RESUMEN
BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
Asunto(s)
Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Mutación , Adulto , Factores de Edad , Anciano , ADN Viral/análisis , ADN Viral/genética , Femenino , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Virulencia/genéticaRESUMEN
BACKGROUND: The hepatitis C virus (HCV) RNA-dependent RNA polymerase, NS5B, is essential for virus RNA replication. It is thus an attractive therapeutic target. Several compound nucleoside analogues, non-nucleoside inhibitors and cyclosporine analogues are being developed to inhibit NS5B activity. However, nucleotide changes in the NS5B gene can confer resistance to them. METHODS: We investigated the prevalence of known substitutions conferring resistance in HCV polymerase in 124 treatment-naive French patients infected with HCV genotypes 1, 2, 3, 4 or 5 by sequencing the NS5B gene. RESULTS: None of the 124 HCV NS5B sequences analysed contained substitutions conferring resistance to nucleoside analogues; however, NS5B polymerases containing substitutions conferring resistance to non-nucleoside inhibitors were frequent within genotype 1 strains (17%) and very common in non-genotype 1 strains. Similarly, substitutions conferring resistance to cyclosporine analogues were more prevalent within the various genotypes. CONCLUSIONS: Naturally occurring substitutions conferring resistance to NS5B inhibitors are common in treatment-naive patients infected with HCV genotype 1, 2, 3, 4 or 5. Their influence on treatment outcome should be assessed.
Asunto(s)
Sustitución de Aminoácidos , Antivirales/farmacología , Farmacorresistencia Viral/genética , Hepacivirus , Hepatitis C/tratamiento farmacológico , ARN Polimerasa Dependiente del ARN/antagonistas & inhibidores , Genotipo , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepacivirus/enzimología , Hepacivirus/genética , Hepatitis C/epidemiología , Hepatitis C/virología , Humanos , Prevalencia , ARN Polimerasa Dependiente del ARN/genética , Análisis de Secuencia de ADN , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND: We compared three hyaluronic acid (HA) assays and analyzed the impact of their variations on FibroMeter scores. METHODS: In a test group of 165 patients, HA levels were assessed with the commonly used ELISA assay from Corgenix, a new ELISA assay from Teco and an immunoturbidimetry assay from Wako, this latter tested across three different instruments. Five different FibroMeter scores were calculated. RESULTS: Correlation across the three assays (r(s) between 0.969 and 0.995) was very good. Means of differences (d) were lower when the immunoturbidimetry assay was compared on different instruments: d between -3.4 and 2.0 µg/L. However, a higher value for HA measurement was observed with Corgenix assay, compared to the other two assays (Teco and Wako): d between 27.1 and 36.4 µg/L. The assessment also demonstrated that HA variations had very little impact on FibroMeter scores: 0.0117 for virus and 0.0416 for alcoholic fibrosis scores, and between 0.58 and 1.71 for the area of fibrosis (expressed in percentage). CONCLUSIONS: The two new assays found lower values of HA, as compared to the Corgenix assay. However, these differences had very little impact on FibroMeter scores and had no impact on clinical evaluation of liver fibrosis.