卡维地洛与普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度效果的对比分析

目的探讨卡维地洛和普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度(HVPG)的幅度、应答率以及用药后不良反应的差异,对卡维地洛降低门静脉压力的有效性和安全性进行评价。方法收集2010年10月-2012年1月在山东大学附属省立医院确诊的64名肝硬化门静脉高压患者,随机分为2组:普萘洛尔组(n=33)和卡维地洛组(n=31),根据血压和心率调整剂量,疗程7 d,均于治疗前后行HVPG测定及肝肾功能指标检测,比较2组患者HVPG降低的幅度及应答率,并观察患者低血压、腹水、肾损伤等不良反应的发生情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验或Fisher精确概率法。结果卡维地洛组和普萘洛尔组的HVPG均明显降低,降低幅度分别为(28.30±22.19)%和(12.38±24.09)%,其中卡维地洛组降低更明显,差异有统计学意义(t=0.223 4,P=0.032)。2组应答率分别为:卡维地洛组56.7%(17/30),普萘洛尔组41.9%(13/31),2组差异无统计学意义(χ2=1.324,P=0.250)。卡维地洛组平均动脉压的降低较普萘洛尔组明显,差异有统计学意义(t=2.338,P=0.024),但患者未出现明显低血压的不良反应;2组患者胆红素、血肌酐和尿素氮在治疗前后无明显升高,亦无腹水生成或加重的趋势。结论本研究提示在短期内卡维地洛降低HVPG的作用较普萘洛尔显著,且无明显不良反应;其用于肝硬化门静脉高压的治疗是安全有效的。     

Hemodynamic effects of nifedipine on hepatic venous pressure gradient in patients with portal hypertension

The effect of Nifedipine on hepatic venous pressure gradient (HVPG) was determined in 10 patients with portal hypertension due to cirrhosis of the liver, and in 7 control subjects, by hepatic vein catheterization. Twenty min. after sublingual application of 10 mg Nifedipine, patients and controls showed significant hemodynamic changes in the systemic circulation. In contrast, HVPG after Nifedipine was not statistically different from the basal values--neither in patients with portal hypertension (p = 16.6 +/- 5.2 mmHg vs 17.9 +/- 5.3 mmHg) nor in the control subjects (p = 2.9 +/- 1.1 mmHg vs. 1.0 mmHg). We conclude that calcium entry blockade by Nifedipine is not effective in acutely reducing portal venous pressure.     

Evaluation of portal hypertension in the cirrhotic patient: hepatic vein pressure gradient and beyond

Portal hypertension (PH) is a major complication of liver cirrhosis, as it predisposes to the development of serious clinical manifestations such as ascites, hepatic encephalopathy and variceal bleeding. Till now, the measurement of hepatic vein pressure gradient (HVPG) is the gold standard method to ascertain the presence and significance of PH, as many studies have shown its correlation with the appearance of varices and the possibility of variceal bleeding. However, the invasiveness of this procedure makes it difficult to be used in daily clinical practice. Several noninvasive methods with adequate capability of evaluating liver fibrosis, including elastographic techniques, are currently used as alternatives to HVPG in order to assess the presence and the severity of PH. The aim of this paper is to express an overview of the literature about the actual role of HVPG and all available noninvasive tests on the prediction of development of PH complications, to highlight their advantages and their potential limitations, and to provide the latest trends on clinical practice.     

The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long-term control of portal pressure.     

非肝硬化门脉高压患者临床特点分析

目的 总结非肝硬化门脉高压症(NCPH)患者的临床特点和肝静脉压力梯度(HVPG)的变化.方法 2017年1月～2019年12月南京市第二医院住院的28例NCPH患者,采用Seldinger法穿刺右侧颈内静脉,使用一次性球囊导管测定肝静脉压力,计算HVPG,接受肝活检检查.结果 在本组28例NCPH患者中,诊断特发性门...     

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.     

Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension

Portal hypertension is a predictor of liver‐related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon‐free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child‐Pugh‐Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open‐label sofosbuvir plus ribavirin at Day 1 or after a 24‐week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by ‐1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow‐up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long‐term follow‐up. (EudraCT 2012‐002457‐29).     

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.     

Invasive diagnosis of portal hypertension in cirrhosis: a critical evaluation of the hepatic venous pressure gradient measurement

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.     

