To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites
To Study the Effect of Nonselective Beta Blockers in Advanced Stage Liver Disease With Ascites
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.
Inclusion Criteria:

 1. Cirrhosis of any etiology with grade 2 ascites including refractory patients and
 varices/variceal hemorrhage requiring prophylaxis

 2. Cirrhosis diagnosed by clinical, analytical, and ultrasonographic findings or
 available histological findings

 3. Both inpatient and outpatient

 4. Child B or C status

 Exclusion

 1. Active infection or recent infection < 2 weeks

 2. Hepatic encephalopathy grade 2 or higher

 3. Renal dysfunction at the time of inclusion

 4. Presence of hepatocellular carcinoma or portal vein thrombosis

 5. Active alcoholism

 6. Pregnancy

 7. HIV infection

 8. Severe heart, respiratory or contraindications for beta blockers(severe chronic
 obstructive pulmonary disease, severe asthma, severe insulin-dependent diabetes
 mellitus, bradyarrhythmia)

 9. Not giving consent