Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2020; 26(18): 2221-2231
Published online May 14, 2020. doi: 10.3748/wjg.v26.i18.2221
Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care
Anuj Bohra, Thomas Worland, Samuel Hui, Ryma Terbah, Ann Farrell, Marcus Robertson
Anuj Bohra, Thomas Worland, Samuel Hui, Ann Farrell, Marcus Robertson, Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
Thomas Worland, Ryma Terbah, Marcus Robertson, Department of Gastroenterology, Austin Health, Heidelberg 3084, Victoria, Australia
Marcus Robertson, Department of Medicine, School of Clinical Sciences, Monash University, Clayton 3168, Victoria, Australia
Author contributions: Bohra A performed the acquisition of data, analysis and interpretation of data, statistical analysis and drafting of manuscript; Worland T and Terbah R performed the acquisition of data; Hui S performed the acquisition of data and statistical analysis; Farrell A designed the study concept, performed acquisition of data and statistical analysis; Robertson M designed the study concept, performed acquisition and analysis of data, drafting of the manuscript and critical revision of the manuscript; all authors approved the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Human Research Ethics Committee at Monash Health as audit activity.
Informed consent statement: The Human Research Ethics Committee at Monash Health provided a waiver for informed consent. Reference number: RES-19-0000-296Q.
Conflict-of-interest statement: We have no financial relationships to disclose.
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:
Corresponding author: Anuj Bohra, BMed, Doctor, Department of Gastroenterology, Monash Health, 246 Clayton Road, Clayton 3168, Victoria, Australia.
Received: December 31, 2019
Peer-review started: December 31, 2019
First decision: February 19, 2020
Revised: March 27, 2020
Accepted: May 1, 2020
Article in press: May 1, 2020
Published online: May 14, 2020
Research background

Hepatic encephalopathy (HE) is a common neuropsychiatric complication in patients with liver cirrhosis and represents the second most common decompensating event after ascites. The current treatment approach for HE includes the reversal of identifiable underlying precipitants and the use of ammonia-lowering agents such as lactulose and rifaximin.

Research motivation

Previous sentinel studies have demonstrated that development of HE is associated with extremely poor transplantation-free survival. There remains a paucity of literature examining the natural history and prognosis of HE in the post-rifaxamin era.

Research objectives

We aimed to evaluate the clinical outcomes and survival probability of cirrhotic patients who developed acute HE requiring admission to hospital and were treated with rifaxamin in addition to current standards-of-care. In addition, we aimed to identify factors at the time of HE that could predict mortality and highlight the need to consider liver transplantation.

Research methods

We performed a retrospective, multi-centre analysis of 188 patients admitted with HE and commenced on rifaxmin with a mean follow-up period of 12 ± 13 mo. Survival probability curves were calculated using the Kaplan-Meier method. Univariate survival analysis was performed using the Cox proportional hazards model. Variables which reached statistical significance (P ≤ 0.05) were subsequently included in a multivariate analysis to identify factors independently associated with survival using the stepwise Cox regression procedure.

Research results

In patients with acute HE requiring hospital admission and treated with current standards-of-care, the probability of survival remains poor with a 1- and 3-year survival probability of 44% and 29% respectively. The majority of patients have an identifiable precipitant for HE and the most common cause of death was liver failure or complications of decompensated cirrhosis. Baseline international normalised ratio and a model for end stage liver disease score ≥ 15 reached statistical significance on multivariate analysis to predict mortality.

Research conclusions

Despite advances in treatment, the development of acute HE in cirrhotic patients continues to confer an extremely poor prognosis and a low probability of survival in the absence of liver transplantation. Both international normalised ratio, a marker of synthetic liver dysfunction, and model for end stage liver disease score, which is well-validated to prognosticate survival in advanced liver disease, were able to independently predict survival probability at the time of admission.

Research perspectives

The development of HE in a cirrhotic patient is an extremely serious complication that typically occurs late in the disease process and confers an extremely poor prognosis. Inpatient management of HE with current standards-of-care can successfully resolve the episode of HE in the majority of cases but has limited ability to affect the natural sequalae of the advanced disease state. In all cirrhotic patients, the development of HE should prompt consideration of the appropriateness of liver transplantation. Further prospective studies would be useful to investigate the survival benefits of rifaxamin in patients with advanced cirrhosis and HE.