Effect of Simvastatin Use in Decreasing the Risk of Hepatic Encephalopathy in Patients with Cirrhosis

Abstract

Purpose: Portal hypertension is a consequence of end-stage liver disease, and is responsible for major clinical complications, such as bleeding from ruptured esophageal varices and the development of hepatic encephalopathy (HE). Simvastatin improves liver perfusion in cirrhosis and decreases portal hypertension via up-regulation of nitric oxide production in the vascular endothelium. Recent animal and human data suggest that statins could decrease intrahepatic vascular resistance and improve flow mediated vasodilatation in the cirrhotic liver. These effects are mediated by an up-regulation of NO production at the liver vasculature via an enhancement in endothelial NO activity. We hypothesized that, in patients with cirrhosis, simvastatin may prevent the development of HE by improving NO production in the liver microcirculation and by decreasing hepatic resistance. Methods: Medical records of 45 cirrhotic patients taking simvastain were compared with 46 cirrhotics not on simvastatin during a 4-year period from 2006- 2010. Univariable analysis and multivariable logistic regression were used to analyze the data. Results: The mean age of patients was 59.3 +/- 10.4 years, and 58.2% were male. Cirrhosis due to alcoholic liver disease was the most common etiology (47.3%), followed by hepatitis C virus (26.4%). Twentytwo percent of subjects on simvastatin had HE, compared to 39% of those not taking simvastain (Figure 1). On univariable analysis, higher MELD, CTP scores, hepatitis C, and low Na level< 135 mEq/ml were significantly associated with the development of HE. After adjusting (Table 1) for CTP scores and Na levels, use of simvastatin was not significantly associated with HE (p=0.67). Subjects with CTP scores B/C and Na < 135 were 5.8 (p=0.002) and 4 (p=0.01) times, respectively, more likely to have HE than those who had CTP score A and Na level > 135.FigureTable: Table. Association of Simvastatin with hepatic Encephalopathy-Multivariable Logistic Regression AnalysisConclusion: Patients with cirrhosis on simvastatin had decreased prevalence of HE, compared to those who were not on Simvastatin. However, simvastatin did not appear to significantly reduce rate of HE in cirrhotic patients, and larger studies are needed.