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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% of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53% of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35% 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.

Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent infections (Group 1). The rate of anti-c100/3 in patients of Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The recognition of anti-c100/3 and anti-core antibodies was significantly higher in Group 2 than in Group 1. A line immunoassay composed of structural and non-structural peptides was used as a confirmation assay. HBV infection, measured by the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies. The duration of HD treatment was correlated with anti-HCV positivity. A high prevalence of 96.7% (Group 2) was found in patients who underwent more than 5 years of treatment. Our results suggest that anti-HCV core ELISA is more accurate for detecting HCV infection than anti-c100/3. Although the risk associated with the duration of HD treatment and blood transfusion was high, additional factors such as a significant non-transfusional spread of HCV seems to play a role as well. The identification of infective patients by more sensitive methods for HCV genome detection should help to control the transmission of HCV in the unit under study.Dois grupos de pacientes em tratamento hemodialítico foram avaliados quanto às respostas de anticorpos contra as proteínas não estrutural c100/3 (anti-c100/3) e estrutural core (anti-HCV core) do vírus da hepatite C (HCV). Quarenta e seis pacientes (Grupo 1) nunca apresentaram alterações dos níveis de alanina aminotransferase (ALT) durante o tratamento hemodialítico, ao passo que 52 pacientes (Grupo 2) têm ou já tiveram elevações desta enzima hepática. Em pacientes sem alterações bioquímicas evidentes (Grupo 1) foram encontradas prevalências de 32.6% e 41.3% para anti-c100/3 e anti-HCV core, respectivamente. No Grupo 2, estas prevalências foram de 71,15% e 86,5%. Um teste composto de peptídeos estruturais e não estruturais imobilizados separadamente e dispostos em bandas paralelas em fitas de nailon, foi usado como teste confirmatório. A infecção pelo HBV, avaliada pela presença de anticorpos anti-HBc foi observada em 39.8% dos pacientes; 6 eram portadores crônicos de HBsAg e 13 possuiam anti-HBs adquiridos naturalmente. O tempo de tratamento hemodialítico teve correlação com a positividade para anti-HCV. A prevalência de 96,7% (Grupo 2) foi encontrada em pacientes que tiveram mais de 5 anos de tratamento. Nossos resultados sugerem que o anti-HCV core é um marcador mais preciso para detectar a infecção pelo HCV do que o anti-c100/3. Apesar dos riscos associados com a duração do tratamento e transfusões sanguíneas, uma significante disseminação não transfusional do HCV parece ocorrer dentro da unidade. A identificação de pacientes infectantes por métodos sensíveis como a detecção do genoma viral deverá auxiliar no controle da transmissão do HCV na unidade em estudo.