肝硬化门脉高压症并发血栓形成机制和治疗研究进展*

肝硬化门脉高压症并发血栓是临床研究实践过程中面临的难题。本文通过对其形成机制和治疗相关研究进展进行总结,重点介绍了近年来国内外关于肝硬化门脉高压并发门脉血栓发生机制和治疗进展。目前认识的主要发生机制包括肝星状细胞的活性、内皮细胞的功能、机体促凝血和凝血抑制失衡等,治疗措施包括低分子肝素等抗凝治疗、β受体阻滞剂和其他药物,如辛伐他汀、利福昔明和益生菌等联合应用以降低门脉压力治疗、提高一氧化氮合成酶磷酸化水平和针对线粒体的抗氧化治疗等措施。     

脾切除联合贲门周围血管离断术治疗肝硬化门脉高压症患者预防门静脉血栓形成研究

目的 探讨脾切除联合贲门周围血管离断术治疗肝硬化门脉高压症患者门静脉血栓(PVT)的预测措施。方法 2017年1月～2019年3月我院肝胆外科诊治的肝硬化并发门脉高压症患者60例,均接受脾切除联合贲门周围血管离断术。术后将患者分成A组和B组。在B组,当出现抗凝指针时给予低分子肝素短期抗凝治疗。使用彩超检查门脉指标和诊断PVT形成。结果 术后,在B组30例患者中有20例(66.7%)接受了短期抗凝治疗;在术后3 w末,超声检查发现PVT患者15例(25.0%),其中A组11例(36.7%),显著高于B组的4例【(13.3%),P<0.05】;血栓形成组门静脉直径为(1.5±0.3)cm,与无血栓形成组比,无显著性差异【(1.4±0.2)cm,P>0.05】,门静脉血流流速为(12.3±1.4)cm/s,显著低于无血栓形成组【(14.5±1.7)cm/s,P＜0.05】;血栓形成组血清D-二聚体水平显著高于无血栓形成组(P＜0.05);血栓形成组外周血血小板计数为(142.6±58.9)×10⁹/L,显著高于无血栓形成组【(91.4±52.4)×10⁹/L,P＜0.05】。结论 在采取脾切除联合贲门周围血管离断术治疗肝硬化并发门脉高压症患者时,需警惕术后PVT的形成。对术后血小板计数急剧升高、血清D-二聚体显著升高和门脉血流减慢的患者应该及时给予抗凝治疗。     

Agreement between wedged hepatic venous pressure and portal pressure in non-alcoholic steatohepatitis-related cirrhosis

1. Download : Download high-res image (181KB)
2. Download : Download full-size image

     

Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients

AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient(HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65(range, 40-82) years. According to the ChildPugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were-1.0 kg(P = 2.04 × 10~(-6)) and-1.3 kg(P = 1.83 × 10~(-5)), respectively. The median HVPG value was 240(range, 105-580) mm H2 O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mm H_2 O in predicting treatment response. The response rate was 87.5%(7/8) in patients with HVPG of 190 mm H2 O or less, whereas it was only 12.5%(2/16) in those with HVPG of greater than 190 mm H2O(P = 7.46 × 10~(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG(P = 0.045) and serum hyaluronic acid(P = 0.017) were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.     

AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers

BACKGROUND/AIMS: The renin-angiotensin system plays an important role in hepatic fibrogenesis and in portal hypertension. To examine the long-term effects of Candesartan cilexetil, an angiotensin type 1 (AT1) receptor blocker, on portal-systemic haemodynamics and on liver fibrosis. METHODS: Forty-seven compensated Child A and Child B (8) cirrhotic patients were randomly assigned to receive Candesartan cilexetil, 8 mg/d (N.24) and no treatment (N.23) for 1 year. Portal-systemic haemodynamic parameters, serological levels of procollagen (PIIINP), hyaluronic acid (HA) and transforming growth factor beta 1 (TGFbeta1) were assessed at baseline and after 12 months. RESULTS: No patients discontinued or decreased the drug. The hepatic venous pressure gradient (HVPG) decreased significantly in treated patients (-8.4%+/-2.4) with a reduction >20% in 25% of cases vs+5.6%+/-2.9 in the untreated group. HA plasma levels decreased significantly in Candesartan treated patients in whom HVPG diminished and rose in untreated patients in whom HVPG increased. CONCLUSIONS: In selected cirrhotic patients, pharmacological inhibition of the AT1 receptor is well tolerated and induced a mild reduction of portal pressure. This haemodynamic effect might be related to liver fibrogenesis activity.     

