Increased sinusoidal resistance is responsible for the basal state and endothelin-induced venoconstriction in perfused cirrhotic rat liver

The localization of increased intrahepatic vascular resistance and the segmental vascular responsiveness to endothelin-1 are not well known in liver cirrhosis. We determined the segmental vascular resistances and their response to endothelin-1 of isolated portally perfused bile duct ligation (BDL)-induced cirrhotic rat livers. The portal occlusion pressure (Ppo) and the hepatic venous occlusion pressure (Phvo) were obtained by analyzing the profiles of the portal (Ppv) and hepatic venous (Phv) pressures during the double occlusion maneuver of simultaneous occlusions of the inflow and outflow perfusion lines. From the pressure gradients among Ppv, Ppo, Phvo, and Phv, the portal-hepatic venous resistance was assigned to three segments of the portal [Rpv = (Ppv − Ppo)/blood flow (Q)], sinusoidal [Rsinus = (Ppo − Phvo)/Q] and hepatic venous [Rhv = (Phvo − Phv)/Q] resistances. Rsinus, but not Rpv or Rhv, was significantly greater in BDL livers than in sham livers. Endothelin-1 (0.1–1 nM) increased Rpv and Rsinus to a similar magnitude, but not Rhv, in both sham and BDL. At 3 nM, the responsiveness of Rpv was smaller in BDL than in sham, but that of Rsinus were similar between in BDL and sham. In conclusion, increased sinusoidal resistance accounts for increased intrahepatic resistance of BDL-induced liver cirrhosis. Endothelin-1 contracts portal veins and sinusoids, but not hepatic veins, in both sham and cirrhotic livers. Sinusoidal contractility to endothelin-1 is not impaired in cirrhotic livers.     

Collateral pathways in portal hypertension

Summary In a retrospective study angiographic image material of percutaneous direct portographies carried out in 43 patients was evaluated according to anatomic and radiologic criteria. These examinations were performed for therapeutic purposes (embolisation of vessels supplying varices). All the hepatofugally perfused veins were analyzed according to their localisation and course. Apart from the known portocaval collateral pathways a number of other collaterals not yet described could be documented by means of angiography.

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Les voies de dérivation veineuse dans l'hypertension portale

Résumé A partir de l'analyse rétrospective de portographies directes effectuées par angiographie percutanée chez 43 patients, différents critères anatomiques et radiologiques ont été précisés. Ces portographies ont été faites dans un but thérapeutique (embolisation des vaisseaux alimentant des varices sophagiennes); la localisation et le trajet de toutes les veines hépatofuges ont été étudiés. A côté de la circulation collatérale porto-cave connue, il existe un certain nombre d'autres voies de dérivation actuellement incomplètement décrites et qui peuvent être précisées par angiographie.

     

肝硬化患者血管紧张素Ⅱ-RIA水平与门脉血流动力学的关系

目的 :探讨肝硬化门脉高 (PTH)的血流动力学变化及其与血中AT Ⅱ的关系。方法 :4 8例肝硬化PTH患者 (代偿期 18例、失代偿期 30例 )及 32例正常人作为研究对象 ,应用双功能多普勒测定门、脾静脉血流量 (PVBF&SVBF) ,同步测定血中AT Ⅱ的水平 ,并分析PVBF&SVBF与AT Ⅱ的相关性。结果 :门脉系统高血流动力学改变存在于肝硬化PTH发病的始终 ,代偿期显著下降的AT Ⅱ与门脉高血流动力学变化无相关性 ,失代偿期显著升高的AT Ⅱ与门脉高血流动力变化呈正相关。结论 :此研究对临床诊治有指导意义。     

门静脉高压症猪肝动脉的结构重建

目的 建立猪门静脉高压症模型,探讨门静脉高压症时肝动脉的结构重建.方法猪以四氯化碳、苯巴比妥、乙醇配合高脂、低蛋白、低胆碱饮食进行混合饲养.通过脾静脉插管测压,取肝动脉常规石蜡包埋、切片,用HE 法、Weigert 法、Aniline blue法,Organge G法分别染组织结构、弹性纤维、胶原纤维和平滑肌,用计算机...     

