Distribution of the human leukocyte antigen class II alleles in Brazilian patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55% of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1%) and HLA-DQB1*02 (52.9 vs 38.7%) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0%) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1%) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.88488

Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.1729173

Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection

Hepatites pós-transfusionais na cidade de Campinas, SP, Brasil: II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo vírus C nos receptores de sangue ou derivados Post-transfusional hepatitis in the city of Campinas, SP, Brazil: II- Presence of anti-HBc and anti-HCV antibodies in blood donors and occurrence of post-transfusional hepatitis C virus in recipients of blood or derivates

Pesquisamos os anticorpos anti-HBc e anti-HCV em amostras de soros provenientes de 799 candidatos a doadores, que tiveram suas unidades de sangue ou derivados transfundidas a 111 receptores. O anti-HBc e o anti-HCV foram reagentes, em respectivamente 9 e 2,1% dos doadores testados. Observamos que entre os 111 receptores, 44 haviam recebido pelo menos uma unidade anti-HBc positiva e 67 haviam sido transfundidos somente com unidades anti-HBc negativas. Houve um risco 4,5 vezes maior de aquisição de hepatite por vírus C pelos receptores que receberam pelo menos uma unidade anti-HBc positiva Se a pesquisa do anti-HBc fosse realizada na triagem sorológica dos doadores de sangue, cerca de 56% dos casos de HVC nos receptores saiam evitados. A população de receptores que recebeu pelo menos uma unidade anti-HCV reagente, apresentou um risco 29 vezes maior de adquirir esta hepatite, quando comparada aos receptores transfundidos com todas as unidades anti-HCV negativas. A realização do teste para a pesquisa do anti-HCV na triagem dos doadores de sangue, preveniria 79% dos casos de HVC pós-transfusionais. Os candidatos a doadores brasileiros parecem ser acometidos simultânea ou sequencialmente, pelos vírus B e C das hepatites, pois, 44,4% dos doadores anti-HCV positivos, também foram anti-HBc positivos. A realização dos testes para as pesquisas dos anticorpos anti-HBc e anti-HCV, nas triagens hemoterápicas, está indicada para prevenir a transmissão de hepatites pós-transfusionais, em nosso meio.<br>We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799 donors which had their blood or derivates transfused to 111 recipients. Anti-HBc and anti-HCV were reactive in respectively 9 and 2.1% of the donors tested. We have observed that among the 111 recipients, 44 had received at least one positive anti-HBc unit and 67 had been transfused only with negative anti-HBc, units. The risk of developing hepatitis C virus was 4.5 times higher for the recipients who received at least one positive anti-HBc unit. If the test for anti-HBc had been made for the blood donors in the serological screening, about 56% of the HCV cases in the recipients could have been avoided. The population of recipients who received at least one reacting unit of anti-HCV, presented a risk 29 times higher of developing this hepatitis, as compared to the transfused recipients with all anti-HCV negative units. Testing blood from donors for anti-HCV would avoid 79% of the post-transfusional HCV cases. Brazilian candidates to blood donors seem to be carriers either simultaneously or sequentially to hepatitis virus B and C, since 44.4% of the positive anti-HCV were also positive for anti-HBc. Testing for anti-HBc and anti-HCV in blood screening must be indicated in order to prevent post-transfusional hepatitis transmission in our community

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.<br>A determinação dos níveis de alanina aminostransferase (ALT) tem sido útil para o diagnóstico de hepatopatias. Ultimamente, a elevação dos níveis séricos de ALT em doadores de sangue, tem sido associada a um maior risco de hepatites pós-transfusionais. Este estudo busca identificar os fatores associados com elevados níveis de ALT entre doadores voluntários de sangue e avaliar as relações entre estes aumentos de ALT e o desenvolvimento de infecção pelo vírus da hepatite C. Assim, 116 doadores voluntários de sangue com níveis de ALT elevados, quando da primeira doação, foram estudados. Todos foram questionados sobre hepatopatias prévias, exposição a hepatites, exposição a produtos químicos, uso de drogas ou medicamentos, comportamento sexual, contacto com sangue ou secreções e consumo de álcool. A cada 3 meses foram medidos os níveis de AST, ALT, fosfatase alcalina, gama-glutamil transferase, colesterol, triglicérides e glicemia durante o período de 1-2 anos. Os níveis séricos de hormônios tireoidianos e a presença de auto-anticorpos também foram mensurados. Ultrassonografia abdominal foi realizada em todos os pacientes com elevação persistente dos níveis de AST ou ALT. Foi realizada biópsia hepática em 9 doadores sem diagnóstico definido após investigação clínica. A presença de anticorpos anti-HCV foi novamente pesquisada em 116 doadores no momento da primeira avaliação clínica. Ao final do follow-up (2 anos) 71 doadores foram re-testados para a presença do anti-HCV. Nenhum doador se tornou reagente para os marcadores dos virus da hepatite B ou hepatite C, durante o seguimento. Dos 116 doadores, 101 (87%) mantiveram níveis séricos de ALT persistentemente aumentados. Obesidade e alcoolismo foram as principais condições associadas à elevação dos níveis séricos de ALT em 91/101 (90,1%) doadores. Hipertrigliceridemia, hipercolesterolemia, hipotireoidismo e diabetes mellitus também se associaram a níveis aumentados de ALT. Somente 1/101 (0,9%) apresentou hepatite crônica ativa não A-G e 3/101 (2,9%) apresentaram biópsia hepática com diagnóstico de hepatite reacional. A determinação rotineira dos níveis de ALT, em bancos de sangue não foi útil para detectar doadores infectados com o vírus da hepatite C no Brasil no período que antecede a soroconversão para anti-vhc

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon