BACKGROUND: We have previously demonstrated that in patients with chronic hepatitis C (CHC), iron depletion improves serum alanine aminotransferase (ALT) levels as well as hepatic oxidative DNA damage. However, it has not been determined whether continuation of iron depletion therapy for CHC favorably influences its progression to hepatocellular carcinoma (HCC). METHODS: We conducted a cohort study on biopsy-proven CHC patients with moderate or severe liver fibrosis who failed to respond to previous interferon (IFN) therapy or had conditions for which IFN is contradicted. Patients were divided into two groups: subjects in group A (n = 35) underwent weekly phlebotomy (200 g) until they reached a state of mild iron deficiency, followed by monthly maintenance phlebotomy for 44-144 months (median, 107 months), and they were advised to consume a low-iron diet (5-7 mg iron/day); group B (n = 40) comprised CHC patients who declined to receive iron depletion therapy. RESULTS: In group A, during the maintenance phase, serum ALT levels decreased to less than 60 IU/l in all patients and normalized (<40 IU/l) in 24 patients (69%), whereas in group B no spontaneous decrease in serum ALT occurred. Hepatocarcinogenesis rates in groups A and B were 5.7% and 17.5% at the end of the fifth year, and 8.6% and 39% in the tenth year, respectively. Multivariate analysis revealed that iron depletion therapy significantly lowered the risk of HCC (odds ratio, 0.57) compared with that of untreated patients (P = 0.0337). CONCLUSIONS: Long-term iron depletion for CHC patients is a promising modality for lowering the risk of progression to HCC.
BACKGROUND: We have previously demonstrated that in patients with chronic hepatitis C (CHC), iron depletion improves serum alanine aminotransferase (ALT) levels as well as hepatic oxidative DNA damage. However, it has not been determined whether continuation of iron depletion therapy for CHC favorably influences its progression to hepatocellular carcinoma (HCC). METHODS: We conducted a cohort study on biopsy-proven CHCpatients with moderate or severe liver fibrosis who failed to respond to previous interferon (IFN) therapy or had conditions for which IFN is contradicted. Patients were divided into two groups: subjects in group A (n = 35) underwent weekly phlebotomy (200 g) until they reached a state of mild iron deficiency, followed by monthly maintenance phlebotomy for 44-144 months (median, 107 months), and they were advised to consume a low-iron diet (5-7 mg iron/day); group B (n = 40) comprised CHCpatients who declined to receive iron depletion therapy. RESULTS: In group A, during the maintenance phase, serum ALT levels decreased to less than 60 IU/l in all patients and normalized (<40 IU/l) in 24 patients (69%), whereas in group B no spontaneous decrease in serum ALT occurred. Hepatocarcinogenesis rates in groups A and B were 5.7% and 17.5% at the end of the fifth year, and 8.6% and 39% in the tenth year, respectively. Multivariate analysis revealed that iron depletion therapy significantly lowered the risk of HCC (odds ratio, 0.57) compared with that of untreated patients (P = 0.0337). CONCLUSIONS: Long-term iron depletion for CHCpatients is a promising modality for lowering the risk of progression to HCC.
Authors: J Kato; M Kobune; Y Kohgo; N Sugawara; H Hisai; T Nakamura; S Sakamaki; N Sawada; Y Niitsu Journal: J Clin Invest Date: 1996-08-15 Impact factor: 14.808
Authors: M P Manns; J G McHutchison; S C Gordon; V K Rustgi; M Shiffman; R Reindollar; Z D Goodman; K Koury; M Ling; J K Albrecht Journal: Lancet Date: 2001-09-22 Impact factor: 79.321
Authors: R G Knodell; K G Ishak; W C Black; T S Chen; R Craig; N Kaplowitz; T W Kiernan; J Wollman Journal: Hepatology Date: 1981 Sep-Oct Impact factor: 17.425
Authors: Massimo Franchini; Giovanni Targher; Franco Capra; Martina Montagnana; Giuseppe Lippi Journal: Hepatol Int Date: 2008-05-08 Impact factor: 6.047