Effect of cimetidine on the hepatic extraction of indocyanine green,the portal pressure and the systemic circulation in patients with cirrhosis of the liver

Summary The effect-of cimetidine on hepatic and systemic haemodynamic parameters was studied in seven patients with portal hypertension due to alcohol-induced cirrhosis of the liver and in one patient with peliosis hepatis following oral contraceptive steroids. The intravenous administration of cimetidine (350 mg as bolus, followed by 2 mg/min over 60 min) reduced the hepatic extraction of continuously infused indocyanine green (ICG) by 27%; this was statistically significant (P<0.01). Since the ICG clearance, calculated independently of hepatic perfusion, was lowered by 19%, this effect seems to be mainly due to a reduced capacity of the liver to remove the dye from the blood, rather than due to changes in perfusion. Cimetidine did not influence the elevated portal pressure in the patients with cirrhosis, or the normal pressure in the patient with peliosis hepatis. No significant effect was observed on heart rate, mean arterial pressure, pulmonary artery pressure, pulmonary capillary pressure and cardiac output. These studies indicate that the reduction of the hepatic ICG extraction following cimetidine is more the result of an inhibited capacity of the liver to remove the dye than of changes in the hepatic perfusion or in the systemic circulation.This work was presented in part at the annual meeting of the American Association for the Study of Liver Diseases, November 1981, in Chicago, and appeared in abstract form in Hepatology (1981) 1:515, No. 25 B     

辛伐他汀通过抑制p38 MAPK活化降低肝硬化门静脉高压大鼠门静脉压力

 目的:探讨p38 MAPK信号通路在辛伐他汀降低肝硬化门静脉高压症大鼠门静脉压力（PP）中的作用。方法:采用四氯化碳复合因素法构建大鼠肝硬化门静脉高压症模型,成模后将存活大鼠随机分为模型组（n=10）、辛伐他汀治疗组（n=11）和p38 MAPK信号通路抑制剂SB203580处理组（n=10）,后2组分别给予辛伐他汀及SB203580干预处理;另设正常对照组（n=8）。处理结束后检测大鼠PP、肝脏总p38 MAPK蛋白、磷酸化p38 MAPK蛋白、总eNOS蛋白、磷酸化eNOS蛋白表达水平以及肝脏一氧化氮（NO）含量的变化。结果:（1）模型组大鼠PP明显高于正常对照组;辛伐他汀治疗组及SB203580处理组PP均明显低于模型组（P＜0.01）,辛伐他汀治疗组PP明显低于SB203580处理组（P＜0.01）。（2）与正常大鼠相比,模型组大鼠肝脏总p38 MAPK蛋白及总eNOS蛋白表达水平无明显变化（P＞0.05）,而磷酸化p38 MAPK蛋白及磷酸化eNOS蛋白表达水平分别增高与降低（P＜0.01）;辛伐他汀治疗组大鼠肝脏磷酸化p38 MAPK蛋白及磷酸化eNOS蛋白表达水平分别降低与增高（P＜0.01）;SB203580处理组大鼠肝脏磷酸化p38 MAPK蛋白及磷酸化eNOS蛋白表达水平分别降低与增高（P＜0.01）,但磷酸化eNOS蛋白表达水平增高的程度低于辛伐他汀治疗组（P＜0.01）。(3)辛伐他汀治疗组肝脏NO含量［（15.73±1.59） μmol/(g protein)］及SB203580处理组肝脏NO含量［（13.98±1.27) μmol/(g protein)］明显高于模型组［（9.81±1.12） μmol/（g protein）］（P＜0.01）,辛伐他汀治疗组NO含量明显高于SB203580处理组（P＜0.01）。结论: 辛伐他汀降低肝硬化门静脉高压症大鼠门静脉压力可能与其抑制p38 MAPK信号通路的活化有关。     

Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension

Background/Aims

Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial.

Methods

Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders.

