UK

    Tingyan Wang

  4. Diagnosis and Treatment Center for Liver Disease, The 960Th Hospital of Chinese PLA Joint Logistics Support Force, Tai’an, 271000, Shandong, China

    Wei Zhang

Authors
  1. Jiaye Liu
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Contributions

Guarantor of the article: FW. WF conceived and supervised the study; JL, WZ, TW designed the study; JL, WZ, TW designed the study search terms; JL, WZ, TW identified studies for inclusion; JL, TW, WZ designed data extraction template; TW, WZ, JL conducted data extraction; WZ, TW, JL assessed data quality; JL, TW, WZ, YC, QH analysed and/or interpreted data; TW, JL, WZ drafted the manuscript; All authors critically reviewed or revised the manuscript and approved the final version of the manuscript.

Corresponding author

Correspondence to Fu-Sheng Wang.

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Conflict of interest

Jiaye Liu, Tingyan Wang, Wei Zhang, Yongqian Cheng, Qing He and Fu-Sheng Wang declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Liu, J., Wang, T., Zhang, W. et al. 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. Hepatol Int 14, 958–972 (2020). https://doi.org/10.1007/s12072-020-10099-x

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  • DOI: https://doi.org/10.1007/s12072-020-10099-x

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