Journal ArticleDOI
Association of intrahepatic cccDNA reduction with the improvement of liver histology in chronic hepatitis B patients receiving oral antiviral agents.
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TLDR
Although one‐year ETV or ADV treatment is insufficient for cccDNA eradication, oral antiviral therapies may improve liver histology, probably by suppressing intrahepatic ccc DNA.Abstract:
Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is difficult to eradicate using current antiviral therapy. This study compares cccDNA reduction with relation to liver histology in nucleoside/nucleotide-naive chronic hepatitis B patients receiving oral antiviral monotherapy (n=35), including entecavir (ETV, n=13), adefovir dipivoxil (ADV, n=22) or placebo (n=14). Serum HBV DNA, intrahepatic total HBV DNA and cccDNA are quantified. Histological hepatic examination is performed at baseline and at 48 weeks of treatment. Treatment with ETV or ADV shows significant median reduction in serum HBV DNA (-6.21 and -4.27 log(10) copies/mL) and intrahepatic total HBV DNA (-1.69 and -1.23 log(10) copies/cell). Intrahepatic cccDNA levels are reduced slightly in the ETV and the ADV groups, but do not differ statistically from the placebo group (-0.17 vs. -0.01 vs. 0.02 copies/cell). Only the level of intrahepatic cccDNA correlates with Knodell necroinflammation activity (r=0.527, P<0.001) and Ishak fibrosis severity (r=0.348, P=0.015) before treatment. Multivariate logistic regression analysis indicates that treatment-induced cccDNA reduction is associated with improved necroinflammation (P=0.041) and fibrosis (P=0.026). In conclusion, baseline intrahepatic cccDNA loads correlate with histologic activity. Although one-year ETV or ADV treatment is insufficient for cccDNA eradication, oral antiviral therapies may improve liver histology, probably by suppressing intrahepatic cccDNA.read more
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Journal ArticleDOI
Reduction of Hepatitis B Surface Antigen and Covalently Closed Circular DNA by Nucleos(t)ide Analogues of Different Potency
Danny Ka-Ho Wong,Wai-Kay Seto,James Fung,Philip P.C. Ip,Fung-Yu Huang,Ching-Lung Lai,Man-Fung Yuen +6 more
TL;DR: In this paper, the authors investigated the effect of different nucleos(t)ide analogues against hepatitis B virus (HBV) on levels of covalently closed circular DNA (cccDNA) and hepatitis B surface antigen (HBsAg) in patients.
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Hepatitis B virus molecular biology and pathogenesis
TL;DR: A comprehensive description of HBV biology is provided, the model systems used for studying HBV infections are summarized, and potential mechanisms that link a chronic HBV-infection to the development of HCC are highlighted.
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The Hepatitis B Virus (HBV) HBx Protein Activates AKT To Simultaneously Regulate HBV Replication and Hepatocyte Survival
TL;DR: It is reported that HBx activates AKT in hepatocytes to reduce HBV replication, and an important effect of HBx activation of AKT is inhibition of apoptosis, which may facilitate persistent, noncytopathicHBV replication.
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The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes
John E. Tavis,Xiaohong Cheng,Yuan Hu,Yuan Hu,Michael Totten,Feng Cao,Eleftherios Michailidis,Rajeev Aurora,Marvin J. Meyers,E. Jon Jacobsen,Michael A. Parniak,Stefan G. Sarafianos +11 more
TL;DR: This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced and differential inhibition of HBV genotype D and HRNAseHs indicates that viral genetic variability will be a factor during drug development.
Journal ArticleDOI
CRISPR/Cas9 nickase-mediated disruption of hepatitis B virus open reading frame S and X.
Madina Karimova,Niklas Beschorner,Werner Dammermann,Jan Chemnitz,Daniela Indenbirken,JH Bockmann,Adam Grundhoff,Stefan Lüth,Frank Buchholz,Julian Schulze zur Wiesch,Joachim Hauber +10 more
TL;DR: This work identified cross-genotype conserved HBV sequences in the S and X region of the HBV genome that were targeted for specific and effective cleavage by a Cas9 nickase, demonstrating the feasibility of using the CRISPR/Cas9 nick enzyme system for novel therapy strategies aiming to cure HBV infection.
References
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Journal ArticleDOI
Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis
Robert G. Knodell,Kamal G. Ishak,William C. Black,Thomas S. Chen,Robert M. Craig,Neil Kaplowitz,T Kiernan,Jerome Wollman +7 more
TL;DR: A Histology Activity Index has been developed which generates a numerical score for liver biopsy specimens obtained from patients with asymptomatic chronic active hepatitis that provides definitive endpoints for statistical analysis of serial changes in liver histology and offers an alternative to the use of conventional pathological descriptions.
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Journal ArticleDOI
Hepatitis B virus infection.
TL;DR: This review addresses many aspects of HBV infection, including the role of the immune system in determining the outcome of clinical infection, recent developments in molecular studies of the virus, and new treatments capable of eradicating chronic infection.
Journal ArticleDOI
Hepatitis B Virus Infection — Natural History and Clinical Consequences
Don Ganem,Alfred M. Prince +1 more
TL;DR: The structure and replication cycle of hepatitis B virus is examined and the natural history of primary infection, the mechanisms of clearance of the virus, and reasons for persistent infection are discussed.
Journal ArticleDOI
A One-Year Trial of Lamivudine for Chronic Hepatitis B
Ching-Lung Lai,R.-N. Chien,N. W. Y. Leung,Ting-Tsung Chang,R. Guan,D.-I. Tai,K.-Y. Ng,P.-C. Wu,Julie C. Dent,J. Barber,S. L. Stephenson,D. F. Gray +11 more
TL;DR: In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B, and a daily dose of 100 mg was more effective than a daily doses of 25 mg.