Author information

1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: pj@clin.au.dk. 2Sanofi Aventis R&D, Paris, France. 3Department of Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark. 4Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Abstract

BACKGROUND & AIMS: It remains unclear whether diabetes increases the risk for hepatic encephalopathy (HE) in cirrhosis patients. We examined this question using data from three randomized trials of satavaptan, a vasopressin receptor antagonist that does not affect HE risk, in cirrhosis patients with ascites.

METHODS: The trials included 1198 patients, and we excluded those with HE before or at randomization and followed the remaining patients for the one-year duration of the trials. They were examined for HE regularly, and we compared ratesoffirst-timeovertHE between diabetics and non-diabetics using Cox regression, adjusting for gender, age, ascites severity, cirrhosis etiology, Child-Pugh class, creatinine, bilirubin, INR, sodium, potassium, albumin, platelets, lactulose use, benzodiazepine/barbiturate use, spironolactone dose, furosemide dose, potassium-sparing diuretic dose, and CirCom comorbidity score.

RESULTS: We included 862 patients of whom 193 (22%) had diabetes. In total, they experienced 115first-timeepisodesofovertHE during the follow-up. Fewerdiabeticsthannon-diabeticswereinChild-PughclassCatbaseline(13%vs.23%), yet they had higher cumulative risk of first-timeovertHE (26.0% vs. 15.8% after 1 year), and their episodes of first-timeovertHE were more likely to progress beyond grade 2 (64% vs. 42% of episodes progressed to grade 3 or 4, P=0.01forindependencebetweendiabetesandhighestHEgrade). After the confounder adjustment, the hazard ratio of first-time overt HE for diabetics vs. non-diabetics was 1.86 (95% CI 1.20-2.87).

CONCLUSIONS: Diabetes increased the risk of first-time overt HE among cirrhosis patients with ascites.