Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis

Abstract

In cirrhotic patients under pharmacologic treatment for portal hypertension, a reduction in hepatic venous pressure gradient (HVPG) of >20% of baseline or to <12 mm Hg markedly reduces the risk of variceal rebleeding. This study was aimed at evaluating whether these hemodynamic targets also prevent other complications of portal hypertension and improve long-term survival. One hundred five cirrhotic patients included in prospective trials for the prevention of variceal rebleeding were studied. Seventy-three of the patients had 2 separate HVPG measurements, at baseline and under pharmacologic therapy with propranolol ؎ isosorbide mononitrate. Patients were followed for up to 8 years. Survival and risk of developing portal hypertension-related complications were compared between responders and nonresponders. Twenty-eight patients showed a reduction of HVPG >20% of baseline or to <12 mm Hg (responders), and 45 patients were nonresponders. Nonresponders had a significantly greater risk of developing variceal rebleeding (P ‫؍‬ .013), ascites (P ‫؍‬ .025), spontaneous bacterial peritonitis (P ‫؍‬ .003), hepatorenal syndrome (P ‫؍‬ .026), and hepatic encephalopathy (P ‫؍‬ .024) than responders. Eight-year cumulative probability of survival was significantly lower in nonresponders than in responders (52% vs. 95%, respectively, P ‫؍‬ .003). At multivariate analysis, being a nonresponder was independently associated with the risk of developing rebleeding, ascites, spontaneous bacterial peritonitis, and lower survival. In conclusion, in cirrhotic patients receiving pharmacologic treatment for prevention of variceal rebleeding, a decrease in HVPG >20% or to <12 mm Hg is associated with a marked reduction in the long-term risk of developing complications of portal hypertension and with improved survival. (HEPATOLOGY 2003;37:902-908.) P ortal hypertension is responsible for the more frequent and severe complications of cirrhosis: gastrointestinal bleeding from gastroesophageal varices, ascites, renal dysfunction, and hepatic encephalopathy. Because of the combined impact of these complications, portal hypertension represents the main cause of death and liver transplantation in patients with cirrhosis. 1 Previous cross-sectional studies have shown that a portal pressure gradient (determined as the hepatic venous pressure gradient; HVPG) above 12 mm Hg is required for variceal bleeding to develop. 2,3 Indeed, longitudinal studies demonstrated that, when HVPG decreases below this threshold, there is total protection from the risk of bleeding. [4][5][6] Subsequent studies showed that, even without reaching this target, a reduction of HVPG of at least 20% from baseline values is associated with a very low residual risk of rebleeding on follow-up. 7-10 However, no study so far has examined whether the hemodynamic response to drug therapy correlates also with the risk of developing other complications of portal hypertension and survival over a long-term follow-up.The present study was aimed at addressing these issues. For that purpos...

Letter: sorafenib in portal hypertension – authors' reply

“…5 We agree with Procopet et al that for studying the antihypertensive effects of sorafenib, patients with HCC are not an ideal patient population, but for lack of other options to test the drug so far, both of our groups did resort to this group of patients to perform a proofof-principle study on the haemodynamic effects of sorafenib in humans.…”

Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis

“…The HVPG and changes in HVPG that occur over time have predictive value for the development of esophagogastric varices, 15,16 the risk of variceal hemorrhage, [17][18][19] the development of non-variceal complications of portal hypertension, 17,20,21 and death. 19,[21][22][23] Single measurements are useful in the prognosis of both compensated and decompensated cirrhosis, while repeat measurements are useful to monitor response to pharmacological therapy and progression of liver disease. Limitations to the generalized use of HVPG measurement are the lack of local expertise and poor adherence to guidelines that will ensure reliable and reproducible measurements, 14 as well as its invasive nature.…”

“…18 Patients whose HVPG decreases to Ͻ12 mmHg or at least 20% from baseline levels ("HVPG responders") not only have a lower probability of developing recurrent variceal hemorrhage, 36 but also have a lower risk of developing ascites, spontaneous bacterial peritonitis, and death. 21 …”

Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation

“…Actually, it has been shown to correlate with survival, decompensation, and development of collaterals. 15,16 These considerations suggest that HVPG could be used as a quantitative marker of disease progression in patients with chronic hepatitis C. 17 This would be particularly relevant in liver transplant recipients with HCV infection recurrence.…”