Lack of hepatic benefit by oxygen inhalation during vasopressin infusion in patients with cirrhosis

Vasopressin has been found to impair hepatic function in patients with cirrhosis. The aim of this study was to investigate whether oxygen inhalation could improve hepatic function during vasopressin infusion. Vasopressin (0.3 iu/min) was infused into eight patients with cirrhosis for 50 min. During the first 30 min they were ventilated by room air and for the following 20 min by oxygen (approximate 50% of FiO2). The extra oxygen inhalation caused a typical increase in arterial (+7%, P less than 0.01), portal venous (+8%, P less than 0.05), and hepatic venous (+9%, P less than 0.01) oxygen content. No effect was noted in arterio-hepatic venous and portal venous-hepatic venous oxygen content difference in comparison with the values after vasopressin alone. The hepatic perfusion remained unchanged. These results suggest that the extra oxygen did not increase hepatic oxygen uptake. Similarly, intrinsic clearance of indocyanine green did not improve. It is concluded that oxygen supplement in this setting has no hepatic benefit in patients with cirrhosis.     

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.     

Relationship between hepatic blood flow,liver tests,haemodynamic values and clinical characteristics in patients with chronic liver disease*

Although hepatic blood flow (HBF) has been measured in patients with liver disease for many years, the results of these studies have not provided clear information concerning the usefulness of this measurement. Hepatic blood flow was measured in 392 patients with either cirrhosis (n= 356) or hepatic fibrosis (n= 36). The control group included 59 subjects with normal liver architecture. Hepatic clearance of indocyanine green (ICG) was markedly reduced in patients with cirrhosis and hepatic fibrosis compared with controls (182±5, 276±22 and 421±25 mL/min, respectively). In patients with cirrhosis, ICG clearance and extraction were significantly correlated, but were not correlated to HBF. Although HBF did not differ between patients with cirrhosis and controls (1.26±0.04 vs 1.35±0.07 L/min, respectively), patients with hepatic fibrosis had lower HBF (1.04±0.07 L/min; P< 0.05). In patients with cirrhosis, no correlation was observed between HBF and cardiac output, mean arterial pressure, azygos blood flow, the hepatic venous pressure gradient or Pugh's score. However, a significant difference in HBF was observed in patients with and without hepatic encephalopathy (1.00±0.09 vs 1.28±0.03 L/min, respectively; P<0.05). In conclusion, the present study shows that, in patients with cirrhosis, HBF is normal and is not related to other haemodynamic values or liver tests. These results discourage the measurement of HBF in the evaluation of patients with cirrhosis.     

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.     

Hemodynamic changes of systemic,hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20–40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.This work was supported in part by a grant from the Italian Ministry of Education (National Project Liver Cirrhosis).     

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。     

Circulating and hepatic endocannabinoids and endocannabinoid‐related molecules in patients with cirrhosis

Background/Aims: Endocannabinoids include anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG). Endocannabinoid‐related molecules like oleoyl‐ethanolamine (OEA) and palmitoyl‐ethanolamine (PEA) have also been identified. AEA contributes to the pathogenesis of cardiovascular alterations in experimental cirrhosis, but data on the endocannabinoid system in human cirrhosis are lacking. Thus, we aimed to assess whether circulating and hepatic endocannabinoids are upregulated in cirrhotic patients and whether their levels correlate with systemic haemodynamics and liver function. Methods: The endocannabinoid levels were measured in peripheral and hepatic veins and liver tissue by isotope‐dilution liquid chromatography‐atmospheric pressure chemical ionization‐mass spectrometry. Systemic haemodynamics were assessed by the transthoracic electrical bioimpedance technique. Portal pressure was evaluated by hepatic venous pressure gradient. Results: Circulating AEA and, to a greater extent, PEA and OEA were significantly higher in cirrhotic patients than in controls. PEA and OEA were also increased in the cirrhotic liver tissue. AEA, OEA and PEA levels were significantly higher in peripheral than in the hepatic veins of cirrhotic patients, while the opposite occurred for 2‐AG. Finally, circulating AEA, OEA and PEA correlated with parameters of liver function, such as serum bilirubin and international normalized ratio. No correlations were found with systemic haemodynamics. Conclusions: The endocannabinoid system is upregulated in human cirrhosis. Peripheral AEA is increased in patients with a high model of end‐stage liver disease score and may reflect the extent of liver dysfunction. In contrast, the 2‐AG levels, the other major endocannabinoid, are not affected by cirrhosis. The upregulation of the endocannabinoid‐related molecules, OEA and PEA, is even greater than that of AEA, prompting pharmacological studies on these compounds.     

