Poor response to hepatitis C treatment in elderly patients.

INTRODUCTION: Treatment of genotype 1 chronic hepatitis C in elderly patients has been associated with low rates of a sustained virological response (SVR), but the reasons are unclear. OBJECTIVE: To determine the SVR rate in patients ≥ 60 years with genotype 1 chronic hepatitis C treated with Peg-IFN and ribavirin, and to identify risk factors related to treatment response in this specific group of patients. Material and methods. Patients were divided into < 60 years (non-elderly) and ≥60 years (elderly) and were compared regarding clinical, laboratory and histological characteristics and response to treatment. RESULTS: A total of 231 patients were included in the study. The elderly group (n=89) presented a predominance of women, more advanced hepatic disease, higher glucose, cholesterol and LDL levels, lower hemoglobin levels, and a larger proportion of overweight subjects. The SVR rate was lower (25% vs 46%) and anemia, ribavirin dose reduction and use of filgrastim and erythropoietin were more frequent in elderly patients. Negative predictive factors of SVR in the whole group (n = 231) were glucose ≥ 100 mg/dL and age ≥ 60 years. In the elderly group, only pretreatment variables (lower serum glucose and higher hemoglobin levels) were associated with SVR. CONCLUSION: The SVR rate was low in elderly patients. However, this poor response was not due to poor tolerance, but mainly to pretreatment conditions. Among elderly patients, the best candidates for hepatitis C treatment are those with elevated pretreatment hemoglobin levels and adequate glycemic control.

Evidence of a significant role for Fas-mediated apoptosis in HCV clearance during pegylated interferon plus ribavirin combination therapy.

BACKGROUND: The role of apoptosis in treatment-induced HCV clearance is controversial. We sought to assess the kinetics of serum apoptosis-related cytokines during pegylated interferon-α2a or -α2b plus weight-based ribavirin therapy for genotype 1 chronic HCV infection. METHODS: Serum levels of soluble Fas (sFas), soluble Fas ligand (sFasL) and soluble tumour necrosis factor receptor I (sTNF-RI) were measured at baseline, week 12 and 24 weeks after the end of therapy. RESULTS: Sustained virological response (SVR) was achieved in 46% of the 164 included patients, 29% had a non-response (NR) and 25% had relapse (RR). NR patients presented with higher levels of sFasL at baseline and lower levels of sTNF-RI at week 12 as compared to RR and SVR patients. Lower concentrations of sFas were observed in SVR patients 24 weeks after treatment as compared to RR and NR patients. An increase in sFas at week 12 followed by a significant drop 24 weeks after therapy was observed among SVR patients. An increase in sFasL during and after treatment was observed in RR and SVR patients. NR patients exhibited an earlier drop in sTNF-RI levels as compared to RR and SVR patients. CONCLUSIONS: Virological response during HCV therapy was associated with an increase of sFas and sFasL, and maintenance of increased concentrations of sTNF-RI.

Gender influence on treatment of chronic hepatitis C genotype 1.

INTRODUCTION: Although various studies have been published regarding the treatment of chronic hepatitis C (CHC) with peginterferon (Peg-IFN) and ribavirin, little is known regarding the real impact of gender on the characteristics that influence the effectiveness and safety of antiviral treatment for CHC patients. The objective of this study was to evaluate the influence of gender on HCV treatment outcomes. METHODS: A retrospective analytical study was conducted among selected carriers of CHC genotype 1, who were treated with Peg-IFN alpha-2b at a dose of 1.5 microg/kg or Peg-IFN alpha-2a at a dose of 180 microg/week plus a ribavirin dose of 1,000-1,250 mg/day, according to weight, between 2001 and 2007. RESULTS: Among 181 patients undergoing treatment, the mean age was 46.4 +/- 11.0 years and 46% were women. At baseline, 32% of the patients had advanced fibrosis (F3-F4 Scheuer), and 83% of the subjects had viral load > 400,000 IU/ml, without significant difference between the genders (p = 0.428 and p = 0.452, respectively). When compared with men, women had higher incidence of many adverse events such as anemia (p < 0.001) and higher need for dose reduction, for both Peg-IFN (p = 0.004) and ribavirin (p = 0.006). However, the rate of sustained virological response (SVR) did not differ between the genders: 45% (female) vs 41% (male); p=0.464. CONCLUSIONS: This study suggests that women and men react differently to combined therapy, especially in relation to the incidence of adverse events and the need for dose modification. Nevertheless, these differences do not influence the SVR rate.

