Retreatment of hepatitis C patients who previously experienced treatment failure

Abstract

In its different formulations, interferon (IFN) alpha combined with ribavirin (RBV) is the best treatment alternative for patients infected with the hepatitis C virus (HCV) [1]. In such patients, the objective is to achieve an end-of-treatment virological response -negative serum HCV ribonucleic acid (RNA) -followed by a sustained virological response (SVR), which is defined as HCV RNA negativity for six months after the suspension of treatment.The treatment regimens for HCV infection have evolved from monotherapy with conventional IFN alpha to combined therapy with IFN and RBV and, more recently, to combined therapy with pegylated IFN (PEG-IFN alpha-2a or alpha-2b) and RBV [2,3]. It is known that approximately 60% of the patients infected with HCV genotype 1 and nearly 40% of those infected with genotype 3 do not achieve an SVR when treated with the conventional regimen of . The availability of PEG-IFNs has reduced the percentage of patients experiencing treatment failure. In large international trials involving treatment-naïve patients, regimens that include the combination of PEG-IFN and RBV have produced significantly higher rates of SVR than those observed with the use of the conventional combination of IFN and RBV (54-56% vs. 44-47%) [5][6][7].Similar to what occurs in treatment-naïve patients, retreatment provides the patient with a new chance to achieve an SVR. Long-term studies have proven that the vast majority of the patients who achieve an SVR usually remain negative for HCV RNA for a long time [8].The arguments in favor of retreating patients would be the possibility of eradicating HCV, reducing fibrosis, and decreasing the risk of evolving to hepatocarcinoma. With regard to the new antiviral agents, we do not know when they will be available or whether all patients will be able to wait several years to initiate retreatment.It is known that patients who experience relapse after treatment with conventional IFN, with or without RBV, respond better to retreatment with PEG-IFN alpha and RBV than do those presenting no response to treatment with conventional IFN (with or without RBV). Krawitt et al. observed an SVR rate of 55% in 66 relapsing patients who were retreated with PEG-IFN alpha-2b (100-150 µg/week) and RBV (1000 mg/day), compared with only 20% in 116 previous nonresponders treated with the same regimen [9]. An SVR was observed in 53% of the relapsing patients infected with genotype 1, compared with 59% of the relapsing patients infected with genotypes 2 or 3. There were, therefore, no significant differences between these groups of patients. This was not observed in the previous nonresponders receiving retreatment. Of those, only 17% of the individuals infected with genotype 1, in comparison with 57% of the individuals infected with genotypes 2 or 3, achieved an SVR. Therefore, genotype had an influence on SVR in the previous nonresponders who underwent retreatment.Studies conducted in Brazil and involving nonresponders to IFN/RBV demonstrated SVR rates resulting from retreatment with the PEG-...