Original article
Pancreas, biliary tract, and liver
Hepatic Encephalopathy Is Associated With Mortality in Patients With Cirrhosis Independent of Other Extrahepatic Organ Failures

https://doi.org/10.1016/j.cgh.2016.09.157Get rights and content

Background & Aims

Although survival times have increased for patients with cirrhosis, hepatic encephalopathy (HE) remains a major complication and its relative contribution toward mortality in North America is unclear. We investigated whether HE is associated with mortality independent of extrahepatic organ failures (EHOFs).

Methods

We collected data from the North American Consortium for Study of End-stage Liver Disease database of hospitalized patients with cirrhosis at tertiary-care centers. EHOFs were defined as need for ventilation (respiratory failure), dialysis (renal failure), or shock (circulatory failure). We analyzed in-hospital and 30-day mortality for patients with varying HE grades and EHOF using adjusted models.

Results

We analyzed data from 1560 patients, 516 with HE (371 grade 1–2 and 145 grade 3–4). Patients with maximum HE grade 3–4 HE during hospitalization had a higher median model for end-stage liver disease (MELD) score (22) than patients with HE grade 1–2 (MELD score, 19) or no HE (MELD score, 18) (P < .0001). Thirty-day mortality for patients with HE grade 3–4 was significantly higher (38%) than for patients with HE grade 1–2 (8%) or no HE (7%). A total of 107 patients had 2 or more EHOFs, with or without HE; 151 had 1 EHOF and 1302 had no organ failure. Unadjusted mortality was highest for patients with HE of grade 3–4 with 2 EHOFs (n = 44). On regression analysis, HE severity was significantly associated with in-hospital and 30-day mortality, independent of any EHOF, white blood cell count, systemic inflammatory response syndrome, or MELD score (odds ratio, 3.3; P < .0001).

Conclusions

In an analysis of more than 1500 patients hospitalized for cirrhosis, HE of grade 3 or 4 was associated with higher in-hospital and 30-day mortality, independently of failure of other organs.

Section snippets

Methods

The prospectively enrolled patients in NACSELD include patients with cirrhosis who are hospitalized for nonelective reasons. The diagnosis of cirrhosis was made using biopsy, endoscopic or radiological evidence of portal hypertension or cirrhosis, and/or signs of hepatic decompensation (HE, ascites, variceal bleeding, jaundice, and/or hepatorenal syndrome). Patients were excluded for human immunodeficiency virus, an unclear diagnosis of cirrhosis, a prior liver transplant, those who had an

Results

We enrolled 1576 patients; 13 had incomplete information regarding maximum HE grade and EHOF, and 7 had incomplete information regarding admission HE grade and EHOF. Therefore, for the maximum HE grade 1560 patients were studied, and 1569 were studied in the analysis of admission HE. The mean age was 57 ± 7 years, most of whom were men (64%). Prior HE on admission was present in 57% of patients, of whom 38% were on rifaximin therapy. Patients who had HE either on admission or those who

Discussion

With the changing landscape of cirrhosis complications, HE has emerged as one of the leading causes for hospitalization and readmission in patients with cirrhosis.1, 11, 12 Because HE can be precipitated by several important factors, such as infections, gastrointestinal bleeding, and electrolyte abnormalities, trends in HE management likely reflect the underlying approach to almost all important cirrhosis-associated reasons for hospitalization.5, 12

The issues with HE grade identification have

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    Conflicts of interest These authors disclose the following: Jasmohan S. Bajaj has served as a consultant for Valeant, Grifols, Norgine, and Abbott. PJT, Jacqueline G. O’Leary, Florence Wong, Patrick S. Kamath, and K. Rajender Reddy have served as consultants for Grifols. The remaining authors disclose no conflicts.

    Funding This study was partly supported by an investigator-initiated grant from Grifols Pharmaceuticals.

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