Results

The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups.

Conclusions

The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.     

Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver

Idiopathic portal hypertension (IPH) is characterized by a long-standing presinusoidal portal hypertension of unknown etiology in adults. Some unidentified agent(s) affect(s) the intrahepatic small portal veins or portal tracts. Immunological disturbance, thromboembolism, infectious etiology and/or increased fibrogenesis in portal tracts are suspected as being candidates for the primary agent(s). During the long clinical course of IPH, several pathological changes may occur, including subcapsular parenchymal atrophy, atrophy of the liver, portal and parenchymal fibrosis, and portal venous phlebosclerosis and thrombosis. The last-named of these lesions is mostly found in patients with a history of splenectomy. Subcapsular parenchymal and hepatic atrophy may result from a hepatocellular dropout via apoptosis or necrosis because of intrahepatic hemodynamic disturbances, particularly chronic portal venous blood insufficiency. Pericellular fibrosis and thin fibrous septa are also frequently found and associated with activated perisinusoidal cells positive for smooth muscle actin. At the same time, vague nodular hyperplasia of hepatocytes not surrounded by fibrous septa is not infrequently seen. It may resemble nodular regenerative hyperplasia, partial nodular transformation, or focal nodular hyperplasia. However, liver cirrhosis does not occur even at the terminal stage. Taking these findings into consideration, a new staging of IPH with a combination of hepatic parenchymal atrophy and portal venous thrombosis was proposed: non-atrophic liver without subcapsular parenchymal atrophy (stage I), non-atrophic liver with subcapsular parenchymal atrophy (stage II), atrophic liver with subcapsular parenchymal atrophy (stage III), and portal venous occlusive thrombosis (stage IV). IPH livers are likely to progress from stage I to stage III. Stage IV, which occurs relatively late, has a poor prognosis. This staging is applicable to clinical and autopsy cases without any histological data.     

Mast cell inhibition by ketotifen reduces splanchnic inflammatory response in a portal hypertension model in rats

Experimental early prehepatic portal hypertension induces an inflammatory exudative response, including an increased infiltration of the intestinal mucosa and the mesenteric lymph nodes by mast cells and a dilation and tortuosity of the branches of the superior mesenteric vein. The aim of this study is to verify that the prophylactic administration of Ketotifen, a stabilizing drug for mast cells, reduces the consequence of splanchnic inflammatory response in prehepatic portal hypertension. Male Wistar rats were used: Sham-operated and with Triple Partial Portal Vein Ligation, which were subcutaneously administered poly(lactide-co-glycolide) acid microspheres with vehicle 24h before the intervention and SO and rats with Triple Partial Portal Vein Ligation, which were administered Ketotifen-loaded microspheres. Around 48h after surgery, the portal pressure was measured; the levels of chymase (Rat Mast Cell Protease-II) were assayed in the superior mesenteric lymph complex and granulated and degranulated mast cells in the ileum and cecum were quantified. Prophylactic administration of Ketotifen reduced portal pressure, the incidence of dilation and tortuosity of the superior mesenteric vein branches, the amount of Rat Mast Cell Protease-II in the superior mesenteric lymph complex and the number of activated mast cells in the cecum of rats with portal hypertension. In summary, the administration of Ketotifen reduces early splanchnic inflammatory reaction in the rat with prehepatic portal hypertension.     

Helicobacter pylori,liver cirrhosis,and portal hypertension: an updated appraisal

Objective: Helicobacter pylori (H. pylori) is the most common cause of gastritis and peptic ulcer. However, H. pylori is even involved in extragastric diseases, and it has been hypothesized that H. pylori could be a risk factor for several hepatic diseases. For instance, a direct involvement of H. pylori in the development of portal hypertension (PH) in cirrhotic patients has been postulated.

Methods: We performed a literature search in major databases to elucidate the relationship between H. pylori, portal hypertension, and liver cirrhosis.

