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
Research background

Sickle cell hepatopathy is a category of pathologies that occur among patients with sickle cell disease, and has been rising in incidence as lifespan has increased. Additionally, based on autopsy studies, sickle cell hepatopathy is felt to be underreported and likely contributes to mortality in more cases than in realized. Previous studies have tried to identify risk factors associated with sickle cell hepatopathy but have been limited by small size.

Research motivation

With the increasing incidence of sickle cell hepatopathy, understanding risk factors and improving its recognition are important to its early diagnosis and treatment.

Research objectives

The main objectives of this study were to describe the prevalence of extreme hyperbilirubinemia, its effect on morbidity and mortality, and any association between sickle cell genotype and sickle cell hepatopathy.

Research methods

We used a retrospective observational cohort study to evaluate the epidemiology and outcomes behind extreme hyperbilirubinemia, a form of sickle cell hepatopathy. This was conducted at a hospital with a large population of patients with sickle cell disease.

Research results

About 5% of patients in our sickle cell disease database developed extreme hyperbilirubinemia. This cohort was associated with higher rates of systemic illness, measured by quick Sequential Organ Failure Assessment scores, higher rates of blood transfusions and higher rates of exchange transfusions. There was not a higher mortality rate in the extreme hyperbilirubinemia group. There were higher rates of patients with hemoglobin SS sickle cell disease among the extreme hyperbilirubinemia group compared to a control group, compared to other genotypes. Additionally, there were not significant differences in hydroxyurea use between groups.

Research conclusion

Our study highlights the increased morbidity and use of blood products seen among patients with extreme hyperbilirubinemia, a form of sickle cell hepatopathy. It also identifies different rates of sickle cell hepatopathy depending on the sickle cell genotype present. Finally, it shows that reported hydroxyurea doses did not have an effect on development of sickle cell hepatopathy.

Research perspective

Our study highlights the need for further study into types of sickle cell hepatopathy, whether strategies other than hydroxyurea can mitigate the risk of development of sickle cell hepatopathy, and whether there are any identifiable risk factors to increase rates of early diagnosis.