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.     

Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis: a randomized comparison

BACKGROUND: Octreotide and terlipressin are widely used in acute variceal hemorrhage to reduce the bleeding rate. They purportedly act by mesenteric arterial vasoconstriction, thus reducing portal venous flow (PVF) and portal pressure. Little is known about the immediate-early hemodynamic effects of these drugs. AIM: To compare the acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis. PATIENTS: Forty-two cirrhotic patients with a history of variceal bleeding were randomized to receive either octreotide 100 microg intravenous bolus followed by a continuous infusion at 250 microg/h (n = 21), or terlipressin 2 mg intravenous bolus (n = 21). METHODS: Mean arterial pressure (MAP), heart rate (HR), hepatic venous pressure gradient (HVPG), and PVF, assessed by duplex Doppler ultrasonography, were measured before and at 1, 5, 10, 15, 20, and 25 min after the start of drug administration. RESULTS: Octreotide markedly decreased HVPG (-44.5 +/- 17.8%) and PVF (-30.6 +/- 13.6%) compared to the baseline at 1 min (p < 0.05). Thereafter, both variables rapidly returned toward the baseline, and by 5 min, no significant differences in HVPG (-7.1 +/- 28.9%) and PVF (10.2 +/- 26.2%) were noted. A similar transient effect on MAP and HR was observed. Terlipressin significantly decreased HVPG (-18.3 +/- 11.9%) and PVF (-32.6 +/- 10.5%) at 1 min (p < 0.05) and sustained these effects at all time points. The effects on arterial pressure and HR were also sustained. CONCLUSIONS: Octreotide only transiently reduced portal pressure and flow, whereas the effects of terlipressin were sustained. These results suggest that terlipressin may have more sustained hemodynamic effects in patients with bleeding varices.     

Early primary prophylaxis with beta-blockers does not prevent the growth of small esophageal varices in cirrhosis: a randomized controlled trial

Background

The efficacy of portal pressure reduction by beta-blockers and the utility of serial hepatic venous pressure gradient (HVPG) measurements for the management of small (≤5 mm) esophageal varices in patients of cirrhosis are not clear.

Aims

The study had the following aims: to study (1) the effect of propranolol on the growth of small varices and (2) whether single or serial HVPG measurements result in a better outcome compared to no measurement in patients with small varices.

Methods

Consecutive cirrhosis patients with small varices, without any history of variceal bleed, were randomized to receive propranolol or placebo and to undergo no HVPG, only baseline HVPG, or serial HVPG measurements.

Results

A total of 150 cirrhotics (cirrhosis predominantly viral or alcohol induced) were included (77 in the beta-blocker and 73 in the placebo group). Baseline characteristics were similar. The actuarial 2-year risk of growth of varices (primary endpoint) was 11 and 16% in the propranolol and placebo group, respectively (P = 0.786). Variceal bleeding and mortality were also comparable in the two groups. Similarly, the outcome was not influenced by HVPG measurements (whether serial, only baseline, or no HVPG). A bilirubin level of ≥1.5 mg/dl was found to be an independent predictor of variceal progression.

Conclusions

In cirrhotics with small esophageal varices, nonselective beta-blockers are unable to prevent the growth of varices, variceal bleed, or mortality. HVPG monitoring of these patients did not change the outcome; however, the role of HVPG-guided therapy modification needs to be studied.     

Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis

BACKGROUND & AIMS: It has been suggested that losartan, an angiotensin II (A-II) type 1 receptor blocker, may have a pronounced portal pressure reducing effect, far greater than that of propranolol. This randomized controlled trial compared the hemodynamic and renal effects of continued 6-week administration of losartan (n = 25) vs. propranolol (n = 15) in portal hypertensive patients with cirrhosis treated endoscopically after a variceal bleeding episode. METHODS: Hepatic venous pressure gradient (HVPG), systemic hemodynamics, renal function, and vasoactive factors were measured before and at 6 weeks of treatment. RESULTS: Losartan did not reduce HVPG (-2% +/- 12%, NS) but significantly decreased mean arterial pressure (MAP, -8% +/- 10%, P = 0.001). On the contrary, propranolol significantly reduced HVPG (-10% +/- 11%, P = 0.003) and cardiac output (-16% +/- 12%, P = 0.001) but did not modify MAP (2.5% +/- 10%, NS). Losartan increased A-II levels, reduced aldosterone, and decreased glomerular filtration rate (GFR) in Child B patients. Propranolol did not modify renal function. Adverse events related to therapy were mild and similar in both groups. CONCLUSIONS: Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patients with moderate liver failure. Therefore, losartan is not an alternative to propranolol in preventing variceal rebleeding.     

Prognostic value of early measurements of portal pressure in acute variceal bleeding.

BACKGROUND & AIMS: Variceal bleeding is the most important complication of portal hypertension. However, the relationship between the increase in portal pressure and the outcome of variceal bleeding has not been well defined. METHODS: We measured the hepatic venous pressure gradient (HVPG) of 65 cirrhotic patients with acute variceal hemorrhage, early after admission (20.6 +/- 15.6 hours). RESULTS: Twenty-three patients had a poor evolution (failure to control bleeding or early variceal rebleeding), and 42 had an uneventful evolution. The only variable associated with outcome was the HVPG, which was higher in patients with a poor evolution (23.7 +/- 6.1 vs. 19.2 +/- 3.3 mm Hg; P < 0.0004). This was confirmed by multivariate analysis. HVPG was >/=20 mm Hg in 19 of 23 patients with poor evolution vs. 12 of 42 patients with uneventful evolution (P < 0.0001). An initial HVPG of >/=20 mm Hg was associated with a significantly longer intensive care unit stay (7 +/- 5 vs. 4 +/- 2 days; P < 0.02), longer hospital stay (19 +/- 10 vs. 14 +/- 6 days; P < 0.02), greater transfusion requirements (9.0 +/- 7.7 vs. 4.7 +/- 3.2 UU; P < 0.007), and a worse actuarial probability of survival (1-year mortality, 64% vs. 20%; P < 0.002). CONCLUSIONS: Early measurement of HVPG in cirrhotic patients during acute variceal bleeding provides useful prognostic information on the evolution of the bleeding episode and long-term survival.     

Editorial: Beta-blockers and the prevention of decompensation in cirrhosis: worth the trouble

Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12?mm?Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.     

Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension: a meta-analysis

OBJECTIVES: 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. METHODS: 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. RESULTS: Ten studies totaling 595 patients undergoing two HVPG measurements were identified. The RR of bleeding was lower in patients achieving an overall (HVPG or=20%) (0.27, 95% CI 0.14-0.52), complete (HVPG 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). CONCLUSIONS: 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.     

Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial

Background

The renin-angiotensin system plays an important role in hepatic fibrosis and portal hypertension. We evaluated the long-term effects of olmesartan, an angiotensin type 1 (AT1) receptor blocker, on hemodynamics and liver fibrosis.

Methods

Forty-eight selected patients with cirrhosis were randomly divided into two groups of 24 patients each, those who received and those who did not receive olmesartan treatment for 1?year. Hepatic hemodynamic studies, and measurements of transforming growth factor-beta1 (TGF-beta1) and blood markers of hepatic fibrosis, including serum hyaluronic acid (HA), type IV collagen, and procollagen III N-terminal propeptide levels, were also performed at the beginning and end of the study.

Results

The median dose of the final drug administration was 20?mg (range 10?C40?mg). Olmesartan reduced the hepatic venous pressure gradient (HVPG) by ?12.9?±?9.1% (p?=?0.035) after 1?year. No significant changes were seen in controls. Six of the 24 patients (25%) in the olmesartan group showed a >20% reduction of HVPG from baseline values. TGF-beta1 was significantly decreased in patients who received olmesartan (7.0?±?8.2 vs. 3.1?±?1.6?ng/mL, p?=?0.046) but there was no decrease in the controls. A significant trend was shown by correlating HA and TGF-beta1 variations in cirrhosis patients (p?=?0.018, r?=?0.377). Fibrosis markers were unchanged at the end of the study in both groups.