Results: The effect of H. pylori on PH may be multifactorial. Endothelial dysfunction, alterations in the vasodilating dynamics, and neoangiogenesis are the most appealing theories about this issue, but the proofs come mainly from experimental studies, therefore a solid pathophysiological basis is still to be demonstrated. Congestive gastropathy (CG) and gastric antral vascular ectasia (GAVE) are two common endoscopic entities responsible for acute/chronic upper gastrointestinal bleeding, and a link with H. pylori has been hypothesized: the gastric mucosa, exposed to H. pylori, could develop both inflammatory microcirculatory alterations and thrombi, resembling the histologic pattern of GAVE.

Conclusions: Despite clues for an association between H. pylori and PH have been shown, these evidences are mostly experimental, therefore, in the absence of a direct proof on human beings, the role of H. pylori in the development of PH is uncertain. However, since this germ may be a cause of peptic ulcer, it should be found and eradicated in cirrhotic patients to reduce the risk of blood loss anemia.     

A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis

AIM: To examine the pathological changes of hepatic arteries in idiopathic portal hypertension (IPH) which is characterized by the obliteration of the intrahepatic portal vein branches and presinusoidal portal hypertension. METHODS AND RESULTS: Liver specimens (biopsied or surgically resected) from 20 patients with IPH, 20 patients with alcoholic fibrosis/cirrhosis (AF/C) and 20 histologically normal livers were used. The vascular lumina of arterial and venous vessels in portal tracts were morphometrically evaluated by an image analysis system. The ratio of portal venous luminal area to portal tract area (portal venous index) of IPH and that of AF/C were significantly reduced compared with normal liver. The portal venous index for IPH was significantly lower than that for AF/C. The ratio of hepatic arterial luminal area to portal tract area for AF/C was significantly higher than that in normal liver; however, that for IPH was similar to normal. The peribiliary vascular plexus was increased in AF/C but not in IPH. In AF/C, the number of mast cells and macrophages known to be the source of angiogenic substances was significantly increased in the portal tract compared with normal liver, while in IPH it was not increased. CONCLUSIONS: In AF/C, a reduction in portal venous lumen was associated with an increase of hepatic arterial lumen and of angiogenesis-related cells in portal tracts. However, such compensatory arterial changes were not evident in IPH, and this compensatory failure may be a feature of IPH.     

Splenectomy ameliorates portal pressure and anemia in animal models of cirrhotic and non-cirrhotic portal hypertension

PurposePortal hypertension (PH)-associated splenomegaly is caused by portal venous congestion and splanchnic hyperemia. This can trigger hypersplenism, which favors the development of cytopenia. We investigated the time-dependent impact of splenectomy on portal pressure and blood cell counts in animal models of non-cirrhotic and cirrhotic PH.Materials and methodsNinety-six rats underwent either partial portal vein ligation (PPVL), bile duct ligation (BDL), or sham operation (SO), with subgroups undergoing additional splenectomy. Portal pressure, mean arterial pressure, heart rate, blood cell counts and hemoglobin concentrations were evaluated throughout 5 weeks following surgery.ResultsFollowing PPVL or BDL surgery, the animals presented a progressive rise in portal pressure, paralleled by decreased mean arterial pressure and accelerated heart rate. Splenectomy curbed the development of PH in both models (PPVL: 16.25 vs. 17.93 ?mmHg, p ?= ?0.083; BDL: 13.55 vs. 15.23 ?mmHg, p ?= ?0.028), increased mean arterial pressure (PPVL: +7%; BDL: +9%), and reduced heart rate (PPVL: ?10%; BDL: ?13%). Accordingly, splenectomized rats had lower von Willebrand factor plasma levels (PPVL: ?22%; BDL: ?25%). Splenectomy resulted in higher hemoglobin levels in PPVL (14.15 vs. 13.08 ?g/dL, p ?< ?0.001) and BDL (13.20 vs. 12.39 ?g/dL, p ?= ?0.097) animals, and significantly increased mean corpuscular hemoglobin concentrations (PPVL: +9%; BDL: +15%). Thrombocytopenia only developed in the PPVL model and was alleviated in the splenectomized subgroup. Conversely, BDL rats presented with thrombocytosis, which was not affected by splenectomy.ConclusionsSplenectomy improves both cirrhotic and non-cirrhotic PH, and ameliorates the hyperdynamic circulation. Hypersplenism related anemia and thrombocytopenia were only significantly improved in the non-cirrhotic PH model.     

