Hepatic Function and Portal Hemodynamics in Patients with Liver Cirrhosis

We investigated the distribution of portal blood flow per kilogram of body weight (PBF/BW) in 112 healthy volunteers and 90 patients with liver cirrhosis using an ultrasonic Doppler duplex system. The PBF/BW in healthy volunteers showed a log-normal distribution, while the distribution was irregular and showed two peaks in patients with cirrhosis. This irregular distribution was thought to reflect their complex physiopathological state. We next analyzed the relationship between PBF/BW and the data from hepatic function tests (serum albumin, total bilirubin, indocyanine green 15-min retention rate, and indocyanine green plasma disappearance rate) in 48 patients with liver cirrhosis. The patients were divided into four groups according to their portal blood flow: group A with a hepatofugal or stagnant portal blood flow, group B with a hepatopetal PBF/BW of less than 12 ml/min/kg, group C with a hepatopetal PBF/BW of 12 or more but less than 20 ml/min/kg, and group D with a hepatopetal PBF/BW of 20 ml/min/kg or more. Among patients with cirrhosis, group A showed the worst results in hepatic function tests, group D the second worst, and group C the best. The effective hepatic blood flow was thought to have decreased because of the development of extrahepatic portosystemic shunts in the patients in groups A and B, whereas it decreased because of the development of intrahepatic shunts in patients in group D. The results of hepatic function tests deteriorated as a consequence of the decrease in the effective hepatic blood flow.     

Effects of Propranolol on Portal Hemodynamics in Patients with Chronic Liver Disease

To elucidate the mechanism by which propranolol reportedly affects portal hemodynamics, we investigated the effect of propranolol on systemic and splanchnic hemodynamics in 15 patients with portal hypertension and esophageal varices by simultaneous catheterization of the portal vein and the right hepatic vein and measurement of portal venous flow using an ultrasound doppler system. Infusion of 5 mg of propranolol significantly decreased pulse rate (-12.6%), cardiac output (-24.5%), portal venous flow (-22.3%), portal venous pressure (-13.3%), and gradient between portal venous pressure and free hepatic venous pressure (-24.8%). Thus, propranolol seems to decrease portal venous pressure by reducing portal venous flow, at least in part, as a result of reduction of cardiac output due to its beta 1 adrenergic receptor blocking action.     

Reduction of Portal Pressure by Chronic Administration of Isosorbide Dinitrate in Patients with Cirrhosis: Effects on Systemic and Splanchnic Hemodynamics and Liver Function

We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis.     

肝硬化门静脉高压无创性检测方法的认识与评价

门静脉高压是导致肝硬化患者出现严重并发症和死亡的主要原因之一。肝静脉压力梯度(HVPG)是评价门静脉高压及其严重程度最准确的方法,但因具有创伤性和不适性,故需特别关注肝硬化门静脉高压无创性检测方法。通过血液学指标、超声检查和CT以及胶囊内镜等无创性检查方法,可初步评估代偿期肝硬化患者是否存在食管胃底静脉曲张。上消化道内镜检查是确定食管胃底静脉曲张的金标准。通过上消化道内镜或超声内镜检测食管静脉曲张压力,可判断药物或分流手术降低重度食管静脉曲张压力的疗效。虽然这些无创性检测方法可有效地评估门静脉高压的严重状况,但对轻度门静脉高压评估能力有限,有待进一步完善和提高。     

Differences in Portal Hemodynamics in Cirrhosis and Idiopathic Portal Hypertension

