Clinical–liver, pancreas, and biliary tractLong-term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 Years
Section snippets
Study Design
This 240-week study consisted of a double-blinded phase of 96 weeks followed by an open-label, long-term safety and efficacy study of 144 weeks (Figure 1). This international, prospective trial enrolled 185 patients between January 10 and June 7, 2000, at 32 sites.13, 14 Patients were randomly assigned to receive 10 mg adefovir dipivoxil (n = 123) or placebo (n = 62; 1 patient did not take study drug) once daily in a double-blind manner for the first 48 weeks. At week 49, 119 patients initially
Patient Disposition and Characteristics
After 96 weeks of randomized, double-blind treatment with adefovir dipivoxil and/or placebo, 125 patients enrolled in the long-term safety and efficacy study. In the placebo-adefovir group, 87% of patients (48/55) received adefovir dipivoxil for 192 weeks (1 patient discontinued the study because of HBsAg seroconversion), and, in the adefovir-adefovir group, 86% of patients (60/70) received adefovir dipivoxil for 240 weeks. The disposition of patients throughout the entire 240-week study is
Discussion
Treatment with adefovir dipivoxil for up to 240 weeks in this study produced sustained suppression of serum HBV DNA levels, normalization of ALT levels, and increasing improvement in liver fibrosis. In addition, most patients with advanced liver disease prior to treatment, including cirrhosis, improved markedly. The first oral antiviral therapy to show reversal of fibrosis with 3 years of treatment was lamivudine; however, improvement was reversed after the frequent development of resistance.25
References (26)
- et al.
Viral hepatitis B
Lancet
(2003) - et al.
Hepatitis B e antigen-negative chronic hepatitis B
Hepatology
(2001) - et al.
A treatment algorithm for the management of chronic hepatitis B virus infection in the United States
Clin Gastroenterol Hepatol
(2004) - et al.
Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B
J Hepatol
(1990) - et al.
A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum
Hepatology
(1997) - et al.
The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B
J Hepatol
(2001) - et al.
Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B
Hepatology
(2000) - et al.
Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine
J Hepatol
(2000) - et al.
Long-term safety of lamivudine treatment in patients with chronic hepatitis B
Gastroenterology
(2003) - et al.
Histological grading and staging of chronic hepatitis
J Hepatol
(1995)
Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks
Hepatology
Final analysis of virological outcomes and resistance during 5 years of adefovir dipivoxil monotherapy in HBeAg-Negative Patients
J Hepatol
Histological outcome during long-term lamivudine therapy
Gastroenterology
Cited by (808)
Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy
2024, Journal of Clinical and Experimental HepatologyRegression of Liver Fibrosis in Patients on Hepatitis B Therapy Is Associated With Decreased Liver-Related Events
2024, Clinical Gastroenterology and HepatologyCan liquid biopsies for MASH help increase the penetration of metabolic surgery? A narrative review
2024, Metabolism: Clinical and ExperimentalHydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial
2023, Clinical Gastroenterology and HepatologyStructure, Function and Responses to Injury
2023, MacSween's Pathology of the Liver, Eighth Edition
Other members of the Adefovir Dipivoxil 438 Study Group are listed in the Appendix.