Clinical characteristics of cirrhosis patients with umbilical vein recanalization: A retrospective analysis

Umbilical Vein Recanalization (UVR) may occur in patients with long-standing portal hypertension and liver cirrhosis. This study aimed to investigate the clinical significance of UVR.Medical records of a cohort of patients with cirrhosis (n = 247) who were hospitalized at the Digestive Medicine Center of the Second Affiliated Hospital of Nanchang University from January 2012 to October 2015 were accessed. The UVR diagnosis was made by ultrasound examination and was confirmed by computerized tomography scan.The UVR incidence was 20.2% (50/247) in the cohort. The size of UVR was 9.9 ± 4.7 mm (range: 5–26.5 mm) in diameter. The UVR and non-UVR groups showed no difference in grades of hepatic encephalopathy (P = .496), Child-Pugh classification (P = .401), the incidence of moderately severe ascites (26% vs 26%, P = 1), the esophageal variceal bleeding rate (32% vs 39%, P = .402), or portal vein thrombosis (8% vs 12%, P = .580). However, the incidence of cavernous transformation of the portal vein was statistically different, that there was 0 case in the UVR group and 8 cases in the non-UVR group (P < .05).Our results suggested that UVR had little impact on the clinical manifestations of patients with liver cirrhosis, the significance of UVR as an intervention method requires further studies.     

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.     

Role of hepatic artery in haemodynamics in normal and cirrhotic livers in rats

To examine the degree of influence of the hepatic artery on microcirculation in the liver, microscopic observation of blood flow in the hepatic minute blood vessels and the sinusoids and pressure measurements at key points in hepatic vascular pathways in vivo were performed before and after hepatic artery ligation in normal and cirrhotic rats. In normal rats, portal vein pressure (109 mmH2O) fell 10 mmH2O after hepatic artery ligation, but the pressures of the terminal portal venule, the terminal hepatic venule and the inferior vena cava did not change. In cirrhotic rats, portal vein pressure (206 mmH2O) and terminal portal venule pressure (106 mmH2O) fell 23 and 10 mmH2O after hepatic artery ligation respectively: the pressures in the terminal hepatic venule and the inferior vena cava did not change. These results suggests that the pressure transmitted from the hepatic artery was mostly supplied to the intrahepatic portal vein in normal rats and both to the intrahepatic portal vein and to the sinusoids in cirrhotic rats. In both normal and cirrhotic rats, however, the pressure transmitted from the hepatic artery was about 10 per cent of the initial portal vein pressure, and the blood flow in minute vessels and sinusoids did not change after hepatic artery ligation. Accordingly, it is believed that the hepatic artery plays only a small role in the haemodynamics of the liver in both normal and cirrhotic rats, irrespective of the distribution and manner of the hepatic arterial termination.     

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).     

Saline-enhanced ultrasonography: prediction of X-ray appearance of hepatic venography in patients with cirrhosis

Abstract

Objective. To examine the efficacy of saline-enhanced ultrasound (US) in predicting the X-ray appearance of hepatic venography. Materials and methods. This prospective study consisted of 50 cirrhosis patients (31 males and 19 females; mean age, 64.2 ± 11.1 years). US patterns in the liver, after injection of agitated saline via balloon-occluded catheter, were evaluated with respect to the findings of CO₂-enhanced hepatic venogram. Results. US demonstrated two patterns: type I showing positive parenchymal enhancement (40 patients) and type II showing negative parenchymal enhancement with detection of hepatic vein (10 patients). There were also two patterns shown by hepatic venography: type A showing retrograde detection of intrahepatic portal vein (41 patients) and type B showing hepatic venous enhancement via intrahepatic venous–venous communications with no detection of intrahepatic portal vein (9 patients). All patients with type I showed retrograde detection of intrahepatic portal vein via hepatic sinusoid on X-ray venograms (type A). Of the 10 patients with type II, nine showed type B and one showed type A. Sensitivity and specificity of type I US pattern to predict the detection of intrahepatic portal vein on the venogram were 100% and 90%, respectively. There was no significant difference in hepatic venous pressure gradient or wedged hepatic venous pressure between patients with type I and type II. Conclusions. Saline-enhanced US is effective in predicting the findings of hepatic venogram. As type II strongly suggests the shunt-modified venogram, image taking in these cases would be superfluous with the added advantage of avoiding unnecessary radiation exposure.     

