Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry.
BACKGROUND
It is unclear whether mild to moderate iron overload in liver diseases other than hereditary haemochromatosis (HH) contributes to hepatocellular carcinoma. This study examined the association between hepatic iron grade and hepatocellular carcinoma in patients with end-stage liver disease of diverse aetiologies.


METHODS
The prevalence of hepatic iron overload and hepatocellular carcinoma was examined in 5224 patients undergoing liver transplantation. Explant pathology reports were reviewed for the underlying pathological diagnosis, presence of hepatocellular carcinoma and degree of iron staining. The distribution of categorical variables was studied using chi(2) tests.


RESULTS
Both iron overload and hepatocellular carcinoma were the least common with biliary cirrhosis (1.8 and 2.8% respectively). Hepatocellular carcinoma was the most common in patients with hepatitis B (16.7%), followed by those with hepatitis C (15.1%) and HH (14.9%). In the overall cohort, any iron overload was significantly associated with hepatocellular carcinoma (P=0.001), even after adjustment for the underlying aetiology of liver disease. The association between hepatic iron content and hepatocellular carcinoma was the strongest in patients with biliary cirrhosis (P<0.001) and hepatitis C (P<0.001).


CONCLUSIONS
Iron overload is associated with hepatocellular carcinoma in patients with end-stage liver disease, suggesting a possible carcinogenic or cocarcinogenic role for iron in chronic liver disease.
Ko
Cynthia
C
Division of Gastroenterology, University of Washington Medical Center, Seattle, WA, USA.
Siddaiah
Narendra
N
Berger
Jose
J
Gish
Robert
R
Brandhagen
David
D
Sterling
Richard K
RK
Cotler
Scott J
SJ
Fontana
Robert J
RJ
McCashland
Timothy M
TM
Han
Steven H B
SH
Gordon
Frederic D
FD
Schilsky
Michael L
ML
Kowdley
Kris V
KV
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000601:surgery; D006432:Hemochromatosis / Q000453:epidemiology* / Q000601:surgery; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000601:surgery; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000601:surgery; D006801:Humans; D017093:Liver Failure / Q000453:epidemiology* / Q000601:surgery; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000601:surgery; D016031:Liver Transplantation / Q000706:statistics & numerical data*; D015995:Prevalence; D012042:Registries / Q000706:statistics & numerical data