Collagen proportionate area correlates to hepatic venous pressure gradient in non-abstinent cirrhotic patients with alcoholic liver disease

AIM To explore the relationship between collagen proportionate area(CPA) and portal hypertension-related clinical manifestations in alcoholic liver disease(ALD).METHODS Retrospective study with chart review of patients with ALD adressed to our center between January 2012 and December 2013 for a transjugular liver biopsy(TJLB) and hepatic hemodynamic study. Patients were included if they met the following criteria:(1) Medical indication for a liver biopsy in the setting of ALD;(2) recent( 15 d) clinical, radiological, endoscopic and biological data available; and(3) estimated follow-up of at least 6 mo. Liver tissue from cirrhotic subjects obtained from transjugular liver biopsies was stained with Picro Sirius red and computer-assisted digital image analysis to determine fibrosis density using CPA was performed. RESULTS We included 61 patients with alcoholic ALD, subdivided in 41 active alcohol drinkers and 20 durably abstinent patients. Nine healthy liver donors served as controls. Mean CPA in patients with ALD was 7.1%, with no difference between active drinkers and abstinent patients(P = 0.17). Using a fibrosis density cutoff of 5%, we observed a positive correlation between high fibrosis density and the hepatic venous pressure gradient(HVPG) only in active drinkers(P = 0.02). At 12-mo of follow-up, in the group of active alcohol drinkers, patients reaching a composite outcome showed a higher HVPG value as compared to those who did not(18.5 mm Hg vs 14.5 mm Hg P 0.04) whereas CPA values were similar(6.9% vs 11%, P = 0.23).CONCLUSION In active alcoholic ALD, CPA correlates to portal pressure but only HVPG predicts clinical events, pointing to the role of alcohol as a modulator of portal hypertension.     

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.     

奥曲肽和特利加压素单用或联用对肝硬化患者肝静脉压力梯度的影响

目的分别观察奥曲肽和特利加压素单用及二者联合对肝静脉压力梯度(HVPG)的影响。方法收集2011年1月-2014年4月山东大学附属省立医院消化科住院的肝硬化并静脉曲张患者49例,将患者分成奥曲肽组(A组)、特利加压素组(B组)、联合用药组(C组)。A组:奥曲肽0.1 mg静推(给药时间1 min),继以25μg/h泵入,分别测给药前及给药后1、5、10和15 min时的HVPG;B组:特利加压素1 mg静推(2 min内完成),分别测给药前及给药后10、20和30 min时的HVPG;C组:首先给予奥曲肽,分别测奥曲肽给药前及给药后1、5、10和15 min的HVPG,继以联合特利加压素静推,分别测定联合特利加压素后10、20和30 min时的HVPG。采用t检验、方差分析和卡方检验对数据进行统计学分析。结果 A组奥曲肽给药后1.5、10和15 min HVPG显著下降(t值分别为13.173、5.364、3.894、4.160,P值均<0.001),但5、10和15 min之间差异无统计学意义(P值均>0.05)。B组特利加压素给药20 min后HVPG显著下降(t=4.062,P=0.002),20和30 min HVPG之间差异有统计学意义(t=4.022,P=0.002)。C组加用特利加压素20 min后HVPG进一步下降(t=4.926,P<0.001),20和30 min HVPG之间差异无统计学意义(t=1.733,P=0.101)。三组疗效差异有统计学意义,C组疗效明显大于A、B组(F=10.423,P<0.05)。结论奥曲肽能很快降低肝硬化门静脉高压患者的HVPG,但短期内有所回升且趋于稳定。特利加压素单独应用亦能降低HVPG,起效时间比奥曲肽慢。奥曲肽加用特利加压素后可进一步降低HVPG,效果优于单独用药。     

Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis

Abstract We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vascodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.     

Diagnosing and monitoring cirrhosis: Liver biopsy, hepatic venous pressure gradient and elastography

In this review we summarize the role of liver biopsy, transient elastography and hepatic venous pressure gradient (HVPG) in the diagnosis and monitoring of patients with liver cirrhosis. Transient elastography is useful for the non-invasive diagnosis of cirrhosis, but relevant information is lost if it is used as a dichotomous test. The development of clinically significant portal hypertension (defined as a hepatic venous pressure gradient ≥ 10 mmHg) is associated with the development of varices and decompensation and it is something that it is worth testing for. Transient elastography has some value for the prediction of clinically significant portal hypertension, but a large proportion of patients have non-diagnostic values. It has also some value for the diagnosis of varices, but non-invasive markers cannot substitute endoscopic screening in cirrhosis. Better dynamic, easily repeatable non-invasive tools are needed to monitor compensated cirrhosis.     

