GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature

Review GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature Impacto da gama glutamiltransferase na resposta terapêutica da hepatite C crônica: revisão sistemática da literatura Maria de Lourdes Albuquerque de QUEIROGA1  2  Raymundo PARANÁ1  José Eymard Moraes de MEDEIROS FILHO3  Giovannini Cesar A FIGUEIREDO2  Ananda Peixoto de ARAÚJO2  Hagley Walson Soares LEITE2  Itiel de Souza AQUINO2  Leonardo Honório de A MELO NETO2  1Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina, Universidade Federal da Bahia, Salvador, BA. 2Centro de Ciências Biológicas e da Saúde, Unidade Acadêmica de Ciências Médicas, Curso de Medicina, Universidade Federal de Campina Grande, PB. 3Universidade Federal da Paraíba, João Pessoa, PB. Brasil. ABSTRACT Background The standard treatment of chronic hepatitis C is the administration of pegylated interferon α2a or α2b in combination with ribavirin, but adverse effects can be observed, as well as the high cost of this therapy. Therefore, there is interest in understanding the predictors of sustained virologic response, as the gamma glutamyltransferase. Objective To evaluate the serum levels of gamma glutamyltransferase as a predictor of response to treatment with pegylated interferon α and ribavirin in chronic hepatitis C. Methods This is a systematic review of literature, conducted by consulting PUBMED, LILACS, MEDLINE, SCOPUS, Cochrane electronic databases, and active search of articles selected between January 2000 and April 2013. Results A total of 4,785 titles were iden tified. Out of those material, following inclusion and exclusion criteria, 273 abstracts were selected, by two independent researchers. After reading those texts, the reviewers consensually included ten studies for systematization and classification, according to the criteria of the Oxford Scale. 1B studies are predominant (prospective cohort study - six studies). Rapid virologic response and early virological response were considered as estimates for the sustained virological response. The frequency of virologic response was identified in three studies and early virological response in two, with a total of 392 and 413 patients, respectively; sustained virologic response was reported in nine articles corresponding to 3,787 patients (76.5 %). Conclusion Gamma glutamyltransferase is a predictor of sustained virologic response in the treatment of chronic hepatitis C with pegylated interferon α2a or α2b associated with ribavirin. Key words: Gamma glutamyltransferase; Hepatitis C; Sustained virological response; Review RESUMO Contexto O tratamento padrão da hepatite C crônica consiste na administração de interferon peguilado α2a ou α2b associado à ribavirina. Contudo, podem ser observados efeitos adversos além do alto custo desta terapêutica. Por isso há interesse no conhecimento dos fatores preditivos de resposta virológica sustentada como a gama glutamiltransferase. Objetivo Avaliar os níveis séricos da gama glutamiltransferase como fator preditivo de resposta terapêutica com interferon peguilado α e ribavirina na hepatite C crônica. Métodos Trata-se de uma revisão sistemática da literatura, conduzida através de consulta às bases eletrônicas de dados PUBMED, LILACS, MEDLINE, SCOPUS e COCHRANE, e busca ativa das referências dos artigos selecionados, no período de janeiro de 2000 a abril de 2013. Resultados Foram identificados 4.785 títulos. Destes, seguindo os critérios de inclusão e exclusão, foram selecionados 273 resumos para a leitura por dois pesquisadores independentes. Após a leitura dos artigos, na íntegra e em consenso, os revisores incluíram dez estudos, para sistematização e qualificação, segundo os critérios da Escala de Oxford. Predominaram os estudos 1B A (Coorte prospectivo - seis estudos), publicações da Alemanha. A frequência de resposta virológica rápida foi identificada em três estudos e resposta virológica precoce em dois estudos, com um total de 392 e 413 pacientes respectivamente; a resposta virológica sustentada foi registrada em nove artigos correspondendo a 3.787 pacientes (76,5%). Conclusão O nível sérico da gama glutamiltransferase é um fator preditivo de resposta virológica sustentada no tratamento da hepatite C crônica com interferon peguilado α2a ou α2b associado à ribavirina. Palavras-Chave: Gama glutamiltransferase; Hepatite C; Resposta virológica sustentada; Revisão INTRODUCTION All over the world the hepatitis C virus (HCV) has been recognized as a major cause of chronic liver disease(21, 28), representing a public health problem. About 170 million (3%) of the world’s population is infected with HCV(28, 31), and may develop liver disease, including cirrhosis and hepatocellular carcinoma(16). In Brazil, Inquérito Nacional de Hepatites Virais (National Survey of Viral Hepatitis) estimated the prevalence of 1.38% for the antibody to HCV(24). The pattern of chronic hepatitis C (CHC) treatment can be started with pegylated interferon (PEG-IFN) α2a or α2b associated with ribavirin (RBV) for genotype 1, 4-6 for 48 weeks, but for genotypes 2 and 3 for 24 weeks(9, 23). The treatment of CHC is costly, and may have side effects. In addition, some factors contribute to the limited rate of sustained virologic response (SVR) of 50 % to 60 % as occurs in genotypes 1 and 4. Thus, before starting the treatment of CHC it is important to assess the predictive of therapeutic response to define who should be treated and when this treatment will be over(8). There are several therapeutic response predictor factors in CHC, such as age at infection, gender, hepatic fibrosis, genotype, viral load, virologic response, and gamma glutamyltransferase (GGT) levels(8). It is important to highlight other predictors of therapeutic response: serum vitamin D(14, 25); and CC (rs 12979860) Interleukin 28B genotype(1, 22, 27). The GGT enzyme catalyzes the degradation of extracellular glutathione (GSH) in the transfer of amino acids and peptides across cell membranes(15, 19), forming a “gamma-glutamyl cycle”(30). GGT is located in hepatocytes, kidney, biliary tract, intestines, heart, spleen, pancreas, and brain(22). However, it may be elevated in liver dysfunction, cholestasis, use of hepatotoxic drugs, as a marker of alcohol intake in pancreatitis, and association with coronary heart diseases risk(3, 19, 30). Despite many studies, there are no conclusive data on the prediction of therapeutic response of GGT. Therefore, there is interest in understanding the predictive factors of SVR and GGT. Therefore, the aim of this systematic review (SR)(5, 17, 18) was to evaluate the serum levels of GGT as a predictor of treatment response in CHC. METHODS Search strategy To develop the SR we have followed the guidelines of t (...truncated)