Serum Ferritin as Risk Factor for Veno-occlusive Disease of the Liver. Prospective Cohort Study

Morado, Marta; Ojeda, Emilio; Garcia-Bustos, J.; Mj, Aguado; Arrieta, R; Quevedo, E; Navas, A. Torres; Hernández-Navarro, Fernando

doi:10.1080/10245332.1999.11746478

Cited by 72 publications

(64 citation statements)

References 14 publications

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“…An association between HVOD and high pretransplant serum ferritin levels, which may reflect elevated body iron stores but may also be a marker of disease activity, has been reported. 64 The observation that the CPS AA genotype offsets the risk of HVOD in patients with C282Y mutations is consistent with prior in vitro studies of recombinant CPS enzyme kinetics. The A-encoded Asn1405 variant is 20-30% more efficient than the C-encoded Thr1405 variant.…”

Section: Discussionsupporting

confidence: 72%

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation

Kallianpur

Hall

Yadav

et al. 2005

Bone Marrow Transplant

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Summary:Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR ¼ 3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR ¼ 1.7, 95% CI 0.4-6.8 in heterozygotes; RR ¼ 8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.

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Section: Discussionsupporting

confidence: 72%

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation

Kallianpur

Hall

Yadav

et al. 2005

Bone Marrow Transplant

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“…In earlier studies, iron overload appeared to be a risk factor of VOD 3 and abnormal liver function test 15 after HSCT, and we could find the association between the ferritin level and bilirubin. In our study, respiratory failure consisted substantial portion of the cause of TRM after allogeneic HSCT, and acute respiratory distress syndrome showed the tendency to increase with elevated ferritin level.…”

Section: Discussionmentioning

confidence: 81%

“…Free iron catalyzes the conversion of reactive oxygen species intermediates to highly toxic-free radicals, which may mediate tissue injury. 2 Recent studies have shown that iron overload is related to hepatic complications, 3 infectious complications [4][5][6] and survival 7,8 in HSCT.…”

Section: Introductionmentioning

confidence: 99%

Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children

Lee

Kang

Kim

et al. 2009

Bone Marrow Transplant

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“…18,21,24,[28][29][30] Previous reports have documented an association between mucositis, opportunistic infections including aspergillus and mucor mucosis, febrile days, GVHD, SOS/VOD, hepatitis C and finally survival. 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.…”

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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Serum Ferritin as Risk Factor for Veno-occlusive Disease of the Liver. Prospective Cohort Study

Cited by 72 publications

References 14 publications

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation

Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children

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

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