Pacientes com insuficiência renal crônica em hemodiálise apresentam níveis séricos mais baixos de alanina aminotransferase. Para estabelecer melhor ponto de corte nos níveis de ALT, no diagnóstico da hepatite C, avaliaram-se mensalmente, durante 6 meses os níveis desta enzima em 235 pacientes em hemodiálise, sendo excluídos aqueles que apresentassem média acima do limite superior da normalidade. O ponto de corte foi identificado através da construção de curva ROC. Entre 202 pacientes, 15 (7,4%) apresentavam anti-VHC positivo e 187 (92,6%) negativo, com média de ALT de 0,7 e de 0,5 do limite superior (p < 0,0001), respectivamente. O ponto de corte para ALT situou-se em 0,6 do limite superior, com sensibilidade de 67% e especificidade de 75% na identificação do anti-VHC. Sugere-se que os limites superiores de normalidade da ALT sejam reduzidos para 60% dos limites convencionais, quando se avaliam pacientes com IRC em hemodiálise.

The patients with chronic renal failure in hemodialysis present low levels of serum alanine aminotransferases. In order to establish a better cutoff value for ALT in hepatitis C screening of hemodialysis patients, the ALT levels were measured monthly in 235 patients, being excluded those that presented average above the upper limit of normality. The cutoff value was identified by construction of a ROC curve (receiver operating characteristic). Among 202 patients, 15 (7.4%) presented antibodies to hepatitis C virus (anti-HCV) and 187 (92.6%) were anti-HCV negative , with an ALT average of 0.7 and of 0.5 from ULN (p <0.0001), respectively. The better cutoff value for ALT was at 0.6 from ULN, with sensitivity of 67% and specificity of 75% in anti-HCV screening. These results suggest that ULN of ALT could be reduced for 60% from conventional limit, when we are evaluating patients with CRF in hemodialysis.

We describe a treatment made with interferon-alpha (IFN-alpha) plus ribavirin of two patients with membranoproliferative glomerulonephritis (MPGN) induced by hepatitis C virus (HCV): Case 1 was a 22-year-old woman with leg and facial edema, hypertension and proteinuria, whose liver biopsy revealed chronic active hepatitis; and Case 2 was a 42-year-old man with anasarca, hypertension and proteinuria, whose liver biopsy indicated cirrhosis. Both had anti-HCV, HCV-RNA and cryoglobulins. IFN-alpha (3 million units (MU), 3 times/week) and ribavirin (1 g/day) were administered for 12 months. The drugs were well tolerated by both patients. Serum alanine aminotransferase (ALT) levels normalized and HCV-RNA became negative. Cryoglobulins disappeared and an improvement in renal disease was seen after 6 months of therapy. However, after 9 months, Case 2 presented ALT elevation, and proteinuria was detected. Two years after the end of therapy, both patients were negative in repeated HCV-RNA and cryoglobulin tests. Case 1 was asymptomatic, with normal liver and renal tests, and Case 2 had normal blood pressure, with mild edema of the ankles. Based on the evolution of these two cases, the association of IFN-alpha and ribavirin may be a therapeutic option for patients with MPGN related to HCV.

Descrevem-se pacientes com glomerulonefrites (GNs) associadas à infecção pelo vírus da hepatite C (HCV). Entre agosto de 93 e julho de 96 foram observados 4 pacientes, com idade mediana de 41 anos, sendo 2 do sexo masculino. Pesquisaram-se o anti-HCV por ensaio imuno-enzimático e o HCV-RNA por PCR. Também foram pesquisadas crioglobulinas séricas, hemácias dismórficas no sedimento urinário e proteinúria de 24h. Viremia, crioglobulinas, hematúria e proteinúria foram observadas nos 4 pacientes. As biópsias hepáticas revelaram atividade inflamatória nos 3 pacientes em que foram realizadas e as do rim revelaram glomerulonefrite membranoproliferativa em 3 e glomerulonefrite proliferativa mesangial em 1 paciente. Dois pacientes vêm recebendo antivirais (IFN associado à ribavirina) e evoluindo com melhora. A presença de viremia e de hepatite concomitante com as alterações urinárias constituem indícios do envolvimento viral na glomerulopatia. Tais achados são reforçados pela melhora das alterações urinárias durante o tratamento específico. Conclui-se que a pesquisa de marcadores virais em pacientes com GNs assume relevância na medida em que pode modificar a conduta terapêutica.

We report 4 patients with glomerulonephritis (GN) associated with hepatitis C virus (HCV) infection seen between August 1993 and July 1996. Two of them were male and median age was 41 years. Anti-HCV was detected by enzyme-immunoassay and HCV-RNA by PCR. Serum cryoglobulins, 24-hour proteinuria, and erythrocyte dismorphism were also determined. Viremia, cryoglobulinemia, hematuria and proteinuria were observed in all patients. Liver biopsies revealed inflammatory activity in 3 cases, and renal biopsies revealed membranoproliferative glomerulonephritis in 3 patients and mesangial proliferative glomerulonephritis in 1 patient. Two patients are on specific therapy for HCV infection (IFN in combination with ribavirin) and have presented clinical and laboratory improvement. The occurrence of active liver disease and viremia concurrent with urinary alterations suggests viral involvement in renal disease, a conclusion supported by the by improvement of urinary alterations observed after treatment for HCV. We conclude that the search for viral markers in patients with GN is important since their detection could change the therapeutic approach.

Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos.

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.