The Hemodynamic Response to Medical Treatment of Portal Hypertension as a Predictor of Clinical Effectiveness in the Primary Prophylaxis of Variceal Bleeding in Cirrhosis

Abstract

In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was <12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow-up was significantly higher in poor responders (41%) than in good responders (7%; P ‫؍‬ .0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow-up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (␤ ‫؍‬ 1.91; SE(␤) ‫؍‬ 0.80; P ‫؍‬ .01). During follow-up 11 patients died of hepatic causes. Survival was related to Child-Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta-blockers or beta-blockers plus nitrates. (HEPATOLOGY 2000;32:930-934.)It is clearly established that prophylaxis with beta-blockers decreases the risk of first variceal bleeding in cirrhotic patients with portal hypertension and esophageal varices at risk of bleeding. 1 Recently, it was also shown that the efficacy of beta-blockers may be enhanced by the addition of long-acting nitrates. 2 These treatments, however, do not abolish the risk of bleeding but decrease it by half or by three quarters, respectively. For these reasons, it may be useful to know factors predicting clinical response or nonresponse to treatment to allow treatment of nonresponders with alternative methodologies.In patients treated with beta-blockers 3-5 or beta-blockers plus nitrates 6 for prevention of rebleeding, it was observed that a decrease in portal pressure under chronic treatment, expressed as a decrease in hepatic venous pressure gradient (HVPG), is a strong predictor of clinical effectiveness. Indeed, decreases of HVPG to 12 mm Hg or less, or decreases by at least 20% from baseline values were associated with a negligible risk of rebleeding, whereas risk of rebleeding was confined to patients not meeting these hemodynamic end points. A single report was unable to confirm the clinical value of these hemodynamic end points. 7 In the clinical setting of prophylaxi...

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

“…Decrease in HVPG to 12 mm Hg or less or decrease by at least 20% of baseline values is associated with low risk of variceal bleeding [47][48][49][50]. Poor hemodynamic response was found to be the main factor predicting bleeding.…”

“…Assessment of hemodynamic response (decrease in HVPG to 12 mm Hg or less or decrease by at least 20% of baseline values) to drugs is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with b-blockers or other portal pressure-reducing drugs [47][48][49][50][51][52].…”

“…Poor hemodynamic response was found to be the main factor predicting bleeding. HVPG response to drugs is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with b-blockers or b-blockers plus nitrates [22,47,51,70,73,74]. The clinical value of HVPG remains unchanged, even when other confounding factors such as the size of varices, presence of red signs, or North Italian Endoscopic Club index were taken into consideration.…”

“…The clinical value of HVPG remains unchanged, even when other confounding factors such as the size of varices, presence of red signs, or North Italian Endoscopic Club index were taken into consideration. It was found that in the prediction of effectiveness of treatment, the hemodynamic response is much more useful than the initial size of varices and the presence of red signs [47]. HVPG measurement, although invasive, is safe and relatively simple.…”

Hepatic Venous Pressure Gradient: To Measure or Not To Measure, That Is the Question

“…It is logical to infer that the improved clinical outcomes reported with combination therapy reflect improved hemodynamics. Surprisingly, however, Merkel et al 4 found that those treated with ␤-blocker alone or with combination therapy were equally likely (ϳ60%) to have a good hemodynamic response. These findings are at odds with those of other studies 5 : the disparity may reflect differences in study populations.…”