Radiological score for hemorrhage in the patients with portal hypertension

Goal: To analyze the risk factors from radiological indices for hemorrhage in the patients with portal hypertension and weight risk factors. Method: We retrospectively analyzed all cases of portal hypertension with hepatitis B from June 2008 to June 2014 in Nanjing Drum Tower hospital. Patients with hepatocellular carcinoma, portal vein thrombosis, or portal hypertension with other causes, such as autoimmune hepatitis, pancreatitis, or hematological diseases were excluded. Results: Ninety-eight patients were recruited and divided into hemorrhage and non-hemorrhage groups. There were no statistical differences in clinical indexes such as age, prothrombin time, serum albumin, serum creatinine, serum sodium, hemameba, and blood platelet count. However, the differences were statistically significant in total bilirubin, hemoglobin, and liver function with the p values of 0.023, 0.000, and 0.039 respectively. For radiological indices, hemorrhage was correlated with diameter of inferior mesenteric vein (P=0.0528), posterior gastric vein (P=0.0283), and esophageal varices scores (P=0.0221). Logistic procedure was used to construct the model with stepwise selection and finally inferior mesenteric vein, posterior gastric vein, esophageal varices, and short gastric vein were enrolled into the model. These veins were scored according to the diameters and the rates of hemorrhage were increased with the score. We then validated the model with 26 patents from July 2014 to December 2014. The AUC value was 0.8849 in ROC curves for this radiological model. Conclusions: A risk model was constructed including inferior mesenteric vein, esophageal varices, posterior gastric vein, and short gastric vein. This radiological scoring model may be a valuable indicator for hemorrhage of portal hypertension.     

门静脉高压症猪肺血管的生物力学特性

目的：探讨门静脉高压症猪肺血管的生物力学特性及为临床晚期肝硬化患者实施肝肺联合移植提供理论依据。方法：采用健康2月龄湖北白种猪4头作为正常对照组，四氯化碳诱导的门静脉高压组湖北白种猪10头，分别取其肺动脉、肺叶动脉、肺段动脉及肺静脉，在软组织生物力学试验机上测定压力一直径关系数据，推导出其弹性模量和顺应性。结果：与正常对照组相比，门静脉高压组（PHT）猪肺动静脉血管的弹性模量随血管内压力的升高而增大；顺应性则随血管内压力的增大而下降。结论：与人类相似，PHT猪可伴有肺血管生物力学特性的改变，且生物力学特性变化的幅度可能与病情变化有关。肝肺联合移植时，移植材料间的生物力学特性也应引起关注。     

The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data

Background/Aims

Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis.

Methods

LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves.

Results

A strong positive correlation between LSM and HVPG was observed in the overall population (r²=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively.

Conclusions

LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.     

Serum laminin — Its concentration increases with portal hypertension in cirrhotic liver disease

Summary The concentrations in serum of the high molecular weight glycoprotein laminin and of the N-terminal propeptide of type III procollagen were determined in various histologically proven fibrotic liver diseases (n=33), of which the portal venous pressure has been measured indirectly. The concentrations of both biomatrix proteins were related to the portal venous pressure.Laminin in serum of normal persons (n=146) ranged from 0.81 to 1.43 U/ml. Compared with the mean normal concentration (1.04 U/ml) the glycoprotein is increased in fibrotic liver lesions in parallel with the severity of the fibrotic organ transformation reaching the highest values (2.58±0.87 U/ml,P<0.001) in liver cirrhosis (n=12). The level of N-terminal propeptide of type III procollagen increased similarly, but the concentrations of both matrix proteins exhibit only weak statistical correlations (r=0.6680). The level of laminin is correlated strongly with the elevation of the portal venous pressure in cirrhotic (r=0.9206) and fibrotic (r=0.7157) subjects. For the propeptide of procollagen the respective correlation isr=0.4808. Molecular sieve chromatography reveals a heterogeneous composition of laminin-related antigens in serum with two main molecular weight fractions of 700 and 300 kD, respectively.Abbreviations AST Aspartate-aminotransferase - CV coefficient of variation - GT -glutamyltransferase - FHVP Free hepatic venous pressure - WHVP Wedged hepatic venous pressure The paper is dedicated to Professor G.A. Martini, Marburg, on the occasion of his 70th birthday     

