Gln与rhGh对肝硬化病人肠黏膜屏障的影响

目的观察Gln与rhGh各单独应用及联合应用对肝硬化病人小肠黏膜屏障形态学和功能学的影响。方法20个肝硬化病人随机分成四组,给予等氮等热量营养支持7d,Gln+rhGh组口服Gln[0.3g/(Kg·d)]和皮下注射rhGh(10U/d);Gln组口服Gln;rhGh组应用皮下注射rhGh;CONT对照组应用相应安慰剂。观察治疗前后患者小肠黏膜通透性和十二指肠黏膜绒毛高度和隐窝深度的变化,分别比较。结果Gln+rhGh组治疗后小肠黏膜通透性有显著性的降低(P<0.05),且显著低于其他三组(P<0.05);十二指肠黏膜绒毛高度和隐窝深度有显著性的增高(P<0.05),且显著高于其他三组(P<0.05)。结论Gln与rhGh联合应用能减低肠道黏膜的通透性和维持其形态学的完整。     

Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy.     

全身炎性反应综合征在乙型肝炎肝硬化合并腹水患者住院结局中的临床意义

目的探讨全身炎性反应综合征(SIRS)在乙型肝炎肝硬化合并腹水住院患者中的发生率及其对患者住院结局的影响。方法收集2013年1月至2018年1月东南大学医学院附属南京市第二医院住院的乙型肝炎肝硬化腹水患者的临床资料,分析SIRS的发生率及其与患者临床指标、住院期间出现死亡及门静脉高压并发症(包括食管胃底静脉曲张破裂出血、肝性脑病、肝肾综合征)的关系,分析乙型肝炎肝硬化合并腹水患者住院期间发生死亡和门静脉高压并发症的预测因素。结果乙型肝炎肝硬化合并腹水住院患者共461例,其中出现SIRS的有185例,发生率为40.1%;合并SIRS组患者与未合并SIRS组相比,存在较高的黄疸发生率、细菌感染率、血清胆红素(TBil)、国际标准化比值(INR)、Child-Pugh评分、MELD评分以及较长的住院时间,存在较低的血红蛋白浓度(Hb)、血小板(PLT)计数、钠离子浓度,差异均有统计学意义(P<0.05)。住院期间,共计22例患者死亡(5.8%),8例发生消化道出血(1.7%),4例发生1型肝肾综合征(0.9%),20例发生肝性脑病(4.3%)。SIRS的发生与患者的死亡(P<0.001)及门静脉高压并发症的出现(P<0.001)均有关。MELD评分可同时预测死亡和门静脉高压相关并发症的发生(P<0.001),而SIRS和血红蛋白可预测门静脉高压并发症的发生(P<0.05)。结论SIRS在乙型肝炎肝硬化合并腹水住院患者中较为常见,可加重患者肝损害,导致其住院期间的病死率和门静脉高压并发症的发生率增高,SIRS的存在可预测患者门静脉高压并发症的发生。     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Impact and persistence of cirrhotic cardiomyopathy after liver transplantation

Cirrhotic cardiomyopathy causes variable degree of systolic and diastolic dysfunction (DD) and conduction abnormalities. The primary aim of our study was to determine whether pre‐transplant DD and prolonged corrected QT (QTc) predict a composite of mortality, graft failure, and major cardiovascular events after liver transplantation. We also evaluated the reversibility of cirrhotic cardiomyopathy after transplantation. Adult patients who underwent liver transplantation at our institution from January 2007 to March 2009 were included. Data were obtained from institutional registry, medical record review, and evaluation of echocardiographic images. Among 243 patients, 113 (46.5%) had grade 1 DD, 16 (6.6%) had grade 2 DD, and none had grade 3 DD. The mean pre‐transplant QTc was 453 milliseconds. After a mean post‐transplant follow‐up of 5.2 years, 75 (31%) patients satisfied the primary composite outcome. Cox regression analysis did not show any significant association between DD and the composite outcome (P=.17). However, longer QTc was independently associated with the composite outcome (HR: 1.01, 95% confidence interval: 1.00–1.02, P=.05). DD (P<.001) and left ventricular mass index (P=.001) worsened after transplantation. In conclusion, QTc prolongation appears to be associated with worse outcomes. Although DD did not impact outcomes, it significantly worsened after transplantation.     