A comparative study of portal hemodynamics was made in 79 cirrhotics (24 cirrhotics with a large spleen greater than or equal to 500 cm3 in volume, 55 cirrhotics with a spleen less than 500 cm3 in volume), 22 patients with idiopathic portal hypertension, and 63 healthy adults who served as the control for portal and splenic venous flows. Portal and splenic venous flows were significantly increased in the group order of the cirrhosis without splenomegaly group, the cirrhosis with splenomegaly group, and idiopathic portal hypertension group. Intrahepatic shunt index was significantly greater in the cirrhosis with splenomegaly group than in the cirrhosis without splenomegaly group, and it was negligible in the idiopathic portal hypertension group. Portal vein pressure was significantly elevated in the cirrhosis with splenomegaly group than in the cirrhosis without splenomegaly and idiopathic portal hypertension groups. Postsinusoidal resistances were significantly greater in the two groups of cirrhosis than in the idiopathic portal hypertension group, whereas presinusoidal resistance was significantly greater in the idiopathic portal hypertension group than in the two groups with cirrhosis. It is concluded that these differences are inconsistent with the view that cirrhosis with splenomegaly comes from idiopathic portal hypertension.     

Portal Hemodynamics After Large-Volume Paracentesis in Patients with Liver Cirrhosis and Tense Ascites

Large-volume paracentesis with a plasma expanderhas been extensively evaluated and shown to be aneffective and safe therapy. While hepatic and systemichemodynamics have been studied extensively, there is little information on portal hemodynamics byduplex Doppler. Portal vein diameter, portal flowvelocity, and portal blood flow were measured withduplex Doppler in 11 cirrhotic patients before and 24 hr after large volume paracentesis. There wereno significant changes in the portal vein diameter (9.88± 2.62 mm vs 10.09 ± 2.73 mm), portal flowvelocity (10.65 ± 2.60 vs 10.01 ± 2.58cm/sec), and portal blood flow (488 ± 288.9 vs502 ± 273.38 ml/min), before and 24 hr afterlarge-volume paracentesis. Thus, significant changes inportal hemodynamics do not occur after large-volumeparacentesis.     

Effects of Vasopressin on Portal Hemodynamics in Patients with Portal Hypertension

In view of the variability in the magnitude of the response of portal venous pressure to vasopressin in man, we investigated the effect of vasopressin on portal hemodynamics in seven patients with portal hypertension by simultaneous catheterization of the portal and the hepatic vein and the measurement of portal venous flow by an echo-Doppler flowmetry. Infusion of vasopressin (0.3 U/min) significantly decreased portal venous pressure (-36%), the gradient between portal venous pressure and free hepatic venous pressure (-50.6%), and portal venous flow (-54.3%) but did not reduce mean arterial pressure and pulse rate. Thus, vasopressin seems to decrease portal venous pressure by reducing portal venous flow.     

经颈静脉肝内门体分流术前后肝硬变患者门静脉血液动力学改变

目的:观察经颈静脉肝内门体分流术前后肝硬变患者门静脉血流动力学变化。方法:采用经颈静脉肝内门体分流术(TIPS)治疗8例肝硬变门静脉高压(CPH)食管静脉曲张出血患者,用彩色多普勒超声显像仪对治疗前后患者门静脉血流动力学改变进行研究。结果:经TIPS术后门静脉血流速度、血流量明显增高,由术前10.26±4.25cm/s、1145.36±436.52ml/min增高至术后一、三周的21.70±5.89cm/s、19.72±5.24cm/s和2238.79±971.4ml/min、2054.71±880.56ml/min,P<0.01、0.05。门静脉压力由3.6kPa和0.7kP9降至1.73kPa和0.35kPa,P<0.01。结论:肝硬变门静脉高压症患者TIPS术后进行彩色多普勒门静脉血液动力学测定,可以了解门静脉血液状态,对判断预后有一定价值。     