门高压鼠血浆前列环素与门脉压力的关系

目的 探讨门脉压力升高和门体分流在前列环素（ＰＧＩ２）或高中的作用。方法 ３６只雄性ＳＤ大随机分为四组：肝前型（ＰＨＰＨ，ｎ＝８）和肝内型门高压（ＩＨＰＨ，ｎ＝９），端侧门腔分流（ＰＣＳ，ｎ＝８）以及手术对照组（ＳＯ，ｎ＝１１），模型制备后２周；（１）测游离门脉压（ＦＰＰ）；（２）应用核素微球技术研究全身及内脏血流血压学；（３）从股动脉采集血样用放射免疫法测血浆６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ     

Percutaneous transhepatic measurement of the pressure gradient between the portal and hepatic veins

Abstract Background: Knowledge of the portal pressure may be of value in the assessment of patients with chronic liver disease but its measurement is problematic. Aims: To evaluate the ease and safety of percutaneous transhepatic measurement of the pressure gradient between the portal and hepatic veins and to determine directly the need for an internal zero. Methods: Sixty-one patients undergoing liver biopsy for suspected liver disease had pressures in branches of portal and hepatic veins measured using a flexible 22G (Chiba) needle. Results: The procedure was successful in all patients, took less than ten minutes in most, and was associated with minimal discomfort. Post-procedure morbidity was similar to that of liver biopsy. Portal pressure using an external zero (either puncture site or sternal angle) was inaccurate compared with pressures obtained using the generally accepted gold standard internal zero, hepatic venous pressure, and led to incorrect classification of the presence or absence of portal hypertension in at least 10% of patients. Variations in hepatic venous pressure were not predictable on clinical grounds. The only histopathological feature predictive of portal hypertension was cirrhosis, 20 of 25 patients with and four of 36 patients without cirrhosis having portal hypertension. Of routine biochemical and haematological tests, only plasma albumin and platelet count jointly (and negatively) predicted hepatic venous pressure gradient on multiple regression analysis (R²= 0.40). Conclusions: The use of an internal zero is essential for accurate measurement of portal pressure and this can be achieved safely using the percutaneous, transhepatic route in patients with well compensated liver disease.     

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。     

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.     

Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension

Introduction and objectivesLaparoscopic splenectomy (LS) is a supportive intervention for cirrhotic patients. However, its efficacy for patients with cirrhotic portal hypertension (CPH) still needs clarification. Studies indicated YKL-40 might be effective targets for treatment of splenomegaly, however deeper insights are unclear. The aim of this study was to investigate the effect of LS on the formation of portal vein thrombosis (PVT) and serum levels of a fibrosis marker, YKL-40, in patients with CPH.Materials and methodsA total of 80 patients who underwent LS and 30 healthy controls were investigated in this study. Serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA). Demographic characteristics including age and gender were recorded. Clinicopathological and laboratory examinations included the severity of esophageal varices and the presence of viral hepatitis. The liver function was assessed according to the Child–Pugh classification. The incidence of PVT before and after operation was also monitored.ResultsSerum YKL-40 was significantly increased in CPH patients, and was associated with Child–Pugh score and HBV infection. Furthermore, elderly patients had an increased risk for postoperative PVT. Higher serum YKL-40 was observed in patients with thrombus at postoperative 7, 14 and 21 days than those without thrombus.ConclusionsLS could reduce serum YKL-40 levels and PVT progression and was a useful treatment for patients <40 years of age with CPH.     

216例肝硬化门静脉高压症患者CT血管成像门静脉侧支血管表现研究

目的探讨肝硬化患者CT 门静脉血管成像中门静脉侧支血管表现,为临床诊断提供依据。方法回顾性研究2013年1月~2014 年1月本院收治的 216 例临床诊断为肝硬化门静脉高压症患者的临床和CT检查资料,针对患者CT门静脉血管成像和门静脉侧支血管三维重建图像进行分析。结果216例患者中,肝硬化门体分流侧支血管的分布、走行及解剖毗邻关系在CT 门静脉血管成像图像上都能得到良好、直观的显示,其中胃左静脉曲张者172例（79.63%）,食管下段静脉曲张者100例（46.30%）,食管旁静脉曲张者 51例（23.61%）,胃/脾肾静脉分流者50例（23.15%）,附脐静脉及腹壁静脉曲张者36例（16.67%）;胃/脾肾静脉分流患者门静脉和脾静脉直径分别为（12.64±1.12） mm和（18.72±3.48） mm,与无分流患者比较有统计学差异[分别为（19.56±5.64） mm和（13.47±2.35）mm,P<0.05]。结论对肝硬化门脉高压患者行CT 门静脉血管成像检查能够对患者侧支循环的部位、严重程度等进行观察,并作出准确的判断。     

Pathophysiology of portal hypertension in HCV-related cirrhosis: Putative role of assessment of portal pressure gradient in Peginterferon-treated patients

