Ação do fator promotor do crescimento do hepatócito na hepatite C

Abstract

Resumo: O interferem foi o primeiro agente a se mostrar benéfico no tratamento da hepatite C, porém, as chances de resposta sustentada após curso de 6 meses são de somente 10% a 20%. Alguns estudos atuais comprovam que a associação do interferon com a ribavirina forneçe melhores resultados.Em 1987, pesquisadores chineses do Hospital das Forças Aéreas, localizado em Guangzhou, China, extraíram do fígado de porco recém-naio uma substância denominada Promoting hepatoeyte growth factor (PHGF) que funcionaria como um estimulador do crescimento do hepatócito. Para tanto, agiria a nível do DNA do hepatócito promovendo síntese e divisão celular, com efeitos antifibrose e antinflamatório. Investigações recentes sugerem que o PHGF possa agir no tratamento das hepatites virais. O trabalho desenvolveu um estudo randomizado e controlado do uso endovenoso do PHGF em 18 pacientes com diagnóstico histológico de hepatite crônica ativa ou cirrose hepática em atividade e RNA-VHC positivo. Todos os pacientes apresentavam aumento da ALT por um período mínimo de 12 meses. Outras causas de hepatopatia foram afastadas(viral, auto-imune, medicamentosa, metabólica e alcoólica).O estudo foi aprovado pela Comissão de Ética do Hospital Universitário Clementino Fraga Filho, Rio de Janeiro.O tratamento foi instituído durante 3 meses e, mensalmente, eram tomadas amostras de sangue para análise do hemograma, leucograma, contagem de plaquetas, TAP e dosagem da ALT. Determinações da carga virai antes e no final do tratamento foram feitas pelo teste Amplicor HCV Monitor - Roche. Todos os pacientes finalizaram o tratamento, sem a ocorrência de efeitos colaterais atribuíveis a medicação. Em três pacientes a ALT normalizou durante o uso do PHGF ( 16.9%), com retorno aos valores basais pré-tratamento, após a interrupção do tratamento. Porém, em relação ao grupo controle os valores da ALT diminuíram sensivelmente no grupo tratado, com significância estatística. Apesar da análise média da carga virai ter mostrado nítida diminuição, estatisticamente significativa, nenhum paciente tratado apresentou negativação do RNA-VHC. Os resultados mostram que a ação do PHGF se fez no processo inflamatório sem influir na replicação virai, sugerindo ação um pouco semelhante à da ribavirina. Seria interessante novo estudo da droga em associação com o interferon.

Abstract: Although treatment with interferon for chronic hepatitis C virus infection is widely available, sustained responses occur in only 10 to 20% of patients. In 1987, Dr. Zhang Yijun et al of Guangzhou Hospital of Air Force-China prepared Promoting Hepatocyte Growth Factor (PHGF) from suckling pig liver, and applied it to the clinics. Now it has already been proved that PHGF has the function of promoting hepatocellular DNA synthesis, cell division and an antifibrotic effect. It has been reported as having a therapeutic effect in various liver diseases as well as increasing the survival rate in fulminant hepatic failure. We carried out a randomizedcontrolled study to demonstrate the efficacy of the PHGF I.V. in virus C hepatitis. We investigated biochemical and virological responses and the safety of treatment. Patients were entered into the trial if they had biopsy findings consistent with a diagnosis of C hepatitis and were positive for antibodies to hepatitis C virus. Seven men and eleven women - mean age 59.5 years, met the criteria and were included in the study. Eleven patients had acquired hepatitis from blood transfusions, and seven had no know source of infection. All patients had raised serum ALT concentrations for a minimum of 12 months before entry into the study. No patients had markers for hepatitis B virus infection or human immunodeficiency virus infection, or alcoholic, drug-related, autoimmune, or metabolic liver disease, and none had received antiviral or immunomodulatory therapy before study entry. Prestudy liver biopsy showed that 14 patients had chronic active hepatitis and 4 had cirrhosis. The trial was approved by the Ethical Committee of the University Hospital Clementino Fraga Filho, Rio de Janeiro- Brazil. All patients were treated with 80mg of I.V. PHGF daily for 4 weeks and thereafter 160mg per day for 8 weeks. Side effects were monitored by questioning and examination. Haemoglobin, white cells, platelets, differential blood cells counts including granulocyte counts, and PT were measured before the start of therapy and at weeks 4, 8 and 12 during treatment. Statistical analyses used the Wilcoxon signed rank test.This study has demonstrated: Serum ALT concentrations decreased in almost all patients during PHGF therapy and in three patients they normalized, but returned to pretreatment concentrations after end of treatment. There was no side effects. HCVRNA was determined in sera at baseline and three months( end of therapy). None of the patients lost HCV-RNA, but there was a important decreased in HCV-RNA titer ( Amplicor quantitative PCR assay-Roche).