ArticleAlimentary pharmacology & therapeutics2015
Liver injury is associated with mortality in sickle cell disease.
Article in Alimentary pharmacology & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Serum or plasma ferritin concentration as an index of iron deficiency and overload.The Cochrane database of systematic reviews · 2021Pooled it
- Pooled it
- Trial
- Non-myeloablative human leukocyte antigen-matched related donor transplantation in sickle cell disease: outcomes from three independent centres.British journal of haematology · 2021Trial
- Review
- Article
- Purine Nucleoside Phosphorylase Inhibition Rebalances Purine Metabolism and Attenuates Organ Damage in Sickle Cell Mice.Journal of cellular and molecular medicine · 2025Article
- Nonmyeloablative Pentostatin-Cyclophosphamide Preconditioning Improves Rates of Engraftment in Adults Undergoing Haploidentical HCT for Sickle Cell Disease.medRxiv : the preprint server for health sciences · 2025Article
- Prevalence, risk factors, and demographic insights of sickle cell hepatopathy in Omani adolescents and adults: A retrospective analysis.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2025Article
- Small-molecule inhibitor screen to identify mechanisms of sickle hemoglobin clearance by liver endothelium.Blood vessels, thrombosis & hemostasis · 2025Article
- Hepatobiliary complications in patients with sickle cell disease: A 30-year review of 1009 patients.Hepatology communications · 2025Article
- Emerging need for a hepato-hematology program for patients with sickle cell disease in Saudi Arabia.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2025Article
- GBT1118, a Voxelotor Analog, Ameliorates Hepatopathy in Sickle Cell Disease.Medicina (Kaunas, Lithuania) · 2024Article
- Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis-induced hepatobiliary injury in sickle cell disease.American journal of physiology. Cell physiology · 2024Article
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease.Biomedicines · 2023Article
- Design and Development of Fe3O4@Prussian Blue Nanocomposite: Potential Application in the Detoxification of Bilirubin.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Iron as a therapeutic target in chronic liver disease.World journal of gastroenterology · 2023Review
- Clinical Vignettes Part I.Hematology/oncology clinics of North America · 2022Review
- Role of Toll-like receptor 4 in intravascular hemolysis-mediated injury.The Journal of pathology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundIncreased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso-occlusion and chronic haemolysis to multiple organ systems.
aimTo report the long-term consequences of liver dysfunction in SCD.
methodsA cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression.
resultsExactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension.
conclusionsFerritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients' ability to tolerate systemic insults.
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Registered trials
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