Chronic HCV infection is the leading aetiologic factor for cirrhosis, end-stage liver disease, hepatocellular carcinoma and liver transplantation worldwide. Pegylation of alfa interferons has improved the management of this disease. Interferon treatment has antifibrotic and immunomodulatory activities. Recent evidence supports the contention that Hepatitis C virus-related cirrhosis of the liver should no more be considered an irreversible disease; fibrosis is a potentially reversible process. Fibrosis and even cirrhosis reversal have been previously demonstrated either in experimental or clinical studies of other liver diseases. Development of portal hypertension is the main drive to the complications of advanced liver diseases: prognosis worsens significantly when portal hypertension becomes clinically significant. It is thus conceivable that within therapeutic trials involving patients with advanced fibrosis of the liver, measurement of the hepatic venous pressure gradient, the gold standard in the clinical assessment of portal hypertension and its management, could provide information on the portal pressure-lowering effects of interferon treatment affecting the fibrosis score. This can be accomplished by either sustained virological response either by fibrosis reduction achieved by chronic low-dose Peginterferon administration. If the introduction of drug therapy with non-selective beta blockers in the treatment of portal hypertension represents a milestone in the treatment of patients with cirrhosis and high-degree portal hypertension, the next step must then be prophylactic reversal of initial portal hypertension prompted by either HCV eradication and pharmacological inhibition of fibrosis progression by long-term Peginterferon before higher degrees of portal hypertension ensue.     

Parallel transjugular intrahepatic portosystemic shunt for controlling portal hypertension complications in cirrhotic patients

AIM: To evaluate the feasibility of a second parallel transjugular intrahepatic portosystemic shunt (TIPS) to reduce portal venous pressure and control complications of portal hypertension.METHODS: From January 2011 to December 2012, 10 cirrhotic patients were treated for complications of portal hypertension. The demographic data, operative data, postoperative recovery data, hemodynamic data, and complications were analyzed.RESULTS: Ten patients underwent a primary and parallel TIPS. Technical success rate was 100% with no technical complications. The mean duration of the first operation was 89.20 ± 29.46 min and the second operation was 57.0 ± 12.99 min. The mean portal system pressure decreased from 54.80 ± 4.16 mmHg to 39.0 ± 3.20 mmHg after the primary TIPS and from 44.40 ± 3.95 mmHg to 26.10 ± 4.07 mmHg after the parallel TIPS creation. The mean portosystemic pressure gradient decreased from 43.80 ± 6.18 mmHg to 31.90 ± 2.85 mmHg after the primary TIPS and from 35.60 ± 2.72 mmHg to 15.30 ± 3.27 mmHg after the parallel TIPS creation. Clinical improvement was seen in all patients after the parallel TIPS creation. One patient suffered from transient grade I hepatic encephalopathy (HE) after the primary TIPS and four patients experienced transient grade I-II after the parallel TIPS procedure. Mean hospital stay after the first and second operations were 15.0 ± 3.71 d and 16.90 ± 5.11 d (P = 0.014), respectively. After a mean 14.0 ± 3.13 mo follow-up, ascites and bleeding were well controlled and no stenosis of the stents was found.CONCLUSION: Parallel TIPS is an effective approach for controlling portal hypertension complications.     

脾切除术联合门奇静脉断流术治疗肝硬化门脉高压症患者疗效研究*

目的 研究腹腔镜门奇静脉断流术联合脾切除术治疗肝硬化门脉高压症合并巨脾患者的效果。方法 2016年12月～2018年12月我院收治的86例肝硬化并发门脉高压症合并巨脾患者被分为两组,每组43例,其中对照组行开腹,而观察组实施腹腔镜下门奇静脉断流术联合脾切除术。结果 观察组术中出血量为(180.8±23.1)ml,显著少于对照组的【(286.4±35.7)ml,P<0.05】,术后住院日为(6.0±1.3)d,显著短于对照组的【(8.6±1.5)d,P<0.05】;观察组术后7 d外周血WBC为(8.9±1.4)×10⁹/L,PLC为(132.0±28.9)×10⁹/L,对照组分别为(7.2±1.8)×10⁹/L,PLC为(125.6±30.3)×10⁹/L,均较术前显著升高(P<0.05);观察组术后门静脉直径为(1.2±0.1)cm,血流量为(911.7±261.7)ml/min,对照组分别为(1.2±0.2)cm,血流量为(888.5±191.5)ml/min,均较术前显著缩小或下降(P<0.05);观察组术后并发症发生率为9.3%,显著低于对照组的37.2%(P＜0.05)。结论 腹腔镜下门奇静脉断流术联合脾切除术治疗肝硬化门脉高压症合并巨脾患者临床疗效确切,创伤小,术后并发症发生率低,恢复快。     

