Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 26, 2021; 9(3): 552-564
Published online Jan 26, 2021. doi: 10.12998/wjcc.v9.i3.552
Role of ammonia in predicting the outcome of patients with acute-on-chronic liver failure
Stefan Chiriac, Carol Stanciu, Camelia Cojocariu, Ana-Maria Singeap, Catalin Sfarti, Tudor Cuciureanu, Irina Girleanu, Razvan Alexandru Igna, Anca Trifan
Stefan Chiriac, Camelia Cojocariu, Ana-Maria Singeap, Catalin Sfarti, Tudor Cuciureanu, Irina Girleanu, Anca Trifan, Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
Stefan Chiriac, Carol Stanciu, Camelia Cojocariu, Ana-Maria Singeap, Catalin Sfarti, Irina Girleanu, Anca Trifan, Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
Razvan Alexandru Igna, Intensive Care, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
Author contributions: Chiriac S wrote the original draft of the manuscript and performed the statistical analysis; Stanciu C coordinated the manuscript drafting and revised it critically; Cojocariu C designed the methodology and edited the manuscript; Singeap A, Cuciureanu T, Girleanu I and Sfarti C participated in the writing of the manuscript and performed the acquisition of data; Igna RA participated in the analysis and interpretation of data; Trifan A, conceptualized and critically revised the manuscript for important intellectual content; all authors read and approved the final version of the manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of the “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania.
Informed consent statement: There was no requirement for the informed written consent because of the retrospective nature of the study; all of the patients signed an informed consent upon hospitalization agreeing to receive treatment.
Conflict-of-interest statement: The authors declare no conflict of interest in relation to this study.
Data sharing statement: No additional data are 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: Camelia Cojocariu, MD, PhD, Assistant Professor, Doctor, Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Street, Iasi 700115, Iasi, Romania. cameliacojocariu@yahoo.com
Received: October 3, 2020
Peer-review started: October 3, 2020
First decision: November 23, 2020
Revised: December 2, 2020
Accepted: December 16, 2020
Article in press: December 16, 2020
Published online: January 26, 2021
Processing time: 108 Days and 21.1 Hours
ARTICLE HIGHLIGHTS
Research background

High venous ammonia (VA) values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis (LC) as well as acute hepatitis. Moreover, VA has been associated with poor prognosis and high mortality in these clinical settings.

Research motivation

VA has been associated with hepatic encephalopathy (HE) and mortality and has been used by clinicians in acute settings. However, the role of ammonia in acute-on-chronic liver failure (ACLF) has not yet been clearly established and a cut-off value for the prediction of in-hospital mortality is not currently available.

Research objectives

We aimed to adequately assess the role of VA in predicting in-hospital mortality of cirrhotic patients with ACLF in a tertiary care center and to establish an indicative cut-off value for poor prognosis in these patients.

Research methods

We retrospectively included consecutive cirrhotic patients fulfilling the Asian Pacific Association for the Study of the Liver (APASL) criteria for ACLF that were hospitalized for acute non-elective indications such as ascites, HE, upper gastrointestinal bleeding, or bacterial infections. The study was conducted in “St. Spiridon” University Hospital, Iasi, Romania, a tertiary care center, between January 2017 and January 2019. Patients diagnosed with non-hepatic malignancy, human immunodeficiency virus infection, hematological disease as well as pregnant women were excluded. ACLF was defined according to the APASL criteria. The APASL ACLF Research Consortium (AARC) score was calculated and ACLF grade was established accordingly. West-haven classification was used for HE. Statistical analysis was performed using IBM SPSS version 22.0.

Research results

Five hundred and twenty patients were screened and after applying the exclusion criteria 446 patients were included, aged 59 (50-65) years, 57.4% men. The main etiology of LC was alcohol (78.7%), followed by hepatitis C virus (HCV) infection (11.2%), hepatitis B virus (HBV) infection (6.1%), alcohol and HBV (1.8%), alcohol and HVC (1.3%), HBV and HVC (0.7%). 66.4% had ACLF grade I, 31.2% ACLF grade II, and 2.5% ACLF grade III. HE was diagnosed in 83.9%, 34% grade I, 37.2% grade II, 23.5% grade III, and 5.3% grade IV. Overall mortality was 7.8% and the mean survival of the deceased patients was 5 (3-10) d. ROC analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score [Area under the curve (AUC) = 0.886], model for end-stage liver disease (MELD) score (AUC = 0.816), VA (AUC = 0.812) and a fair accuracy for the Child-Pugh score (AUC = 0.799). A cut-off value for the prediction of mortality was identified for VA (152.5 μmol/L, sensitivity = 0.706, 1-specificity = 0.190). We identified acute kidney injury, severe HE (grade III or IV), VA ≥ 152.5 μmol/L, MELD score ≥ 22.5, Child-Pugh score ≥ 12.5, and AARC score ≥ 8.5 to be associated with in-hospital mortality. Multivariate analysis found AARC score ≥ 8.5 and venous ammonia ≥ 152 μmol/L to be independent predictors of in-hospital mortality.

Research conclusions

Our data indicated that VA represented a useful prognostic marker for patients with ACLF diagnosed according to the APASL definition. Moreover, the cut-off value of 152.5 μmol/L was independently associated with the risk of death with a sensitivity = 0.706 for a 1-specificity = 0.190.

Research perspectives

Prospective large additional studies should be performed in order to confirm whether the use of ammonia lowering agents guided by VA levels could improve survival in patients with ACLF.