Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection

Published on Nov 1, 2018in Clinical Gastroenterology and Hepatology7.96
· DOI :10.1016/j.cgh.2018.11.001
Sang Hoon Ahn46
Estimated H-index: 46
(Yonsei University),
Won Kim13
Estimated H-index: 13
(Seoul Metropolitan Government)
+ 25 AuthorsKwang Hyub Han3
Estimated H-index: 3
(Yonsei University)
Background & Aims Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea. Methods We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA Results After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV–BSV and 85.7% of patients in the TDF–BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups. Conclusions BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. no: NCT01937806.
  • References (27)
  • Citations (2)
Published on Jan 1, 2018in Journal of Hepatology18.95
Kosh Agarwal32
Estimated H-index: 32
(King's College),
Maurizia Rossana Brunetto49
Estimated H-index: 49
(UniPi: University of Pisa)
+ 26 AuthorsHo Bae4
Estimated H-index: 4
Background & Aims Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials. Methods In two international t...
Published on Nov 15, 2017in Gut and Liver2.97
Ji Hye Park18
Estimated H-index: 18
(Yonsei University),
Kyu Sik Jung14
Estimated H-index: 14
(Yonsei University)
+ 6 AuthorsJun Yong Park41
Estimated H-index: 41
(Yonsei University)
Published on Aug 1, 2017in Journal of Hepatology18.95
P. Lampertico39
Estimated H-index: 39
Kosh Agarwal32
Estimated H-index: 32
+ 5 AuthorsFrank Tacke61
Estimated H-index: 61
Summary Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis...
Published on Feb 1, 2017in Alimentary Pharmacology & Therapeutics7.73
Wkw Seto5
Estimated H-index: 5
(HKU: University of Hong Kong),
E. H. Y. Lau1
Estimated H-index: 1
(HKU: University of Hong Kong)
+ 6 AuthorsMan-Fung Yuen69
Estimated H-index: 69
(HKU: University of Hong Kong)
SummaryBackground The temporal relationship between nucleoside analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level. Aim To investigate the impact of nucleoside analogue prescription on liver cancer incidence in a CHB-prevalent region. Methods We obtained territory-wide nucleoside analogue prescription data from 1999, when nucleoside analogue was first available in Hong Kong, to 2012 and the population-based liver cancer inciden...
Published on Feb 1, 2017in Liver International5.54
Tung-Hung Su24
Estimated H-index: 24
(NTU: National Taiwan University),
Estimated H-index: 67
(NTU: National Taiwan University)
This is in reference to the article by SU TH et al.(1). They had recuited 1818 treatment-naive patients with cirrhosis and baseline HBV-DNA≥2000 IU/mL and found a significant decrease of the development of hepatocellular carcinoma(HCC), liver-related and all-cause mortality as well as cirrhotic complications including variceal bleeding, spontaneous bacterial peritontis(SBP) due to the long-term entecavir therapy. However, to our understanding, there are still some key points worth up for discuss...
Published on Nov 1, 2016in The Lancet Gastroenterology & Hepatology
Maria Buti59
Estimated H-index: 59
(ISCIII: Instituto de Salud Carlos III),
Edward Gane68
Estimated H-index: 68
+ 19 AuthorsHarry L.A. Janssen71
Estimated H-index: 71
Summary Background The novel prodrug tenofovir alafenamide delivers the nucleotide reverse transcriptase inhibitor tenofovir to target cells more efficiently at a lower dose than tenofovir disoproxil fumarate, thereby reducing systemic exposure. We compared the efficacy and safety of the two drugs in patients with HBeAg-negative chronic hepatitis B virus (HBV) infection in a non-inferiority study. Methods In this ongoing randomised, double-blind, phase 3, non-inferiority study in 105 centres in ...
Background: The use of nucleotide analogs (NTAs) can be associated with negative effects on renal function and bone mineral density (BMD) due to proximal tubular dysfunction and hypophosphatemia; however, prospective data assessing the bone and renal safety of these agents are limited. Objective: This study aimed to evaluate the prevalence of bone diseases among chronic hepatitis B (CHB) patients without cirrhosis and the changes in BMD and glomerular filtration rate (GFR) between patients recei...
Published on Jan 1, 2016in Hepatology14.97
Norah A. Terrault66
Estimated H-index: 66
(UCSF: University of California, San Francisco),
Natalie Bzowej27
Estimated H-index: 27
(Ochsner Medical Center)
+ 3 AuthorsM. Hassan Murad89
Estimated H-index: 89
(Mayo Clinic)
Aasld Guidelines for Treatment of Chronic Hepatitis B Norah Terrault;Natalie Bzowej;Kyong-Mi Chang;Jessica Hwang;Maureen Jonas;Hassan Murad; Hepatology
Published on May 1, 2015in Digestive Diseases and Sciences2.94
Maria Buti59
Estimated H-index: 59
Naoky Tsai20
Estimated H-index: 20
(U.H.: University of Hawaii at Manoa)
+ 11 AuthorsPrista Charuworn5
Estimated H-index: 5
Background Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks).
Published on Apr 1, 2015in Journal of Hepatology18.95
George V. Papatheodoridis54
Estimated H-index: 54
(Athens State University),
H. L.-Y. Chan71
Estimated H-index: 71
(CUHK: The Chinese University of Hong Kong)
+ 2 AuthorsP. Lampertico39
Estimated H-index: 39
(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)
Summary In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated ...
Cited By2
Published on May 3, 2019in Expert Opinion on Pharmacotherapy3.04
Hans L. Tillmann51
Estimated H-index: 51
(ECU: East Carolina University),
Hans L. Tillmann (ECU: East Carolina University), Gbeminiyi Samuel (ECU: East Carolina University)
ABSTRACTIntroduction: Hepatitis B virus (HBV) infection remains a global challenge with several hundred million infected individuals. Disease activity can be controlled, and adverse outcomes prevented when treatment can be provided. Frequently life-long therapy is required instead of defined treatment periods such as with the case of Hepatitis C Virus (HCV) infection.Areas covered: In this review, the authors provide an overview of current start of the art therapy for HBV and indicate where vari...