[show abstract][hide abstract] ABSTRACT: Early detection of antiviral drug-resistant mutations enables prompt initiation of rescue therapy. The aim of this study was to determine the accuracy and sensitivity of a new line probe assay in the detection of antiviral drug-resistant HBV mutations.
One-hundred samples from 54 patients with virologic breakthrough during entecavir, lamivudine or adefovir treatment and 21 samples from 21 nucleoside-naïve patients were tested by direct sequencing and an updated line probe assay (Innogenetics, HBV DR v.3) which incorporates probes that can detect mutations at 11 positions of the reverse transcriptase region of the HBV polymerase gene.
Complete concordance between line probe and sequencing results was observed for 90/121 samples (74.3%) and 1291/1331 amino acid positions (96.9%). Testing of follow-up samples and clonal analysis of discordant samples confirmed the presence of mutations where line probe assay but not direct sequencing detected mutations. HBV DR v.3 assay consistently detected mutations present in > or = 5% of the virus population when HBV DNA concentration was > or = 4 log10copies/mL.
The updated version of the line probe assay (HBV DR v.3) has high concordance with direct sequencing in detecting antiviral drug-resistant mutations but its sensitivity in detecting mutations at some positions needs to be improved.
Journal of Hepatology 12/2008; 50(1):42-8. · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: We sought to identify mutations associated with treatment failure to adefovir (ADV) and to determine virologic response to tenofovir (TDF) alone and in combination with emtricitabine (FTC) in these patients.
Serum samples prior to and after the change in treatment to TDF/TDF+FTC from 13 patients were analyzed by direct sequencing and clonal analysis.
ADV-resistant mutations, rtA181V and rtN236T, were detected on direct sequencing in 3 of 8 patients who had virologic breakthrough. Among patients with suboptimal virologic response, rtA181T, rtI233V, and rtN236T were present on clonal analysis in 3 patients. Ten patients received TDF, 8 achieved virologic response. One had ADV-resistance at baseline and persistence of ADV-resistant mutations during TDF treatment, addition of FTC resulted in a further decrease in HBV DNA. Another patient had no ADV-resistance at baseline, and selection of ADV-resistant mutations during TDF treatment. All 3 patients who received TDF+FTC had undetectable HBV DNA within 3-12 months including 2 who had ADV-resistance at baseline.
TDF monotherapy is effective for patients with virologic breakthrough or suboptimal response to ADV, but combination therapy with a nucleoside analogue should be considered in patients with ADV-resistance. No novel mutations were detected.
Journal of Hepatology 04/2008; 48(3):391-8. · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: This is a concise review of recent developments in the field of viral hepatitis, based on publications between December 2005 and November 2006.
Elevated hepatitis B virus DNA levels in patients in their 40s with perinatally acquired hepatitis B virus infection increases the risk for cirrhosis and hepatocellular carcinoma. Six approved therapies are available for chronic hepatitis B. Entecavir is a potent antiviral for nucleoside-naïve patients. For lamivudine resistant hepatitis B virus infection, adefovir should be added to lamivudine to reduce the risk of adefovir-resistant mutations; however, tenofovir may be a more promising alternative to adefovir. A shorter duration of treatment wth pegylated interferon and ribavirin is sufficient for genotype 2 hepatitis C infection but the benefits of extending treatment to 72 weeks for genotype 1 needs to be confirmed. Pegylated interferon monotherapy was shown to be effective in patients with hepatitis D and ribavirin provides no additional benefit.
New developments in the past year will help us fine tune the treatment of viral hepatitis. Even as new treatments are approved, the potential benefits of treatment should be weighed against the risk of drug-resistant mutations with long-term therapy.
Current Opinion in Gastroenterology 06/2007; 23(3):263-7. · 4.10 Impact Factor