Viral kinetics during the first month of treatment in patients with genotype 1 chronic hepatitis C.

OBJECTIVE: to identify predictive factors of response to pegylated interferon alpha-2b and ribavirin in patients with genotype 1 chronic hepatitis C. Viral kinetics were studied in weeks 2 and 4. METHODS: a prospective and consecutive study of patients with genotype 1 chronic hepatitis C referred to our Hepatology Clinic between January 2004 and October 2006 for antiviral treatment. Baseline data were recorded and viremia levels were determined hours before the weekly dose of pegylated interferon by qualitative and quantitative PCR. RESULTS: 57 patients were included in the study, although 3 of these were excluded during follow up; 65% were male (n = 35), with a mean age of 42 (26-65) years. Baseline viremia levels were > 800,000 IU/mL in 67% (n = 36). Liver biopsy was performed in 86% (n = 46), 22% (n = 12) had advanced fibrosis. Forty were naïve, 4 relapsing and 10 non-responders. Ribavirin dose was modified in one patient alone due to adverse effects. End treatment response and sustained virological response (SVR) were 59 and 41%, respectively. A univariate analysis revealed a statistically significant association of SVR with baseline viremia (p = 0.006), baseline GGT (p = 0.025), and a reduction in viremia > or =2 logs at 2, 4 and 12 weeks (p = 0.001). The extent of viremia reduction at week 2 was associated with 100% SVR, and at 4 weeks the positive predictive values was 84% and the negative predictive values was 96.5%. A subanalysis of the naïve group yielded analogous results. CONCLUSIONS: in our study, a reduction in viremia > or = 2 logs 2 weeks after treatment could ensure SVR. At 4 weeks, most non-responders could be identified.

Time course of serum hepatitis C virus-RNA during chronic hepatitis C treatment accurately predicts the type of response.

AIM: To establish the value of alanine aminotransferase normalization and hepatitis C virus-RNA clearance as predictors of sustained virological response in naïve and relapser chronic hepatitis C patients on mono or combination therapy. METHODS: A total of 282 hepatitis C patients were studied: 98 naïves on interferon, and 64 naïves and 75 relapsers on interferon plus oral ribavirin; 45 patients were excluded. Drugs were administered at standard doses for 12 months. Alanine aminotransferase and hepatitis C virus-RNA were determined at baseline and at weeks 4, 12, 24, 48, and at 72 and 96 weeks after completion of therapy. RESULTS: The rate of sustained response was greater (P < 0.05) in naïves and relapsers on combination therapy (33% and 48%, respectively) than in naïves on interferon alone (16%). Hepatitis C virus-RNA significantly decreased from baseline by week 4 in naïves on interferon and relapsers on combination therapy and by week 12 in naïves on combination therapy. Alanine aminotransferase levels paralleled viremic load in naïves on interferon, yet in patients on combination therapy, alanine aminotransferase normalized independently of the virological response. During treatment, the main factor associated with sustained response was hepatitis C virus-RNA clearance by week 4 in naïves on interferon and relapsers on combination therapy, and by week 24 in naïves on combination therapy. CONCLUSION: Clearance of viraemia constitutes the best predictor of a sustained response to therapy, but needs to be measured at patient-specific times.

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. AIM: To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. PATIENTS AND METHODS: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. RESULTS: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). CONCLUSIONS: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.