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.

An expert consensus for the management of chronic hepatitis B in Asian Americans

“…Seven patients in the pegylated interferon alone group and five patients in the pegylated interferon plus LAM group achieved HBsAg seroconversion, whereas no patients treated with LAM achieved this endpoint (4% vs 2.8% vs 0%, P = 0.029). Additional studies combined pegylated interferon alfa‐2a with NAs such as LAM, ADV, telbivudine, entecavir, and TDF, but due to limited evidence, these regimens have not been incorporated into practice guidelines.…”

Systematic review with meta‐analysis: combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance

“…However, at present, it is unknown which strategy is more effective. Published meta‐analyses were mainly conducted to compare efficacy between combination therapy and monotherapy. Therefore, this meta‐analysis was performed to establish the overall proportion of HBsAg loss in different combination strategies.…”

Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector

“…A constant suppression of the viral replication is then required with available treatments involving polymerase inhibitors such as lamivudine (3TC), entecavir (ETV) and tenofovir-diisoproxyl fumarate (TDF) or tenofovir alafenamide (TAF) [2]. Although these drugs are very effective at controlling virus infection, long-term treatments may cause drug resistance or severe side effects and more importantly, none of these drugs can cure HBV infections [3, 4]. …”