Hepatic venous pressure gradient determination in patients with hepatitis C virus-related and alcoholic cirrhosis

OBJECTIVES: Few data exist regarding the degree of portal hypertension in hepatitis C virus (HCV)-related cirrhosis, as the majority of studies have included mainly patients with alcoholic cirrhosis. This study was aimed at comparing the severity of portal hypertension in patients with HCV-related or alcoholic cirrhosis. METHODS: In total, 59 cirrhotic patients with portal hypertension (HCV-related in 34 cases and alcoholic in 25) underwent main right hepatic vein catheterization, with determination of the wedged and free hepatic venous pressures, and of hepatic venous pressure gradient (HVPG). RESULTS: HVPG values did not differ between the two groups of patients (19.4 +/- 6.0 mmHg vs 18.5 +/- 3.5 mmHg; P = 0.51). The prevalence and degree of oesophageal and gastric varices and portal hypertensive gastropathy did not correlate with the aetiology. Patients with viral cirrhosis had a lower prevalence of previous bleeding than those with alcoholic cirrhosis, despite a similar proportion of large varices in the two groups and similar HVPG levels. In both groups of patients, HVPG did not differ between patients with previous bleeds and those without. CONCLUSIONS: The degree of portal hypertension in cirrhotic patients does not correlate with the cause of the disease. Thus, current statements on the management of portal hypertension, although based upon studies including mainly patients with alcoholic cirrhosis, can be applied also to patients with viral-related cirrhosis.     

Intrahepatic Heterogeneity of Hepatic Venous Pressure Gradient in Human Cirrhosis

Background: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension. Methods: We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls). Results: In the controls, the two measurements differed by 0.0 ± 1.8 mmHg (mean ± s , n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s ). HVPG ranged from-0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within ± 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature. Discussion: Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.     

A 3-month course of long-acting repeatable octreotide (sandostatin LAR) improves portal hypertension in patients with cirrhosis: a randomized controlled study

OBJECTIVE: In patients with cirrhosis, acute octreotide administration may transiently decrease the hepatic venous pressure gradient (HVPG). Information on long-term effects of octreotide is limited and controversial. We evaluated portal and systemic hemodynamics following a prolonged administration of long-acting octreotide in patients with cirrhosis. METHODS: Eighteen cirrhotic patients (alcoholic 12; age 55 yr [44-69]; Pugh's score 7.8; HVPG 17.3 mmHg [12-22]), no steatohepatitis on histology, were randomized to intramuscular octreotide 20 mg (group A) q 4 wk for 3 months or placebo (group B) in a double-blind fashion. At baseline and 3 months, we measured the HVPG, systemic hemodynamics, endothelin-1 (ET-1), and vascular endothelial growth factor (VEGF) in hepatic venous blood. RESULTS: Patients remained compensated except for one episode of infection in each group. At 3 months, the HVPG decreased in group A but not in group B (16.5 +/- 1.3 to 11.8 +/- 1.5 mmHg, P < 0.01; 18.2 +/- 1 to 17 +/- 1.1 mmHg, P= 0.4). Systemic hemodynamics and liver function remained unchanged. In group A, but not in group B, VEGF decreased (21.2 +/- 4.7 to 13.7 +/- 3.5 pg/mL, P < 0.01; 22.5 +/- 7.8 to 19.2 +/- 5.4 pg/mL, P= 0.4). ET-1 remained stable. Changes in HVPG and VEGF were correlated (r = 0.49, P < 0.05). CONCLUSIONS: Three months of long-acting octreotide in selected cirrhotic patients with portal hypertension decreases the HVPG independent of systemic hemodynamics and liver function. The decrease in VEGF blood levels suggests an improvement in splanchnic hyperemia.     

Intrahepatic heterogeneity of hepatic venous pressure gradient in human cirrhosis

BACKGROUND: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension. METHODS: We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls). RESULTS: In the controls, the two measurements differed by 0.0 +/- 1.8 mmHg (mean +/- s, n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s). HVPG ranged from -0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within +/- 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature. DISCUSSION: Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.     

Hemodynamic effects of nifedipine on hepatic venous pressure gradient in patients with portal hypertension

The effect of Nifedipine on hepatic venous pressure gradient (HVPG) was determined in 10 patients with portal hypertension due to cirrhosis of the liver, and in 7 control subjects, by hepatic vein catheterization. Twenty min. after sublingual application of 10 mg Nifedipine, patients and controls showed significant hemodynamic changes in the systemic circulation. In contrast, HVPG after Nifedipine was not statistically different from the basal values--neither in patients with portal hypertension (p = 16.6 +/- 5.2 mmHg vs 17.9 +/- 5.3 mmHg) nor in the control subjects (p = 2.9 +/- 1.1 mmHg vs. 1.0 mmHg). We conclude that calcium entry blockade by Nifedipine is not effective in acutely reducing portal venous pressure.     

