RESUMEN
Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Anciano , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteínas Recombinantes , Ribavirina/uso terapéutico , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
summary. Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy, followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN alpha-2b 5 MU daily (Group A: 59 patients) or IFN alpha-2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000-1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively (P = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.
Asunto(s)
Antivirales/administración & dosificación , Hepacivirus/crecimiento & desarrollo , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Modelos Logísticos , Masculino , ARN Viral/sangre , ARN Viral/genética , Proteínas Recombinantes , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate the distribution and clinical significance of hepatitis C virus (HCV) genotypes in European patients with compensated cirrhosis due to hepatitis C (Child class A) seen at tertiary referral centres. HCV genotypes were determined by genotype-specific primer PCR in 255 stored serum samples obtained from cirrhotics followed for a median period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, absence of complications of cirrhosis and exclusion of all other potential causes of chronic liver disease. The proportion of patients with types 1b, 2, 3a, 1a, 4 and 5 were 69%, 19%, 6%, 5%, 0.5% and 0.5%, respectively. Kaplan-Meier 5-year risk of hepatocellular carcinoma (HCC) was 6% and 4% for patients infected by type 1b and non-1b, respectively (P=0.8); the corresponding figures for decompensation were 18% and 7% (P=0.0009) and for event-free survival were 79% and 89% (P=0.09), respectively. After adjustment for baseline clinical and serological features, HCV type 1b did not increase the risk for HCC [adjusted relative risk=1.0 (95% confidence interval=0.47-2.34)], whereas it increased the risk for decompensation by a factor of 3 (1.2-7.4) and decreased event-free survival by a factor of 1.7 (0.9-3.10). In conclusion, type 1b and, to a lesser extent, type 2, are the most common HCV genotypes in European patients with cirrhosis. HCV type 1b is not associated with a greater risk for HCC, but increases the risk for decompensation by threefold in patients with cirrhosis.
Asunto(s)
Hepacivirus/genética , Hepatitis C/epidemiología , Cirrosis Hepática/virología , Adulto , Factores de Edad , Anciano , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Supervivencia sin Enfermedad , Europa (Continente)/epidemiología , Femenino , Hepacivirus/química , Hepacivirus/clasificación , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , ARN Viral/genética , Factores Sexuales , Estadísticas no Paramétricas , Reacción a la Transfusión , Resultado del TratamientoRESUMEN
BACKGROUND: The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined. AIMS: To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B. PATIENTS/METHODS: Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6 years. RESULTS: At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, gamma-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8 to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively. CONCLUSIONS: HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.