Acoustic radiation force impulse to measure liver stiffness and predict hepatic decompensation in pregnancy with cirrhosis: A cohort study

Background and study aimsPregnancy in association with cirrhosis is a rather uncommon and highly risky situation for both mother and child. We aim to study all factors and the utility of liver stiffness (LS) measurement by Acoustic Radiation Force Impulse elastography (ARFI) to predict hepatic decompensation in pregnant cirrhotic patients.Patients and methodsWe prospectively recruited 224 pregnant women at the multidisciplinary clinic of liver disease with pregnancy, Cairo University. LS was measured using ARFI (Siemens ACUSON S3000 ultrasound system) during the second trimester and 8–12 weeks post-delivery. The outcome of pregnancy and the incidence of hepatic decompensation were assessed.ResultsOur cohort comprised 128 normal pregnancies, 37 patients with pregnancy-related liver disease (Intrahepatic cholestasis (n = 6), preeclampsia (n = 23), and hyperemesis gravidarum (n = 8)) and 59 patients with an established chronic liver disease not related to pregnancy. In all patients, LS significantly decreased after delivery from 1.19 m/s to 0.94 m/s (P < 0.001). In multivariate analysis, LS was an independent predictor for the outcome of pregnancy in all patients (odds ratio (OR) = 5.442 (3.01–6.82), cut-off = 1.21 m/s). Patients with cirrhosis, mean LS was 1.57 ± 0.66 m/s and 26 (44%) patients had hepatic decompensation (hepatocellular jaundice (n = 8), ascites (n = 9) and variceal bleeding (n = 6)). In multivariate analysis; LS, platelets, albumin, and bilirubin were independent predictors of decompensation post-delivery and the OR for LS was 6.141(4.32–7.98). The optimal cut off value of LS to predict decompensation was 1.46 m/s (8.4 kPa) with AUROC of 0.827.ConclusionLS can be used to predict hepatic decompensation after delivery in pregnant women with manifest cirrhosis.     

Cardiac and systemic haemodynamic complications of liver cirrhosis

Cardiovascular complications of liver cirrhosis include cardiac dysfunction and abnormalities in the central-, splanchnic,- and peripheral circulation. Vasodilatation prevails, but vascular beds with various degrees of reduced and increased haemodynamic resistance are the results of massive activation of powerful homeostatic, regulatory systems. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being often clinical latent, cirrhotic cardiomyopathy can be unmasked by physical and pharmacological strain. Cardiac failure is an important cause of mortality after liver transplantation and stressful procedures as insertions of transjugular intrahepatic portal systemic shunt (TIPS), peritoneal venous shunting, and other types of surgery. Improvement of liver function has been shown to reverse the cardiovascular complications. The clinical significance is an important topic for future research. At present, no specific treatment can be recommended, and the cardiac failure in cirrhosis should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and beta-adrenergic blocking agents. Special care should be taken with the use of ACE-inhibitors and angiotensin antagonist in these patients.     

Therapeutic Management Algorithm in Cirrhotic and Noncirrhotic Patients in Primary or Secondary Liver Masses

The treatment of hepatic tumors in cirrhotic and noncirrhotic patients still represents a major issue in decision making for oncologists and surgeons. The high mortality of open liver surgery, particularly in cirrhotic patients, has pushed physicians to research new modalities. In this review paper we summarize the available and alternative methods for the treatment of liver masses using new modalities and a minimally invasive approach, which will benefit the quality of life of the patients. We also outline therapeutic plan options.     

复方甘草酸苷治疗慢性乙型肝炎肝硬化疗效和对一氧化氮的影响

目的:观察复方甘草酸苷对慢性乙型肝炎肝硬化的临床疗效和对NO的影响。方法:选择110例慢性乙型肝炎肝硬化患者,随机分为治疗组55例,对照组55例。对照组进行保肝综合治疗,治疗组在保肝综合治疗的基础上加用复方甘草酸苷,12周为一疗程。观察患者临床症状,检测肝功能、Child-pugh计分、肝纤维化指标,行超声检查,检测血清中NO、cNOS、iNOS含量。结果:治疗组患者ALT、AST、ALB、TBIL,Child-pugh计分,肝纤维化指标HA、LN、PCⅢ、IVC改善明显优于对照组;B超检查,门静脉内径和脾脏厚度改善优于对照组;血清中NO和iNOS含量明显降低。结论:复方甘草酸苷可用于慢性乙型肝炎肝硬化患者的治疗。