Decrease In Hepatic Venous Pressure Gradient Research Articles

Acute Hemodynamic Response to β-Blockers and Prediction of Long-term Outcome in Primary Prophylaxis of Variceal Bleeding

Studies of variceal bleeding have shown that a hemodynamic response to treatment of portal hypertension is appropriate when the hepatic venous pressure gradient (HVPG) decreases below 12 mmHg or by > 20% from baseline. However, in primary prophylaxis, many nonresponders do not bleed and 2 invasive procedures are needed to assess response. We investigated the long-term prognostic value of an acute response to beta-blockers and whether the target reduction in HVPG can be improved in primary prophylaxis. An initial hemodynamic study was performed in patients with large varices and without previous bleeding. After baseline measurements were made, propranolol was administered intravenously and measurements were repeated 20 minutes later. Patients were given nadolol daily and a second hemodynamic study was performed. Of 105 patients, 15% had variceal bleeding. Using receiver operating characteristic curve analysis, a decrease of HVPG > or = 10% was the best value to predict bleeding. In the initial study, 75 patients (71%) were responders (HVPG decreased to < or = 12 mmHg or by > or = 10%) and had a lower probability of first bleeding than nonresponders (4% vs 46% at 24 months; P < .001). Acute responders also had a lower risk of developing ascites (P = .001). Chronic responders had a lower probability of bleeding than nonresponders (P < .001). There was a correlation between acute and chronic changes in HVPG (r = 0.62; P = .01). The acute hemodynamic response to beta-blockers can be used to predict the long-term risk of first bleeding. An HVPG reduction > 10% from baseline is the best target to define response in primary prophylaxis.

Variceal Bleeding

Oesophageal varices and ascites may develop when the hepatic venous pressure gradient (HVPG) increases above 10 mmHg, and variceal bleeding may occur when the HVPG rises above 12 mmHg. Pharmacological therapy of portal hypertension may prevent bleeding by reducing the HVPG below 12 mmHg. Even if this threshold level is not reached, the risk of bleeding decreases markedly with reductions in HVPG that are >20% from baseline.Endoscopic therapy is a local treatment that prevents bleeding by obliterating the varices, and has no effect on the pathophysiological mechanisms that lead to portal hypertension and variceal rupture. When used together, both pharmacological and endoscopic therapies may have an additive effect, which has been demonstrated in different clinical settings. In acute oesophageal variceal bleeding, vasoactive drugs (either terlipressin or somatostatin) should be started as soon as possible (before diagnostic endoscopy) and maintained for 2-5 days. The efficacy of pharmacotherapy is improved with the addition of emergency endoscopic therapy. Adding endoscopic variceal ligation (EVL) improves the efficacy and safety achieved with the combination of emergency sclerotherapy and vasoactive drugs. Antibacterial prophylaxis should be an integral part of therapy in acute bleeding.To prevent rebleeding, both EVL and the combination of beta-adrenoceptor antagonists (beta-blockers) and isosorbide mononitrate (ISMN) may be a valid first-line choice. Adding beta-blockers improves the efficacy of EVL alone. Haemodynamic responders to beta-blockers with or without ISMN (i.e. those with a decrease in HVPG to <12 mmHg or by >20% of baseline) have a reduction in the risk of haemorrhage to below 10% of patients and, consequently, will not need further treatment, while rescue therapies should be provided to nonresponders. Transjugular intrahepatic portosystemic shunts are the recommended rescue therapy when EVL and/or beta-blockers with or without ISMN fail. beta-Blockers significantly reduce the risk of a first haemorrhage in patients with large varices and improve survival. Compared with beta-blockers, EVL reduces the risk of first bleeding without any differences in mortality and should be offered to patients with large varices who have contraindications or an intolerance to beta-blockers.

