No abstract

The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

Although progression of fibrosis in the chronic hepatitis C depends on environmental, viral, and host factors, genetic polymorphisms have been associated recently with this progression, including the expression of integrins, adhesion proteins. Some integrins expressed on the platelet membrane show polymorphic antigenic determinants called human platelet antigens (HPA), where the major ones are HPA-1, -3, -5. The association between HCV infection and HPA-5b has been demonstrated. Similarly, the HPA profile could determine if HPA is related to progression of fibrosis. The goal of this study was to evaluate the association between the frequencies of HPA-1, -3, and -5 and degree of fibrosis in HCV-infected patients. Genomic DNA from 143 HCV-infected patients was used as the source for HPA genotyping by PCR-SSP or PCR-RFLP. Progression of fibrosis was evaluated using the METAVIR scoring system, and the patients were grouped according to degree of fibrosis into G1 (n = 81, with F1, portal fibrosis without septa or F2, few septa) and G2 (n = 62, with F3, numerous septa, or F4, cirrhosis). Statistical analysis was performed using the proportional odds model. The genotypic frequency of HPA-1a/1b was significantly higher in the patients in G2. To evaluate the influence of the time of infection to the development of fibrosis and its effect on the genetic factor HPA-1, 96 patients from 143 studied were evaluated considering the time of HCV infection, and these results suggest that the HPA-1a/1b genotype promotes the development of fibrosis in HCV infection with time.

Devido à similaridade nas rotas de transmissão, a co-infecção HIV/HCV é freqüente, afetando em média 30 a 50% dos portadores de HIV. O presente estudo visou avaliar uma possível associação entre os subtipos do HIV e genótipos do HCV em pacientes co-infectados, com base na análise das freqüências em pacientes mono e co-infectados. Para determinação da freqüência dos subtipos HIV e genótipos HCV, foram analisados respectivamente 124 e 496 pacientes mono-infectados. O estudo da co-infecção foi realizado num grupo de 150 pacientes HIV positivos e esteve presente em 22 (14,7%) dos pacientes. A freqüência dos subtipos do HIV-1 em mono-infectados foi: subtipo B (85,5%), subtipo F (12,9%) e recombinante B/F (1,6%), enquanto nos genótipos HCV foi: 1a (25%), 1b (29,4%), 1a/1b (3,6%), 3a (35%), 2 (1,8%) e 5 (0,4%). Nos co-infectados o padrão de distribuição dos subtipos HIV-1 é semelhante aos mono-infectados, ou seja, subtipo B (85,0%), seguido do subtipo F (15,0%). A distribuição de freqüência de genótipos HCV nos co-infectados foi: 1a (36,3%), 1b (27,3%), 1a/1b (9,1%) e 3a (27,3%) mostrando um aumento de 10% na freqüência do genótipo 1, queda de 7,7% no genótipo 3 e ausência de outros genótipos. A análise estatística de associação entre os subtipos HIV e genótipos HCV (Goodman) mostrou que no genótipo 1 (HCV) ocorreu predominância do subtipo B, enquanto no genótipo 3 (HCV) a distribuição dos subtipos B e F (HIV-1) foi casual. Isto aponta para a necessidade de mais estudos desse grupo e um maior valor amostral.

The combination of pegylated interferon (PEG-INF) and ribavirin is currently the best treatment for chronic hepatitis C, providing a sustained virological response (SVR) in 54%-63% of patients. In patients infected with hepatitis C virus (HCV) genotype 1, the SVR rate is 42%-52%. To evaluate the treatment efficacy of this drug combination, we conducted an open, prospective study of 58 consecutive treatment-naïve patients infected with HCV genotype 1 and treated at a university hospital, comparing those presenting an SVR (SVRs), nonresponders (NRs), and relapsers (RELs). Among the intent-to-treat patients, an end-of-treatment virological response was achieved in 69% of the sample as a whole and in 52% of the SVRs. We found that being an SVR was significantly associated with mild fibrosis (p = 0.04) and with undetectable HCV RNA at weeks 12 and 24 of treatment (p < 0.0001). Comparing the SVR and REL groups, we observed that being older than 40 was significantly associated with being a REL (p = 0.04). Being an NR was found to be associated with severe fibrosis and moderate inflammatory infiltrates (portal or periportal). In the polytomous logistic regression, no independent factors were associated with the REL group when compared with the SVR group. We conclude that RELs and NRs differ in comparison with SVRs. The RELs accounted for 17% of the sample. The HCV RNA test results at weeks 12 and 24 of treatment, although independent predictors of non-response (OR: 4.8 and 8.2, respectively), did not differ between SVRs and RELs.