RESUMO
BACKGROUND/AIMS: Virological factors associated with hepatitis B virus reactivation (HBV-R), following chemotherapy for cancer in hepatitis B surface antigen (HBsAg)-negative patients, are not well known. MATERIALS AND METHODS: HBV strains from 16 patients presenting HBV-R following chemotherapy were studied and compared to those obtained from 51 HBV chronically-infected patients. RESULTS: HBsAg variability was significantly increased within the major hydrophilic region, the a determinant and the C-terminal region. Amino acid substitutions were more frequently found in HBV-R patients as compared to controls at 17 and 11 positions within HBsAg and HBV-RT, respectively. This resulted in atypical serological testing in 56% of patients and detection of resistance mutation to nucleoside analogs in 12.5%. CONCLUSION: HBsAg and HBV-RT mutations are frequently encountered in patients with HBV-R, resulting in atypical serological testing and emergence of HBV strains resistant to nucleos(t)ides analogs.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/fisiologia , DNA Polimerase Dirigida por RNA/genética , Ativação Viral , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Neoplasias/tratamento farmacológicoRESUMO
The rate of eradication of chronic hepatitis C considerably increases with direct-acting antiviral agents, particularly hepatitis C virus (HCV) polymerase inhibitors. While implementing full-length HCV NS5B polymerase sequencing in our clinical microbiology laboratory, we identified atypical HCV sequences, classified as subtype 2l, from 2 patients. HCV-2l NS5B polymerase sequences were detected from 5 and 14 additional patients by screening our laboratory hepatitis virus sequence database and the NCBI GenBank sequence database. Phylogenetic analyses show unambiguously that all HCV-2l sequences are clustered apart from HCV 2 non-l sequences, which compose a second cluster. Mean (±SD) nucleotide identity between near full-length NS5B fragments of subtype 2l was 93.4 ± 0.8% (range: 92.4-95.1). Of note, all HCV-2l sequences obtained in our laboratory and in other centers were from serum samples collected in France. Analysis of the HCV-2l NS5B polymerase amino acid sequences at 30 positions critical for interaction with or resistance to HCV polymerase inhibitors showed specific patterns.
Assuntos
Hepacivirus/genética , Hepatite C Crônica/virologia , RNA Polimerase Dependente de RNA/genética , Proteínas não Estruturais Virais/genética , Adulto , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sequência de Bases , Bases de Dados de Ácidos Nucleicos , Feminino , França , Genoma Viral , Genótipo , Hepacivirus/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , RNA Polimerase Dependente de RNA/classificação , Análise de Sequência de DNA , Proteínas não Estruturais Virais/classificaçãoRESUMO
We studied polymorphisms of three genes, UDP-glucuronosyltransferase1A7 (UGT1A7), Glutathione-S-transferaseM1 (GSTM1) and X-Ray Cross Complementing group 1 (XRCC1), involved in detoxification of xenobiotics or DNA-repair in a population of 133 liver-transplanted patients, including 56 patients with hepatocellular carcinoma (HCC) and 77 without HCC, and in 89 healthy controls originating from the south of France. Multiple logistic regression analysis showed that, among liver-transplanted patients, interactions between XRCC1-G/G or -G/A and GSTM1-nul polymorphisms were independently associated with hepatocellular carcinoma (p interaction=0.027) concurrently with increasing age (p<0.001), male sex (p=0.037) and chronic hepatitis B or C virus infection (p=0.018 and p=0.001 respectively). On the contrary, no relationship was observed between UGT1A7 polymorphisms considered alone or in interaction with GSTM1 or XRCC1 polymorphisms and HCC. This suggests that concomitant impaired metabolism of carcinogenic compounds and impaired DNA-repair function play an important role in liver carcinogenesis in high-risk cirrhotic patients originating from the south of France.
Assuntos
Carcinoma Hepatocelular/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Glucuronosiltransferase/genética , Glutationa Transferase/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Carcinógenos/metabolismo , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/cirurgia , Enzimas Reparadoras do DNA/metabolismo , Eletroforese em Gel de Ágar , Feminino , Amplificação de Genes , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Progressive multifocal leucoencephalopathy due to JC virus is a rare complication of liver transplantation. Only four cases have already been described in the literature. This disease is difficult to differentiate from leucoencephalopathy associated with immunosuppressive drugs such as cyclosporin or tacrolimus. Positive diagnosis of progressive multifocal leucoencephalopathy no longer requires cerebral biopsy. It must be confirmed by positive JC virus RNA amplification in the cerebrospinal fluid. We report a case of progressive multifocal leucoencephalopathy occurring 18 months after liver transplantation for hepatitis C-related cirrhosis.
