Objective Entecavir (ETV) is a potent inhibitor of viral replication in chronic hepatitis B and prolonged treatment may result in regression of fibrosis. The aim of this study was to investigate the effect of ETV on disease progression.
Design In a multicentre cohort study, 372 ETV-treated patients were investigated. Clinical events were defined as development of hepatocellular carcinoma (HCC), hepatic decompensation or death. Virological response (VR) was defined as HBV DNA <80 IU/ml.
Results Patients were classified as having chronic hepatitis B without cirrhosis (n=274), compensated cirrhosis (n=89) and decompensated cirrhosis (n=9). The probability of VR was not influenced by severity of liver disease (p=0.62). During a median follow-up of 20 months (IQR 11–32), the probability of developing clinical events was higher for patients with cirrhosis (HR 15.41 (95% CI 3.42 to 69.54), p<0.001). VR was associated with a lower probability of disease progression (HR 0.29 (95% CI 0.08 to 1.00), p=0.05) which remained after correction for established risk factors such as age. The benefit of VR was only significant in patients with cirrhosis (HR 0.22 (95% CI 0.05 to 0.99), p=0.04) and remained after excluding decompensated patients (HR 0.15 (95% CI 0.03 to 0.81), p=0.03). A higher HBV DNA threshold of 2000 IU/ml was not associated with the probability of disease progression (HR 0.20 (95% CI 0.03 to 1.10), p=0.10).
Conclusion VR to ETV is associated with a lower probability of disease progression in patients with cirrhosis, even after correction for possible baseline confounders. When using a threshold of 2000 IU/ml, the association between viral replication and disease progression was reduced, suggesting that complete viral suppression is essential for nucleoside/nucleotide analogue treatment, especially in patients with cirrhosis.
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Funding The study was sponsored by the Foundation for Liver and Gastrointestinal Research Rotterdam (SLO) and conducted with support from the European Network of Excellence for Vigilance against Viral Resistance (VIRGIL) and a research grant from Bristol-Myers Squibb (BMS). BMS has not been involved in the design of the study, data collection, writing of the manuscript or decision to publish.
Competing interests RZ has received speaker's honoraria from Roche and Bristol-Myers Squibb (BMS); JR has received speaker's honoraria from Novartis and BMS; FZ is consultant for BMS, Gilead, Roche and Novartis; AB advises MSD, Roche, BMS, Gilead and Novartis; DJM has received honoraria and grants from BMS; JP is consultant for Gilead, Novartis, MSD, BMS, Roche and Janssen-Cilag and received research support from Roche, BMS, Novartis and Glaxo Smith Kline; MB has received speaker's honoraria and advisory board fee from Gilead, MSD, BMS and Novartis; TB is a consultant for and on the speakers' bureau of Gilead, Roche, Novartis and MSD; HW received research grants and speaker's honoraria from BMS, Gilead, Roche and Novartis; HLAJ received grants from and is consultant for BMS, Gilead Sciences, Novartis, Roche and Merck. The remaining authors have nothing to disclose.
Ethics approval The study was approved by the medical ethics committee of Erasmus MC Rotterdam.
Provenance and peer review Not commissioned; externally peer reviewed.
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