Clinical Characteristics of Portal Hemodynamics in Alcoholic Liver Cirrhosis

Background: Low incidence of reversal blood flow at the portal vein has been reported by measurement in larger and extrahepatic blood vessels but not in intrahepatic blood vessels in patients with liver cirrhosis. Moreover, there is little information regarding the incidence of reversal blood on the basis of the cause of liver cirrhosis. The aim of this study was to measure the reversal blood flow in the portal vein including intrahepatic branches in patients with alcoholic and viral cirrhosis.
Methods: The blood flow in the portal vein and existence of portosystemic shunt were studied in 52 and 27 patients with alcoholic and viral cirrhosis, respectively, by Doppler ultrasonography. The parameters of liver function test and the prevalence of ascites and esophageal varices were compared between patients with and without reversal blood flow.
Results: Reversal blood flow at the portal vein was found only in patients with only alcoholic cirrhosis (17 of 52 patients) but not in any patients with viral cirrhosis (0 of 27 patients; p < 0.05). The incidence of portosystemic ascites and red color of esophageal varices was also higher in patients with alcoholic cirrhosis with reversal blood flow in the portal vein compared with patients without reversal blood flow ( p < 0.05).
Conclusions: Reversal blood flow in the portal vein is a characteristic feature of alcoholic cirrhosis. The presence of reversal blood flow indicates severe liver diseases, and this feature may have prognostic importance for patients with alcoholic cirrhosis.     

肝硬化门脉高压患者糖代谢异常的临床研究

目的：探讨肝硬化门脉高压患者糖代谢异常的病因和机理。方法：对30例肝硬化门脉高压患者，32例Ⅱ型糖尿病患者和15例正常人进行了空腹和餐后血糖，糖化血红蛋白，空腹胰岛素，C肽，胰高血糖素试验，计算胰岛素释放指数和胰岛素敏感性指数，对各组检查结果进行比较分析。结果：肝硬化组存在着糖耐量异常，餐后血糖，糖化血红蛋白，血清胰岛素，C肽和胰高血糖素多种指标显著高于正常对照组（P＜0．01。胰岛素敏感指数显著低于正常对照组（P＜0．01）。肝硬化Child分级比较，随着病情加重，糖代谢紊乱逐渐突出。肝硬化者胰岛素，C肽和胰岛素释放指数显著高于Ⅱ型糖尿病患者（P＜0．01），但胰岛素敏感指数和胰高血糖素比较两组之间无明显差异（P＞0．05）。结论：肝硬化门脉高压患者存在糖代谢异常，这种代谢异常主要是由于肝功能损害，胰岛素抵抗和胰高血糖素升高所致。     

Portal and Systemic Hemodynamics and Humoral Factors in Cirrhosis with and without Ascites

The pathogenesis of salt and water retention in cirrhosis remains unclear. Systemic and portal hemodynamic parameters, including cardiac output, portal pressure gradient and systemic vascular resistance, were measured in six patients with untreated ascites and in six patients with hepatic cirrhosis with no history of ascites. Renal blood flow, urinary volume, and humoral factors, including plasma renin, aldosterone, angiotensin II, and urine kallikrein, were measured. Significant differences were seen between the two groups in urine volume, urine sodium and fractional sodium excretion, plasma angiotensin II, and the ratio between plasma renin activity and urinary kallikrein excretion (PRA:UKallV). A strong correlation existed between urinary sodium excretion and the PRA:UKallV ratio. No significant differences were detected between the groups in portal, renal, and systemic hemodynamics. The present results suggest that humoral changes occur early in ascites. Altered relationships between intrarenal hormone systems, such as the renin-angiotensin and kallikrein-kinin systems, may be important in salt and water retention.     

普奈洛尔治疗肝硬化门静脉高压100例疗效分析

目的分析普奈洛尔治疗肝硬化门静脉高压的疗效。方法 100例肝硬化门静脉高压患者,口服普奈洛尔,从10 mg,3次/日开始,剂量逐渐增加到能使心率降低到基础心率的75%(不低于60次/min),维持该剂量。观察治疗前后门静脉、脾静脉的宽度,脾脏大小的变化,食道、胃底静脉曲张程度。结果观察1年以上的87例患者,治疗后各项指标均有明显改善,差异有统计学意义(P<0.05),上消化道出血率由21%降至5%。结论普奈洛尔治疗肝硬化门静脉高压症的患者,可减低门静脉压力,预防和减少静脉曲张所致食道、胃底静脉破裂出血。     

