To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites

Overview

Cirrhosis is the leading cause of death in India and worldwide and leading causes in developed world include alcoholic liver disease, hepatitis C, and more recently, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH). As cirrhosis advances, portal hypertension develops, resulting in complications such as ascites, hepatic encephalopathy, and variceal hemorrhage. Ascites is the most common major complication of cirrhosis, occurring in 50-60% of patients within ten years of diagnosis . Development of ascites is an ominous landmark in disease progression as 15% of patients with ascites will die within 1 year, and 44% within 5 years. Less than 10% patients develop refractory ascites and is associated with a poor prognosis with a high mortality, approximately 50% within 6 months and 75% at 1 year with the median survival approximately 6 months . Refractory ascites occurs as a result of splanchnic vasodilatation and maximal activation of the sympathetic nervous system (SNS) and the renin - aldosterone system (RAAS) . The therapeutic options available for these patients are serial therapeutic paracentesis, liver transplantation and trans jugular intrahepatic portosystemic shunts .The model for end stage liver disease( MELD) score predicts survival in patients with cirrhosis . However, other factors in patients with cirrhosis and ascites are also associated with poor prognosis, including low mean arterial pressure; low serum sodium, low urine sodium, and high Child-Pugh score . Variceal bleed is the most dreaded complication of cirrhosis and screening endoscopic is recommend in these patients. About 60% of patients with decompensated cirrhosis have varices at the time of diagnosis. Majority of these patients will require non selective beta blockers (NSBB) as standard of care as primary or secondary prophylaxis in prevention of variceal hemorrhage. NSBB reduce portal pressure by decreasing cardiac output and by producing splanchnic vasoconstriction.. Endoscopic variceal band ligation (EVL) is another modality of treatment of esophageal varices and meta-analysis showed EVL to be associated with significantly lower incidence of first variceal hemorrhage without differences in mortality compared to NSBB. NSBB also has shown to improve survival in these patients with nonhemodynamic effects. Some of the patients may progress to end stage liver disease characterized by the development of refractory ascites and other complications. Most of the studies of NSBB comparing to EVL for primary/secondary prevention of variceal hemorrhage included patients of predominantly child A/B cirrhosis with variable number with ascites without any mention of ascites grading and some of trials excluded patient's with refractory ascites. These patients with ascites received diuretics and salt restricted diet as standard of care. However none of these studies mentioned about control of ascites and survival benefit in patients with advanced stage (child B and C) cirrhosis with ascites .In recent years the role of NSBB for prevention of variceal hemorrhage in refractory ascites patients has been questioned because of the deleterious effect on survival.However the use of NSBB in end stage liver disease has shown mixed results and controversial. Therefore this study is being planned to know the effects of NSBB in advanced stage liver disease patients with ascites and varices in preventing variceal hemorrhage ,effect on ascites and survival.