Ascites in Cirrhosis With Severe Portal Hypertension
Ascites in Cirrhosis With Severe Portal Hypertension
OBJECTIVES: In compensated cirrhosis, a threshold value of hepatic venous pressure gradient (HVPG) ≥10 mm Hg is required for the development of decompensation. However, whether the treatment of portal hypertension (PHT) can prevent the transition into development of ascites once this level has been reached is unclear. Our aim was to assess the relationship between changes in HVPG induced by β-blockers and development of ascites in compensated cirrhosis with severe PHT.
METHODS: Eighty-three patients without any previous decompensation of cirrhosis, with large esophageal varices and HVPG ≥12 mm Hg were included. After baseline hemodynamic measurements nadolol was administered and a second hemodynamic study was repeated 1–3 months later.
RESULTS: During 53±30 months of follow-up, decompensation occurred in 52 patients (62%) and in 81% of them ascites was the first manifestation. Using receiver operating characteristic curve analysis a decrease in HVPG ≥10% was the best cutoff to predict ascites. As compared with nonresponders, patients with an HVPG decrease ≥10% had a lower probability of developing ascites (19% vs. 57% at 3 years, P<0.001), refractory ascites (P=0.007), and hepatorenal syndrome (P=0.027). By Cox regression analysis hemodynamic nonresponse was the best predictor of ascites. By stepwise logistic regression, development of ascites was independently associated with nonresponse, whereas refractory ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis were not.
CONCLUSIONS: In patients with compensated cirrhosis and large varices treated with β-blockers, an HVPG decrease ≥10% significantly reduces the risk of developing ascitic decompensation and other related complications such as refractory ascites or hepatorenal syndrome.
The natural history of cirrhosis involves the progression from a compensated to a decompensated stage characterized by the development of complications, such as ascites, variceal bleeding, or encephalopathy. Decompensation is a key event heralding the onset of significant morbidity and mortality. Portal hypertension (PHT), usually estimated by the hepatic venous pressure gradient (HVPG), is involved in the development of most complications of cirrhosis and is the strongest predictor of clinical decompensation. Even in the compensated phase of cirrhosis, two stages with different probability of survival have been delineated based on the presence or absence of varices. Clinically significant PHT is diagnosed when HVPG is ≥ 10 mm Hg as both varices and decompensation of cirrhosis may appear at this point. However, once this threshold has been reached the relationship between changes in HVPG (such as those induced by drug therapy) and development of decompensation has not been sufficiently investigated. The prognostic value of HVPG monitoring to predict bleeding is well established, but its utility in the prediction of other complications is unclear. Ascites is the most frequent complication of cirrhosis and is often the first decompensation to appear. It has been demonstrated that, in patients with decompensated cirrhosis receiving drug therapy to prevent variceal rebleeding, a reduction of HVPG to <12 mm Hg or ≥ 20% from baseline, in addition to a marked decrease in rebleeding risk, is also associated with a significant reduction of the risk of ascites, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, and also with an improvement in survival. However, whether pharmacological treatment of PHT by reducing portal pressure can prevent the transition of compensated cirrhosis into development of ascites is unclear, particularly in the stage with varices in which the risk of decompensation is higher. Furthermore, predictors of development of ascites in patients with compensated cirrhosis and severe PHT remain undefined.
The aim of this study was to elucidate the relationship between the changes in induced by β-blocker on PHT and development of first ascitic decompensation in patients with compensated cirrhosis, severe PHT, and large esophageal varices treated for primary prophylaxis of bleeding. Other predictive factors of development of ascites were also investigated.
Abstract and Introduction
Abstract
OBJECTIVES: In compensated cirrhosis, a threshold value of hepatic venous pressure gradient (HVPG) ≥10 mm Hg is required for the development of decompensation. However, whether the treatment of portal hypertension (PHT) can prevent the transition into development of ascites once this level has been reached is unclear. Our aim was to assess the relationship between changes in HVPG induced by β-blockers and development of ascites in compensated cirrhosis with severe PHT.
METHODS: Eighty-three patients without any previous decompensation of cirrhosis, with large esophageal varices and HVPG ≥12 mm Hg were included. After baseline hemodynamic measurements nadolol was administered and a second hemodynamic study was repeated 1–3 months later.
RESULTS: During 53±30 months of follow-up, decompensation occurred in 52 patients (62%) and in 81% of them ascites was the first manifestation. Using receiver operating characteristic curve analysis a decrease in HVPG ≥10% was the best cutoff to predict ascites. As compared with nonresponders, patients with an HVPG decrease ≥10% had a lower probability of developing ascites (19% vs. 57% at 3 years, P<0.001), refractory ascites (P=0.007), and hepatorenal syndrome (P=0.027). By Cox regression analysis hemodynamic nonresponse was the best predictor of ascites. By stepwise logistic regression, development of ascites was independently associated with nonresponse, whereas refractory ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis were not.
CONCLUSIONS: In patients with compensated cirrhosis and large varices treated with β-blockers, an HVPG decrease ≥10% significantly reduces the risk of developing ascitic decompensation and other related complications such as refractory ascites or hepatorenal syndrome.
Introduction
The natural history of cirrhosis involves the progression from a compensated to a decompensated stage characterized by the development of complications, such as ascites, variceal bleeding, or encephalopathy. Decompensation is a key event heralding the onset of significant morbidity and mortality. Portal hypertension (PHT), usually estimated by the hepatic venous pressure gradient (HVPG), is involved in the development of most complications of cirrhosis and is the strongest predictor of clinical decompensation. Even in the compensated phase of cirrhosis, two stages with different probability of survival have been delineated based on the presence or absence of varices. Clinically significant PHT is diagnosed when HVPG is ≥ 10 mm Hg as both varices and decompensation of cirrhosis may appear at this point. However, once this threshold has been reached the relationship between changes in HVPG (such as those induced by drug therapy) and development of decompensation has not been sufficiently investigated. The prognostic value of HVPG monitoring to predict bleeding is well established, but its utility in the prediction of other complications is unclear. Ascites is the most frequent complication of cirrhosis and is often the first decompensation to appear. It has been demonstrated that, in patients with decompensated cirrhosis receiving drug therapy to prevent variceal rebleeding, a reduction of HVPG to <12 mm Hg or ≥ 20% from baseline, in addition to a marked decrease in rebleeding risk, is also associated with a significant reduction of the risk of ascites, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, and also with an improvement in survival. However, whether pharmacological treatment of PHT by reducing portal pressure can prevent the transition of compensated cirrhosis into development of ascites is unclear, particularly in the stage with varices in which the risk of decompensation is higher. Furthermore, predictors of development of ascites in patients with compensated cirrhosis and severe PHT remain undefined.
The aim of this study was to elucidate the relationship between the changes in induced by β-blocker on PHT and development of first ascitic decompensation in patients with compensated cirrhosis, severe PHT, and large esophageal varices treated for primary prophylaxis of bleeding. Other predictive factors of development of ascites were also investigated.