Plasma erythropoietin level in patients with cirrhosis and its relationship to the severity of cirrhosis and renal function

BACKGROUND AND AIM: The level of plasma erythropoietin (EPO) in patients with cirrhosis is controversial. It is known that overproduction of nitric oxide (NO) plays, in part, a role for the development of peripheral arterial vasodilatation in cirrhosis with portal hypertension. It has also been hypothesized that a possible interaction is noted between endogenous EPO and NO production. The current study was undertaken to evaluate the relationship between plasma EPO levels and the severity of liver disease, hemodynamic values, renal functions, and plasma nitrate/nitrite levels in patients with cirrhosis. METHODS: The authors measured the biochemistry, plasma EPO and nitrate/nitrite levels in 67 patients with cirrhosis (Child-Pugh class A in 23 and Child-Pugh class B and C in 44) and compared their values with those in 34 healthy subjects. Systemic and splanchnic hemodynamic measurements and effective renal plasma flow were obtained from cirrhotic patients. RESULTS: Plasma EPO and nitrate/nitrite levels were significantly increased in patients with cirrhosis compared with healthy subjects. Additionally, plasma EPO values were higher in cirrhotic patients with ascites or with anemia than in those without ascites or without anemia, respectively. Plasma EPO levels were positively correlated to the hepatic venous pressure gradient (HVPG) and Child-Pugh score, negatively correlated to the renal and hepatic blood flows, but were not correlated to nitrate/nitrite level and systemic vascular resistance in cirrhotic patients. Multiple regression analysis showed that HVPG and renal plasma flow were independent predictors for the elevated EPO level in cirrhotic patients. CONCLUSIONS: Plasma EPO levels were increased in patients with cirrhosis compared with those in healthy subjects. The increase in plasma EPO levels is related to the degree of portal hypertension, the severity of cirrhosis and the renal plasma flow. In contrast, the EPO levels had no correlation to the nitrate/nitrite levels and systemic vascular resistance in patients with cirrhosis.     

Hepatic venous pressure gradient measurement: Time to learn!

Portal hypertension is a clinical syndrome defined by a pathological increase in portal pressure. The development of cirrhosis of the liver is characterized by clinical manifestations related to portal hypertension like esophageal varices, ascites, bleeding, and encephalopathy. Direct measurement of portal pressure is invasive, inconvenient, and clinically impractical. Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG), i.e., the difference between the wedged (WHVP) and the free hepatic venous pressures. HVPG represents the gradient between pressures in the portal vein and the intra-abdominal portion of inferior vena cava. When blood flow in a hepatic vein is stopped by a wedged catheter, the proximal static column of blood transmits the pressure from the preceding communicated vascular territory (hepatic sinusoids) to the catheter. Thus, WHVP reflects hepatic sinusoidal pressure and not the portal pressure itself. In the normal liver, due to pressure equilibration through interconnected sinusoids, wedged pressure is slightly lower than portal pressure, though this difference is clinically insignificant. In liver cirrhosis, the static column created by balloon inflation cannot be decompressed at the sinusoidal level due to disruption of the normal intersinusoidal communications; therefore, WHVP gives an accurate estimation of portal pressure in cirrhosis. The normal HVPG value is between 1 to 5 mmHg. Pressure higher than this defines the presence of portal hypertension, regardless of clinical evidence. HVPG >/= 10 mmHg (termed clinically significant portal hypertension) is predictive of the development of complications of cirrhosis, including death. HVPG above 12 mmHg is the threshold pressure for variceal rupture. The main advantages of HVPG are its simplicity, reproducibility, and safety. This review summarizes the technique of the HVPG measurement.     

Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis

BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic venous pressure gradient (HVPG) < 12 mmHg. METHODS: Forty-four patients with cirrhosis and HVPG < 12 mmHg underwent a haemodynamic study. They were compared with 36 cirrhotic patients with clinically significant portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS: The fraction with prolonged Q-T(c) interval (> 0.440 s(1/2)) was similar in the two cirrhotic groups (49 vs 50%, ns) and significantly above that of the controls (5%, P < 0.005). Q-T(c) was normal in patients with normal HVPG. Likewise, mean Q-T(c) was 0.449 and 0.447 s(1/2) in the two cirrhotic groups (ns), values which are significantly above that of the controls (0.410 s(1/2), P < 0.01). In the mild portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P < 0.02). CONCLUSIONS: Delayed repolarisation of the myocardium already occurs in a substantial fraction of patients with cirrhosis with only a mild increase in portal pressure. The prolonged Q-T(c) interval may be related to liver dysfunction and to the presence of portal hypertension.     

