Prevalence of hepatic iron overload and association with hepatocellular cancer in end‐stage liver disease: results from the National Hemochromatosis Transplant Registry

Ko, Cynthia W.; Siddaiah, Narendra; Berger, Jose; Gish, Robert G.; Brandhagen, David J.; Sterling, Richard K.; Cotler, Scott J.; Fontana, Robert J.; McCashland, Timothy M.; Han, Steven‐Huy B.; Gordon, F; Schilsky, Michael L.; Kowdley, Kris V.

doi:10.1111/j.1478-3231.2007.01596.x

Cited by 85 publications

(57 citation statements)

References 53 publications

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“…40,41 Associations with suspected cofactors for HCC should also be examined, including alcoholism 24 and steatohepatitis, 25 obesity, 42 diabetes mellitus, 43 and iron storage diseases. 44 This report may underestimate recent increases in HCC incidence rates because of delays in reporting 16 and an estimated rate of under-reporting of 2.5% because of absence of data on Veterans' Affairs hospital patients, 5 a population which may be at elevated risk for HCC compared with the general population. 45 Despite these limitations, the findings strongly suggest that HCC incidence and mortality continue to increase in the United States.…”

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confidence: 83%

Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005

Altekruse

McGlynn

Reichman

2009

JCO

1,526

1,113

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A B S T R A C T PurposeHepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Incidence rates are increasing in the United States. Monitoring incidence, survival, and mortality rates within at-risk populations can facilitate control efforts. MethodsAge-adjusted incidence trends for HCC were examined in the Surveillance, Epidemiology, and End Results (SEER) registries from 1975 to 2005. Age-specific rates were examined for birth cohorts born between 1900 and 1959. Age-adjusted incidence and cause-specific survival rates from 1992 to 2005 were examined in the SEER 13 registries by race/ethnicity, stage, and treatment. United States liver cancer mortality rates were also examined. ResultsAge-adjusted HCC incidence rates tripled between 1975 and 2005. Incidence rates increased in each 10-year birth cohort from 1900 through the 1950s. Asians/Pacific Islanders had higher incidence and mortality rates than other racial/ethnic groups, but experienced a significant decrease in mortality rates over time. From 2000 to 2005, marked increases in incidence rates occurred among Hispanic, black, and white middle-aged men. Between 1992 and 2004, 2-to 4-year HCC survival rates doubled, as more patients were diagnosed with localized and regional HCC and prognosis improved, particularly for patients with reported treatment. Recent 1-year survival rates remained, however, less than 50%. ConclusionHCC incidence and mortality rates continue to increase, particularly among middle-aged black, Hispanic, and white men. Screening of at-risk groups and treatment of localized-stage tumors may contribute to increasing HCC survival rates in the United States. More progress is needed.

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confidence: 83%

Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005

Altekruse

McGlynn

Reichman

2009

JCO

1,526

1,113

View full text Add to dashboard Cite

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“…1,19,26,[31][32][33][34][35] Patients with hemachromatosis have an increased incidence of cirrhosis, hepatocellular carcinoma and some other malignancies. [35][36][37][38][39][40] Similarly, CLD is one of the major long-term complications in HSCT survivors. Whereas Strasser et al, 4 reported a cumulative incidence of CLD in 3.8% by 20 years after transplantation in a series of 3721 patients, Tomas et al, 6 reported CLD in 57.5% of their cohort of 106 patients in 2 years follow-up, which strongly correlated with siderosis.…”

Section: Discussionmentioning

confidence: 99%

The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?

Sucak

Yeğin

Özkurt

et al. 2008

Bone Marrow Transplant

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Abnormalities in liver function tests are common in hematopoietic SCT (HSCT) recipients. We retrospectively investigated the role of liver biopsy in determining the cause of elevated liver enzymes and its impact on the management of patients in the post-HSCT setting. A total of 24 consecutive liver biopsies were obtained from 20 patients from September 2003 to December 2007. A definite histopathologic diagnosis was obtained in 91.7% of the biopsies. Iron overload (IO) was found in 75% and GVHD in 54.2% of the patients. The initial clinical diagnosis of GVHD was confirmed in 56.5% and refuted in 43.5% of the allogeneic HSCT recipients. The median number of post transplant transfusions, percent transferrin saturation and ferritin levels were found to be higher in patients who had histologically proven hepatic IO (p1 ¼ 0.007, p2 ¼ 0.003 and p3 ¼ 0.009, respectively). Regression analysis showed a significant correlation between serum ferritin levels and histological grade of iron in the hepatocytes. Our data suggest that hepatic IO is a frequent finding in the post-HSCT setting, which contributes to hepatic dysfunction and it should be considered in the differential diagnosis, particularly in patients with high serum ferritin levels.

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“…Chronic hepatitis C is characterized by iron accumulation in the liver, which constitutes an important risk factor for HCC development (Ko et al, 2007). Reduced levels of hepcidin, a key negative regulator of iron absorption (Nemeth & Ganz, 2006;Roy et al, 2007), have been linked to iron accumulation in HCV patients (Nagashima et al, 2006;Fujita et al, 2007;Nishina et al, 2008).…”

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confidence: 99%

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site

Kotta‐Loizou

Vassilaki

Pissas

et al. 2013

Journal of General Virology

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Chronic viral hepatitis C is characterized by iron accumulation in the liver, and hepcidin regulates iron absorption. Hepatitis C virus (HCV) core+1/ARFP is a novel protein produced by a second functional ORF within the core gene. Here, using reporter assays and HCV bicistronic replicons, we show that, similarly to core, core+1/ARFP decreases hepcidin expression in hepatoma cells. The activator protein 1 (AP1) binding site of the human hepcidin promoter, shown here to be relevant to basal promoter activity and to the repression by core, is essential for the downregulation by core+1/ARFP while the previously described C/EBP (CCAAT/enhancer binding protein) and STAT (signal transducer and activator of transcription) sites are not. Consistently, expression of the AP1 components c-jun and c-fos obliterated the repressive effect of core and core+1/ARFP. In conclusion, we provide evidence that core+1/ARFP downregulates AP1-mediated transcription, providing new insights into the biological role of core+1/ARFP, as well as the transcriptional modulation of hepcidin, the main regulator of iron metabolism.

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Prevalence of hepatic iron overload and association with hepatocellular cancer in end‐stage liver disease: results from the National Hemochromatosis Transplant Registry

Abstract: 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.

Cited by 85 publications

References 53 publications

Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005

Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005

The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site

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