Endotoxinemia in the portal and the systemic circulation in obstructive jaundice

Abstract. Endotoxinemia in patients with obstructive jaundice is linked to acute renal failure and sepsis and remains a major cause of complications during postoperative treatment. The current study examines the mechanisms of endotoxinemia in the portal and the systemic circulation in obstructive jaundice. As an experimental model of the disease we used rabbits subjected to sham operation. Serum total bilirubin aminotransferases and endotoxin concentrations were determined at 2, 5, 8, and 13 days after operation. Endotoxin concentrations were estimated by the limulus lysate endotoxin test. A high frequency of portal or systemic endotoxinemia is observed in obstructive jaundice, but no difference between endotoxinemia levels in the portal and systemic circulation was observed.     

Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data

Background/Aims

This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.

Methods

Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.

Results

Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality.

Conclusions

A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.     

幽门螺杆菌感染在肝硬化、肝癌高动力循环及胃黏膜病变中的作用

目的：为探讨幽门螺杆菌感染在肝硬化、肝硬化并发肝癌患者高动力循环及胃黏膜病变中的作用.方法：应用快速尿素酶试验、14C-尿素呼气试验、鲎血试验定量法、免疫印迹试验、亚硝酸盐比色法及ELISA法检测肝硬化、肝硬化并发肝癌患者胃黏膜标本HP感染;胃黏膜组织、外周血IL-1、IL-8、TNF-α、内毒素、一氧化氮（NO）、内皮素（ET）及VacA和CagA抗体水平;应用彩色多普勒超声检测门静脉系统血流量参数.结果：肝硬化患者HP感染率77.1%,VacA和CagA抗体同时阳性率为60.4%;VacA和CagA抗体阳性HP感染的肝硬化患者胃黏膜组织、外周血IL-1、IL-8、TNF-α、内毒素、NO及ET水平明显高于VacA和CagA抗体阴性HP感染的肝硬化患者（P＜0.05,P＜0.01）,VacA和CagA抗体阳性HP感染的肝硬化患者其脾静脉血流量（SVF）与肠系膜上静脉血流量（SMVF）之和显著大于、门静脉血流量（PVF）显著小于VacA和CagA抗体阴性HP感染的肝硬化患者SVF与SMVF之和及PVF.结论：产毒素幽门螺杆菌感染在肝硬化、肝癌高动力循环及其胃黏膜病变中具有重要作用.     

The effects of intraportl infusions of glucagon on the hepatic arterial and portal venous vascular beds of the dog: Inhibition of hepatic arterial vasoconstrictor responses to noradrenaline

The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. Glucagon was infused into the hepatic portal vein (1–10 g/min); it caused increases in hepatic portal vascular resistance and tended to reduce the hepatic arterial vascular resistance. Extrahepatic effects of intraportal infusions of glucagon included increases in superior mesenteric blood flow and heart rate and falls in systemic arterial pressure.A test dose of noradrenaline (10 g) injected into either the hepatic artery or the portal vein caused both hepatic arterial and portal venous vasoconstriction. The hepatic arterial constrictor responses to noradrenaline were antagonized intraportal infusions of glucagon. In contrast, intraportal glucagon did not antagonize the portal constrictor responses to intraarterial or intraportal noradrenaline.Elevated portal blood glucagon concentrations may protect the hepatic arterial blood flow from vasoconstriction due to elevated systemic levels of vasoactive substances including catecholamines.