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

Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.


To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.


All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012–2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin.


188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality.


Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Keywords: Hepatic encephalopathy, Cirrhosis, Portal hypertension, Prognosis, Rifaximin, Lactulose

Core tip: The development of hepatic encephalopathy in cirrhotic patients continues to be associated with an extremely poor prognosis despite current standards-of-care and newer therapeutic options such as Rifaximin. In this study, the probability of survival at 12-mo was 44% after an episode of acute hepatic encephalopathy requiring hospital admission. Thus, in all patients with hepatic encephalopathy the appropriateness of urgent liver transplantation assessment should be considered.