Reduction In Hepatic Venous Pressure Gradient Research Articles

Effect of Sustained Viral Response on Hepatic Venous Pressure Gradient in Hepatitis C–Related Cirrhosis

Interferon-based therapy can improve hepatic histology in chronic hepatitis C (CHC)-related cirrhosis but its effect on portal hypertension is unclear. The aims of this study were to investigate the effect of treatment with peginterferon alfa-2a and ribavirin on hepatic venous pressure gradient (HVPG) in CHC with compensated cirrhosis. Forty-seven patients with compensated biopsy examination-proven cirrhosis were recruited from 2 metropolitan teaching hospitals and were treated for 48 weeks with combination peginterferon alfa-2a 180 microg by subcutaneous injection weekly and ribavirin 800-1200 mg/day orally. A transjugular liver biopsy examination and HVPG measurement were performed at baseline, and 33 patients had a repeat HVPG measurement after 6 months of treatment-free follow-up evaluation. The overall sustained viral response (SVR) was 21%. Posttreatment there was a significant decrease in HVPG level in sustained responders compared with nonresponders (-2.1 +/- 4.8 vs 0.6 +/- 2.8 mm Hg; P = .05). Among patients with portal hypertension, a higher proportion of sustained responders achieved a 20% or greater reduction in HVPG level compared with nonresponders (71% vs 20%; P = .01). There was a significant association between a 20% or greater reduction in HVPG and both histologic response and SVR. Treatment with combination peginterferon plus ribavirin may produce clinically significant reductions in HVPG in patients with CHC-related cirrhosis who achieve an SVR.

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.

Hepatic Vein Pressure Gradient Reduction and Prevention of Variceal Bleeding in Cirrhosis: A Systematic Review

A reduction of the hepatic venous pressure gradient (HVPG) to </=12 mm Hg or by >/=20% of baseline prevents variceal bleeding in cirrhosis. Because some inconsistent data have argued against the clinical application of these hemodynamic targets, we performed a systematic review of available studies from the Cochrane Library and MEDLINE. Hemodynamic targets were HVPG reduction (1) to </=12 mm Hg; (2) by >/=20% with final value >12 mm Hg; (3) by >/=20% or to </=12 mm Hg. Meta-regression analysis was used to explore heterogeneity. Twelve studies were identified including 943 patients. Pooled odds ratios for bleeding for the 3 hemodynamic targets were, respectively, 0.21 (95% CI: 0.10-0.45; P = .0001), 0.25 (95% CI: 0.11-0.56; P = .001), and 0.17 (95% CI: 0.09-0.33; P = .001). A significant heterogeneity was found for the 2 last estimates, and meta-regression analysis showed that this was caused by an exceedingly long interval between HVPG measurements in 1 study. After exclusion of that study, heterogeneity disappeared, and the pooled odds ratios were, respectively, 0.19 (95% CI: 0.11-0.34; P = .0001) and 0.14 (95% CI: 0.09-0.21; P = .0001). The beneficial effect of HVPG reduction for first bleeding was similar to that for recurrent bleeding. Mortality was significantly reduced for HVPG reduction by >/=20% or to </=12 mm Hg (pooled odds ratio, 0.39; 95% CI: 0.19-0.81, P = .012). HVPG reduction to </=12 mm Hg or by >/=20% significantly reduces the risk of bleeding, and a reduction of >/=20% significantly reduces mortality. These hemodynamic targets should be considered for clinical practice and for randomized controlled trials.

Multicenter timolol study: The value of timolol and hemodynamic monitoring in the management of portal hypertensive cirrhotics with no esophageal varices

Multicenter timolol study: The value of timolol and hemodynamic monitoring in the management of portal hypertensive cirrhotics with no esophageal varices

Recent Variceal Bleeding: Doppler US Hepatic Vein Waveform in Assessment of Severity of Portal Hypertension and Vasoactive Drug Response

