The effectiveness of combination therapy with interferon and nucleoside analogs in pediatric patients with chronic hepatitis B: a systematic review and meta-analysis

Hepatol Int. 2023 Feb;17(1):52-62. doi: 10.1007/s12072-022-10415-7. Epub 2022 Dec 5.

Abstract

Background: It is a challenging issue regarding the optimal antiviral treatment of children with chronic hepatitis B (CHB). The efficacy comparison of interferon (IFN) or nucleos(t)ide analogs (NAs) monotherapy with their combination could better understand this issue.

Methods: PubMed, EMBASE, Cochrane Library, Wanfang, CNKI, and abstracts of major international hepatology meetings were searched from inception to Feb 8, 2022. Randomized control trials and observational studies reporting the efficacy of combination therapy with IFN and NAs in children with CHB were eligible.

Results: A total of 17 studies were included. Compared with IFN monotherapy, combination therapy with IFN and NAs was significantly associated with increased rates of HBV DNA undetectable, HBeAg clearance, HBeAg seroconversion, alanine transaminase (ALT) normalization as well as the composite treatment response both at the end of treatment and during the follow-up period (RRs ranged from 1.23 to 1.75). A favorable trend for HBsAg seroconversion was found in IFN plus NAs-treated children, but not for the HBsAg clearance at the end of treatment. Although a similar trend towards the superiority of the combination therapy versus NAs monotherapy was observed (RRs ranged from 1.24 to 2.33) except for the HBV DNA undetectable rate at the end of treatment, the number of reported studies was limited.

Conclusions: Combination therapy with IFN and NAs is more effective than IFN monotherapy in viral suppression and serological response for children with CHB. More studies were still needed to reveal the efficacy of this combination therapy compared with NAs monotherapy.

Keywords: Adefovir; Efficacy; Entecavir; Interferon; Lamivudine; Meta-analysis; Nucleos(t)ide analogs; Pediatric; Pegylated IFN; Tenofovir.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Child
  • DNA, Viral
  • Drug Therapy, Combination
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Interferons* / therapeutic use
  • Nucleosides / therapeutic use
  • Treatment Outcome

Substances

  • Interferons
  • Nucleosides
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • DNA, Viral
  • Antiviral Agents