Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients.

Heon Ju Lee,Soo Young Park,Jae Seok Hwang,Won Young Tak,Jeong Ill Suh,Chang Hyeong Lee,Byoung Kuk Jang,Byung Seok Kim,Hyun Young Woo,Sang Jin Kim,Young Oh Kweon,Jeong Heo,Woo Jin Chung,Jose Ignacio Herrero

doi:10.1371/journal.pone.0190581

Abstract

BackgroundThe efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.MethodsIn this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.ResultsPatients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000)ConclusionsStable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.Trial registrationClinicalTrials.gov NCT01732367

Highlights

The goal of chronic hepatitis B (CHB) therapy is to improve the quality of life and duration of survival by preventing the progression of the disease to hepatocellular carcinoma (HCC) and death
After a mean follow-up period of 96 weeks, the proportion of hepatitis B virus (HBV) reactivation observed was 6.8% (4/58) in the LAM+adefovir dipivoxil (ADV) group and 4.5% (5/111) in the tenofovir disoproxil fumarate (TDF) group by using intention-to-treat analysis
Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA

Summary

Introduction

The goal of chronic hepatitis B (CHB) therapy is to improve the quality of life and duration of survival by preventing the progression of the disease to hepatocellular carcinoma (HCC) and death. This can be achieved by suppressing the replication of hepatitis B virus (HBV). Lamivudine (LAM), a nucleoside analog, was the first oral antiviral agent used as a standard treatment for CHB. The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear

Methods

Results

Conclusion