肝硬化门静脉血栓形成的临床分析

目的　探讨肝硬化 (LC)门静脉血栓 (PVT)形成对LC病程发展的影响。方法　检索我院自 1 995至 2 0 0 2年肝硬化PVT形成患者 ,血栓诊断依据彩色多普勒和 (或 )CT。 4 8例肝硬化PVT形成患者入选血栓组 ;同阶段LC门脉高压症的非血栓病例中选择 5 2例作为对照组。对两组患者的肝功能Child Pugh分级、凝血功能、门静脉、脾静脉宽度及脾脏面积、厚度进行比较。行t检验 ,χ2 检验 ,Logistic回归分析。结果　肝硬化PVT形成除继发于脾切除等手术后 ,75 .0 %隐匿发病 ,85 .4 %的血栓发生于门静脉主干 ,脾脏增大与门静脉增宽是PVT形成的危险因素 (P =0 .0 0 3、0 .0 1 0 )。血栓组门静脉及脾静脉宽度分别为 (1 .4 8± 0 .2 6 )cm ,(1 .2 3± 0 .38)cm ,与对照组比较差异有显著性 [(1 .37± 0 .2 2 )cm ,(1 .0 5± 0 .30 )cm ,P =0 .0 37,0 .0 31 ]。血栓组脾面积平均值为 (96 .6 4± 33.4 )cm2 ,脾厚径为 (6 .0 7± 1 .2 0 )cm ,分别大于对照组的 (80 .81± 2 8.9)cm2 ,(5 .2 3± 1 .0 8)cm(P =0 .0 36 ,0 .0 0 1 )。血栓组食管胃底静脉曲张程度重于非血栓组 ,大出血、大量腹水比例高 (P <0 .0 5 )。血栓形成后 1年内死亡率为1 6 .6 % ,较非血栓组增高 (P =0 .0 2 3)。两组肝功能Child Pugh分级、凝血功能、血小板计     

Use of portal pressure studies in the management of variceal haemorrhage

Portal hypertension occurs as a complication of liver cirrhosis and complications such as variceal bleeding lead to significant demands on resources. Endoscopy is the gold standard method for screening cirrhotic patients however universal endoscopic screening may mean a lot of unnecessary procedures as the presence of oesophageal varices is variable hence a large time and cost burden on endoscopy units to carry out both screening and subsequent follow up of variceal bleeds. A less invasive method to identify those at high risk of bleeding would allow earlier prophylactic measures to be applied. Hepatic venous pressure gradient (HVPG) is an acceptable indirect measurement of portal hypertension and predictor of the complications of portal hypertension in adult cirrhotics. Varices develop at a HVPG of 10-12 mmHg with the appearance of other complications with HPVG > 12 mmHg. Variceal bleeding does not occur in pressures under 12 mmHg. HPVG > 20 mmHg measured early after admission is a significant prognostic indicator of failure to control bleeding varices, indeed early transjugular intrahepatic portosystemic shunt (TIPS) in such circumstances reduces mortality significantly. HVPG can be used to identify responders to medical therapy. Patients who do not achieve the suggested reduction targets in HVPG have a high risk of rebleeding despite endoscopic ligation and may not derive significant overall mortality benefit from endoscopic intervention alone, ultimately requiring TIPS or liver transplantation. Early HVPG measurements following a variceal bleed can help to identify those at risk of treatment failure who may benefit from early intervention with TIPS. Therefore, we suggest using HVPG measurement as the investigation of choice in those with confirmed cirrhosis in place of endoscopy for intitial variceal screening and, where indicated, a trial of B-blockade, either intravenously during the initial pressure study with assessment of response or oral therapy with repeat HVPG six weeks later. In those with elevated pressures, primary medical prophylaxis could be commenced with subsequent close monitoring of HVPG thus negating the need for endoscopy at this point. All patients presenting with variceal haemorrhage should undergo HVPG measurement and those with a gradient greater than 20 mmHg should be considered for early TIPS. By introducing portal pressure studies into a management algorithm for variceal bleeding, the number of endoscopies required for further intervention and follow up can be reduced leading to significant savings in terms of cost and demand on resources.     

肝硬化合并门静脉血栓形成的临床特点

目的分析肝硬化患者合并门静脉血栓形成(PVT)的临床特点及危险因素,了解该类患者药物性预防措施是否有效.方法 2008年1月至2011年3月各种原因的肝硬化住院患者共339例,将其分为两组,分别为肝硬化合并有门静脉血栓形成组及未合并有门静脉血栓组.记录患者年龄、性别、凝血酶原时间(PT)、总胆红素、白蛋白、肝硬化的病因...