Treatment With Pegylated Interferon and Ribavirin in Chronic HCV
Treatment With Pegylated Interferon and Ribavirin in Chronic HCV
Background: The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated.
Aim: To evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin.
Patients and methods: Patients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment.
Results: At week 4, a strong correlation was found between HCV-RNA and Cmin of ribavirin plasma level (r = −0.376, P = 0.002) and AUC0→12h of ribavirin plasma level (r = −0.277, P = 0.018). At week 12, a strong correlation was found between HCV-RNA and Cmin of ribavirin plasma level (r = −0.384, P lt; 0.0001) and AUC0→12h of ribavirin plasma level (r = −0.257, P = 0.002). In genotype 1 patients, AUC0→12h ribavirin and Cmin were significantly correlated with negative HCV-RNA at week 12 and SVR. In the multiple logistic regression model, the only factor independently associated with SVR in genotype 1 patients was negative HCV-RNA at week 12.
Conclusion: Cmin of ribavirin at weeks 4 and 12 was significantly higher in sustained virological responders compared with relapser or nonresponder patients. However, in genotype 1 patients, plasma ribavirin level at weeks 4 and 2 was not associated with SVR.
The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR), currently defined as undetectable HCV-RNA in peripheral blood determined using the most sensitive PCR technique 24 weeks after the end of treatment. The current standard in hepatitis C treatment consists of combination regimens of pegylated interferon (PEG-IFN) α with ribavirin. Such treatment schemes are quite successful in patients with genotypes 2 and 3 infection achieving HCV eradication rates of 75-90%. However, they are much less effective in patients with genotypes 1 and 4 infections with eradication rates ranging between 45% and 52%. The main predictive factors of a poor SVR are HCV genotype other than genotype 2 or 3, high baseline viral load and a dose of ribavirin lt; 10.6 mg/kg of body weight. However, the impact of the pharmacological properties of ribavirin has not been fully investigated and requires complementary studies. Two clinical trials have suggested that ribavirin dose adjustment for body weight could be beneficial. Ribavirin has a large distribution volume and large interindividual variability in concentrations. Two studies in HCV patients receiving interferon and ribavirin found no correlation between ribavirin dose adjusted for body weight and a single ribavirin time point serum concentration at weeks 4 or 12. However, a low ribavirin serum concentration was associated with a low SVR rate. Recently, it has been shown that ribavirin exposure at day 0 was significantly related to SVR and a minimum AUC 0-4 h threshold of 1755μg h/L at day 0 was proposed as a target for ribavirin adjustment.
The aim of this prospective study was to evaluate the association between ribavirin plasma level and SVR response in a large cohort of HCV patients treated with PEG-IFN and ribavirin and to determine the cut-off of ribavirin level associated with SVR.
Abstract and Introduction
Abstract
Background: The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated.
Aim: To evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin.
Patients and methods: Patients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment.
Results: At week 4, a strong correlation was found between HCV-RNA and Cmin of ribavirin plasma level (r = −0.376, P = 0.002) and AUC0→12h of ribavirin plasma level (r = −0.277, P = 0.018). At week 12, a strong correlation was found between HCV-RNA and Cmin of ribavirin plasma level (r = −0.384, P lt; 0.0001) and AUC0→12h of ribavirin plasma level (r = −0.257, P = 0.002). In genotype 1 patients, AUC0→12h ribavirin and Cmin were significantly correlated with negative HCV-RNA at week 12 and SVR. In the multiple logistic regression model, the only factor independently associated with SVR in genotype 1 patients was negative HCV-RNA at week 12.
Conclusion: Cmin of ribavirin at weeks 4 and 12 was significantly higher in sustained virological responders compared with relapser or nonresponder patients. However, in genotype 1 patients, plasma ribavirin level at weeks 4 and 2 was not associated with SVR.
Introduction
The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR), currently defined as undetectable HCV-RNA in peripheral blood determined using the most sensitive PCR technique 24 weeks after the end of treatment. The current standard in hepatitis C treatment consists of combination regimens of pegylated interferon (PEG-IFN) α with ribavirin. Such treatment schemes are quite successful in patients with genotypes 2 and 3 infection achieving HCV eradication rates of 75-90%. However, they are much less effective in patients with genotypes 1 and 4 infections with eradication rates ranging between 45% and 52%. The main predictive factors of a poor SVR are HCV genotype other than genotype 2 or 3, high baseline viral load and a dose of ribavirin lt; 10.6 mg/kg of body weight. However, the impact of the pharmacological properties of ribavirin has not been fully investigated and requires complementary studies. Two clinical trials have suggested that ribavirin dose adjustment for body weight could be beneficial. Ribavirin has a large distribution volume and large interindividual variability in concentrations. Two studies in HCV patients receiving interferon and ribavirin found no correlation between ribavirin dose adjusted for body weight and a single ribavirin time point serum concentration at weeks 4 or 12. However, a low ribavirin serum concentration was associated with a low SVR rate. Recently, it has been shown that ribavirin exposure at day 0 was significantly related to SVR and a minimum AUC 0-4 h threshold of 1755μg h/L at day 0 was proposed as a target for ribavirin adjustment.
The aim of this prospective study was to evaluate the association between ribavirin plasma level and SVR response in a large cohort of HCV patients treated with PEG-IFN and ribavirin and to determine the cut-off of ribavirin level associated with SVR.
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