胰岛素抵抗与肝硬化门脉高压的关系

胰岛素抵抗与疾病发生的关系受到众多学者的关注 ,胰岛素敏感指数是客观反映胰岛素抵抗的指标。肝硬化患者普遍存在高胰岛素血症现象 ,胰岛素抵抗是否与门脉高压的发生有关值得探讨。我们对 46肝硬化患者的胰岛素敏感指数、门脉内径、血流速度、流量、尿钠浓度进行联合测定 ,并与 12例健康对照者比较。现将结果报道如下。对象与方法1.对象 :( 1)肝硬化组 46例 ,均为 1998～ 1999年住院的肝炎性肝硬化患者 ,按Ｃｈｉｌｄ分级 :Ａ级 16例 ,Ｂ级 18例 ,Ｃ级 12例 ,年龄 35～ 72岁 ,平均年龄 5 3岁。 ( 2 )对照组 12人 ,为健康查体者 ,年龄 2 8…     

Interrelationship between Type of Spontaneous Portal Systemic Shunt and Portal Vein Pressure in Patients with Liver Disease

The interrelationship between the type and degree of spontaneous portal systemic shunting, and portal vein pressure was studied in 155 patients with liver disease by catheterizing the portal vein. The degree of portal vein shunting was measured in 100 patients and that of splenic vein shunting in 50 and that of total portal systemic shunting in 52, using macroaggregated radioalbumin. Increasing portal vein pressures were associated with progressively higher indices of portal vein shunt, splenic vein shunt, and total portal systemic shunt up to a certain level. Beyond this level, portal vein pressure did not increase further, and rather it decreased with further increasing degrees of splenic vein shunt and total portal systemic shunt. These results indicate that spontaneous portal systemic shunt keeps the portal vein pressure within certain limits or decreases it.     

Effect of Phenoxybenzamine (POB) on Portal Venous Pressure in Patients with Portal Hypertension

In order to assess an effect of phenoxybenzamine (POB) on portal circulation, POB (0.5-1.0 mg./kg.) was administered intravenously to six patients with portal hypertension and two patients without portal hypertension. In patients with portal hypertension, POB reduced portal venous pressure (PVP) from 362.5 +/- 53.8 mm. H2O to 282.5 +/- 50.4 mm. H2O (P less than 0.001) where central venous pressure (CVP) was maintained constant. In patients without portal hypertension, change in PVP was in parallel with that in CVP where the decrease in PVP was regarded as not specific. This preferential reduction of PVP in portal hypertension seemed to implicate functional vasoconstriction of the portal venous system. In the treatment of bleeding esophageal varices, use of POB with blood transfusion after decompression of the Sengstaken-Blakemore tube should be beneficial because of its prolonged effect of lowering PVP and preventing ischemic liver damage.     

Regulation of Hepatic Thrombopoietin Production by Portal Hemodynamics in Liver Cirrhosis

Objective: This study was designed to clarify how thrombopoietin (TPO) functions in and, to some extent, causes thrombocytopenia complicating liver cirrhosis and portal hypertension.
Methods: Our study population consisted of 19 cirrhotic and six noncirrhotic patients who underwent percutaneous transhepatic portography (PTP) and hepatic venography.
Results: The platelet counts of the cirrhotic patients were significantly lower than those of the noncirrhotic patients (  8.7 ± 4.1 vs 17.4 ± 7 × 10⁴/μl  ;   p < 0.01  ). The flow direction in the splenic vein was confirmed by PTP. Ten hepatofugal and nine hepatopetal flow directions in the splenic vein were noted among the cirrhotics. The hepatofugal group showed lower portal venous pressure (  20 ± 10 vs 32 ± 4 cm H₂O  ;   p < 0.01  ) than the hepatopetal group and had a higher incidence of hepatic encephalopathy (six of 10 vs zero of nine;   p < 0.01  ). The hepatic vein-portal difference in TPO did not differ substantially between the cirrhotics and noncirrhotics (  0.12 ± 0.04 vs 0.24 ± 0.07  fmol/ml). Comparisons of this value among the three groups showed the TPO difference to be lowest in the hepatofugal group (hepatofugal:  0.04 ± 0.03  , hepatopetal:  0.21 ± 0.07  , noncirrhotic:  0.24 ± 0.07  ;   p < 0.05  ).
Conclusions: Our findings suggest that TPO production in the cirrhotic liver is regulated by the portal blood supply to the liver. Thus, portal hemodynamics may play a critical role in the development of thrombocytopenia.     

