Efficacy and Safety of Carvedilol in Cirrhosis Patients With Uncomplicated Ascites Without High Risk Esophageal Varices
Status:
Recruiting
Trial end date:
2023-08-30
Target enrollment:
Participant gender:
Summary
The cumulative risk of refractory ascites is in the order of 20% within five years of the
development of ascites. An elevated sinusoidal pressure is essential for the development of
ascites, as fluid accumulation does not develop at portal pressure gradient below 8 mm Hg,
and rising corrected sinusoidal pressure correlates with decreased 24-hour urinary excretion
of sodium.More recently, it has been hypothesised that bacterial translocation associated
with portal hypertension in cirrhosis and related pathogen-associated, molecular pattern
activated innate immune responses lead to systemic inflammation.This is associated with
vasodilatation as well as release of proinflammatory cytokines, reactive oxygen and nitrogen
species, contributing to organ dysfunction.This activates sympathetic nervous system
stimulating reabsorption of sodium in proximal,distal tubules, loop of Henle and collecting
duct as well as the renin-angiotensin-aldosterone system, leading to sodium absorption from
distal tubule and collecting duct.[5]Renal sodium retention and eventual free water clearance
due to non-osmoticrelease of arginine-vasopressin and its action on V2 receptor in the
collectingduct underlie the fluid retention associated with oedema and ascites in
cirrhosis.The lowering of portal pressure using non selective beta blocker has also been
shown to reduce the development of ascites, refractory ascites and hepatorenal
syndrome.Furthermore, the effect of non slective beta blocker on intestinal permeability,
bacterial translocation and inflammatory response has been proposed to mitigate the risk of
developing spontaneous bacterial peritonitis.