Value of the Hepatic Venous Pressure Gradient to Monitor Drug Therapy for Portal Hypertension: A Meta-Analysis

The use of the hepatic venous pressure gradient (HVPG) to assess the efficacy of the pharmacological treatment of portal hypertension in cirrhosis is controversial. Our aim was to establish whether target HVPG reduction predicts variceal bleeding in cirrhotic patients receiving variceal bleeding prophylaxis. Data sources were MEDLINE, EMBASE, Cochrane Controlled Trials Register, citation lists, and abstracts (most recent search March 2006). Cohorts of patients on drug therapy from randomized and nonrandomized studies correlating variceal bleeding and HVPG change were used. Heterogeneity was explored by metaregression analysis. Ten studies totaling 595 patients undergoing two HVPG measurements were identified. The RR of bleeding was lower in patients achieving an overall (HVPG <or=12 mmHg or decrease >or=20%) (0.27, 95% CI 0.14-0.52), complete (HVPG <or=12 mmHg) (0.48, CI 0.28-0.81), or partial (HVPG decrease >or=20%) (0.41, CI 0.20-0.81) response, with significant heterogeneity. Regression analysis identified the interval between the HVPG measurements significantly associated with the RR of bleeding. Heterogeneity was no longer significant after exclusion of an outlier trial, which showed the longest interval to HVPG remeasurement and the lowest quality score. Even considering nonvaluable patients because of bleeding as HVPG responders, the RR of bleeding was lower in overall responders than in nonresponders (0.66, CI 0.51-0.86). Overall response was associated with lower liver-related mortality (RR 0.58, CI 0.37-0.91). Current evidence supports the validity of HVPG end points to monitor drug therapy efficacy for variceal bleeding prophylaxis. HVPG monitoring also provides valuable prognostic information.

Efficacy of Antiviral Therapy on Hepatitis C Recurrence After Liver Transplantation: A Randomized Controlled Study

Recurrence of hepatitis C virus (HCV) infection is a relevant problem of liver transplantation programs. We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients. Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n = 54) were randomized to no treatment (group A, n = 27) or peginterferon alfa-2b/ribavirin for 48 weeks (group B, n = 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n = 27). All patients (n = 81) underwent a liver biopsy at baseline and after follow-up; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients. Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed > or =1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P = .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P = .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] =3.7, 95% confidence interval [CI] 1.3 to 10, P = .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P = .01; respectively). Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.

Antiviral Therapy Decreases Hepatic Venous Pressure Gradient in Patients with Chronic Hepatitis C and Advanced Fibrosis

Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown. This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension. Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score. HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11). AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

Hemodynamic response–guided therapy for prevention of variceal rebleeding

The clinical usefulness of assessing hemodynamic response to drug therapy in the prophylaxis of variceal rebleeding is unknown. An open-labeled, uncontrolled pilot trial was performed to evaluate the feasibility and efficacy of using the hemodynamic response to pharmacological treatment to guide therapy in this setting. Fifty patients with acute variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were initiated, and a second HVPG was measured 15 days later. Responder patients (> or =20% decrease in HVPG from baseline) were maintained on drugs, partial responders (> or =10% and <20%) had banding ligation added to the drugs, and nonresponders (<10%) received a transjugular intrahepatic portal-systemic shunt (TIPS). Mean follow-up was 22 months. Eight patients (16%) did not receive the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42 patients, 24 were classified as responders (57%); 10 as partial responders (24%), who had banding added; and 8 as nonresponders (19%), who received a TIPS. Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended to present more early rebleedings, less response to drugs and needed more TIPS. Variceal rebleeding occurred in 22% of all patients but only in 12% of patients whose hemodynamic response was assessed. The 3 therapeutic groups were not different. In conclusion, using hemodynamic response to pharmacological treatment to guide therapy in secondary prophylaxis to prevent variceal bleeding is feasible and effectively protects patients from rebleeding. In this context, viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis.

