Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: A multicenter, prospective, randomized, controlled trial

Abstract

Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus (HCV). We therefore conducted a randomized, controlled trial comparing iron reduction by phlebotomy with iron reduction followed by retreatment with interferon in 96 patients with chronic hepatitis C who had previously not responded to a course of interferon. During the initial phase when all patients were undergoing phlebotomy, we found that serum alanine transaminase (ALT) activities decreased but by less than 50% from baseline in 67 patients (89%), decreased by more than 50% in 12 patients (13%) and became normal in 9 patients (9%) with no overall change in HCV-RNA levels. Subsequently no patient in either treatment group achieved a sustained virologic response. Improvements in necroinflammatory changes were noted in liver biopsy specimens in those patients receiving phlebotomy plus interferon (mean index 8.59 vs. 7.37, P F .05). A slight but not statistically significant decrease in histologic activity index was noted in those subjects treated by phlebotomy alone (mean index 8.4 vs. 7.75, P not significant). We conclude that, although prior phlebotomy therapy does not improve the rate of sustained response to interferon retreatment, it does result in less liver injury manifested by a decrease in serum transaminase activity and a slight improvement in liver histopathology. (HEPATOLOGY 2000;32:135-138.)

Iron as a comorbid factor in chronic viral hepatitis

“…Neither group achieved significant improvements in terms of cure of CHC, but both showed evidence of histological improvements, with less severe hepatic inflammation (22). These favorable effects of iron reduction alone confirmed and extended earlier reports showing significant improvements in serum ALT levels in patients with CHC who previously had not responded to interferon when they underwent iron reduction by therapeutic venesection (23,24).…”

Chronic hepatitis C: hepatic iron content does not correlate with response to antiviral therapy

“…The lack of a correlation between HIC and response of patients with hepatitis C to antiviral treatment agrees with the majority of the results regarding phlebotomy as coadjuvant treatment 7,10,19 . DI BISCEGLIE et al 10 showed that in patients with hepatitis C not responding to interferon monotherapy iron depletion by phlebotomy did not result in a higher SVR rate during retreatment, despite an association with improved liver injury manifested by a decrease in transaminases and improved liver histopathology after phlebotomy.…”

“…DI BISCEGLIE et al 10 showed that in patients with hepatitis C not responding to interferon monotherapy iron depletion by phlebotomy did not result in a higher SVR rate during retreatment, despite an association with improved liver injury manifested by a decrease in transaminases and improved liver histopathology after phlebotomy. Similarly, in the study of HERRERA 19 iron depletion by phlebotomy did not improve SVR in the retreatment of patients who were previously non-responders.…”

Iron Inactivates the RNA Polymerase NS5B and Suppresses Subgenomic Replication of Hepatitis C Virus

“…Increased iron indices have also been associated with poor response to treatment with interferon-␣ (9 -12). In other studies, however, hepatic iron concentration did not influence the response to interferon-␣ treatment (13,14), and phlebotomy did not substantially improve the efficacy of antiviral therapies (15,16).…”