Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil

ABSTRACT: Soroprevalence for Hepatitis C virus is reported as 2.12% in Northern Brazil, with about 50% of the patients exhibiting a sustained virological response (SVR). Aiming to associate polymorphisms in Killer Cell Immunoglobulin-like Receptors (KIR) with chronic hepatitis C and therapy responses we investigated 125 chronic patients and 345 controls. Additionally, 48 ancestry markers were genotyped to control for population stratification. The frequency of the KIR2DL2 and KIR2DL2+HLA-C^Asp80 gene and ligand was higher in chronic infected patients than in controls (p < 0.0009, OR = 3.4; p = 0.001, OR = 3.45). In fact, KIR2DL3 is a weaker inhibitor of NK activity than KIR2DL2, which could explain the association of KIR2DL2 with chronic infection. Moreover, KIR2DS2 and KIR2DS2+HLA-C^Asp80 (p < 0.0001, OR = 2.51; p = 0.0084, OR = 2.62) and KIR2DS3 (p < 0.0001; OR = 2.57) were associated with chronic infection, independently from KIR2DL2. No differences in ancestry composition were observed between control and patients, even with respect to therapy response groups. The allelic profile KIR2DL2/KIR2DS2/KIR2DS3 was associated with the chronic hepatitis C (p < 0.0001; OR = 3). Furthermore, the patients also showed a higher mean number of activating genes and a lower frequency of the homozygous AA profile, which is likely secondary to the association with non-AA and/or activating genes. In addition, the KIR2DS5 allele was associated with SVR (p = 0.0261; OR = 0.184).The ancestry analysis of samples ruled out any effects of population substructuring and did not evidence interethnic differences in therapy response, as suggested in previous studies.

Soroprevalência da infecção pelo Vírus da hepatite B e Vírus da hepatite C em mulheres profissionais do sexo em Augusto Corrêa, Barcarena, Belém e Bragança - Pará, Brasil

Segundo a Organização Mundial de Saúde (OMS), existem no mundo, aproximadamente, 350 milhões de pessoas infectadas cronicamente pelo VHB e outras 170 milhões com infecção crônica pelo VHC. Assim, o presente trabalho teve como objetivo verificar a incidência da infecção pelos VHB e VHC e analisar possíveis fatores de risco entre 365 mulheres profissionais do sexo no Estado do Pará, sendo 32 participantes em Augusto Corrêa, 99 em Barcarena, 175 em Belém e 59 em Bragança. Destas participantes foram colhidas amostras de sangue , sendo os plasmas analisados por meio de um ensaio imunoenzimático e características epidemiológicas foram coletadas por meio de um questionário epidemiológico. Os resultados revelaram uma prevalência da infecção pelo VHB de 63,6%, sendo que para o HBsAg foi de 1,1% e para o anti-HBc de 61,9%. A soroprevalência do anti-VHC foi de 7,7% e, no que se refere à sororreatividade ao VHB e VHC simultaneamente foi de 4,4%. Entre as participantes, a imunização ao VHB foi observada em apenas 4,7% e 29,0% demonstraram suscetibilidade à infecção pelo VHB e VHC. Houve uma correlação significativa entre a soropositividade para os marcadores virais do VHB com a baixa renda familiar, o desconhecimento de doença hepática sob forma de hepatite e o uso ocasional do preservativo nas relações sexuais. Entretanto, não houve essa correlação entre as variáveis epidemiológicas com a sororreatividade para o marcador do VHC. Assim, as prevalências de infecção pelo VHB e o VHC na população de mulheres profissionais do sexo do Estado do Pará revelam padrão de intensa circulação desses vírus nessa população.

Evaluation of the therapeutic response of hepatitis C in coinfected patients (HIV/HCV): a study of cases from a hospital for chronic liver diseases in the Eastern Brazilian Amazon

INTRODUCTION: The aim of this study was to evaluate the therapeutic response of hepatitis C in patients coinfected with human immunodeficiency virus (HIV-1). METHODS: A retrospective study of 20 patients coinfected with HIV-1/HCV who were treated in the outpatient liver clinic at the Sacred House of Mercy Foundation Hospital of Pará (Fundação Santa Casa de Misericórdia do Pará - FSCMPA) from April 2004 to June 2009. Patients were treated with 180µg PEG interferon-α2a in combination with ribavirin (1,000 to 1,250mg/day) for 48 weeks. The end point was the sustained virological response (SVR) rate (HCV RNA negative 24 weeks after completing treatment). RESULTS: The mean age of the patients was 40±9.5 years, of which 89% (n=17) were male, and the HCV genotypes were genotype 1 (55%, n=11/20), genotype 2 (10%, n=2/20) and genotype 3 (35%, n=7/20). The mean CD4+ lymphocyte count was 507.8, and the liver fibrosis stages were (METAVIR) F1 (25%), F2 (55%), F3 (10%) and F4 (10%). The early virological response (EVR) was 60%, the end-of-treatment virological response (EOTVR) was 45% and the SVR was 45%. CONCLUSIONS: The median HCV viral load was high, and in 85% of cases in which highly active antiretroviral therapy (HAART) was used, none of the patients with F3-F4 fibrosis responded to treatment. Of the twenty patients treated, 45% achieved SVR and 45% achieved EOTVR. Studies that include cases from a wider region are needed to better evaluate these findings.