Iron reduction in chronic hepatitis C by repeated phlebotomy: A study using a less aggressive protocol

Background: Iron accumulation is common in chronic hepatitis C (CHC), and iron depletion through phlebotomy may serve as a kind of alternative therapy for CHC patients (pts) who are unsuited for interferon plus ribavirin treatment. Aim: To acquire experience with this therapeutic modality using a novel phlebotomy protocol which is less aggressive than those described earlier. Subjects: 27 CHC pts (17 men, 10 women; age: 37 to 68 ys) with pathological serum alanine aminotransferase (ALT) levels and a transferrin saturation (TFS) of >25%. They were nonresponder or intolerant to or on a waiting list for interferon-ribavirin therapy. None of them had hemochromatosis. Methods: The pts underwent 400ml phlebotomy monthly until an iron deficiency (TFS <20%) was achieved, and thereafter less frequently in order to keep the iron saturation around 10% with acceptable hematocrit levels. They were treated for 6 months and laboratory tests were performed every 3 months. A more than 50% decrease in serum ALT was considered a good biochemical response. The circulating levels of tumor necrosis factor-alpha (TNF-α; a major proinflammatory cytokine contributing to hepatic necroinflammation) and procollagen III N-terminal peptide (PIIINP; a marker of fibrogenesis) were also determined. Results: The phlebotomy protocol was well tolerated by the pts, and led to significant (p<0.05) decreases in the mean serum ALT and gamma-glutamyltransferase activities, serum iron concentration and TFS. Moreover, it did not hamper subsequent use of interferon + ribavirin. Treatment for 6 months led to statistically significant (P<0.05) decrease in the mean serum ALT activity (from 176±108 to 83.1±55.6 IU/L). A good therapeutic response was associated with significant decreases in the circulating concentrations of TNF-α and PIIINP, too. Conclusion: This study indicates that iron depletion by this well-tolerable phlebotomy protocol may exert a beneficial effect on hepatic necroinflammation and fibrogenesis and can lead to a substantial biochemical improvement in a part of pts with CHC.