The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 ± 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53 percent of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53 percent of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35 percent of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 ± 14 and 60 ± 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 ± 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.

High prevalence of hepatitis C infection among brazilian hemodialysis patients in Rio de Janeiro a one year follow-up study

Aproxidamente 400 pacientes de hemodialise tratados em 5 diferentes unidades no Rio de Janeiro foram acompanhados durante 1 ano para presenca de marcadores virais de hepatite B e C. Durante o mesmo periodo, amostras foram tambem de 35 pacientes ambulatoriais de dialise peritonial continua (CAPD) e de 242 funcionarios das unidades. Dependendo da unidade em estudo foram detectadas prevalencias de anti-HCV variando de 47 por cento a 82 por cento (media 65 por cento ). Pacientes de prevalencia de anti-HCV em funcionarios foi de 2,9 por cento . Observamos uma taxa de ataque de hepatite C de 11,5 por cento por ano na populacao paciente de hemodialise anti-HCV negativo. Uma media de 9,4 por cento de pacientes de hemodialise eram portadores cronicos do virus da hepatite B (VHB) (taxa de 1.8 por cento a 20.4 por cento ), enquanto 48.9 por cento apresentaram marcadores de infeccao passada de HBV. A taxa de ataque de HBV foi de 4.5 por cento por ano (taxa de 0 por cento a 6 por cento ). Esses resultados indicam uma alarmante prevalencia alta anti-HCV em pacientes de hemodialise dessa regiao estudada.

Hepatitis B and C prevalences among blood donors in the south region of Brazil

The prevalence of hepatitis B and C infection has been determined in a seroepidemiological survey among blood donors from the south of Brazil (Florianópolis, State of Santa Catarina). These markers has also been correlated with the levels of alanine aminotransferase (ALT), a surrogate marker to prevent post-transfusion hepatitis. Sera from 5000 donors were randomly collected in the period of April to November 1991. The prevalences of HBsAg, anti-HBs and anti-HBc were respectively 0.78, 7.02 and 13.98. The anti-HCV prevalence after confirmation testing with line immunoassay (LIA), was 1.14. Normal values of ALT ( < = 32 U/ml) were found in 59.78, values slightly above the mean (ALT between 32-70 U/ml) in 37.74 and high values of ALT ( > = 70 U/ml) in 2.48. The positivity of anti-HCV antibodies increased with the elevation of ALT levels. This correlation was not observed in relation to HBsAg. There exists a diversity in the recognition of HCV epitopes among HCV positive donors. Via the confirmation test used, we could observe that 94.7 of donors recognize the structural core antigen. Besides that, we observed that 5.26 of the HCV reactive sera recognized only epitopes located in the NS4 and/or NS5 region, indicating the importance of these epitopes for the improvement of assays.

Anti-HCV related to HCV PCR and risck factors analysis in a blood donor population of central Brazil

Ainda sao raros os casos de infeccao por hepatite C (HCV)na regiao central do Brasil. Neste estudo, 2.350 doadores voluntarios de sangue foram avaliados, resultando em prevalencias para o anti-HCV de 2,2 (por cento), pelo ELISA de segunda geracao, e de 1,4 por cento, apos o ensaio confirmatorio "line immunoassay". Anticorpos contra os antigenos "core", NS4 e NS5 do HCV foi observada em 76,6 (por cento) dos doadores anti-HCV positivos. A positividade da reacao em cadeia da polimerase (PCR) mostrou-se relacionada a reatividade aos diferentes antigenos do HCV no "line immunoassay". A maioria dos doadores positivos tiveram historia previa de exposicao parenteral. A combinacao de ALT>50 UI/1 e positividade ao anti-HBc parece nao ser eficaz como marcadores indiretos para a infeccao pelo HCV, entretanto a dosagem do ALT e a deteccao de anti-HCV sao indicadas na triagem de doadores de sangue brasileiros.

Human antibodies to dengue and yellow fever do not react in diagnostic assays for hepatitis C virus

Hepatitis C virus (HCV) is a recently described causative agent of the great majority of post-transfusion non A-non B hepatitis and is classified within the Flaviviridae family. Due to a high prevalence of anti-HCV and other flaviviruses circulating in Brazil, such as dengue and yellow fever, we investigated the possibility of serological cross-reactivity between these viruses. Different panels of human sera positive for dengue type 1 (9 cases) and type 2 (7 cases) from 6 patients naturally infected with yellow fever and from 94 adults vaccinated against the 17D strain of yellow fever were tested against HCV antigens used in diagnostic assays. Two enzyme immunoassay systems were tested: one, an in-house test using recombinant antigens from core, NS3 and NS5 regions of the HCV genome (Research Foundation for Microbial Disease of Osaka University, Japan); and another, using synthetic peptides representing immunodominant epitopes of structural core and non-structural NS4 and NS5 HCV regions (INNOTEST HCV Ab, Innogenetics, Belgium). A line immunoassay (INNO-LIA HCV Ab, Innogenetics, Belgium) was used as a confirmatory test. In this, HCV antigens are coated as discrete lines on a nylon strip with plastic backing. Besides 4 control lines on each strip, a total of 6 HCV lines are present: line A consists of several NS4 epitopes, line B consists of several NS5 epitopes and lines C-F contain several core epitopes. This test not only confirms but differentiates antibodies to hepatitis C virus. No positive results were detected with these tests, indicating that hepatitis C infection can be evaluated by current assays in regions where flaviviruses are endemic