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Researchers find diabetes to be first-time risk factor for overt HE

Diabetes was found to be associated with an increased risk of first-time overt hepatic encephalopathy among patients with cirrhosis and ascites, according to data published in the Journal of Hepatology.

The researchers analyzed data from three clinical trials conducted between July 2006 and December 2008 that evaluated the efficacy of satavaptan (Aquilda, Sanofi-Aventis) for the treatment of ascites in cirrhotic patients. Among these patients, 462 had diuretic-manageable ascites, 496 with ascites managed by diuretics and occasional paracentesis and 240 had diuretic-resistant ascites managed by therapeutic paracentesis. The patients who experienced a previous hepatic encephalopathy (HE) episode (n = 306), had HE at the time of the trial (n = 26), had no observed Child-Pugh class (n = 3) or serum biochemistry (n = 1) were excluded from the final analysis.

“The risk factors for first-time development of HE may be different from the risk factors for recurrence of HE or progression of HE, and our interest was in first-time development,” the researchers wrote.

Among 862 patients, 115 experienced first-time occurrences of overt HE during follow-up. Of all the patients, 22% had diabetes (n = 193). The patients with diabetes had a higher cumulative risk for first-time overt HE compared with the non-diabetic patients after 1 year (26% vs. 15.8%), with a confounder-adjusted hazard ratio of 1.86 (95% CI, 1.2-2.87).  In addition, the diabetic patients were more likely to have more severe first-time overt HE and have it progress beyond grade 2 compared with the non-diabetic patients (64% vs. 42%; P = .01), according to the research.

Patients with diabetes treated with insulin (n = 85) had an increased first-time overt HE risk compared with non-diabetic patients (adjusted HR = 2.19; 95% CI, 1.26-3.81). Diabetics treated with metformin (n = 25) also showed an increased risk compared with non-diabetic patients (adjusted HR = 2.03; 95% CI, 0.83-4.96) and diabetic patients treated with dieting alone (adjusted HR = 1.70; 95% CI, 0.78-3.70). The diabetic patients treated with oral antidiabetic drugs (n = 36) besides metformin had the same rate of first-time risk of overt HE as the non-diabetic patients (adjusted HR = 1.13; 95% CI, 0.4-3.19).

Predictors of an increased rate of first-time overt HE were poor liver status, high bilirubin, low albumin, low sodium, high creatinine and lactulose use.

“The clinical implications of our findings are limited by the observational study design, but clinicians might consider lactulose treatment for primary prevention of HE in cirrhosis patients with diabetes, particularly in those who also possess other risk factors for HE development. … It should be noted that diabetes had the same HE-promoting effect among current users or non-users of lactulose. This finding indicated that lactulose does not eliminate the effect of diabetes on HE development.”

The researchers concluded: “Diabetes is a risk factor for first-time development of overt HE in cirrhosis patients with ascites, and … diabetics’ HE episodes are more severe and develop earlier in the clinical course of cirrhosis.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.