Review Hepatitis B Virus Resistance to Lamivudine and its Clinical Implications

2002 ◽  
Vol 13 (3) ◽  
pp. 143-155 ◽  
Author(s):  
Xuefeng Liu ◽  
Raymond F Schinazi
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Lamivudine Therapy ◽  
Combination Strategy ◽  
B Virus ◽  
Ymdd Motif

Lamivudine is the first orally available drug approved for treatment of chronic hepatitis B, but hepatitis B virus (HBV) resistance to lamivudine appears to be a sine qua non in the therapy of HBV. The mutations at the FLLA and YMDD motif in the domains B and C of HBV polymerase contribute to this resistance. These mutations are found at codon (or AA) rtL180M and rtM204V/I in the reverse transcriptase (RT) domain of the HBV polymerase for all genotypes according to a new standardized RT domain numbering system. The resistant HBV may be less replication-competent in vitro and in vivo, and it is rarely associated with markedly increased HBV replication or liver injury. Therefore, certain physicians favour continuing lamivudine therapy even after emergence of HBV resistance with the expectation of maintaining lower-than baseline HBV DNA, alanine aminotransferase, and histological improvement, and avoiding reversion to wild-type HBV until additional antiviral strategies are developed. Ultimately, once several antiviral agents are approved, combination strategy is likely to be incorporated in antiviral treatment for chronic HBV to suppress, prevent or minimize the emergence of resistant virus.

scholarly journals Emergence of a Novel Mutation in the FLLA Region of Hepatitis B Virus during Lamivudine Therapy

2005 ◽  
Vol 49 (7) ◽  
pp. 2618-2624 ◽  
Author(s):  
S. Balakrishna Pai ◽  
A. Mithat Bozdayi ◽  
Rekha B. Pai ◽  
Tolunay Beker ◽  
Mustafa Sarioglu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Novel Mutation ◽  
Site Directed Mutagenesis ◽  
Human Hepatoma Cells ◽  
Lamivudine Therapy ◽  
Major Mechanism ◽  
B Virus ◽  
Novel Variant ◽  
Ymdd Motif

ABSTRACT The emergence of resistance to lamivudine has been one of the major stumbling blocks to successful treatment and control of hepatitis B virus (HBV) infections. The major mechanism of resistance has been attributed to the alteration in the YMDD motif of the HBV polymerase due to an amino acid change of rtM204 to V/I and an accompanying rtL180M conversion. A novel mutation pattern in a patient having clinical breakthrough under lamivudine therapy was discovered. The mutant had a rtL180C/M204I genotype and was detected after 2 years of therapy with lamivudine. To characterize this novel variant, site-directed mutagenesis was performed using a vector construct containing the HBV genome. Transient transfection studies in human hepatoma cells with HBV carrying the new mutant demonstrated that the rtL180C/M204I mutant was resistant to lamivudine up to 10 μM. The resistance profile was comparable to that of the previously reported rtL180 M/M204I-containing virus. These observations were further confirmed by generation of stable cultures transfected with the mutant virus.

Effect of 3′-azido-3′-deoxythymidine on replication of duck hepatitis B virus in vivo and in vitro

1989 ◽  
Vol 29 (4) ◽  
pp. 244-248 ◽  
Author(s):  
Hideaki Haritani ◽  
Toshikazu Uchida ◽  
Yasunori Okuda ◽  
Toshio Shikata
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

In vitro and in vivo anti-hepatitis B virus activities of the lignan nirtetralin B isolated from Phyllanthus niruri L.

2014 ◽  
Vol 157 ◽  
pp. 62-68 ◽  
Author(s):  
Sheng Liu ◽  
Wanxing Wei ◽  
Yubin Li ◽  
Xing Lin ◽  
Kaichuang Shi ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phyllanthus Niruri ◽  
B Virus

scholarly journals Anti-Hepatitis B Virus Activity of Esculetin from Microsorium fortunei In Vitro and In Vivo

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3475 ◽  
Author(s):  
Si-Xin Huang ◽  
Jun-Fei Mou ◽  
Qin Luo ◽  
Qing-Hu Mo ◽  
Xian-Li Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Antiviral Drug ◽  
Liver Carcinoma ◽  
Dependent Manner ◽  
Duck Hepatitis ◽  
B Virus

Coumarins are widely present in a variety of plants and have a variety of pharmacological activities. In this study, we isolated a coumarin compound from Microsorium fortunei (Moore) Ching; the compound was identified as esculetin by hydrogen and carbon spectroscopy. Its anti-hepatitis B virus (HBV) activity was investigated in vitro and in vivo. In the human hepatocellular liver carcinoma 2.2.15 cell line (HepG2.2.15) transfected with HBV, esculetin effecting inhibited the expression of the HBV antigens and HBV DNA in vitro. Esculetin inhibited the expression of Hepatitis B virus X (HBx) protein in a dose-dependent manner. In the ducklings infected with duck hepatitis B virus (DHBV), the levels of DHBV DNA, duck hepatitis B surface antigen (DHBsAg), duck hepatitis B e-antigen (DHBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly after esculetin treatment. Summing up the above, the results suggest that esculetin efficiently inhibits HBV replication both in vitro and in vivo, which provides an opportunity for further development of esculetin as antiviral drug.

Duck hepatitis B virus polymerase gene mutants associated with resistance to lamivudine have a decreased replication capacity in vitro and in vivo

2001 ◽  
Vol 34 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Béatrice Seignères ◽  
Stéphanie Aguesse-Germon ◽  
Christian Pichoud ◽  
Isabelle Vuillermoz ◽  
Catherine Jamard ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Replication Capacity ◽  
Polymerase Gene ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

Genetic immunization against hepatitis B virus with calcium phosphate nanoparticles in vitro and in vivo

2020 ◽  
Vol 110 ◽  
pp. 254-265
Author(s):  
Leonardo Rojas-Sánchez ◽  
Ejuan Zhang ◽  
Viktoriya Sokolova ◽  
Maohua Zhong ◽  
Hu Yan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Calcium Phosphate ◽  
Hepatitis B ◽  
Genetic Immunization ◽  
B Virus ◽  
Calcium Phosphate Nanoparticles

In vitro and in vivo anti-hepatitis B virus activities of the lignan niranthin isolated from Phyllanthus niruri L.

2014 ◽  
Vol 155 (2) ◽  
pp. 1061-1067 ◽  
Author(s):  
Sheng Liu ◽  
Wanxing Wei ◽  
Kaichuang Shi ◽  
Xun Cao ◽  
Min Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phyllanthus Niruri ◽  
B Virus

scholarly journals In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 353 ◽  
Author(s):  
Constance N. Wose Kinge ◽  
Nimisha H. Bhoola ◽  
Anna Kramvis
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
In Vitro Model ◽  
Antiviral Agents ◽  
Model Systems ◽  
Effective Vaccine ◽  
B Virus ◽  
In Vitro Systems ◽  
Vitro Model

Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity.

scholarly journals Interaction between ganciclovir and foscarnet as inhibitors of duck hepatitis B virus replication in vitro.

1996 ◽  
Vol 40 (5) ◽  
pp. 1180-1185 ◽  
Author(s):  
G Civitico ◽  
T Shaw ◽  
S Locarnini
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Duck Hepatitis ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Dose Limiting Toxicity

Safe and effective treatments for chronic hepatitis B virus (HBV) infection have yet to be developed. Both ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) and foscarnet (trisodium phosphonoformate hexahydrate) are potent inhibitors of hepadnavirus replication when used individually in vitro and in vivo. However, the clinical usefulness of each drug is reduced by dose-limiting toxicity, especially during long-term monotherapy. Here we demonstrate additive inhibition of duck HBV DNA replication in cultures of primary duck hepatocytes congenitally infected with duck HBV by combinations of ganciclovir and foscarnet at low, clinically achievable concentrations. These results suggest that the effects of ganciclovir and foscarnet against HBV may be additive in vivo.

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