Conclusions

Olmesartan induced a mild reduction of portal pressure and TGF-beta1 for 1?year, but did not suppress hepatic fibrosis markers.     

Comparison of Doppler ultrasonography and the hepatic venous pressure gradient in assessing portal hypertension in liver cirrhosis

BACKGROUND AND AIM: This prospective study aimed to determine whether Doppler ultrasonography can represent the hepatic venous pressure gradient (HVPG) as an assessment of the severity of portal hypertension and the response to terlipressin, which reduces the portal pressure in liver cirrhosis. METHODS: The HVPG and the Doppler ultrasonographic parameters, such as the portal venous velocity and the splenic venous velocity, the pulsatility and the resistive index of the hepatic, splenic and renal arteries were measured in 138 patients with liver cirrhosis. The changes in the HVPG and the portal venous velocity after administering terlipressin were evaluated in 43 of the 138 patients. The patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as responders to terlipressin. RESULTS: None of the Doppler ultrasonographic parameters correlated with the HVPG. Both the HVPG (28.0 +/- 19.8%) and the portal venous velocity (29.7 +/- 13.2%) showed a significant reduction after terlipressin administration. However, the portal venous velocity decreased significantly, not only in the responders (31.0 +/- 12.0%) but also in the non-responders (25.2 +/- 16.4%). CONCLUSIONS: Doppler ultrasonography does not represent the HVPG, and is therefore not suitable for replacing HVPG as a means of assessing the severity of portal hypertension and the response to drugs which reduce the portal pressure in liver cirrhosis.     

Hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

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 > or =20% taken as responder. RESULTS: 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. 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.     

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 >or=20% of baseline or to or=20% of baseline or to or=20% or to 相似文献   

The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis

BACKGROUND: In cirrhosis, repeated flares of portal pressure and collateral blood flow provoked by postprandial hyperaemia may contribute to variceal dilation and rupture. AIM: To examine the effect of the extent of the collateral circulation on the postprandial increase in portal pressure observed in cirrhosis. PATIENTS AND METHODS: The hepatic venous pressure gradient (HVPG), hepatic blood flow and azygos blood flow were measured in 64 patients with cirrhosis before and after a standard liquid meal. RESULTS: Peak increases in HVPG (median+14.9%), hepatic blood flow (median+25.4%), and azygos blood flow (median+32.2%) occurred at 30 min after the meal. Compared with patients with marked postprandial increase in HVPG (above the median, n = 32), those showing mild (<15%, n = 32) increase in HVPG had a higher baseline azygos flow (p<0.01) and underwent a greater postprandial increase in azygos flow (p<0.02). Hepatic blood flow increased similarly in both groups. Postprandial increases in HVPG were inversely correlated (p<0.001) with both baseline azygos flow (r = -0.69) and its postprandial increase (r = -0.72). Food intake increased nitric oxide products in the azygos (p<0.01), but not in the hepatic vein. Large varices (p<0.01) and previous variceal bleeding (p<0.001) were more frequent in patients with mild increase in HVPG. CONCLUSIONS: Postprandial hyperaemia simultaneously increases HVPG and collateral flow. The extent of the collateral circulation determines the HVPG response to food intake. Patients with extensive collateralisation show less pronounced postprandial increases in HVPG, but associated with marked flares in collateral flow. Collateral vessels preserve their ability to dilate in response to increased blood flow.     

Hepatic Venous Pressure Gradient: Worth Another Look?

