Identification de facteurs pronostiques délétères dans la cirrhose compliquée d'ascite réfractaire

Cirrhosis is characterized by the progressive development of portal hypertension. Portal hypertension, associated with sodium retention, leads to the formation of ascites. Ascites may be difficult to treat and, thereby, become "refractory". To date, the mortality of patients with refractory ascites remains high. In order to offer patients adequate treatment, it is important to identify complications that may develop and the factors of good and poor prognosis affecting their survival. One can retain five specific complications of cirrhosis with ascites: hepatorenal syndrome, spontaneous bacterial peritonitis, paracentesis induced circulatory dysfunction, hepatic hydrothorax and dilutional hyponatremia. This thesis reported an update of pathogenesis, complications and treatment of refractory ascites. Our original clinical research has, meanwhile, focused on the identification of different prognostic factors in refractory ascites in direct relation to these five complications. We have focused on the effect of the administration of beta blockers in patients with refractory ascites: this treatment is widely prescribed for prevention of gastrointestinal bleeding. It is associated in these patients with higher mortality and a high incidence of paracentesis induced circulatory dysfunction. We specified that the severe hyponatremia, leading to withhold diuretic therapy, is a more accurate prognostic factor than the MELDNa score in refractory ascites. With regard to the hepatorenal syndrome of slow onset (type 2), we emphasized the high frequency of this syndrome in refractory ascites. We showed that there was an association between the level of portal hypertension and the incidence of spontaneous bacterial peritonitis. Furthermore, we demonstrated that the presence of bacterial DNA in ascites of outpatients suffering from refractory ascites was particularly low. The detection of this DNA is not a precursor to infection of ascites. In conclusion, with a systematic analysis of various prognostic factors related to complications of ascites in cirrhotic patients, this work gives a better understanding of their chances of survival. This will allow a more adequate stratification in the decision trees for a cure of the disease such as liver transplantation.Doctorat en Sciences médicales