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.