Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.

Hepatite auto-imune / Autoimmune hepatitis

Os autores fazem revisäo da literatura médica a respeito da hepatite auto-imune, enfatizando os aspectos laboratoriais, clínicos e terapêuticos desta entidade. Discutem a importância dos auto-anticorpos, mostrando a proliferaçäo de novos marcadores imunológicos e detalhando a sua utilizaçäo no diagnóstico e terapêutica. Por fim, ressaltam a importância do diagnóstico acertado e precoce, já que se trata de uma doença em que a terapia imunossupressiva prolonga muito a sobrevida.

Vírus da hepatite C: este inimigo oculto / Hepatitis C viruses: this hidden enemy

Os autores fazem uma revisao a respeito do vírus da hepatite C (VHC). Enfatizam sua importância epidemiológica, principalmente devido ao desconhecimento em relaçao à transmissao nos casos "esporádicos", que somam cerca de 50 por cento, e à ampla disseminaçao mundial. O tratamento da doença hepática crônica pelo VHC encontra-se em um momento de expectativa e frustraçao, já que o interferon, além de baixa eficácia, tem custo muito elevado. Muito há que se pesquisar e aprender a respeito deste vírus, um inimigo astuto que muitas vezes ataca de forma desconhecida e deixa seqüelas importantes, quando nao leva ao êxito letal.