Pathogenesis of ascites and predictors of resistance to therapy


Professor Roberto de Franchis, Department of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy. Email:


Abstract  Ascites is one of the most frequent complications of cirrhosis. Its appearance is considered as the marker of the transition from the compensated to the decompensated stage of the disease. Appearance of ascites also has prognostic significance, as it causes a sharp drop in the expected survival rate. Portal hypertension is a sine qua-non for the development of ascites. Although no precise portal pressure threshold has been defined for the development of ascites, the latter rarely develops with portal pressures below 12 mmHg. In addition, in patients treated with interventions that markedly decrease portal pressure, such as surgical porta-caval shunts or transjugular intrahepatic portalsystemic shunts, a disappearance or a marked reduction of ascites can be observed. The currently most accepted theory of ascites formation is the so-called ‘forward’ theory. According to this theory, the development of ascites is related to the presence of severe sinusoidal portal hypertension, which causes marked splanchnic arterial vasodilation and a forward increase in the splanchnic production of lymph. Splanchnic arterial vasodilation also causes a significant reduction of the effective blood volume, leading to activation of sodium and water-retaining mechanisms. The retained sodium and water, however, while increasing total plasma volume, are unable to compensate for the reduced effective blood volume, initiating a vicious cycle. In the advanced stages of cirrhosis, the extreme underfilling of the arterial circulation leads to a maximal stimulation of the vasoconstrictor mechanisms which override the protective effect of renal vasodilator factors and cause renal vasoconstriction, further aggravating ascites and leading to functional renal insufficiency. Renal insufficiency is also one of the main causes of resistance to diuretic therapy. While several studies have investigated the predictors of survival in cirrhotic patients with ascites, this has not been done for the occurrence of resistance to therapy. However, as the mechanisms of refractoriness are associated with advanced disease and short survival, the models developed for predicting survival should be employed also to verify if they can exert such additional prediction.

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