To prospectively evaluate both the correlation between abnormal Doppler ultrasonography (US) hepatic vein waveforms and the hepatic venous pressure gradient (HVPG) and the response to drug treatment in patients with cirrhosis. Ethics committee approval and informed consent of patients and control subjects were obtained. In 78 patients with cirrhosis (70 men, eight women; mean age, 49.4 years +/- 9.7 [standard deviation]) and a history of variceal bleeding, both the hepatic vein waveform--as measured with Doppler US--and the HVPG were measured, and the relationship between them was analyzed. Hepatic vein Doppler waveforms were classified as triphasic, biphasic, or monophasic. Severe portal hypertension was defined as an HVPG of more than 15 mm Hg. In a subgroup of 21 patients, changes in hepatic vein waveform and HVPG were evaluated after intravenous administration of 2 mg of terlipressin. Statistical analyses were performed with Spearman rank correlation, logistic regression analysis, and cross tabulation. Abnormal hepatic vein waveforms were seen in 72 patients (92%). Forty-four patients (56%) had biphasic waveforms, 28 (36%) had monophasic waveforms, and six (8%) had triphasic waveforms. A positive correlation was found between the extent of abnormalities in hepatic vein waveforms and the increase in HVPG (P < .05). Monophasic waveforms were associated with severe portal hypertension, with a sensitivity of 74% and a specificity of 95%. Twenty patients in the terlipressin subgroup had abnormal baseline waveforms; the baseline waveform improved in 18 patients in association with the HVPG reduction after injection of terlipressin. Doppler US hepatic vein waveform assessment is useful in the noninvasive evaluation of the severity of portal hypertension and the response to vasoactive drugs in patients with portal hypertension and variceal bleeding.

Pharmacological Reduction of Portal Pressure and Long-Term Risk of First Variceal Bleeding in Patients with Cirrhosis

A reduction in hepatic venous pressure gradient (HVPG) of > or =20% of baseline or to < or =12 mmHg (responders) is associated with a reduced risk of first variceal bleeding. The aim of this study was to evaluate whether this protective effect is maintained in the long term and if it extends to other portal hypertension complications. Seventy-one cirrhotic patients with esophageal varices and without previous variceal bleeding who entered into a program of prophylactic pharmacological therapy and were followed for up to 8 yr were evaluated. All had two separate HVPG measurements, at baseline and after pharmacological therapy with propranolol +/- isosorbide mononitrate. Forty-six patients were nonresponders and 25 were responders. Eight-year cumulative probability of being free of first variceal bleeding was higher in responders than in nonresponders (90% vs 45%, p= 0.026). The lack of hemodynamic response and low platelet count were the only independent predictors of first variceal bleeding. Additionally, reduction of HVPG was independently associated with a decreased risk of spontaneous bacterial peritonitis (SBP) or bacteremia. No significant differences in the development of ascites, hepatic encephalopathy, or survival were observed. The hemodynamic response in cirrhotic patients is associated with a sustained reduction in the risk of first variceal bleeding over a long-term follow-up. Reduction of HVPG also correlate with a reduced risk of SBP or bacteremia.

Understanding the splenic contribution to portal flow: The role of splenic artery ligation as inflow modification in living donor liver transplantation

Understanding the splenic contribution to portal flow: The role of splenic artery ligation as inflow modification in living donor liver transplantation

Primary prophylaxis with nadolol in cirrhotic patients: Doppler patterns of splanchnic hemodynamics in good and poor responders

We aimed to characterize by echo-color-Doppler the splanchnic hemodynamics of patients good and poor responders to primary prophylaxis with nadolol. Thirty cirrhotic patients (Child-score 7.0+/-1.8) with medium/large esophageal varices without previous bleedings were consecutively enrolled. At inclusion and after 3 months of treatment with nadolol, they underwent a splanchnic echo-color-Doppler study and a measurement of hepatic venous pressure gradient (HVPG). Nadolol (60+/-36 mg/day; range 20-160) induced a significant reduction of HVPG (16.6+/-6.1 vs. 19.4+/-4.6 mmHg, P < 0.0001). 13 patients (43.3%) were hemodynamic responders. Responders and Poor-responders had similar baseline clinical characteristics. Poor-responders at baseline were characterized by lower impedance indexes in superior mesenteric artery (SMA) (PI 2.29+/-0.45 vs. 2.74+/-0.46; P = 0.01; RI 0.83+/-0.04 vs. 0.86+/-0.03; P = 0.02), hepatic artery (HA) (PI 1.41+/-0.19 vs. 1.79+/-0.48; P = 0.03; RI 0.71+/-0.05 vs. 0.80+/-0.07; P = 0.02), and splenic artery (SA) (PI 1.18+/-0.27 vs. 1.73+/-0.40; P = 0.01; RI 0.66+/-0.07 vs. 0.73+/-0.09; P = 0.02), and by higher mean flow velocity of HA (52.6+/-21.6 vs. 26.5+/-9.5 cm/s; P = 0.02) and SMA (49.7+/-14.5 vs. 33.9+/-13.1 cm/s; P = 0.06). Cirrhotic patients poor-responders to nadolol show a pronounced arterial splanchnic vasodilatation at a baseline echo-color-Doppler study. This can be considered a non-invasive clue for the a priori identification of this subgroup of patients.

Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis

In patients with alcoholic hepatitis (AH), inflammation contributes to the severity of portal hypertension. This study evaluates the acute effects of albumin dialysis, using the Molecular Adsorbents Recirculating System (MARS), on portal pressure in AH. Eleven patients with AH and portal hypertension were treated with MARS (n=8) or haemofiltration (n=3). All patients had associated organ failure manifested by hepatic encephalopathy (Grade 2 or more) or renal failure. Hepatic venous pressure gradient (HVPG) was measured before, during and after the treatment session. A rapid significant reduction of HVPG was observed by 6 h (falling by > or =20% in 7/8 patients, reaching 12 mmHg in 6/8), which was sustained up to 18 h after stopping dialysis. Similar rapid sustained improvements of systemic haemodynamics were also observed. No changes occurred in three patients receiving haemofiltration alone. Albumin dialysis produces clinically significant, acute reduction in portal pressure but the mechanism by which this effect is achieved is not clear. Our results suggest that MARS may be a useful adjunct in management of portal hypertension, particularly in patients with severe AH with associated organ failure.

Monitoring of HVPG during pharmacological therapy: Evidence in favor of the prognostic value of a 20% reduction

An objective of our commissioned paper was to stimulate debate on monitoring hepatic venous pressure gradient (HVPG) following variceal bleeding. We stress that our critique pertains to the clinical applicability of HVPG measurements based on current evidence, and not on the pathophysiological importance of a reduced portal pressure. Whilst we do not disagree with the rebleeding rates in responders with a ≥20% reduction in HVPG but without a decrease to ≤12 mmHg, we have emphasized,1 both in response to their review2 and in our peer-reviewed article,3 the need to separate primary and secondary prevention due to very different bleeding risks.4 The secondary prevention studies5-9 are a homogeneous cohort (risk of [re]bleeding is highest, these HVPG measurements should be most useful). However, many patients were excluded, not having baseline or repeat HVPG measurements; in some studies5 rebleeding was worse in responders than in nonresponders, and some patients rebled early, before remeasurement,up to 22%.9 These factors make it difficult to evaluate the utility of monitoring the reduction of HVPG in all the population at risk. The heterogeneity extends to the proportion of Child-Turcotte-Pugh C patients (6%-47%)5, 9 defining in part the risk of early rebleeding. In some studies,5, 10 rebleeding is only 7% or 8% within 3 months. The clinical applicability of HVPG measurements is dependent on the measurement's timing, because if performed too late, many patients will have rebled, whereas if performed early on, it would capture most patients at risk. Our colleagues accept this view, proposing a second HVPG measurement at 2 weeks,1 although there is no study that confirms this interval; they themselves have data based only on a median of 3 months.5, 10 We agree our study8 is “anomalous,” having the longest interval to remeasurement (mean, 5.3 months) and having many alcoholics(70%); some patients abstained, which this may account for the many responders due to improvement of liver function. Seven patients8 had HVPG measurements after having rebled, comparable to 5 patients in the study of Feu et al.,5 and we noted this fact.3 We agree there is little variability with HVPG with correct measurements of HVPG; but at lower HVPG baseline values, measurement errors are greatest, in percentage terms. We found that baseline HVPG and rebleeding were correlated9; this fact was not commented on by others and would benefit from prospective evaluation. The ability to obtain a reduction of HVPG by 20% or more may reflect a lower baseline HVPG. Unfortunately, this effect cannot be deduced from published studies, but it is a plausible scenario. In simple terms, if HVPG is reduced by 20%, from 28 to 22.3 mmHg, does this confer the same protection against rebleeding as does a 20% reduction, from 19 to 15.2 mmHg? A suggestion that baseline HVPG is important is shown in the second Villanueva study7 in which drugs were beneficial solely in Child-Turcotte-Pugh A patients, whilst in the first study,6 in which mean baseline HVPG was lower (17.7 ± 3.4 vs. 19.9 + 3.5 mm Hg), rebleeding was reduced in all Child-Turcotte-Pugh classes. The relationship between baseline and repeated HVPG, and severity of liver disease (potentially improving or worsening with time) should also be prospectively studied. The improvement in liver function or its absence was not commented on by Abraldes et al.10 in relation to reduction of HVPG. Extending HVPG measurement to assess progression, or regression with therapy, of chronic hepatitis C is one of our proposals,11 but it is separate from the clinical applicability of HVPG measurements for preventing variceal bleeding. We hold the view that new prospective HVPG monitoring studies are needed for prevention of variceal bleeding. New studies could justify the extra resources and training required and prove the cost-effectiveness of implementing routine HVPG monitoring compared to empirical use of propranolol—a very cheap and simple management strategy. Andrew K Burroughs*, Ulrich Thalheimer*, Maria Mela*, David Patch*, * Hepatobiliary Medicine & Liver Transplant, Royal Free Hospital, London, UK.

