Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B.
ABSTRACT Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n=182) or placebo (n=61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P<0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P<0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. CONCLUSION: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.BMC Infectious Diseases 08/2014; 14(1):439. · 3.03 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB.World journal of gastroenterology : WJG. 05/2014; 20(20):6262-6278.
- [Show abstract] [Hide abstract]
ABSTRACT: Chronic infection with hepatitis B virus (HBV) leads to the development of hepatocellular carcinoma and/or chronic liver failure. Despite extensive research, the immunopathogenesis is not completely understood. Viral persistence and clinical outcomes following HBV infection depend on viral factors and host factors; including genetic factors that determine a host's immune mechanisms. The primary goal of chronic hepatitis B (CHB) treatment is to eradicate HBV or to at least maintain suppression of HBV replication. Despite recent advances in anti-viral agents for chronic HBV infection, complete eradication of the virus has been difficult to achieve. Agents for the treatment of CHB are divided mainly into two groups: immunomodulating agents and antiviral nucleos(t)ide analogues (NAs). Although NAs are safe, effective and easily administered orally, their long-term use poses the risk of drug resistance. Currently, international evidence-based guidelines have been developed to support physicians in managing CHB patients. However, treatment of patients with drug resistance is still challenging, as only a few classes of anti-HBV drugs are available and cross-resistance between drugs can occur. In addition, as the currently available genotypic test for detection of drug resistance still has limitations in identifying the different substitutions present in the same viral genome, the development of a new virologic test to overcome this limitation is necessary. Among the predictive factors associated with response to pegylated interferon (PEG-IFN) therapy, hepatitis B surface antigen quantification is considered to be a surrogate marker for monitoring response to PEG-IFN. Current practice guidelines stress the importance of profound and durable HBV viral suppression in the treatment of CHB patients. To this end, it is essential to choose a potent antiviral drug with a low risk of resistance for initial treatment of CHB to achieve sustained virological response. This review highlights recent advances in the understanding of the immunopathogenesis of HBV and currently available and developing treatment strategies against HBV infection.World journal of gastroenterology : WJG. 10/2014; 20(37):13293-13305.