35 research outputs found
In Vivo Suppression of Precore mRNA Synthesis Is Associated with Mutations in the Hepatitis B Virus Core Promoter
AbstractWe have examined the in vivo effect of hepatitis B virus (HBV) core promoter mutations on the expression of precore mRNA and pregenomic RNA transcripts in the liver of 24 patients with chronic HBV infection, applying a novel transcript-specific RT-PCR assay. The double A1762T/G1764A mutation in the basic core promoter was detected in 11 cases. This mutation was in all cases associated with absence or low levels of precore mRNA transcripts without significantly affecting the levels of total core promoter-directed transcription in the liver of infected patients. Precore mRNA synthesis was suppressed by the A1762T/G1764A mutation regardless of the presence of the precore stop codon mutation G1896A, suggesting that in addition to downregulating an immunomodulatory protein this double basic core promoter mutation may also confer a replication advantage to the virus. Additional mutations detected in the core promoter may also contribute to the observed changes in precore mRNA levels. Our in vivo study shows therefore that the double A1762T/G1764A mutation is associated with the specific suppression of precore mRNA synthesis directed by the HBV core promoter
Early Predictors of Anemia in Patients With Hepatitis C Genotype 1 Treated With Peginterferon Alfa-2a (40KD) Plus Ribavirin
Adherence to ribavirin is one factor that is critically important in the treatment of hepatitis C virus infection. However, ribavirin can be associated with clinically significant hemolytic anemia resulting in dose modifications in up to one-quarter of patients. Currently, baseline predictors of considerable anemia are not sufficiently discriminating for routine therapeutic intervention. The objective of this analysis was to elucidate baseline and on-treatment factors predictive of a considerable hemoglobin drop at week 4
Management of hepatitis C virus genotype 4: recommendations of an international expert panel.
HCV has been classified into no fewer than six major genotypes and a series of subtypes. Each HCV genotype is unique with respect to its nucleotide sequence, geographic distribution, and response to therapy. Genotypes 1, 2, and 3 are common throughout North America and Europe. HCV genotype 4 (HCV-4) is common in the Middle East and in Africa, where it is responsible for more than 80% of HCV infections. It has recently spread to several European countries. HCV-4 is considered a major cause of chronic hepatitis, cirrhosis, hepatocellular carcinoma, and liver transplantation in these regions. Although HCV-4 is the cause of approximately 20% of the 170 million cases of chronic hepatitis C in the world, it has not been the subject of widespread research. Therefore, this document, drafted by a panel of international experts, aimed to review current knowledge on the epidemiology, natural history, clinical, histological features, and treatment of HCV-4 infections
Why and How to Treat Chronic Hepatitis C
Chronic hepatitis
C (CHC) is a major health problem worldwide, with approximately
200 million affected individuals and a significant rate of
progression to end-stage cirrhosis and hepatocellular carcinoma
(HCC). If hepatitis C virus (HCV) infection is left untreated in
the population, then the number of liver-related deaths will soon
double and the need for liver transplantation may increase to five
times that seen today. Available therapies for CHC are restricted
to interferon alpha (IFN-α ) monotherapy and to the combination
of IFN-α and ribavirin. Despite their high cost and side effects,
both of these therapies have proved to be cost effective, particularly
combination therapy. IFN-α monotherapy for one year can
induce sustained response (SR) rates of approximately 10% in naive
patients infected with HCV genotype 1, and above 50% in
those infected with other genotypes. Combination therapy can
double or even triple the rate of SR in genotype 1 infections and
may further increase the SR rate in the other HCV genotypes.
Combination therapy has also been proven to be effective in approximately
50% of relapsed responders to IFN-α monotherapy. In
clinical practice, the decision to treat should be individualized and
tailored on the basis of several virus- and host-related factors, particularly
the grade and stage of liver disease, HCV genotype and
levels of viremia. Appropriate monitoring of therapy by careful
clinical evaluation, liver biochemistry and serumHCVRNAtesting
is mandatory. IFN-α therapy may also prove to be effective in
reducing the rate of HCC development in CHC regardless of
whether a virological response is achieved, but this remains to be
established
The rate of Entecavir resistance in Naïve and Lamivudine-resistance chronic hepatitis B patients during 3 years of treatment
Colonno RJ. AASLD 2006. Abstract 110.<p><b>Copyright information:</b></p><p>Taken from "The role of entecavir in the treatment of chronic hepatitis B"</p><p></p><p>Therapeutics and Clinical Risk Management 2007;3(6):1077-1086.</p><p>Published online Jan 2007</p><p>PMCID:PMC2387288.</p><p>© 2007 Dove Medical Press Limited. All rights reserved</p
Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients
Hepatitis B virus (HBV) covalently dosed circular DNA (cccDNA) is
responsible for viral persistence in the natural course of chronic HBV
infection and during prolonged antiviral therapy and serves as the
template for the production of HBV pregenomic RNA (pgRNA), the primary
step in HBV replication. In this study, we have developed and applied
sensitive and specific quantitative real-time polymerase chain reaction
(PCR) assays for the measurement of intrahepatic concentration, pgRNA
production, and replicative activity of cccDNA in liver biopsy samples
from 34 non-treated patients with chronic hepatitis B (CHB); 12
hepatitis B e antigen (HBeAg) (+) and 22 HBeAg(-). Median copy number
for cccDNA was 1.5 per cell and for pgRNA significantly higher, 6.5
copies per cell, with a good correlation between cccDNA and pgRNA levels
in all samples. In HBeAg(-) patients, median values of cccDNA and pgRNA
levels were 10-fold and 200-fold lower than in HBeAg(+), respectively,
reflecting the differences in viral activity and clinical
characteristics of the two groups. Furthermore, the replicative activity
of intrahepatic cccDNA was significantly lower in HBeAg(-) patients
harboring mutant HBV strains than in HBeAg(+) patients: median 3.5
versus 101 pgRNA copies per cccDNA molecule. In conclusion, the levels
of both HBV cccDNA, a marker of HBV persistence, and pgRNA, an indicator
of viral replication, in the liver of chronically infected patients
correlate with viral activity and the phase of HBV infection. The
combined measurement of cccDNA and pgRNA levels provides valuable
information on the presence and replicative activity of intrahepatic HBV
cccDNA