Diagnostic invasif de l’hypertention portale au cours des hépatopathies chroniques: Étude critique de la mesure du gradient de pression porto-cave

Portal hypertension is defined by an increased pressure gradient between the portal vein and the inferior vena cava (N < 5 mmHg). The most commonly used technique to assess the severity of portal hypertension is the catheterization of one hepatic vein with measurement of pressures in a free position and in a wedged position using preferably a balloon catheter. The hepatic venous pressure gradient is calculated by the difference between both pressures. In most cirrhotic processes, venous pressure gradient gives a good evaluation of portal hypertension however, portal vein pressure can be higher than wedged hepatic venous pressure, particularly in presence of an increased pre-sinusoidal resistance. In such cases, a direct access to portal vein might be needed to assess the severity of portal hypertension. For an accurate interpretation of the hepatic venous pressure gradient, several strict criteria must be followed; otherwise the validity of measurements might be seriously questioned. Hepatic venous pressure gradient has been used as a prognostic marker of portal hypertension, particularly for the occurrence of bleeding from gastrophageal varices which almost never occur below a threshold value of 12 mmHg. However, the prognostic value of the hepatic venous pressure gradient for survival is still a controversial matter On the other hand, the use of hepatic venous pressure gradient has been proposed to monitor the pharmacological treatment of portal hypertension and it is generally accepted that reaching a same threshold value of 12 mmHg should almost completely abolish the risk of first or recurrent variceal bleeding. A large number of studies have also reported that a 20% hepatic venous pressure gradient decrease should be considered as a significant response to therapy, the risk of the first or recurrent bleeding being significantly reduced in responders. But again there are conflicting results.

Early HVPG measurement and TIPS for acute variceal hemorrhage: Is sooner really better?

Early HVPG measurement and TIPS for acute variceal hemorrhage: Is sooner really better?

Hemodynamic Effects of Terlipressin and High Somatostatin Dose during Acute Variceal Bleeding in Nonresponders to the Usual Somatostatin Dose

High dose of somatostatin infusion achieves a greater reduction of hepatic venous pressure gradient (HVPG) than the usual dose, and terlipressin decreases HVPG through mechanisms other than somatostatin. Our aim was to assess the hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. Hemodynamic studies were performed in 80 patients with cirrhosis and variceal bleeding during the first 3 days of admission. After baseline measurements, somatostatin was administered (250 microg/h with an initial bolus of 250 microg). Patients were considered responders when the HVPG decreased by >10% from baseline (n = 31). Nonresponders were randomized under double-blind conditions to a control group (n = 7), or to receive terlipressin (2 mg IV bolus, n = 22), or high dose of somatostatin (500 microg/h, n = 20). Final measurements were obtained 30 min later. Terlipressin caused a decrease in HVPG (from 22.2 +/- 5 to 19.1 +/- 5.2, p < 0.01) and heart rate (p < 0.01), while mean arterial pressure increased (p < 0.01). High somatostatin dose also reduced HVPG (from 21.8 +/- 3.4 to 19.6 +/- 3.1, p < 0.01), although this decrease was more pronounced with terlipressin (15%+/- 9%vs 10%+/- 6% from baseline, p= 0.05). Both terlipressin and high somatostatin dose achieved a significantly higher rate of response than that in the control group. A decrease in HVPG >20% was observed in 36% of cases with terlipressin versus 5% with high somatostatin dose (p= 0.02). In nonresponders to usual somatostatin dose, both terlipressin and high-dose of somatostatin infusion significantly decreased HVPG and increased the rate of hemodynamic responders. Such effects were greater with terlipressin. Both treatments may be an alternative when standard somatostatin fails.

A1166C Angiotensin II Type 1 Receptor Gene Polymorphism May Predict Hemodynamic Response to Losartan in Patients with Cirrhosis and Portal Hypertension

