Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis.

BACKGROUND AND

OBJECTIVES

Chronic hepatitis B virus remains a significant cause of liver disease in the developing world, leading to sequelae such as hepatocellular carcinoma. While entecavir (ETV) serves as a first-line treatment, its growing resistance rates underscore the need to explore viable alternatives. Tenofovir disoproxil fumarate (TDF) monotherapy and entecavir plus tenofovir (TDF + ETV) combination therapy are both employed as treatments, but one's efficacy over another is in question. This meta-analysis aims to investigate any primacy of either treatment.

METHODS

We conducted a comprehensive literature search across PubMed/Medline, Embase, Cochrane Central, Web of Science, and China National Knowledge Infrastructure from inception till 7th October 2024. Studies comparing the safety and efficacy of TDF monotherapy versus TDF + ETV combination therapy in patients resistant to entecavir were considered. Data about the virologic response (VR), virologic breakthrough, HbeAg seroconversion, HbeAg/HbsAg seroclearance, and alanine aminotransferase normalization were extracted. Relative risks (RRs) and their corresponding 95% confidence intervals (CIs) were calculated, pooled, and analyzed in a random-effects model. P-value <0.05 was regarded as significant for all analyses.

RESULTS

Nine studies, comprising 335 patients undergoing monotherapy and 352 patients undergoing combination therapy, satisfied the criteria. TDF + ETV combination therapy was found slightly advantageous to TDF monotherapy, stimulating a VR at 48 weeks (RR 1.081 95% CI: [1.001-1.167] P = 0.046, I2 = 0%), along with the HbeAg seroconversion rate (RR 1.711 95% CI: [1.005-2.913] P = 0.048, I2 = 0%). There were no significant adverse events in individual studies to warrant a meta-analysis.

CONCLUSIONS

TDF + ETV shows slightly better efficacy to TDF monotherapy over a 48-week treatment regimen, with minimal safety concerns. However, further high-quality studies like randomized controlled trials are needed to further solidify conclusions, with this meta-analysis only achieving borderline significances.

REGISTRATION: This review is registered on the PROSPERO database (ID: CRD42024581443).