Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2019; 11(3): 287-293
Published online Mar 27, 2019. doi: 10.4254/wjh.v11.i3.287
Extreme hyperbilirubinemia: An indicator of morbidity and mortality in sickle cell disease
John Paul Haydek, Cesar Taborda, Rushikesh Shah, Preeti A Reshamwala, Morgan L McLemore, Fuad El Rassi, Saurabh Chawla
John Paul Haydek, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States
Cesar Taborda, Rushikesh Shah, Preeti A Reshamwala, Saurabh Chawla, Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, United States
Morgan L McLemore, Fuad El Rassi, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30329, United States
Author contributions: Shah R, Reshamwala PA, McLemore ML, El Rassi F and Chawla S designed research; Haydek JP and Taborda C collected clinical data; Haydek JP and Shah R analyzed data; Haydek JP wrote the manuscript.
Institutional review board statement: The study was reviewed and approved by the Emory Institutional Review Board under project number IRB00092809.
Informed consent statement: This study was retrospective in nature and was not associated with any clinical intervention and thus was exempt from informed consent per our institutional policies.
Conflict-of-interest statement: We have no financial relationships to disclose.
STROBE statement: The authors have read the STROBE statement and the manuscript was prepared and revised according to its checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Saurabh Chawla, MD, FACG, Associate Professor, Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, 49 Jesse Hill Jr. Dr. SE, Suite 431, Atlanta, GA 30303, United States.
Telephone: +1-404-7781684 Fax: +1-404-7781681
Received: November 25, 2018
Peer-review started: November 26, 2018
First decision: December 10, 2018
Revised: January 16, 2019
Accepted: January 28, 2019
Article in press: January 28, 2019
Published online: March 27, 2019

Sickle cell disease (SCD) is a disorder that results in increased hospitalizations and higher mortality. Advances in management have resulted in increases in life expectancy and led to increasing awareness of sickle cell hepatopathy (SCH). However, its impact in patients on the natural history and outcomes of SCD is not known. Our study aims to describe the prevalence of extreme hyperbilirubinemia (EH), one form of SCH, its effect on morbidity and mortality, and correlations between sickle cell genotype and SCH type. We hypothesize that EH is associated with higher morbidity and mortality.


To investigate the effects of EH on morbidity and mortality among patients with SCD.


This retrospective cohort study was performed using a database of patients with SCD treated at Grady Memorial Hospital between May 2004 and January 2017. Patients with EH (defined as total bilirubin above 13.0 mg/dL) were identified. A control group was identified from the same database with patients with total serum bilirubin ≤ 5.0 mg/dL. Electronic medical records were used to extract demographic information, laboratory values, radiology results, current medications, need for transfusions and mortality data. Two samples T-test, chi-squared test and Fisher’s exact test were then used to compare the parameters between the two groups.


Out of the database, fifty-seven charts were found of patients with bilirubin > 13 mg/dL. Prevalence of severe SCH as defined by EH was 4.8% (57/1172). There were no demographic differences between patients with and without EH. Significant genotypic differences existed between the two groups, with hemoglobin SS SCD being much higher in the EH group (P < 0.001). Patients with severe EH had a significant elevations in alanine aminotransferase (157.0 ± 266.2 IU/L vs 19.8 ± 21.3 IU/L, P < 0.001), aspartate aminotransferase (256.5 ± 485.9 U/L vs 28.2 ± 14.7 U/L, P < 0.001) and alkaline phosphatase (218.0 ± 176.2 IU/L vs 85.9 ± 68.4 IU/L, P < 0.001). Patients with EH had significantly higher degree of end organ failure measured with quick Sequential Organ Failure Assessment scores (0.42 ± 0.68 vs 0.01 ± 0.12, P < 0.001), increased need for blood products (63% vs 5%, P < 0.001), and exchange transfusions (10.5% vs 1.3%, P = 0.022).


Among patients with SCD, elevated levels of total bilirubin are rare, but indicative of elevated morbidity, mortality, and need for blood transfusions. Large differences in sickle cell genotype also exist, but the significance of this is unknown.

Keywords: Sickle cell disease, Sickle cell hepatopathy, Liver diseases, Extreme hyperbilirubinemia, Mortality

Core tip: Sickle cell hepatopathy is a rarely studied complication of sickle cell disease. Little is known about prognostic factors related to it. In our study, we identified patients with one indicator of sickle cell hepatopathy, extreme hyperbilirubinemia, and analyzed outcomes related to their clinical state. High levels of bilirubin are indicative of elevated morbidity and need for blood transfusion among patients with sickle cell disease.