Jepsen et al. BMC Gastroenterology (2016) 16:77 DOI 10.1186/s12876-016-0487-3
RESEARCH ARTICLE
Open Access
Epilepsy as a risk factor for hepatic encephalopathy in patients with cirrhosis: a cohort study Peter Jepsen1,2* , Jakob Christensen3, Karin Weissenborn4, Hugh Watson5 and Hendrik Vilstrup1
Abstract Background: Epilepsy is associated with an increased mortality among cirrhosis patients, but the reasons are unknown. We aimed to determine whether epilepsy is a risk factor for developing hepatic encephalopathy (HE), which is a strong predictor of mortality. Methods: We used data from three randomized 1-year trials of satavaptan in cirrhosis patients with ascites. With Cox regression, we compared the hazard rates of HE grade 1–4 between those cirrhosis patients who did or did not have epilepsy. We adjusted for confounding by gender, age, cirrhosis etiology, diabetes, history of HE, Model for Endstage Liver Disease (MELD) score, serum sodium, albumin, lactulose use, rifaximin use, and benzodiazepine/ barbiturate sedation. In a supplementary analysis we examined the association between epilepsy and the hazard rate of HE grade 2–4. Results: Of the 1120 cirrhosis patients with ascites, 21 (1.9 %) were diagnosed with epilepsy. These patients had better liver function at inclusion than the patients without epilepsy (median MELD score 7.9 vs. 11.4), and only one died during the trials. Nevertheless, seven patients with epilepsy had an HE episode during the follow-up, and the adjusted hazard ratio of HE grade 1–4 for patients with epilepsy vs. controls was 2.12 (95 % CI 0.99–4.55). The corresponding hazard ratio of HE grade 2–4 was 3.83 (95 % CI 1.65–8.87). Conclusions: Our findings suggest that epilepsy is associated with an increased risk of HE in patients with cirrhosis. Keywords: End-stage liver disease, Neurology, Seizures, Liver failure, Prognosis
Background We have previously shown that patients with liver cirrhosis who have been given a diagnosis of epilepsy have a higher mortality than other patients with cirrhosis [1]. Unfortunately, we could not determine the reasons for that association, and no one else has studied it. However, sporadic case reports have described that hepatic encephalopathy (HE) may manifest as status epilepticus [2, 3], and since HE is a very strong predictor of mortality in cirrhosis patients [4], we thought that epilepsy might increase the risk of HE in cirrhosis patients.
* Correspondence: [email protected] 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus, Denmark 2 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Full list of author information is available at the end of the article
Epilepsy has a prevalence of about 3 % among Danish cirrhosis patients [1], and these patients have a 1-year HE risk around 15 % [4]. Therefore it is necessary to have a large cohort of cirrhosis patients to obtain meaningful estimates of the association between epilepsy and HE risk. We had access to the complete original dataset from three large randomized controlled trials of satavaptan treatment of ascites in nearly 1200 patients with cirrhosis who were followed for 1 year, and these data presented a unique opportunity to study epilepsy as a risk factor for HE. Satavaptan had no effect on the development of HE [5]. Given this background, the aim of this study was to examine the effect of epilepsy on HE risk in patients with cirrhosis. Understanding the risk of 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.