Possible Treatment Strategies for Portal Hypertension in Liver Cirrhosis

Purpose of the Review

Chronic liver injury leading to fibrosis and complicated by portal hypertension is an emerging burden for health systems worldwide, but current treatments are few and poorly effective. Therefore, this review aims to present diverse potential treatment approaches that are currently under investigation or on their way to clinical use.

Recent Findings

These options involve statins, the renin-angiotensin system and their downstream effectors, the anticoagulation system, farnesoid-x receptor agonism, and various other targets.

Summary

Since activated hepatic stellate cells play a pivotal role in both fibrogenesis and portal hypertension, most of these potential treatment approaches target directly or indirectly this profibrotic and procontractile cells in liver fibrosis with portal hypertension. Special focus should be paid to cell-specific treatments to minimize side effects and systemic complications in treatment of liver fibrosis and portal hypertension.

     

48-Hour Hemodynamic Effects of Octreotide on Postprandial Splanchnic Hyperemia in Patients with Liver Cirrhosis and Portal Hypertension

Octreotide is effective during 48 h in the treatment of acute variceal bleeding, probably by reducing variceal blood flow and pressure. Its basal and postprandial effects on splanchnic and systemic hemodynamics, and hormonal changes over this time interval have not yet been studied. Twenty-four patients with cirrhosis and portal hypertension were randomized to receive a liquid meal and either octreotide (Oct, 100 g bolus intravenous, followed after 2 h by a continuous infusion of 25 g/hr for 20 hr) or placebo (Plac) given at three consecutive days. Splanchnic (Doppler ultrasound) and systemic hemodynamics (noninvasive cardiac monitoring) were assessed on four consecutive days (one control day and three treatment days) during 2 hr. The postprandial increase in mean blood velocity of the superior mesenteric artery (SMA-V _mean, +44%), portal blood velocity (PV-V _mean, +44%) and total hepatic blood flow (HBF, +40%) observed in the placebo group during the control day was abolished during the first day of treatment (SMA-V_mean, +3%, P < 0.01; PV-V_mean, +6%, P < 0.05; HBF, –25%, P < 0.01) and still reduced after 48 hr in the octreotide group (SMA-V_mean, +28%, P < 0.05; PV-V_mean, +22%, P > 0.05; HBF, –8%, P < 0.05). The postprandial increase in cardiac index (CI, +10%) and decrease in systemic vascular resistance index (SVRI, –6%) were blunted after the initial injection of octreotide only (CI, –8%, P < 0.05; SVRI, +18%, P < 0.01). Endothelin-1-levels, which were increased at baseline (Plac 25 ± 17, Oct 16 ± 13 ng/liter, P > 0.05) decreased significantly after 48 hr of treatment with octreotide (Plac 27 ± 20, Oct 8 ± 4 ng/liter, P < 0.05). Octreotide is effective during 48 hr in the prevention of postprandial hyperemia in cirrhotics, even if its efficacy is decreasing over time. Moreover it may have positive effects on systemic vasodilation in cirrhotics. These findings suggest a potential role of this drug in the chronic treatment of portal hypertension.