Portal hypertension is one of the most important complications of chronic liver disease and accounts for significant morbidity and mortality. Measurement of the hepatic venous pressure gradient (HVPG) is a simple, invasive, and reproducible method of assessing portal venous pressure. Measurement of HVPG provides the clinician an estimate of the degree of intrahepatic portal flow resistance, guides therapy for variceal bleeding (primary and secondary prophylaxis), assesses feasibility of resection in patients with hepatocellular cancer, and predicts response to therapy of patients with chronic hepatitis C. Achieving hemodynamic targets of reducing the HVPG to <10 mmHg or a 20% reduction from baseline virtually eliminates complications related to portal hypertension from chronic liver disease. This review explores the role of HVPG measurement in the contemporary treatment of patients with cirrhosis and portal hypertension.     

Maintenance of hemodynamic response to treatment for portal hypertension and influence on complications of cirrhosis

BACKGROUND/AIMS: Following treatment with beta blockers in patients with cirrhosis and portal hypertension, reduction of hepatic venous pressure gradient (HVPG) to <12 mmHg or by >20% of baseline induces an extremely low risk of variceal bleeding. However, several factors such as compliance to therapy or alcohol abstinence may change the initial response after a long follow-up, and the effect of response on other complications of cirrhosis is less clear. The aim of this study was to assess the long-term maintenance of hemodynamic response and its influence on complications of cirrhosis. METHODS: One hundred and thirty two cirrhotic patients received nadolol and isosorbide mononitrate to prevent variceal rebleeding. HVPG was measured at baseline, after 1 to 3 months under treatment and again 12 to 18 months later. RESULTS: Sixty four patients were responders. After a longer follow-up, earlier response did not change in 81% of cases. Changes of response were mainly related to modifications in medication dose or in alcohol intake. As compared with poor-responders, responders had a lower probability of developing ascites (P<0.001) and related conditions, a greater improvement of Child-Pugh score (P=0.03), and a lower likelihood of developing encephalopathy (P=0.001) and of requiring liver transplantation (P=0.002). Eleven responders and 22 poor-responders died (P=0.029). CONCLUSIONS: Hemodynamic response to treatment of portal hypertension is usually sustained after a long-term follow-up. Response decreases the probability of developing complications of cirrhosis and the need for liver transplantation, and significantly improves survival.     

Correlation of hepatic venous pressure gradient with variceal bleeding, size of esophageal varices, etiology, ascites and degree of liver dysfunction in cirrhosis of liver

An elevated hepatic venous pressure gradient (HVPG) has been associated with risk of variceal bleeding, and outcome and survival after variceal bleeding. In this pilot study, we measured HVPG in 40 patients with liver cirrhosis and studied its relationship with etiology of liver disease, esophageal variceal size, history of variceal bleeding or ascites, biochemical liver tests and Child-Pugh class. There was no procedurerelated complication. The mean (SD) HVPG was similar in patients who had history of variceal bleeding as compared to those who did not (15.4 [2.8] mmHg vs. 13.9 [2.7] mmHg, p=0.1); HVPG had no significant association with etiology of cirrhosis (p=0.4). HVPG levels were significantly higher in patients with larger esophageal varices (grade III/IV vs. I/II: 15.2 [2.7] mmHg vs.13.1 [2.8] mmHg, p=0.04), poorer Child-Pugh class (B or C versus A), and presence of ascites (p=0.04). Thus, HVPG correlated with variceal size, Child-Pugh class, and presence of ascites, but not with variceal bleeding status.     

Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis

During variceal bleeding, several factors may increase portal pressure, which in turn may precipitate further bleeding. This study investigates the early effects of endoscopic injection sclerotherapy (EIS) and endoscopic band ligation (EBL) on hepatic venous pressure gradient (HVPG) during acute bleeding and the possible influence in outcome. In 50 cirrhotic patients with bleeding esophageal varices treated with EIS (n = 25) or EBL (n = 25), we performed repeated HVPG measurements before and immediately after endoscopic treatment (time 0) and every 24 hours for a 5-day period. Endotherapy was continued until the varices were too small for further treatment. Both groups were comparable with regard to age, gender, Child-Turcotte-Pugh grade, and HVPG. In the EBL and EIS groups, a significant (P <.0001) increase was observed in mean portal pressure (20.7 mm Hg +/- 4.4 SD and 21.5 mm Hg +/- 4.5 SD, respectively) immediately after treatment (time 0) as compared with pretreatment (18.1 +/- 4.5 and 18.1 +/- 4.0). However, HVPG in the EBL group returned to baseline values within 48 hours after treatment, while in the EIS group it remained high during the 120-hour study period (P <.0001). Bleeding stopped in all patients after endotherapy. During the 42-day follow-up period, the rebleeding rate over time was lower in the EBL group compared with the EIS group (P =.024). Patients with an initial HVPG greater than 16 mm Hg had, despite endoscopic treatment, a significantly higher likelihood of death (P =.024) and overall failure (P =.037) [correction]. In conclusion, during acute variceal bleeding EIS, but not EBL, causes a sustained increase in HVPG, which is followed by a higher rebleeding rate.     

Perendoscopic variceal pressure measurement: A reliable estimation of portal pressure in patients with cirrhosis?

OBJECTIVES: In patients with cirrhosis, the hepatic venous pressure gradient (HVPG) is the reference method for the assessment of portal hypertension (PHT). Variceal pressure (VP) may be measured at endoscopy, but its relationship to the HVPG remains controversial. The aim of the study was to retrospectively compare HVPG and VP values obtained in a cohort of patients with cirrhosis and PHT. METHODS: Within 8 days (range: 6-10 days), 64 patients in a stable condition with biopsy-proven cirrhosis [alcoholic: 47; other 17; mean age: 56.5 yrs (35-70); mean Child-Pugh's score: 9.4 +/- 1.9; ascites: 37/64; previous variceal bleeding (="bleeders"): 24/64) and oesophageal varices (grade 2: 49; grade 3: 15)] underwent both measurement of the HVPG during transjugular liver biopsy and VP at endoscopy using a "home made" pressure sensitive gauge in the absence of needle puncture of the varix. Alcoholic hepatitis was present in 28 patients with alcoholic cirrhosis. RESULTS: The pressure sensitive gauge was well tolerated. The mean HVPG and VP values were 18.5 +/- 3.4 mmHg and 19 +/- 3.7 mmHg, respectively. A significant difference was observed between "bleeders" (n=24) and non "bleeders" (n=40) in terms of VP values (21.4 +/- 3.3 vs 17.2 +/- 3.2 mmHg, P<0.001), but not for HVPG values (19.4 +/- 4.1 vs 17.9 +/- 2.8 mmHg, P=0.075). A positive correlation was observed between VP and HVPG values (r=0.62, P<0.0001). CONCLUSIONS: In this group of patients with cirrhosis and oesophageal varices, a "home-made" pressure sensitive gauge allowed a non invasive perendoscopic measurement of VP. The positive correlation between VP and HVPG values suggests that measurement of VP may be a reliable estimate of portal pressure in these patients.     

Prognosis in patients with cirrhosis and mild portal hypertension

OBJECTIVE: Sixty to 70% of upper gastrointestinal bleeding episodes in patients with cirrhosis are caused by oesophageal varices. Prophylaxis is indicated in patients with varices and a hepatic venous pressure gradient (HVPG) above 12 mmHg. The study of the natural history of patients with lower HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. MATERIAL AND METHODS: Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient Registries. Variceal bleeding, hepatic encephalopathy and death related to cirrhosis were registered. Thirty-nine patients were graded as Child class A, 19 as class B and 3 as class C. Median survival time was 11 years. RESULTS: Twenty-eight patients (46%) developed one or more complications: variceal bleeding in 10 (16%) and hepatic encephalopathy in 18 patients (30%). Twenty-three patients (38%) died from complications of cirrhosis. Two patients (3%) died from variceal bleeding, another two (3%) from gastrointestinal bleeding of unidentified source. Survival rate was significantly decreased compared with that in the background population. CONCLUSIONS: The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare.