Relationship between degree of portal hypertension and liver histologic lesions in patients with alcoholic cirrhosis

The relationship between the degree of portal hypertension and histologic liver lesions was studied in a group of 84 patients with histologically proven alcoholic cirrhosis. The degree of portal hypertension was evaluated by the gradient between wedged and free hepatic venous pressures. Five histologic lesions were quantified: liver cell necrosis, Mallory bodies, neutrophilic infiltrate, fibrosis, and fatty infiltration. The gradient between wedged and free hepatic venous pressures was significantly correlated with the degree of liver cell necrosis and the degree of neutrophilic infiltrate. The stepwise regression analysis showed that only liver cell necrosis has a significant and independent correlation for the degree of portal hypertension. The value for the gradient between wedged and free hepatic venous pressures was significantly higher in patients with (N=48) than in those without (N=36) acute alcoholic hepatitis (19.4±0.8 and 16.5±0.7 mmHg, respectively). Thus, histologic liver lesions observed in acute alcoholic hepatitis may play a role in the risk of complications of portal hypertension in patients with alcoholic cirrhosis.     

肝硬化后门静脉血栓形成的临床特点研究

目的研究肝硬化(liver cirrhosis,LC)后门静脉血栓(portal vein thrombosis,PVT)形成的临床特点。方法对9678例LC患者进行回顾性分析,采用腹部B超/腹部增强CT及腹部增强MRI检查门脉主干或左右分支,筛选出LC伴PVT形成者(PVT组),同时将LC后无PVT患者纳为对照组,比较2组的Child-Pugh分级、门静脉及脾静脉宽度、脾脏面积及厚度、腹水、上消化道出血、肝性脑病和肝肾综合征等并发症。结果 LC患者中有396例(4.09%)PVT形成。PVT组中LC的病因主要有乙型肝炎、酒精性及丙型肝炎LC,PVT主要分布在门静脉主干、门静脉右支、肠系膜上静脉、门静脉左支和脾静脉。按Child-Pugh进行分级,PVT组与对照组比较,肝损伤较重(P<0.01)。PVT组合并腹水、上消化道出血、肝性脑病及肝肾综合征等并发症的发病率均较对照组高(P<0.01)。PVT组门静脉和脾静脉宽度分别为(1.50±0.23)cm和(1.25±0.34)cm,对照组为(1.38±0.23)cm和(1.06±0.29)cm。PVT组脾脏面积为(97.48±32.90)cm2,脾脏厚度为(6.09±1.21)cm;对照组分别为(81.19±29.10)cm2和(5.26±0.99)cm。PVT组门静脉及脾静脉宽度和脾脏厚度均大于对照组,差异有统计学意义(P<0.05)。PVT组有侧支循环开放的患者占96.21%,对照组为78.25%,2组比较差异有统计学意义(P<0.05)。结论 LC后PVT形成对LC患者的临床转归有重要影响。     

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.     

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.     

Captopril reduces portal pressure effectively in portal hypertensive patients with low portal venous velocity

Background The effect of an angiotensin II blockade in lowering the portal pressure in patients with liver cirrhosis and portal hypertension is controversial. This prospective study was undertaken to evaluate the portal hypotensive effect of captopril compared to that of propranolol, and to determine the factors that contribute to a successful reduction in the portal pressure after longterm captopril administration in patients with liver cirrhosis.Methods The hepatic venous pressure gradient (HVPG) and portal venous velocity (PVV) were measured both before and 3 months after initiation of the administration of captopril (n = 29) or propranolol (n = 29) in cirrhotic patients with a variceal bleeding episode. Patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as being responders.Results At 3 months, the mean reduction in the HVPG after captopril was less than that after propranolol (–3.0 ± 9.3% vs –28.5% ± 4.1%; P 0.05). However, of the 29 patients receiving captopril, 9 were classified as being responders. On multivariate analysis with parameters including age, cause, Child-Pugh score, HVPG, and PVV, only low PVV was found to be a significant independent factor for responders (PVV 12cm/s; odds ratio [OR], 12.2; 95% confidence interval [CI], 1.47–102.40) in the captopril group.Conclusions Longterm captopril administration reduces the portal pressure effectively in cirrhotic patients with a low PVV. This suggests that the reduction in portal pressure after captopril administration is a result of improved portal venous outflow brought about by a decrease in the intrahepatic vascular resistance. When the PVV is below 12cm/s, a captopril trial might be useful in preventing variceal bleeding in portal hypertensive patients.Part of this work has appeared in abstract form, in J Hepatol 2002;36 (Suppl 1):64     

硫化氢对大鼠实验性肝硬化门静脉压力的影响

目的应用内源性硫化氢（H2S）供体硫氢化钠（NaHS）探讨内源性H2S/胱硫醚-γ-裂解酶（CSE）体系对大鼠肝硬化门静脉压力的影响。方法将32只健康雌性SD大鼠随机分为4组：C组和C＋S组采用复合因素法复制肝硬化模型。模型制备52 d后,N＋S组和C＋S组大鼠腹腔注射NaHS 56μmol/（kg.d）,N组和C组腹腔注射同等剂量的生理盐水。1周后分别测定各组大鼠门静脉压力（PVP）及门静脉血浆中H2S含量;采用免疫组织化学方法检测大鼠肝门区门静脉平滑肌细胞中CSE蛋白表达。结果与N组和N＋S组相比,C组和C＋S组PVP均升高,H2S含量及CSE蛋白表达均降低;与C组相比,C＋S组PVP降低,H2S含量及CSE蛋白表达均升高。结论 NaHS作为H2S供体可能具有改善肝硬化大鼠门脉高压的作用,其机制可能与H2S含量及CSE蛋白表达升高有关。     

部分脾动脉栓塞术对肝硬化门静脉高压症血流动力学的影响

目的探讨部分脾动脉栓塞术（PSE）治疗肝硬化门静脉高压症的临床疗效及应用价值。方法 23例不同原因肝硬化门静脉高压患者行PSE治疗,PSE术前及术后1周、1、3、6个月彩色多普勒分别检测患者门静脉和脾静脉的内径、血流速度,计算血流量,并与PSE术前配对分析。结果术后各期患者脾静脉、门静脉血流速度及血流量较术前降低（P〈0.05）;脾静脉内径术后各期与术前相比明显缩小（P〈0.05）;而门静脉主干内径术后6个月内缩小不明显（P〉0.05）。结论 PSE能有效的降低门静脉压力。     

肝硬化患者血栓前状态分子标志物对门静脉血栓形成的监测意义

目的探讨肝硬化患者及肝硬化合并门静脉血栓患者血栓前状态分子标志物的变化。方法将32例河南省濮阳市油田总医院2011年-2013年住院的肝硬化合并门静脉血栓的患者设为血栓组(PVT组),40例肝硬化非门静脉血栓的患者设为非血栓组(非PVT组),采用ELISA法检测血小板颗粒膜蛋白-140(GMP-140)、血管性假性血友病因子(v WF:Ag)、血栓调节蛋白(TM)、D二聚体(DD)的含量并进行分析。计量资料组间比较采用t检验。结果 PVT组GMP-140、TM、v WF:Ag、DD含量分别为(20.68±1.49)μg/L、(47.24±1.36)μg/L、(194.32±7.68)%、(0.86±0.12)mg/L,均明显高于非PVT组(13.05±0.97)μg/L、(34.05±5.03)μg/L、(136.21±3.68)%、(0.42±0.08)mg/L,两组比较差异均有统计学意义(P值均0.01),PVT组伴中重度食管静脉曲张患者血浆GMP-140、TM、v WF:Ag、DD水平分别为(19.68±1.29)μg/L、(45.24±1.26)μg/L、(196.32±6.68)%、(0.79±0.12)mg/L,显著高于轻度食管静脉曲张患者(12.05±1.07)μg/L、(35.05±4.83)μg/L、(141.21±3.45)%、(0.36±0.08)mg/L,差异均有统计学意义(P值均0.01);PVT组伴消化道出血患者血浆GMP-140、TM、v WF:Ag、DD水平分别为(18.98±1.18)μg/L、(46.78±1.35)μg/L、(197.32±6.39)%、(0.81±0.14)mg/L显著高于无出血患者(11.98±1.12)μg/L、(36.02±4.78)μg/L、(138.21±4.12)%、(0.35±0.12)mg/L,差异均有统计学意义(P值均0.01)。结论血栓前状态分子标志物水平可能对肝硬化门静脉血栓形成有监测作用。     

Indications for portal pressure measurement in chronic liver disease

Abstract

Portal hypertension leads to development of serious complications such as esophageal varices, ascites, renal and cardiovascular dysfunction. The importance of the degree of portal hypertension has been substantiated within recent years. Measurement of the portal pressure is simple and safe and the hepatic venous pressure gradient (HVPG) independently predicts survival and development of complications such as ascites, HCC and bleeding from esophageal varices. Moreover, measurements of HVPG can be used to guide pharmacotherapy for primary and secondary prophylaxis for variceal bleeding. Assessment of HVPG should therefore be considered as a part of the general characterization of patients with portal hypertension in departments assessing and treating this condition.     

重视肝硬化患者门静脉压力的检测——从研究工具到临床应用

肝硬化是各种致病因素长期作用于肝脏引起肝细胞损伤、纤维化和结节再生的结果.肝硬化逐渐进展所产生的并发症如食管胃静脉曲张破裂出血、肝性脑病、肝肾综合征、肝细胞癌等才是造成患者死亡的主要原因. 了解肝硬化的自然病史以及寻找预测其预后的指标对于检测肝硬化进展、预防其并发症的发生有重要意义. 用Child - Pugh分数评估肝硬化严重度,从而预测Child -Pugh A、B、C级患者的预后;用终末期肝硬化MELD或MELD- Na等评分系统预测终末期肝硬化预后并对肝移植器官分配需求做出判断已得到大家的公认.肝活检及企图替代肝活检的多种无创检测手段对肝纤维化的诊断有一定作用,但它们均不能对慢性肝病进展到肝硬化及其并发症进行预测.     

Biliary lipid composition in patients with non-cirrhotic portal fibrosis – a comparison with compensated cirrhosis of the liver

ABSTRACT— Patients with non-cirrhotic portal fibrosis (NCPF) are known to have mild hepatic functional abnormalities. To study the biliary lipid composition in these patients, duodenal bile was collected from 18 patients with NCPF, 15 patients with non-alcoholic compensated cirrhosis of the liver and 18 matched, non-obese, healthy control subjects. There were no significant differences in the mean (± SD) concentrations of cholesterol, phospholipids and bile acids in patients with NCPF and healthy controls. On the other hand, patients with cirrhosis had significantly lower concentrations of all the three biliary lipids as compared with the NCPF patients and controls (p<0.05). The cholesterol solubilizing capacity of the bile was the same in NCPF patients, cirrhotics and controls. It is concluded that the relative proportions of the three biliary lipids remain unchanged in patients with NCPF despite mild hepatic derangement.     

Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis

Abstract The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 ± 4.8 mmHg and 6.2 ± 1.6 L/min, mean ± s.d.) were significantly lower than in both Pugh's B (16.8 ± 4.3 mmHg and 7.3 ± 2.1 L/min) and Pugh's C (18.8 ± 5.5 mmHg and 7.4 ± 2.3 L/min) patients ( P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 ± 369 dyn/s per cm⁵) was significantly higher than in both Pugh's B (1016 ± 345 dyn/s per cm⁵) and Pugh's C (935 ± 234 dyn/s per cm⁵) patients ( P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 ± 4.0, 17.0 ± 4.8 and 18.0 ± 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension.     

部分脾动脉栓塞术治疗肝硬化门静脉高压症的疗效及安全性观察

[目的]探讨部分脾动脉栓塞术(PSE)治疗肝硬化门静脉高压症的临床疗效及安全性。[方法]对48例不同原因肝硬化门静脉高压患者行PSE治疗,观察术前及术后1周、1、3、6个月血常规、肝功能、脾脏厚度、脾静脉和门静脉内径、Child-Pugh分级变化及并发症情况。[结果]PSE后患者白细胞和血小板计数均明显升高(P0.01);术后1个月患者脾静脉和门静脉内径明显缩小(P0.05,P0.01),术后6个月脾脏厚度明显缩小(P0.05);术后患者凝血酶原时间缩短(P0.01),总胆红素升高(P0.01),但谷草转氨酶、谷丙转氨酶及ChildPugh分级变化PSE前、后差异无统计学意义(P0.05);PSE后并发症较多,但未发现严重的并发症。[结论]PSE治疗肝炎肝硬化门静脉高压症合并脾功能亢进安全有效。     

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).     

Model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor and its correlation with portal pressure in patients with liver cirrhosis.

BACKGROUND: The models for end-stage liver disease (MELD) and serum sodium (SNa) are important prognostic markers in cirrhosis. A novel index, MELD to SNa ratio (MESO), was developed to amplify the opposing effect of MELD and SNa on outcome prediction. METHODS: A total of 213 cirrhotic patients undergoing hepatic venous pressure gradient (HVPG) measurement were retrospectively analyzed. RESULTS: The MESO index correlated with HVPG (r=0.258, P<0.001) and Child-Pugh score (rho=0.749, P<0.001). Using mortality as the end point, the area under receiver operating characteristic curve (AUC) was 0.860 for SNa, 0.795 for the MESO index and 0.789 for MELD (P values all >0.3) at 3 months. Among patients with Child-Pugh class A or B, the MESO index had a significantly higher AUC compared with MELD (0.80 vs. 0.766, P<0.001). A MESO index <1.6 identified 97% of patients who survived at 3 months and the predicted survival rate was 96.5%. In survival analysis, MESO index >1.6 independently predicted a higher mortality rate (relative risk: 3.32, P<0001) using the Cox model. CONCLUSIONS: The MESO index, which takes into account the predictive power of both MELD and SNa, is a useful prognostic predictor for both short- and long-term survival in cirrhotic patients.     

Altered basal and postprandial plasma melatonin, gastrin, ghrelin, leptin and insulin in patients with liver cirrhosis and portal hypertension without and with oral administration of melatonin or tryptophan

Abstract:  This investigation was designed to assess the effects of oral administration of melatonin (10 mg) and tryptophan (Trp) (500 mg) on fasting and postprandial plasma levels of melatonin, gastrin, ghrelin, leptin and insulin in 10 healthy controls and in age-matched patients with liver cirrhosis (LC) and portal hypertension. Fasting plasma melatonin levels in LC patients were about five times higher (102 ± 15 pg/mL) than in healthy controls (22 ± 3 pg/mL). These levels significantly increased postprandially in LC patients, but significantly less so in controls. Treatment with melatonin or l -Trp resulted in a further significant rise in plasma melatonin, both under fasting and postprandial conditions, particularly in LC patients. Moreover, plasma gastrin, ghrelin, leptin and insulin levels under fasting and postprandial conditions were significantly higher in LC subjects than in healthy controls and they further rose significantly after oral application of melatonin or Trp. This study shows that: (a) patients with LC and portal hypertension exhibit significantly higher fasting and postprandial plasma melatonin levels than healthy subjects; (b) plasma ghrelin, both in LC and healthy controls reach the highest values under fasting conditions, but decline postprandially, especially after oral application of melatonin or Trp; and (c) plasma melatonin, gastrin, ghrelin and insulin levels are altered significantly in LC patients with portal hypertension compared with that in healthy controls possibly due to their portal systemic shunting and decreased liver degradation.     

Effects of transjugular intrahepatic portosystemic shunt treatment of patients with liver cirrhosis and portal hypertension: Case series

Rationale:Transjugular intrahepatic portosystemic shunt (TIPS) is well established as an effective treatment tool for portal hypertension. However, the effects of TIPS in patients with liver cirrhosis and portal hypertension have not been adequately verified in clinical trials.Patient Concerns:To evaluate the effects of TIPS in patients with liver cirrhosis and portal hypertension with or without portal vein thrombosis (PVT).Interventions:A total of 55 patients with liver cirrhosis and portal hypertension received TIPS treatment from December 2014 to April 2018 were enrolled. Clinical data, including portal pressure, Child-Pugh score, and relevant complications were recorded.Outcomes:TIPS was successfully performed in 54 patients. The overall technical success rate was 98.19% without serious technical complications. After TIPS treatment, portal pressure was significantly reduced from 38.13 ± 4.00 cmH₂O to 24.14 ± 3.84 cmH₂O (P < 0.05). In addition, symptoms including gastrointestinal bleeding and ascites were improved after TIPS treatment. During the 6 to 21-month follow up, hepatic encephalopathy in 15 patients (27.8%), shunt dysfunction in 5 patients (9.3%), rebleeding in 12 patients (22.2%) and deterioration of liver function in 2 patients (3.7%) were recorded. Moreover, there were no significant differences in the rates of rebleeding and hepatic encephalopathy between patients with PVT and the non-PVT group, whereas the occurrence rate of TIPS dysfunction was higher in the PVT group, but not statistically significant.Lessons:TIPS treatment could alleviate the symptoms of liver cirrhosis and portal hypertension in individuals with or without PVT. However, complications during follow-up should be appropriately noted and addressed with corresponding treatments.     

Variceal pressure is a strong predictor of variceal haemorrhage in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension

BACKGROUND: Variceal pressure is a strong predictor for a first variceal bleed in patients with cirrhosis. AIMS: To evaluate whether variceal pressure is also a determinant of the risk of a first variceal bleed in patients with non-cirrhotic portal hypertension. METHODS: Variceal pressure was measured non-invasively in 25 patients with non-cirrhotic portal hypertension and large varices while receiving a stable therapeutic regimen. Factors predictive of bleeding were compared with those observed in 87 cirrhotics. RESULTS: The one year incidence of variceal bleeding was 32% (n=28) for the cirrhotic and 20% (n=5) for the non-cirrhotic patients. There was no difference in factors predicting the risk of bleeding between the groups, except for variceal pressure. For the same level of variceal pressure, the risk of variceal bleeding was lower in patients with non-cirrhotic portal hypertension. Multiple logistic regression analysis revealed the following variables as having a significant predictive power: variceal pressure (p=0.0001), red spots (p=0.004), and the time interval between the first observation of the varices and the moment of variceal pressure measurement (p=0. 0046). For the non-cirrhotics the risk of bleeding increased with higher Child-Pugh score (p=0.0024); this was not the case for the cirrhotic patients (p=0.9521). CONCLUSION: Variceal pressure is a major predictor of variceal bleeding in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension. The risk of bleeding in non-cirrhotics is less than in cirrhotics for the same level of variceal pressure. In patients with non-cirrhotic portal hypertension the risk of variceal bleeding increases more with advancing disease.