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。     

肝硬化非常见侧支循环临床特点研究

目的 探讨肝硬化患者门体循环之间非常见侧支循环形成的临床特点及意义。方法 对临床确诊为肝硬化的患者运用64排螺旋CT和三维血管成像结合电子胃镜检查,观察其门体循环之间非常见侧支循环的形成。结果 ①700例肝硬化患者中118例(16.86%)存在非常见侧支循环,依次为脾肾静脉分流、胃肾静脉分流、椎旁静脉分流、腹膜后静脉分流、胃脾分流和心膈角静脉分流。②非常见侧支循环形成与肝硬化Child-Pugh分级相关(P<0.01)。③与常见侧支循环形成组比较,非常见侧支循环组较少出现重度食管和(或)胃底静脉曲张、重度门静脉高压性胃病及大量腹水(P<0.01)。④非常见侧支循环组中肝性脑病和慢性血氨升高的发生率高于常见侧支循环组(P<0.01)。结论 ①肝硬化患者中非常见侧支循环并不"非常见";②非常见侧支循环形成与肝功能Child-Pugh分级有关;③非常见侧支循环形成可缓解门静脉高压引起的相关并发症,但增大了肝性脑病和慢性血氨升高的发病率。     

Renal function and cognitive impairment in patients with liver cirrhosis

Objective. Cognitive impairment is a common problem in patients with liver cirrhosis. Its pathogenesis is multifactorial and ammonia is considered to play a central role. Renal function has been shown to be important for ammonia metabolism in cirrhosis. Although renal dysfunction is common in cirrhotic patients, its effect on cognitive function is largely unexplored. Material and methods. A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of cognitive dysfunction according to the West-Haven criteria and by means of two psychometric tests. Serum creatinine, sodium and potassium as well as plasma ammonia concentrations were assessed. Glomerular filtration rate was also measured by ⁵¹Cr- EDTA clearance in a subgroup of patients. Results. Forty-one patients (32%) were found to have cognitive dysfunction (clinical evaluation and/or psychometric tests). Sixteen patients (13%) found with serum creatinine levels above reference values had cognitive dysfunction more frequently than patients with creatinine within the normal range (69% versus 31%; p=0.001), but did not differ in aetiology or severity of cirrhosis (p>0.1). Patients with loop diuretics versus without did not differ in creatinine values (p>0.1). Multivariate analysis showed that cognitive dysfunction was related to hospital admission at inclusion in the study, international normalized ratio and serum creatinine (p<0.05 for all), but not to potassium or sodium levels. Plasma ammonia concentration was related to serum creatinine (r=0.26, p=0.004) and the glomerular filtration rate (r=?0.44, p=0.023). Conclusions. Renal dysfunction seems to be related to cognitive impairment in patients with liver cirrhosis and might be implicated in the pathogenesis of hepatic encephalopathy.     

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

AIM:To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis(AL-LC).METHODS:The subjects included 35 patients with ALLC(34 men,1 woman;mean age,58.9±10.7 years;median age,61 years;range:37-76 years).All patientswere enrolled in this study after obtaining written informed consent.Liver function was measured with tests measuring albumin(Alb),prothrombin time(PT),brain natriuretic peptide(BNP),branched amino acid and tyrosine ratio(BTR),branched chain amino acid(BCAA),tyrosine,ammonia(NH3),cholinesterase(Ch E),immunoreactive insulin(IRI),total bile acid(TBA),and the retention rate of indocyanine green 15 min after administration(ICG R15).Hepatic blood flow,hepatic arterial tissue blood flow(HATBF),portal venous tissue blood flow(PVTBF),and total hepatic tissue blood flow(THTBF)were simultaneously calculated using xenon computed tomography.RESULTS:PVTBF,HATBF and THTBF were 30.2±10.4,20.0±10.7,and 50.3±14.9 m L/100 m L/min,respectively.Alb,PT,BNP,BTR,BCAA,tyrosine,NH3,Ch E,IRI,TBA,and ICG R15 were 3.50±0.50 g/d L,72.0%±11.5%,63.2±56.7 pg/m L,4.06±1.24,437.5±89.4μmol/L,117.7±32.8μmol/L,59.4±22.7μg/d L,161.0±70.8 IU/L,12.8±5.0μg/d L,68.0±51.8μmol/L,and 28.6%±13.5%,respectively.PVTBF showed a significant negative correlation with ICG R15(r=-0.468,P<0.01).No significant correlation was seen between ICG 15R,HATBF and THTBF.There was a significant correlation between PVTBF and Alb(r=0.2499,P<0.05),and NH3 tended to have an inverse correlation with PVTBF(r=-0.2428,P=0.0894).There were also many significant correlations between ICG R15 and liver function parameters,including Alb,NH3,PT,BNP,TBA,BCAA,and tyrosine(r=-0.2156,P<0.05;r=0.4318,P<0.01;r=0.4140,P<0.01;r=0.3610,P<0.05;r=0.5085,P<0.001;r=0.4496,P<0.01;and r=0.4740,P<0.05,respectively).CONCLUSION:Our investigation showed that there is a close correlation between liver function and hepatic blood flow.