Targeting portal pressure measurements: a critical reappraisal.

Many of the complications of cirrhosis reflect the presence of portal hypertension, which is commonly expressed as the hepatic venous pressure gradient (HVPG). Baseline and repeat measurements of HVPG have been recommended for the management of patients with cirrhosis in the setting of pharmacologic prophylaxis of variceal bleeding and for gaining information about prognosis. However, published studies have demonstrated problems with the interpretation of the data on HVPG monitoring, making its use controversial. We view the current data as insufficient evidence to support the monitoring of a targeted reduction of HVPG as routine clinical practice. We recommend the performance of new prospective studies to establish the clinical importance of HVPG measurements.

Portal pressure response to losartan compared with propranolol in patients with cirrhosis

Objectives Losartan, an angiotensin II receptor blocker, has portal hypotensive effects. This study evaluates the effect of losartan on portal pressure after 14 days and compares it with that of propranolol. Methods A total of 39 individuals with cirrhosis were randomized into two groups of 19 and 20 patients each and were treated with losartan and propranolol, respectively. Hepatic venous pressure gradient was measured at baseline and on day 14 of therapy. Responders to therapy had hepatic venous pressure gradient reduction of ≥20% of baseline value. Results With losartan, 15 of 19 (78.94%) patients were responders and with propranolol, nine of 20 (45%) patients were responders ( p < 0.05). Although the hepatic venous pressure gradient reduction ( i.e., percentage from baseline) with losartan (26.74 ± 21.7%) was higher than with propranolol (14.52 ± 32%), the difference was not significant. The reduction in hepatic venous pressure gradient with losartan was contributed mainly by a significant drop of wedge hepatic venous pressure from 32.42 ± 6.61 mm of Hg to 28.31 ± 5.09 mm of Hg ( p < 0.05) compared to that with propranolol, which was from 34.55 ± 5.41 mm of Hg to 32.75 ± 8.13 mm of Hg ( p > 0.05). Responders among alcohol-abusing patients were significantly higher with losartan (81.8%) compared to those on propranolol (27.2%; p < 0.05). In the losartan group, all seven nonascitic cirrhotic individuals, as compared with two of five in the propranolol group, responded to the drugs. During the study, no significant side effects were observed in either group (who were not receiving diuretics) or in follow-up with diuretics. Conclusions Losartan is as effective as propranolol in reducing portal pressure in cirrhotic patients who are not receiving diuretics. Losartan is also superior to propranolol for achieving target level hepatic venous gradient for prevention of variceal bleeding in nonascitic and alcohol-abusing cirrhotic patients.

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).

Propranolol in primary and secondary prophylaxis of variceal bleeding among cirrhotics in India: a hemodynamic evaluation

OBJECTIVE: In the present study, we attempted to complete the hemodynamic assessment of propranolol response in cirrhotics with esophageal varices at high risk of bleeding, in one sitting, so as to identify nonresponders at the earliest. Some noninvasive indicators of this response were also evaluated. METHODS: Hepatic venous pressure gradient (HVPG) was measured in 33 such cases (18 nonbleeders, 15 bleeders) before and 90 min after an oral dose of 80 mg propranolol, and reduction by ≥20% taken as responder. RESULTS: Twenty-two patients (66.67%) responded (HVPG reduction ≥26%), whereas 11 (33.33%) did not (HVPG reduction ≤6%). Postdrug HVPG between responders and nonresponders showed a significant difference ( p < 0.001). Neither baseline HVPG ( p > 0.1), baseline CI ( p = 0.665), nor baseline stroke volume index ( p > 0.1) could predict responder status. Difference of HVPG reduction (percent) between bleeders (21.49 ± 35.53) and nonbleeders (40.58 ± 23.95) approached, but did not reach, statistical significance ( p = 0.076). However, logistic regression showed this difference to be significant ( p = 0.026). Age of responders was found to be significantly lower than that of nonresponders ( p ≈ 0.05). During a follow-up of 9–38 months, only one of 22 responders (on propranolol) had an episode of variceal bleed. None in whom HVPG fell to ≤12 mm Hg bled. CONCLUSION: The study suggests that single-sitting hemodynamic assessment of acute response to high-dose oral propranolol clearly differentiates between responders and nonresponders. Moreover, it appears that prior history of variceal bleeding and old age negatively influences the effect of propranolol.

Propranolol in primary and secondary prophylaxis of variceal bleeding among cirrhotics in India: a hemodynamic evaluation.