Gender influence on treatment of chronic hepatitis C genotype 1 / Influência do gênero no tratamento da hepatite C crônica genótipo 1

INTRODUCTION: Although various studies have been published regarding the treatment of chronic hepatitis C (CHC) with peginterferon (Peg-IFN) and ribavirin, little is known regarding the real impact of gender on the characteristics that influence the effectiveness and safety of antiviral treatment for CHC patients. The objective of this study was to evaluate the influence of gender on HCV treatment outcomes. METHODS: A retrospective analytical study was conducted among selected carriers of CHC genotype 1, who were treated with Peg-IFN α-2b at a dose of 1.5 μg/kg or Peg-IFN α-2a at a dose of 180 μg/week plus a ribavirin dose of 1,000-1,250 mg/day, according to weight, between 2001 and 2007. RESULTS: Among 181 patients undergoing treatment, the mean age was 46.4 ± 11.0 years and 46 percent were women. At baseline, 32 percent of the patients had advanced fibrosis (F3-F4 Scheuer), and 83 percent of the subjects had viral load > 400,000 IU/ml, without significant difference between the genders (p = 0.428 and p = 0.452, respectively). When compared with men, women had higher incidence of many adverse events such as anemia (p < 0.001) and higher need for dose reduction, for both Peg-IFN (p = 0.004) and ribavirin (p = 0.006). However, the rate of sustained virological response (SVR) did not differ between the genders: 45 percent (female) vs 41 percent (male); p=0.464. CONCLUSIONS: This study suggests that women and men react differently to combined therapy, especially in relation to the incidence of adverse events and the need for dose modification. Nevertheless, these differences do not influence the SVR rate.

INTRODUÇÃO: Apesar dos vários estudos publicados a respeito do tratamento da hepatite C crônica (CHC) com Peg-Interferon (Peg-IFN) e ribavirina, se desconhece o real impacto do gênero sobre as características que influenciam a eficácia e a segurança da terapia antiviral em portadores de CHC. O objetivo deste estudo foi avaliar a influência do gênero no tratamento da CHC. MÉTODOS: Foi realizado um estudo analítico retrospectivo de portadores de CHC genótipo 1 tratados com Peg-IFN α-2b na dose de 1,5μg/kg ou Peg-IFN α-2a na dose de180μg/sem associado à ribavirina 1.000-1.250 mg/dia, de acordo com o peso, entre 2001 e 2007. RESULTADOS: Entre 181 pacientes submetidos ao tratamento, a média de idade foi de 46,4±11,0 anos e 46 por cento eram mulheres. No pré-tratamento, 32 por cento dos pacientes apresentavam fibrose avançada (F3-F4 Scheuer), e 83 por cento dos indivíduos apresentavam carga viral >400.000IU/mL, sem diferença significativa entre os gêneros (p=0,428 e p=0,452, respectivamente). Quando comparadas aos homens, as mulheres exibiram maior incidência de eventos adversos como anemia (p<0,001) e maior necessidade de redução de dose tanto do Peg-IFN (p=0,004) quanto da ribavirina (p=0,006). Entretanto, as taxas de resposta virológica sustentada (RVS) não diferiram entre os gêneros (45 por cento (mulheres) . vs 41 por cento (homens); p=0,464). CONCLUSÕES: Este estudo sugere que homens e mulheres reagem à terapia combinada de forma diferente, especialmente com relação aos eventos adversos e à necessidade de modificação de dose. No entanto, essas diferenças não influenciam as taxas de RVS.

Ocorrência de hepatites virais em profissionais da área de saúde / Occurrence of viral hepatitis among health care workers

Profissionais da área de saúde (PAS) apresentam maior risco ocupacional de aquisiçäo de determinadas doenças, principalmente as transmissíveis por sangue ou derivados, como as hepatites B e C. Entre 1986 e 1998 foi realizado levantamento dos casos de hepatites virais que ocorreram em PAS atendidos no Ambulatório de Hepatites da Disciplina de Gastroenterologia da Escola Paulista de Medicina/Unifesp. Os PAS foram divididos em três categorias: médicos, pessoal de enfermagem (enfermeiras, auxiliares, atendentes) e outros profissionais (dentistas, biomédicos e técnicos de laboratório). Dentre os 4.211 pacientes com hepatite atendidos neste período, 141 (3,3 por cento) foram em PAS, sendo 39,7 por cento no pessoal de enfermagem, 35,5 por cento em outros profissionais e 24,8 por cento em médicos. Dos 114 casos, 13,5 por cento foram de hepatite A aguda, 26,9 por cento de B aguda, 26,9 por cento de B crônica, 26,9 por cento de C crônica e 5,8 por cento de hepatite NANB. A hepatite A aguda mostrou predomínio em outros profissionais (42,1 por cento) e médicos (36,9 por cento), seguido pelo pessoal de enfermagem (21 por cento). Na hepatite B aguda, outros profissionais (36,9 por cento) e pessoal de enfermagem (34,2 por cento) foram dominantes em relaçäo a médicos (28,9 por cento). Nas hepatites crônicas B e C houve predomínio do pessoal de enfermagem (39,5 por cento e 47,4 por cento, respectivamente), seguido por outros profissionais (28,9 por cento e 39,5 por cento) e médicos (31,6 por cento e 13,1 por cento). Näo houve casos de hepatite NANB em médicos, mas somente em pessoal de enfermagem (75 por cento) e outros profissionais (25 por cento). A comparaçäo da incidência das hepatites virais entre 1986-1991 e 1992-1997 mostrou uma tendência à diminuiçäo da maioria delas. A diminuiçäo dos casos de hepatite B pode ser atribuída à maior difusäo das precauçöes universais, em decorrêencia do HIV, e também da vacinaçäo contra a hepatite B a partir de 1991. A hepatite C crônica constitui exceçäo, com aumento significativo de 1 para 36 casos diagnosticados; isso se explica pelo fato do diagnóstico de certeza da hepatite C ter se tornado disponível a partir de 1991.