Losartan, a dose of 25 mg/day, has been found to be effective in 50% of patients with portal hypertension without adverse effects. We evaluated the relationship between genetic polymorphisms of the renin-angiotensin system (A1166C angiotensin II type 1 receptor (AT1R), angiotensinogen T174M and M235T, and angiotensin-converting enzyme I/D) and the effects of losartan on portal and systemic hemodynamic in patients with cirrhosis and portal hypertension. We performed a longitudinal study that included 23 consecutive patients with cirrhosis and esophageal varices who received 25 mg/day of losartan during 12 wk. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured at baseline and after treatment. Genomic DNA was extracted from peripheral blood leukocytes; genetic polymorphisms of the renin-angiotensin system were investigated by polymerase chain reaction and restriction fragment length polymorphisms. The homozygous patients for AT1R A allele showed higher pulmonary-wedged and free hepatic venous pressure on baseline. After treatment, they showed a higher decrease of HVPG (32.5%+/- 19.2) in comparison with patients with AC/CC genotype (2.4%+/-18.9), p < 0.01. Ten of 15 patients with AA genotype were responders, while only one of eight with AC/CC genotype (p < 0.002); genotype AA showed a positive predictive value of 66.6% and negative predictive value of 87.5%. These results suggest that there is a relationship between the AT1R A1166C polymorphisms and the therapeutic response to losartan. The genetic testing may be used as a predictive factor of this response.

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

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. (H epatology 2003;37:902-908.)

A randomized study of losartan vs propranolol: Effects on hepatic and systemic hemodynamics in cirrhotic patients

Background & aims: The potential use of losartan, an angiotensin II type 1 receptor blocker, in the treatment of portal hypertension is still under debate. This randomized controlled trial compared the effects of losartan vs. propranolol on portal and systemic hemodynamics in patients with cirrhosis. Methods: Twenty-seven compensated patients were randomized to receive losartan 25 mg/day (n = 17) or propranolol (n = 10). Hepatic venous pressure gradient (HVPG), portal blood flow (Doppler duplex ultrasound) and systemic hemodynamics were measured at baseline and after 12-week treatment. Portal resistance was calculated as HVPG/portal blood flow. Results: Propranolol induced a reduction in cardiac output (p 0.002), heart rate (p 0.0001) and HVPG [from 16.4 (± 4.1) to 13.1 (± 3.6) mmHg (p 0.07)]; six patients showed a reduction equal or greater than 20% and were considered responders. Losartan caused a decrease in HVPG [from 15.6 (± 4.2) to 11.8 (± 3.5) mmHg (p 0.002)], without changes in portal blood flow and systemic hemodynamics. Changes in HVPG correlated with variations in portal resistance (r 0.88, p < 0.0001). Losartan induced a reduction in HVPG between 10 and 19% in 5/17 patients, and 20% or more in 8/17. Five out of eight patients who respond to losartan showed severe portal hypertension, with higher baseline HVPG (equal or greater than 16 mmHg). Conclusions: the administration of losartan in a doses of 25 F per day may be effective in lowering portal pressure in patients with compensated cirrhosis, particularly in those with more severe portal hypertension

Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis

Short-term carvedilol administration is more powerful than propranolol in decreasing hepatic venous pressure gradient (HVPG) in cirrhotic patients, but induces arterial hypotension that may prevent its long-term use in portal hypertensive patients. This study compared the HVPG reduction and safety of long-term carvedilol and propranolol. Fifty-one cirrhotic patients were randomly assigned to receive carvedilol (n = 26) and propranolol (n = 25). Hemodynamic measurements and renal function were assessed at baseline and after 11.1 ± 4.1 weeks. Carvedilol caused a greater decrease in HVPG than popranolol (−19 ± 2% vs. −12 ± 2%; P < .001). The proportion of patients achieving an HVPG reduction ≥20% or ≤12 mm Hg was greater after carvedilol (54% vs. 23%; P < .05). Carvedilol, but not propranolol caused a significant decrease in mean arterial pressure (MAP) (−11 ± 1% vs. −5 ± 3%; P = .05) and a significant increase in plasma volume (PV) and body weight (11 ± 5% and 2 ± 1%, respectively; P < .05). Glomerular filtration rate (GFR) was unchanged with either drug, but the dose of diuretics was increased more frequently after carvedilol (27% vs. 8%; P = .07). Adverse events requiring discontinuation of treatment occurred in 2 patients receiving carvedilol and in 3 receiving propranolol. In conclusion, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis. However, its clinical applicability may be limited by its systemic hypotensive effects. Further trials are needed to confirm the therapeutic potential of carvedilol. (H EPATOLOGY 2002;36:1367-1373.)

Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis

Short-term carvedilol administration is more powerful than propranolol in decreasing hepatic venous pressure gradient (HVPG) in cirrhotic patients, but induces arterial hypotension that may prevent its long-term use in portal hypertensive patients. This study compared the HVPG reduction and safety of long-term carvedilol and propranolol. Fifty-one cirrhotic patients were randomly assigned to receive carvedilol (n = 26) and propranolol (n = 25). Hemodynamic measurements and renal function were assessed at baseline and after 11.1 ± 4.1 weeks. Carvedilol caused a greater decrease in HVPG than popranolol (− 19 ± 2% vs. − 12 ± 2%; P &lt; 0.001). The proportion of patients achieving an HVPG reduction ≥20% or ≤ 20 mm Hg was greater after carvedilol (54% vs. 23%; P &lt; 0.05). Carvedilol, but not propranolol caused a significant decrease in mean arterial pressure (MAP) (- 11 ± 1% vs. - 5 ± 3%; P = 0.05) and a significant increase in plasma volume (PV) and body weight (11 ± 5% and 2 ± 1%, respectively; P &lt; 0.05). Glomerular filtration rate (GFR) was unchanged with either drug, but the dose of diuretics was increased more frequently after carvedilol (27% vs. 8% P = 0.07). Adverse events requiring discontinuation of treatment occurred in 2 patients receiving carvedilol and in 3 receiving propranolol. In conclusion, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis. However, its clinical applicability may be limited by its systemic hypotensive effects. Further trials are needed to confirm the therapeutic potential of carvedilol. (Hepatology2002;36:1367-1373).

Somatostatin Treatment and Risk Stratification by Continuous Portal Pressure Monitoring During Acute Variceal Bleeding

Background & Aims: During acute variceal bleeding, several factors may lead to elevations of hepatic venous pressure gradient (HVPG), which may precipitate further hemorrhage. Whether somatostatin can suppress these increments is unknown. This study monitored somatostatin effects on HVPG during acute bleeding and assessed whether the changes affect outcome. Methods: In 40 patients with acute variceal bleeding treated with sclerotherapy, a catheter was placed into a main hepatic vein for 24-hour serial measurements of HVPG. After baseline measurements, patients received somatostatin (N = 25) or placebo (N = 15) under double blind conditions. Results: Somatostatin but not placebo produced a sustained decrease in HVPG (from 20.7 ± 3.7 mm Hg to 17.7 ± 2.7, P < 0.01). In patients receiving placebo, HVPG increased after a test meal ( P = 0.018) and after blood transfusion ( P = 0.034). Somatostatin completely prevented these increments. HVPG decreased significantly only in patients without further bleeding. One of 27 patients with HVPG <20 mm Hg at baseline or decreased >10% rebled vs. 9 of 13 who had neither of these 2 criteria ( P < 0.0001). Both criteria had independent prognostic value for further bleeding. Conclusions: During acute variceal bleeding, somatostatin produces a significant and sustained decrease in HVPG and prevents secondary elevations. Monitoring HVPG may stratify further bleeding risk and discriminate treatment response.

Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension.

Noninvasive measurements of variceal pressure adequately reflect the hemodynamic effects of propranolol on portal hypertension. However, the prognostic value of variceal pressure responses during continued propranolol therapy has not been evaluated, and it is unclear whether this may substitute invasive measurements of portal pressure response. Fifty-five portal hypertensive patients with cirrhosis were studied before and at 4 months of continued propranolol therapy. Variceal pressure was measured using an endoscopic pressure gauge. Portal pressure was evaluated as the hepatic venous pressure gradient (HVPG). Over a 28 +/- 11 month follow-up, 16 patients experienced variceal bleeding. Baseline characteristics were similar in bleeders and nonbleeders. At 4 months, reduction in variceal pressure was less marked in bleeders than in nonbleeders (5% +/- 20% vs. -15% +/- 24%; P =.03). A fall in variceal pressure 20% or greater of baseline was an independent predictor of absence of variceal bleeding; which occurred in 5% of patients with a 20% or greater fall in variceal pressure versus 42% of patients with less than a 20% reduction (P =.004). The HVPG response had similar independent prognostic value (decrease > or =20%: 6% bleeding; decrease <20%: 45% bleeding; P =.004) but identified different patients. Achieving a 20% decrease in either variceal pressure or HVPG was highly sensitive (85%) and specific (93%) identifying patients not bleeding on follow-up. Endoscopic measurements of variceal pressure response to continued pharmacotherapy provide useful prognostic information on the risk of variceal bleeding. As with HVPG response, a fall in variceal pressure of 20% or greater is associated with a very low risk of variceal bleeding. The combination of both parameters allows almost optimal prognostication.

Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the ?- blocker alone

The association beta-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to beta-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to nadolol is effective in decreasing portal pressure in most poor responders to nadolol alone. A decrease in outflow resistance is the main mechanism involved.

Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the beta- blocker alone

The association beta-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to beta-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to nadolol is effective in decreasing portal pressure in most poor responders to nadolol alone. A decrease in outflow resistance is the main mechanism involved. (Hepatology 1997 Jul;26(1):34-9)

Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis

SummaryIn patients with variceal bleeding as a complication of hepatic cirrhosis, propranolol therapy reduces the risk of recurrent variceal haemorrhage. However, the relation between portal pressure response to pharmacological treatment and clinical events has not been well defined. This relation was prospectively investigated in 69 cirrhotic patients receiving continued propranolol therapy after an episode of variceal bleeding. Hepatic venous pressure gradient (HVPG) was measured before and at 3 months of continued drug therapy.At 3 months HVPG had fallen by 20% or more in 25 patients. During follow-up of 28 (SD 17) months rebleeding occurred in 2 of these 25 patients compared with 23 of 44 who had lesser reductions in HVPG. Cumulative probability of rebleeding at 1, 2, and 3 years was 4%, 9%, and 9% in patients with a decrease in HVPG ≽20%, and 28%, 39%, and 66% in patients with a decrease in HVPG <20% (p<0·001, log-rank test). On multivariate analysis, a decrease in HVPG ≽20% was the only independent predictor of rebleeding (relative risk 0·09, 95% Cl 0·02-0·41. Of the 8 patients in whom the HVPG fell to 12 mm Hg or less, none rebled.This study suggests that measurement of the HVPG response to pharmacotherapy will provide useful prognostic information on the long-term risk of variceal rebleeding.

Propanolol does not decrease the development of large esophageal varices in patients with cirrhosis. A controlled study: Groupe Français de la Prévention Pré-Primaire∗

Background & Aims: During acute variceal bleeding, several factors may lead to elevations of hepatic venous pressure gradient (HVPG), which may precipitate further hemorrhage. Whether somatostatin can suppress these increments is unknown. This study monitored somatostatin effects on HVPG during acute bleeding and assessed whether the changes affect outcome. Methods: In 40 patients with acute variceal bleeding treated with sclerotherapy, a catheter was placed into a main hepatic vein for 24-hour serial measurements of HVPG. After baseline measurements, patients received somatostatin (N = 25) or placebo (N = 15) under double blind conditions. Results: Somatostatin but not placebo produced a sustained decrease in HVPG (from 20.7 ± 3.7 mm Hg to 17.7 ± 2.7, P < 0.01). In patients receiving placebo, HVPG increased after a test meal (P = 0.018) and after blood transfusion (P = 0.034). Somatostatin completely prevented these increments. HVPG decreased significantly only in patients without further bleeding. One of 27 patients with HVPG <20 mm Hg at baseline or decreased >10% rebled vs. 9 of 13 who had neither of these 2 criteria (P < 0.0001). Both criteria had independent prognostic value for further bleeding. Conclusions: During acute variceal bleeding, somatostatin produces a significant and sustained decrease in HVPG and prevents secondary elevations. Monitoring HVPG may stratify further bleeding risk and discriminate treatment response.