Hagen-Poiseuille’s law:The link between cirrhosis,liver stiffness,portal hypertension and hepatic decompensation

The onset of hepatic decompensation in cirrhosis heralds an accelerated downhill course with poor outcome. The sole predictor of this decompensationin cirrhosis is increased hepatic vein to portal vein gradient hepatic venous pressure gradient(HVPG). Surrogate markers of liver function or hepatic reserve appear to be less relevant. The hepatic sinusoids become less elastic and more rigid as liver fibrosis and cirrhosis progress. We propose that the HagenPoiseuille’s law,which applies to rigid,but not elastic vessels,determines the pressure-flow characteristics in the sinusoids. In the rigid cirrhotic liver,HVPG rises dramatically with any change in net surface area or radius,r4 of the vasculature that follows surgical resection. This review relates liver stiffness to the risk of decompensation in patients with cirrhosis. The liver has a unique dual blood supply comprising a low pressure portal vein and high pressure hepatic artery. We compare the complexity of autoregulation in the normal elastic liver with that in the rigid cirrhotic liver. Therapeutic modalities to reduce portal pressure may reduce the risk of hepatic decompensation and improve outcomes in cirrhosis.     

Liver cirrhosis

Liver cirrhosis is a frequent consequence of the long clinical course of all chronic liver diseases and is characterized by tissue fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Portal hypertension is the earliest and most important consequence of cirrhosis and underlies most of the clinical complications of the disease. Portal hypertension results from an increased intrahepatic resistance combined with increased portal (and hepatic arterial) blood flow. The fibrotic and angio-architectural modifications of liver tissue leading to increased intrahepatic resistance and the degree of portal hypertension seem to be highly correlated until HVPG values of 10-12 mmHg are reached. At this stage, which broadly represents the turning point between 'compensated' and 'decompensated' cirrhosis, additional extra-hepatic factors condition the further worsening of PH. Indeed, a HVPG ≥10-12 mmHg represents a critical threshold beyond which chronic liver disease becomes a systemic disorder with the involvement of other organs and systems. The progressive failure of one of the fundamental functions of the liver, i.e. the detoxification of potentially harmful substances received from the splanchnic circulation and particularly bacterial end-products, is responsible for the establishment of a systemic pro-inflammatory state further accelerating disease progression. The biology of liver cirrhosis is characterized by a constant stimulus for hepatocellular regeneration in a microenvironment characterized by chronic inflammation and tissue fibrosis, thus representing an ideal condition predisposing to the development of hepatocellular carcinoma (HCC). In reason of the significant improvements in the management of the complications of cirrhosis occurred in the past 20 years, HCC is becoming the most common clinical event leading to patient death. Whereas evidence clearly indicates reversibility of fibrosis in pre-cirrhotic disease, the determinants of fibrosis regression in cirrhosis are not sufficiently clear, and the point at which cirrhosis is truly irreversible is not established, either in morphologic or functional terms. Accordingly, the primary end-point of antifibrotic therapy in cirrhotic patients should be the reduction of fibrosis in the context of cirrhosis with a beneficial impact on portal hypertension and the emergence of HCC.     

Combined liver vein and spleen pulp pressure measurements in patients with portal or splenic vein thrombosis

BACKGROUND: Patients with thrombosis of the portal or splenic vein may develop portal hypertension with bleeding from oesophageal or gastric varices. The relevant portal pressure cannot be measured by liver vein catheterization or transhepatic puncture of the portal vein because the obstruction is peripheral to the accessible part of the portal system. METHODS: Liver vein catheterization was combined with percutaneous splenic pressure measurement in 10 patients with portal or splenic vein thrombosis and no cirrhosis, and 10 cirrhotic patients without thrombosis. The splenic pressure was measured by percutaneous puncture below the curvature of the ribs with an angle of the needle to skin of 30 degrees in order to minimize the risk of cutting the spleen if the patient took a deep breath. RESULTS: None of the patients in whom the described procedure was followed had complications. Pressure measurements in the spleen pulp and splenic vein were concordant. The pressure gradient across the portal venous system (splenic-to-wedged hepatic vein pressure) was -1.3 to 8.5 mmHg (median, 2.8 mmHg) in cirrhosis patients and 0-44 mmHg (median, 18 mmHg) in thrombosis patients, the variation reflecting various degrees of obstruction to flow in the portal venous system. Peripheral portal pressure (splenic-to-free liver vein pressure gradient) was 1.1-28 mmHg (median, 17 mmHg) in cirrhotic patients and 11-52 mmHg (median, 23 mmHg) in thrombosis patients. CONCLUSIONS: Liver vein catheterization combined with percutaneous splenic pressure measurement is feasible in quantifying pressure gradient across a thrombosis of the portal/splenic vein and in quantifying portal pressure peripheral to this kind of thrombosis.     