In the present study, we attempted to complete the hemodynamic assessment of propranolol response in cirrhotics with esophageal varices at high risk of bleeding, in one sitting, so as to identify nonresponders at the earliest. Some noninvasive indicators of this response were also evaluated. Hepatic venous pressure gradient (HVPG) was measured in 33 such cases (18 nonbleeders, 15 bleeders) before and 90 min after an oral dose of 80 mg propranolol, and reduction by > or =20% taken as responder. Twenty-two patients (66.67%) responded (HVPG reduction > or =26%), whereas 11 (33.33%) did not (HVPG reduction < or =6%). Postdrug HVPG between responders and nonresponders showed a significant difference (p < 0.001). Neither baseline HVPG (p > 0.1), baseline CI (p = 0.665), nor baseline stroke volume index (p > 0.1) could predict responder status. Difference of HVPG reduction (percent) between bleeders (21.49 +/- 35.53) and nonbleeders (40.58 +/- 23.95) approached, but did not reach, statistical significance (p = 0.076). However, logistic regression showed this difference to be significant (p = 0.026). Age of responders was found to be significantly lower than that of nonresponders (p approximately equals 0.05). During a follow-up of 9-38 months, only one of 22 responders (on propranolol) had an episode of variceal bleed. None in whom HVPG fell to < or = 12 mm Hg bled. The study suggests that single-sitting hemodynamic assessment of acute response to high-dose oral propranolol clearly differentiates between responders and nonresponders. Moreover, it appears that prior history of variceal bleeding and old age negatively influences the effect of propranolol.

Relationship of portal pressure and colorectal vasculopathy in patients with cirrhosis.

We studied the relationship between portal pressure and colorectal mucosal vascular lesions in cirrhotics and the effectiveness of drug therapy in treating these lesions. Colonoscopy and hepatic venous pressure gradient (HVPG) studies were performed in 21 cirrhotics. Oral spironolactone plus transdermal nitroglycerin were given to patients who had diffuse mucosal cherry-red spots and/or rectal varices. The colonoscopy and HVPG determinations were repeated after four weeks. Colonoscopic findings included vascular ectasias in 13 patients (62%), diffuse cherry-red spots in the rectum in five patients (24%), and rectal varices in eight patients (38%). Overall, colorectal mucosal vascular lesions were found in 16 cirrhotics (76%). These findings were not found in 21 age- and sex-matched noncirrhotic controls. Vascular ectasias appeared without relationship to the HVPG. Patients with diffuse cherry-red spots (N = 5, 22.4+/-3.4 mm Hg) had a significantly higher HVPG than those without (N = 16, 16.6+/-3.3 mm Hg, P < 0.01). However, no significant difference was found in HVPG between patients with rectal varices (N = 8, 19.4+/-4.6 mm Hg) and patients without rectal varices (N = 13, 17.2+/-3.8 mm Hg). After four weeks of drug therapy, diffuse cherry-red spots became less obvious when the HVPG decreased more than 20%. Rectal varices did not change their appearance with HVPG reduction. We found that colorectal vascular lesions are common in cirrhotics. Diffuse cherry-red spots are probably dependent on elevated portal pressure, but vascular ectasias and rectal varices are not related to the degree of portal pressure. Chronic drug therapy with reduction of portal pressure improves colonoscopic findings such as diffuse cherry-red spots.

Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate in the treatment of portal hypertension

Background & Aims: The association of prazosin to propranolol enhances the decrease in portal pressure but may cause hypotension and sodium retention. The aim of this study was to compare the portal pressure reduction and safety of the combination of propranolol plus prazosin with that of propranolol plus isosorbide-5-mononitrate (ISMN). Methods: Fifty-six portal-hypertensive cirrhotics received randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28) orally for 3 months. Hemodynamics and liver and renal function were assessed at baseline and after 3 months. Results: Propranolol plus prazosin caused a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (−24.2% ± 11% vs. −16.1% ± 11%; P < 0.01). A reduction in HVPG of >20% was significantly more frequent in the propranolol plus prazosin group than in the propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified hepatic blood flow, quantitative liver function test results, glomerular filtration rate, plasma renin activity, or plasma aldosterone level. Side effects occurred in 13 patients receiving propranolol plus prazosin compared with 7 receiving propranolol plus ISMN ( P = 0.16). Conclusions: Propranolol plus prazosin has a greater portal pressure–lowering effect than propranolol plus ISMN. Both therapies were safe for liver and renal function. However, the combination of propranolol plus prazosin caused a greater decrease in arterial pressure and was less well tolerated than propranolol plus ISMN. GASTROENTEROLOGY 1998;115:116-123