|Keywords:||Cirrosi hepàtica; Cirrosis hepática; Hepatic cirrhosis; Insuficiència hepàtica; Insuficiencia hepática; Liver failure|
|Full text PDF:||http://hdl.handle.net/10803/396157|
Patients with cirrhosis may develop significant complications of renal function manifested initially by increased sodium retention followed by impaired solute-free water excretion, and finally with renal vasoconstriction. These alterations are responsible for fluid accumulation in the form of ascites, hyponatremia and hepatorenal syndrome respectively. Patients with cirrhosis and hyponatremia have high levels of vasopressin. Patients with cirrhosis that develop acute complications such as ascites, hepatic encephalopathy, hyponatremia, gastrointestinal bleeding, and/or bacterial infections can be classified into those with mere decompensated cirrhosis and those in whom an acute event ifs followed with progressive liver and/or extrahepatic organ failure(s). These latter patients have a poor prognosis and have been defined as having acute on chronic liver failure (ACLF) ACLF defines a subgroup of cirrhotic patients who develop organ failure(s) following hospital admission with or without an identifiable precipitating event. Therapy for cirrhotic patients with hyponatremia with an antagonist of vasopressin (Tolvaptan) and the relationship of hyponatremia and ACLF remain unknown. The aim of this thesis was to evaluate the safety and efficacy of tolvaptan in raising serum sodium levels in patients with cirrhosis and ascites and determine the specific effects hyponatremia on the outcome of patients with ACLF. Patients with cirrhosis and hyponatremia that received tolvaptan for 1 month effectively increased serum sodium concentration in hyponatremic patients with cirrhosis. Compared to placebo tolvaptan also caused a significant increase in urine output and fluid intake and a negative fluid balance during first day after the initial dose. There also was a significant improvement in some components of health related quality of life (SF 12 health survey mental component scores) at the end of the study. Serum sodium levels reverted to baseline levels 1 week after stopping tolvaptan. In a sub-analysis of the CANONIC study ( a large study that re-defined ACLF in several European centers) patients with cirrhosis ACLF was more common in patients with hyponatremia (36%) compared to those without it (20%). On the other hand, the prevalence of hyponatremia in patients with ACLF was double than that in patients without ACLF (24% vs 12%, respectively). The most important finding of this analysis was the demonstration that hyponatremia influences the outcome of patients with ACLF. Moreover, both hyponatremia and ACLF independently affect this outcome. This means that hyponatremia in patients without ACLF significantly increases the risk of dying. However, even more interesting is the fact that if patients have both ACLF and hyponatremia (compared to those without either) then the risk of dying is almost 7 times higher. These findings indicate that hyponatremia influences the outcome of patients with ACLF.