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Epilepsy linked to hepatic encephalopathy in patients with cirrhosis

Patients with cirrhosis and epilepsy are at higher risk for hepatic encephalopathy, according to research published in BMC Gastroenterology.

“Our motivation for this study was to understand why epilepsy was associated with a 1.31-fold increased mortality among patients with cirrhosis,” Peter Jepsen, MD, PhD, of the department of hepatology and gastroenterology at Aarhus University Hospital in Denmark, and colleagues wrote. “Understanding the risk of [hepatic encephalopathy (HE)] in patients with epilepsy may add to our understanding of the pathogenesis of HE and improve our management of cirrhosis patients who have epilepsy.”

Researchers used Cox regression analysis while examining three randomized trials using Aquilda (satavaptan, Sanofi-Aventis) to treat ascites. The trials included 1,120 patients with cirrhosis and varying degrees of ascites. Of these, 1.9% (n = 21) had an epilepsy diagnosis.

Each trial was intended to last 52 weeks, Jepsen and colleagues wrote, but poor risk–benefit ratios forced the second and third trials to end prematurely, resulting in 622.2 person-years of follow-up. Researchers found 304 patients with cirrhosis had an occurrence of HE and 45 patients died without developing HE.

Despite a median MELD score of 7.9 in the patients with epilepsy vs. 11.4 in those without epilepsy (P < .02), seven of the 21 patients had an HE episode during follow-up. Occurrence of HE was 0.67 episodes per person-year for these patients. The occurrence of HE was 0.49 episodes per person-year for the 1,099 cirrhosis patients without epilepsy.

After adjusting for confounding factors, the rate of patients with HE and epilepsy vs. those who did not have it more than doubled (adjusted HR = 2.12; 95% CI, 0.99–4.55).

Secondary analysis
Researchers also put patients through a second categorization process, in which 0.7% (n = 8) had “definite epilepsy,” defined as epilepsy diagnosis and use of antiepileptic drugs; 1.1% (n = 12) had a background of seizures but were not taking antiepileptic drugs at the time; and 1.4% (n = 16) used antiepileptic drugs for reasons not associated with epilepsy.

Researchers found the point estimate for definite epilepsy vs. controls (adjusted HR = 2.49; 95% CI, 0.78–7.9) mirrored the estimate for epilepsy vs. controls in the primary analysis. Patients classified as having unspecified seizures and those using antiepileptic drugs for non-epilepsy indications had higher HE rates than the controls, but not as high as patients with definite epilepsy.

“Epilepsy’s association with HE development in the trial data suggests that epilepsy might also have been a risk factor for mortality if patients had been followed for longer than 1 year,” Jepsen and colleagues wrote. “It is evident that this study is limited by the small number of patients with epilepsy and the short duration of follow-up, but a stronger dataset will not emerge in the foreseeable future.” – by Janel Miller

Disclosure: Jepsen received funding from the Danish Council for Independent Research under the Danish Agency for Science, Technology and Innovation (10-081838/FSS).  The other researchers report no relevant financial disclosures.