RESUMEN
GOALS: To examine the treatment efficacy of a combination of pegylated interferon α (PegIFNa) plus ribavirin in patients chronically infected with hepatitis C virus genotype 5 (HCV-5) and to assess the on-treatment virological responses as predictors of sustained virological response (SVR). BACKGROUND: HCV-5 is uncommonly reported, and little therapeutic data is available regarding previous retrospective studies yielding contradictory results. STUDY: In a prospective, open-label, single-center study, 27 treatment-naive HCV-5 patients, treated for 48 weeks with PegIFNa-2a/ribavirin, were evaluated. Rapid viral response (RVR), early viral response (EVR), 24-week viral response (24-wVR), end-of-treatment response (ETR), and SVR were assessed, defined as negative viral load at weeks 4, 12, 24, 48, and 72 after treatment initiation, respectively. RESULTS: Attainment of SVR was observed in 17 of the 27 (63%) patients. RVR, EVR, and 24-wVR occurred in 16 (59.3%), 25 (92.6%), and 24 (88.9%) patients, respectively. All but 1 patient achieving 24-wVR went on to achieve ETR (rate: 85.2%), but 6 patients subsequently relapsed (relapse rate: 26.1%). The positive/negative predictive values on SVR were: 93.8%/81.8% for RVR, 68%/100% for EVR, and 66.7%/66.7% for 24-wVR. CONCLUSIONS: Patients with HCV-5 showed an overall good response to a 48-week combined antiviral treatment (SVR: 63%). Albeit the ETR was high (85.2%), attainment of SVR remained affected by a substantial relapse rate, in our setting 26.1%. The predictive value of early viral dynamics on SVR merits adequate consideration in larger clinical trials targeting to optimize treatment for patients infected with HCV-5.
Asunto(s)
Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Carga Viral , Anciano , Alanina Transaminasa/sangre , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C/sangre , Humanos , Masculino , Memoria Episódica , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteínas Recombinantes/uso terapéuticoRESUMEN
OBJECTIVES: Previous studies, mostly retrospective using conventional interferon, have suggested a favorable prognosis for patients with chronic hepatitis C and a sustained virological response (SVR). However, long-term outcome, including changes in the degree of hepatic fibrosis, of SVR patients in the era of pegylated interferon (PegIFN) remains underdefined. We prospectively evaluated the long-term virological, clinical, and biochemical outcomes, including aspartate aminotransferase-to-platelet ratio index (APRI), in chronic hepatitis C patients with an SVR. PATIENTS AND METHODS: We included 145 consecutive, treatment-naive chronic hepatitis C patients (mean age 47.3±9.1 years; 87 men; 42.1% genotype 1; 36.6% genotype 2/3) who achieved an SVR after combination therapy with PegIFN-α/ribavirin. RESULTS: The mean follow-up time was 68.8±35 months. The overall incidence of hepatocellular carcinoma (HCC) and liver-related death was 1.4 and 0.7%, respectively. Among nine (7.6%) patients with pretreatment cirrhosis, two (22.2%) developed HCC and one of them (11.1%) died. No patient had conclusive evidence of late virological relapse. All patients retained normal liver biochemistry, except for five of 145 (3.5%), who had persistently elevated transaminase levels, all of whom were diagnosed with new liver disease. APRI values improved significantly with treatment (0.95±1.09 vs. 0.66±0.64, P<0.001) and continued to improve after a mean of 61.4±45.5 months from an SVR in patients (n=54; 37.2%) with significant (Metavir ≥F2) pretreatment fibrosis (1.13±0.66 vs. 0.67±0.45, P<0.001). CONCLUSION: The long-term outcome, including APRI, of chronic hepatitis C patients treated successfully with PegIFN/ribavirin and followed for a mean of 5.7 years is favorable. However, a high risk of progression to HCC and liver-related death remains for patients with pretreatment cirrhosis, in our setting, as high as 22.2 and 11.1%, respectively.
Asunto(s)
Antivirales/uso terapéutico , Aspartato Aminotransferasas/sangre , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Recuento de Plaquetas , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Biomarcadores/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virología , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Grecia , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/mortalidad , Humanos , Interferón alfa-2 , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
Hepatitis C virus (HCV) genotype 5 (G5) is a rare genotype reported mainly in South Africa. However, increasing data suggest the sporadic presence of this genotype in different European countries. To assess the epidemiology of HCV-G5 in Greece, genotyping was performed in 973 consecutive patients infected with HCV, referred to 7 hepatology centers throughout Greece, from January 2005 to December 2009. Genotype 5a (19 patients, 1.9%) was the fifth most prevalent genotype after genotype 1 (408 patients, 41.9%), genotype 3 (318 patients, 32.7%), genotype 4 (158 patients, 16.2%), and genotype 2 (70 patients, 7.2%). The majority of patients infected with G5 (16/19,84.2%) were referred to the General Hospital of Rhodes, an island in south-east Greece. The HCV genotype distribution in that particular island, indicates a particularly high G5 prevalence of 12.8%, after genotype 1 (40%), genotype 3 (28%), and genotype 4 (15%). Among the patients from Rhodes infected with G5 (n = 16), 13 (81.2%) were females. The mean age was 62.3 ± 6.5 years, significantly older than the patients infected with other HCV genotypes (mean age 40.6 ± 7.2, P < 0.0001). Nine out of the 16 cases (56.2%) presented features of high pre-treatment viral loads. Advanced liver fibrosis (Metavir F3-F4) was found in four out of five performed liver biopsies. Ten patients received treatment with pegylated interferon plus ribavirin and a sustained viral response were achieved in six cases. The source of infection is unknown but parenteral iatrogenic routes of transmission seem to have contributed significantly to the spread of genotype 5a in this region.