Liver injury is associated with mortality in sickle cell disease

Autor:	Gregory J. Kato, Netanya G. Sandler, Christopher Koh, T. Shields, Mark T. Gladwin, Jay H. Hoofnagle, David E. Kleiner, James G. Taylor, Daniel C. Douek, Jordan J. Feld, James S. Nichols, Theo Heller, T. Jake Liang, Mariana Hildesheim, V. Haynes-Williams
Rok vydání:	2015
Předmět:	Adult Liver Cirrhosis Male medicine.medical_specialty Pathology Iron Overload Adolescent Anemia Iron Portal venous pressure Anemia Sickle Cell Gastroenterology Article Young Adult Fibrosis Internal medicine medicine Humans Pharmacology (medical) Aged Liver injury Hepatology biology business.industry Liver Diseases Middle Aged medicine.disease Haemolysis United States Ferritin Ferritins biology.protein Portal hypertension Female business Hepatic fibrosis
Zdroj:	Alimentary Pharmacology & Therapeutics. 42:912-921
ISSN:	0269-2813
DOI:	10.1111/apt.13347
Popis:	Summary Background Increased 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. Aim To report the long-term consequences of liver dysfunction in SCD. Methods A 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. Results Exactly, 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. Conclusions Ferritin 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.
Databáze:	OpenAIRE
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