肝硬化门静脉高压患者门静脉压力与FibroScan检测值相关性分析

目的探讨应用彩色多普勒超声显像仪以及瞬时弹性成像(Fibro Scan)观察和分析肝硬化患者门静脉压力与Fibro Scan之间的关系。方法选择2012年3月-2014年3月中山市第二人民医院收治的乙型肝炎肝硬化门静脉高压患者235例,另选健康人100例作为对照,使用彩色超声多普勒显像仪检测门静脉宽度(PVD)、门静脉平均血流速度(PVVmean)、门静脉血流量(PVQ),利用公式门静脉压力(Ppv)=1.895 1+0.001 1PVQ估算出Ppv。同时进行Fibro Scan检测。计量资料以均数±标准差(x±s)表示,组间比较采用t检验,各参数与Ppv关系采用双变量相关分析。结果肝硬化门静脉高压患者PVD、PVQ、Ppv和Fioro Scan值分别为(1.42±0.12)cm、(1238±145.23)ml/min、(3.28±0.17)k Pa和(27.81±7.52)k Pa,明显高于正常对照组(P值均0.05),Fibro Scan值和PVQ与肝硬化患者Ppv呈正相关,相关系数r分别为0.52、0.61,P值均0.001。结论 Fibro Scan测值可作为无创性评估肝硬化Ppv参考指标。     

Role of hepatic vein catheterisation and transient elastography in the diagnosis of idiopathic portal hypertension

Background

Idiopathic portal hypertension is a rare cause of portal hypertension, frequently misdiagnosed as cryptogenic cirrhosis. This study evaluates specific findings at hepatic vein catheterisation or liver stiffness in idiopathic portal hypertension.

Methods

39 cases of idiopathic portal hypertension patients were retrospectively reviewed. Hepatic vein catheterisation and liver stiffness measurements were compared to matched patients with cirrhosis and portal hypertension, and non-cirrhotic portal vein thrombosis, included as controls.

Results

Hepatic vein-to-vein communications were found in 49% idiopathic portal hypertension patients precluding adequate hepatic venous pressure gradient measurements in 12. In the remaining 27 patients, mean hepatic venous pressure gradient (HVPG) was 7.1 ± 3.1 mmHg. Only 5 patients had HVPG ≥ 10 mmHg. HVPG was markedly lower than in cirrhosis (17 ± 3 mmHg, p < 0.001). Mean liver stiffness in idiopathic portal hypertension was 8.4 ± 3.3 kPa; significantly higher than in non-cirrhotic portal vein thrombosis (6.4 ± 2.2 kPa, p = 0.009), but lower than in cirrhosis (40.9 ± 20.5 kPa, p = 0.005). Only 2 idiopathic portal hypertension patients had liver stiffness >13.6 kPa.

Conclusions

Patients with idiopathic portal hypertension frequently have hepatic vein-to-vein communications and, despite unequivocal signs of portal hypertension, HVPG and liver stiffness values much lower than the cut-off for clinical significant portal hypertension in cirrhosis. These findings oblige to formally rule-out idiopathic portal hypertension in the presence of signs of portal hypertension.     

Correlation between platelet blood levels and the hepatic venous pressure gradient among patients with cirrhosis

BACKGROUND: Determination of hepatic venous pressure gradient is the main method used to assess portal pressure. Recently, platelet blood levels has been indicated as a non-invasive marker of the presence of portal hypertension. AIM: To correlate platelet blood levels with the hepatic venous pressure gradient among patients with cirrhosis. PATIENTS AND METHODS: A total of 83 cirrhotic patients who had undergone hepatic venous pressure gradient over the last 6 years were included. Patients were divided in groups according to Child-Pugh classification. All had upper digestive endoscopy to assess the presence of esophageal varices and platelet serum levels were recorded. RESULTS: Platelet serum levels range varied between 45,000/mm(3) and 389,000/mm(3) (mean: 104,099; standard deviation: 58,776). Mean hepatic venous pressure gradient was 15.2 mm Hg with a standard deviation of 6.4 mm Hg (range: 1 to 29 mm Hg). Simple linear regression analysis was applied to verify an association of hepatic venous pressure gradient and platelet serum levels, revealing a weak correlation between both variables. We observed a progressive reduction of serum platelet levels as esophageal varices diameter increased and hepatocellular function (established by Child-Pugh classification) decreased. However, these findings did not reach statistical significance. CONCLUSION: Despite the lack of a statistical significant correlation among serum platelet levels and hepatic venous pressure gradient or hepatocellular function, there was a clear tendency indicating that those variables could be involved in the pathogenesis of low platelet levels.