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HBV Mutations (hbv + mutation)
Selected AbstractsEvolution of multi-drug resistant hepatitis B virus during sequential therapy,HEPATOLOGY, Issue 3 2006Hyung Joon Yim Multi-drug resistant hepatitis B virus (HBV) has been reported in hepatitis B patients who received sequential antiviral therapy. In vitro studies showed that HBV constructs with mutations resistant to lamivudine and adefovir have marked reduction in sensitivity to combination of lamivudine and adefovir, whereas constructs with mutations resistant to either drug remain sensitive to the other drug. We conducted this study to determine whether mutations conferring resistance to multiple antiviral agents co-locate on the same HBV genome in vivo and to describe the evolution of these mutations. Sera from six patients who had been found to have multi-drug resistant HBV mutations to lamivudine + adefovir, lamivudine + hepatitis B immunoglobulin (HBIG), or lamivudine + entecavir on direct sequencing were cloned after nested polymerase chain reaction (PCR). Analysis of 215 clones from 11 samples with multi-drug resistant mutations on direct sequencing showed that 183 (85%) clones had mutations to both therapies on the same genome; 31 clones had lamivudine-resistant mutants only. Clonal analysis of serial samples from three patients showed progressive evolution from all clones with lamivudine-resistant HBV mutations only to mixtures of clones that have multi-drug resistant mutations and clones that have lamivudine-resistant HBV mutations only, and ultimately all clones having multi-drug resistant HBV mutations. In conclusion, mutations conferring resistance to multiple antiviral agents co-locate on the same viral genome, suggesting that combination therapy directed against mutants resistant to each treatment may not be adequate in suppressing multi-drug resistant HBV. De novo combination therapy may prevent the emergence of multi-drug resistant mutants. (HEPATOLOGY 2006;44:703,712.) [source] Hepatitis B virus BCP, precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in IndiaJOURNAL OF MEDICAL VIROLOGY, Issue 7 2010Mohammad Asim Abstract The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P,<,0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India. J. Med. Virol. 82: 1115,1125, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular and clinical characteristics of hepatitis B virus in KoreaJOURNAL OF MEDICAL VIROLOGY, Issue 7 2010Sang Hoon Ahn Abstract Korea is an endemic area of hepatitis B virus (HBV) infection but very little is known about the molecular characteristics of HBV isolates from Korean patients or the association with disease progression. The complete HBV genome sequences from 53 Korean patients with chronic hepatitis B, advanced cirrhosis, or hepatocellular carcinoma (HCC) were analyzed to identify (i) subgenotype distribution and genetic diversity and (ii) signature mutations associated with liver disease progression. With the exception of 1 patient infected with HBV/B, all 52 patients (98.1%) were infected with HBV/C, subgenotype C2. These strains were 98.4% identical and the frequency of amino acid substitutions occurring within key immunological epitopes increased with disease severity. A number of amino acid/nucleotide substitutions were associated with HCC, namely sR24K (HBsAg), SI126T (HBsAg), and pcA1846T (precore gene) mutations (P,=,0.029, 0.001, and 0.008, respectively). HBV harboring deletions in the pre-S region were also associated with increased liver disease severity (chronic hepatitis B vs. cirrhosis, P,=,0.040; chronic hepatitis B vs. HCC, P,=,0.040). Despite the high degree of sequence conservation, several key HBV mutations were associated with disease progression. Prospective studies with larger cohorts of patients are required to evaluate further the clinical manifestation of HBV/C2 in Korea. J. Med. Virol. 82: 1126,1134, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular epidemiology of hepatitis B virus in Dakar, SénégalJOURNAL OF MEDICAL VIROLOGY, Issue 3 2006Muriel Vray Abstract Using DNA chip technology and real-time quantitative PCR, molecular profile of HBV strains infecting blood donors and patients in Dakar, Sénégal was studied. All HBsAg-positive blood donors (n,=,175) and all patients who presented with chronic hepatitis B (n,=,29) between 1st June 2003 and 31st July 2003 were studied. One patient, a blood donor, was coinfected by HCV, and nine patients had anti-HDV antibodies. Few persons in either group were HBeAg-positive. Viral load values were relatively low but correlated with biochemical abnormalities. Patients were infected mainly by genotype E (72%). Patients infected by genotype A (28%) tended to be younger than other patients. There was no significant difference between the blood donors and the patients with hepatitis B as regards virological markers, including viral load, when the HBV genotype was taken into account. The BCP A1762T and G1764A mutations were found in four patients and one patient, respectively; the two mutations were never found in the same patient. The W28* mutation at position 1896 of the core was detected in 19 of the 32 genotyped patients, 18 (83%) of whom had genotype E infection. ALT levels were not influenced by HBV mutations. This study shows a low frequency of clinical signs in HBsAg-positive blood donors, a relatively low level of viral replication, and a high frequency of pre-core mutants in this West African population. These results underline the importance of molecular characterization of HBV infection as specific treatments become available in this region. J. Med. Virol. 78:329,334, 2006. © 2006 Wiley-Liss, Inc. [source] Virological analysis, genotypes and mutational patterns of the HBV precore/core gene in HBV/HCV-related hepatocellular carcinomaJOURNAL OF VIRAL HEPATITIS, Issue 9 2006M. S. De Mitri Summary., We investigated the replicative profile of hepatitis B (HBV) and hepatitis C (HCV) viruses and the mutational pattern of the HBV precore/core (pre-C/C) domain in hepatocellular carcinoma (HCC). Thirty-eight consecutive patients with HCC were included in the study , 18 of them with HBV/HCV co-infection and 20 with HBV single infection. Twenty-three additional patients with co-infection, without HCC were recruited as the control group. Replication activity was evaluated by detecting and quantitating both HBV and HCV genomes. The HBV pre-C/C region, encompassing the pregenome encapsidation signal involved in viral replication, was analysed by direct sequencing. HBV viraemia levels were significantly lower (P = 0.04) in patients with co-infection in comparison with single-infected HCC, whereas two different HBV viraemia profiles were detected in co-infection with or without circulating HCV. HBV genotype D was prevalent in the three groups and HCV genotype 1b was found to be the infecting strain in all patients. Lower variability in the pre-C/C region was found in co-infection in comparison with HBV single infection (P = 0.0004). A synonymous T1936C mutation was found in all co-infected HCC cases not related to the presence or absence of circulating HCV, and a hypermutated pre-C strain, characterized by the same mutational pattern, was identified in three HCC cases. The mutational pattern of the pre-C/C region was closely related to HBV replication efficiency, and specific HBV mutations selectively associated with HCV co-infection could be linked with accelerated HBV/HCV-related disease progression. [source] | ||||||||||