title: Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C.
abstract: 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.
authors.affiliation: Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Sapporo 060-8543, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.forename: Koji
authors.initials: K
authors.lastname: Miyanishi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.forename: Tokiko
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawano
authors.forename: Sho
authors.initials: S
authors.lastname: Takahashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Niitsu
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D015331:Cohort Studies; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000628:therapy; D006801:Humans; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018962:Phlebotomy; D012307:Risk Factors
chemical_list: D019266:Iron, Dietary; D000410:Alanine Transaminase