Histological improvement in chronic hepatitis B patients treated with nucleos(t)ide analogues combined with (pegylated-) interferon: a systematic review and Meta-analysis

Abstract

Abstract: Objective To evaluate the efficacy of nucleos(t)ide analogs (NAs) and (pegylated-) interferon (IFN) combination therapy in histological improvement in chronic hepatitis B (CHB) patients. Methods For comparing combination therapy with NAs and IFN versus either NAs or IFN monotherapy for CHB treatment, we searched randomized controlled trials (RCTs) and nonrandomized studies of interventions (NRSIs) in PubMed, Embase, and the Cochrane Library up to May 31, 2024. Results A total of 14 studies (13RCTs and 1 NRSI) involving 1411 patients were included. There were no statistically significant differences in the improvement of liver necroinflammation rate (RR=1.07, 95% CI: 0.82-1.40) or liver fibrosis rate (RR=1.00, 95% CI: 0.71-1.40) between NAs-IFN combination therapy and NAs monotherapy. Similarly, there were no statistically significant difference in the improvement of liver necroinflammation rate (RR=1.88, 95% CI: 0.91-3.90) between NAs-IFN combination therapy and IFN monotherapy. However, in studies recruiting patients with 75th percentile of age ≥45 years old, combination therapy significantly improved liver necroinflammation rate than IFN monotherapy (RR=3.02, 95% CI: 1.49-6.16). In studies with a baseline mean HBV DNA level of ≥7 log₁₀ IU/mL, combination therapy significantly improved the liver necroinflammation rate (RR=1.41, 95% CI: 1.07-1.87) and liver fibrosis rate (RR=1.55, 95% CI: 1.08-2.22) than NAs monotherapy. Conclusion The combination therapy of NAs and IFN shows similar efficacy to monotherapy in improving liver necroinflammation and fibrosis. However, in studies involving older patients or those with higher baseline HBV DNA levels, the combination therapy demonstrates a significant advantage in histological improvement compared to NAs monotherapy.

Key words: Chronic hepatitis B, Nucleostide analogs, Interferon, Liver necroinflammation, Liver fibrosis, Meta-analysis

SHI Li-chen, LI Shun, MENG Tong-tong, HUANG Cheng, WANG Hao, XU Xiao-qian, JIA Ji-dong, KONG Yuan-yuan. Histological improvement in chronic hepatitis B patients treated with nucleos(t)ide analogues combined with (pegylated-) interferon: a systematic review and Meta-analysis[J]. Chinese Hepatolgy, 2025, 30(5): 638-644.

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