Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

Abstract

Background: 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.

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

Methods: 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.

Results: 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.

Conclusion: 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: Cirrhosis; Hepatic encephalopathy; Lactulose; Portal hypertension; Prognosis; Rifaximin.

Figure 1

Recruitment flowchart. HE: Hepatic encephalopathy; HCC: Hepatocellular carcinoma.

Figure 2

Transplant-free survival probability following commencement of rifaximin.