Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2020; 26(33): 4983-4995
Published online Sep 7, 2020. doi: 10.3748/wjg.v26.i33.4983
Acute liver failure and death predictors in patients with dengue-induced severe hepatitis
Tongluk Teerasarntipan, Roongruedee Chaiteerakij, Piyawat Komolmit, Pisit Tangkijvanich, Sombat Treeprasertsuk
Tongluk Teerasarntipan, Roongruedee Chaiteerakij, Piyawat Komolmit, Sombat Treeprasertsuk, Department of Medicine, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, and Thai Red Cross, Bangkok 10330, Thailand
Pisit Tangkijvanich, Department of Biochemistry, Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Author contributions: Teerasarntipan T designed the study, collected information, analysed data and drafted the manuscript, and was involved in data collection; Chaiteerakij R, Komolmit P, and Tangkijvanich P assisted in manuscript draft; Treeprasertsuk S oversight the study, contributed to data analysis and assisted in manuscript draft; all authors read and approved the final manuscript.
Supported by the Fatty Liver Unit, Foundation of the Faculty of Medicine, Chulalongkorn University.
Institutional review board statement: This study was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (IRB. No. 326/63).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare that there is no conflict of interest.
Data sharing statement: Not available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sombat Treeprasertsuk, MD, PhD, Doctor, Professor, Department of Medicine, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, and Thai Red Cross, No. 1873 Rama 4 Road, Pathumwan District, Bangkok 10330, Thailand. sombat.t@chula.ac.th
Received: May 15, 2020
Peer-review started: May 15, 2020
First decision: June 4, 2020
Revised: June 17, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: September 7, 2020
Processing time: 106 Days and 4.1 Hours
ARTICLE HIGHLIGHTS
Research background

Liver injury from dengue infection is frequently observed, but it is usually mild and transient. Approximately 10% of dengue patients have dengue-induced severe hepatitis (DISH), which is defined by a more than 10-fold elevation in transaminase. Acute liver failure (ALF) from dengue infection is extremely rare but results in a high mortality rate.

Research motivation

The prognosis of patients with DISH has not been well studied. Moreover, information regarding the risk of transitioning from DISH to ALF and death is limited. Evidence regarding effective therapeutic options for patients with ALF from dengue is still lacking, and therefore, early identification of patients who are at risk of ALF and prompt treatment are keys to improving clinical outcomes.

Research objectives

We aimed to identify the predictive factors of ALF and death in hospitalized dengue patients, regardless of dengue severity, who had severe hepatitis at presentation. We also aimed to analyze the clinical characteristics of all patients who transitioned from DISH to ALF.

Research methods

We retrospectively reviewed 2311 serologically confirmed adolescent and adult dengue patients who were hospitalized during a 12-year study period. Patients with DISH (n = 134) and DISH with subsequent ALF (n = 17) were included. Predictors of ALF and in-hospital death were identified using logistic regression analysis.

Research results

The mortality rate was low in DISH patients (0.8%) but was remarkably high if ALF developed (58.8%). In univariate analysis, age, sex, hematocrit, white blood count, atypical lymphocyte count, platelet count, international normalized ratio (INR), bilirubin, serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, alkaline phosphatase, albumin, creatinine, Model for End-Stage Liver Disease (MELD) score, presence of liver comorbidity and presence of capillary leakage syndrome (CLS) were identified as potential prognostic parameters for ALF or death. In multivariate analysis, the MELD score remained the only predictor of ALF, with an adjusted odds ratio (aOR) of 1.3 [95% confidence interval (CI): 1.1-1.5, P < 0.001]. An initial MELD score > 15 was associated with ALF from DISH with an AUROC of 0.91, sensitivity of 88.2% and specificity of 87.3%. An independent factor associated with death was baseline INR (aOR 10.4, 95%CI: 2.6-40.5, P = 0.001). INR > 1.5 predicted death from DISH with an area under the receiver operating characteristic of 0.83 (sensitivity of 81.8% and specificity of 86.8%).

Research conclusions

The MELD score was the best predictor of ALF in DISH patients, a complication from dengue that is associated with high mortality. The presence of ALF and the baseline INR level were independent predictors of death among DISH patients.

Research perspectives

ALF developing from DISH is rare, but it has a very poor prognosis. Early detection of patients who are at risk of ALF and death is essential. The MELD score and INR level are basic parameters that showed good predictive values for ALF and death among DISH patients.