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Jepsen et al. BMC Gastroenterology (2016) 16:77
Methods Between July 2006 and December 2008 three multinational randomized controlled trials were conducted to examine whether satavaptan was efficacious in treating ascites in cirrhosis patients [6]. The three trials included patients with differing severity of ascites, but were otherwise similar and included 1,198 patients in total. Patients with a functioning transjugular intrahepatic portosystemic shunt were excluded from the trials, as were patients with variceal bleeding or spontaneous bacterial peritonitis in the 10 days before randomization. Other reasons for exclusion were: serum creatinine >151 μmol/L, serum potassium ≥5.0 mmol/L, serum sodium >143 mmol/ L (because satavaptan may increase the serum sodium concentration), serum bilirubin >150 μmol/L, INR >3.0, platelets
RESEARCH ARTICLE
Open Access
Epilepsy as a risk factor for hepatic encephalopathy in patients with cirrhosis: a cohort study Peter Jepsen1,2* , Jakob Christensen3, Karin Weissenborn4, Hugh Watson5 and Hendrik Vilstrup1
Abstract Background: Epilepsy is associated with an increased mortality among cirrhosis patients, but the reasons are unknown. We aimed to determine whether epilepsy is a risk factor for developing hepatic encephalopathy (HE), which is a strong predictor of mortality. Methods: We used data from three randomized 1-year trials of satavaptan in cirrhosis patients with ascites. With Cox regression, we compared the hazard rates of HE grade 1–4 between those cirrhosis patients who did or did not have epilepsy. We adjusted for confounding by gender, age, cirrhosis etiology, diabetes, history of HE, Model for Endstage Liver Disease (MELD) score, serum sodium, albumin, lactulose use, rifaximin use, and benzodiazepine/ barbiturate sedation. In a supplementary analysis we examined the association between epilepsy and the hazard rate of HE grade 2–4. Results: Of the 1120 cirrhosis patients with ascites, 21 (1.9 %) were diagnosed with epilepsy. These patients had better liver function at inclusion than the patients without epilepsy (median MELD score 7.9 vs. 11.4), and only one died during the trials. Nevertheless, seven patients with epilepsy had an HE episode during the follow-up, and the adjusted hazard ratio of HE grade 1–4 for patients with epilepsy vs. controls was 2.12 (95 % CI 0.99–4.55). The corresponding hazard ratio of HE grade 2–4 was 3.83 (95 % CI 1.65–8.87). Conclusions: Our findings suggest that epilepsy is associated with an increased risk of HE in patients with cirrhosis. Keywords: End-stage liver disease, Neurology, Seizures, Liver failure, Prognosis
Background We have previously shown that patients with liver cirrhosis who have been given a diagnosis of epilepsy have a higher mortality than other patients with cirrhosis [1]. Unfortunately, we could not determine the reasons for that association, and no one else has studied it. However, sporadic case reports have described that hepatic encephalopathy (HE) may manifest as status epilepticus [2, 3], and since HE is a very strong predictor of mortality in cirrhosis patients [4], we thought that epilepsy might increase the risk of HE in cirrhosis patients.
* Correspondence: [email protected] 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus, Denmark 2 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Full list of author information is available at the end of the article
Epilepsy has a prevalence of about 3 % among Danish cirrhosis patients [1], and these patients have a 1-year HE risk around 15 % [4]. Therefore it is necessary to have a large cohort of cirrhosis patients to obtain meaningful estimates of the association between epilepsy and HE risk. We had access to the complete original dataset from three large randomized controlled trials of satavaptan treatment of ascites in nearly 1200 patients with cirrhosis who were followed for 1 year, and these data presented a unique opportunity to study epilepsy as a risk factor for HE. Satavaptan had no effect on the development of HE [5]. Given this background, the aim of this study was to examine the effect of epilepsy on HE risk in patients with cirrhosis. Understanding the risk of 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.
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Jepsen et al. BMC Gastroenterology (2016) 16:77
Methods Between July 2006 and December 2008 three multinational randomized controlled trials were conducted to examine whether satavaptan was efficacious in treating ascites in cirrhosis patients [6]. The three trials included patients with differing severity of ascites, but were otherwise similar and included 1,198 patients in total. Patients with a functioning transjugular intrahepatic portosystemic shunt were excluded from the trials, as were patients with variceal bleeding or spontaneous bacterial peritonitis in the 10 days before randomization. Other reasons for exclusion were: serum creatinine >151 μmol/L, serum potassium ≥5.0 mmol/L, serum sodium >143 mmol/ L (because satavaptan may increase the serum sodium concentration), serum bilirubin >150 μmol/L, INR >3.0, platelets