Role of hepatic vein catheterisation and transient elastography in the diagnosis of idiopathic portal hypertension

Background

Idiopathic portal hypertension is a rare cause of portal hypertension, frequently misdiagnosed as cryptogenic cirrhosis. This study evaluates specific findings at hepatic vein catheterisation or liver stiffness in idiopathic portal hypertension.

Methods

39 cases of idiopathic portal hypertension patients were retrospectively reviewed. Hepatic vein catheterisation and liver stiffness measurements were compared to matched patients with cirrhosis and portal hypertension, and non-cirrhotic portal vein thrombosis, included as controls.

Results

Hepatic vein-to-vein communications were found in 49% idiopathic portal hypertension patients precluding adequate hepatic venous pressure gradient measurements in 12. In the remaining 27 patients, mean hepatic venous pressure gradient (HVPG) was 7.1 ± 3.1 mmHg. Only 5 patients had HVPG ≥ 10 mmHg. HVPG was markedly lower than in cirrhosis (17 ± 3 mmHg, p < 0.001). Mean liver stiffness in idiopathic portal hypertension was 8.4 ± 3.3 kPa; significantly higher than in non-cirrhotic portal vein thrombosis (6.4 ± 2.2 kPa, p = 0.009), but lower than in cirrhosis (40.9 ± 20.5 kPa, p = 0.005). Only 2 idiopathic portal hypertension patients had liver stiffness >13.6 kPa.

Conclusions

Patients with idiopathic portal hypertension frequently have hepatic vein-to-vein communications and, despite unequivocal signs of portal hypertension, HVPG and liver stiffness values much lower than the cut-off for clinical significant portal hypertension in cirrhosis. These findings oblige to formally rule-out idiopathic portal hypertension in the presence of signs of portal hypertension.     

丹参等活血化淤中药对门脉高压血流动力学影响的临床与实验研究

目的探讨丹参、当归等及硝苯啶对门脉高压血流动力学的影响。方法采用血管插管测定胆管结扎肝硬化犬门脉系统压力变化；超声多普勒观测肝硬化患者门脉血流动力学变化。结果（１）静脉滴注丹参、当归后，肝硬化犬门静脉压（Ｐｐｖ）、嵌塞肝静脉压（ＷＨＶＰ）、肝静脉压力梯度（ＨＶＰＧ）显著降低（Ｐ＜０．０５～０．０１），平均动脉压（ＭＡＰ）、心率（ＨＲ）无明显变化（Ｐ＞０．０５），硝苯啶则使Ｐｐｖ，ＷＨＶＰ，ＭＡＰ．ＨＲ显著降低（Ｐ＜０．０５）。（２）丹参、丹参＋硝苯啶．丹参＋水＋硝苯啶口服药１０－１２周，能显著降低肝硬化患者门静脉内径（Ｄｐｖ）、脾静脉内径（Ｄｓｖ）．门静脉血流量（Ｑｐｖ），脾静脉血流量（Ｑｓｖ）（Ｐ＜０．０５－０．０１，当归作用较弱。结论对比表明，丹参、当归等中药较硝苯啶对门脉压力作用为慢，但较持久，无副反应。     

Performance of Doppler ultrasound in the prediction of severe portal hypertension in hepatitis C virus-related chronic liver disease.

PURPOSE: To evaluate the correlation between hepatic vein pressure gradient measurement and Doppler ultrasonography (DUS) in patients with chronic liver disease (CLD). PATIENTS AND METHODS: Sixty-six patients with fibrotic to cirrhotic hepatitis C virus-related CLD, were consecutively included upon referral to our haemodynamic laboratory. Superior mesenteric artery pulsatility index (SMA-PI), right interlobar renal and intraparenchymal splenic artery resistance indices, were determined, followed by hepatic venous pressure gradient (HVPG) measurement. RESULTS: A correlation was found between HVPG and intraparenchymal splenic artery resistance index (SA-RI) (r=0.50, P<0.0001), SMA-PI (r=-0,48, P<0.0001), right interlobar renal artery resistance index (RRA-RI) (r=0.51, P<0.0001) in the whole patient population. However, dividing patients according to the presence/absence of severe portal hypertension (i.e. HVPG > or =12 mmHg), a correlation between HVPG and intraparenchymal SA-RI (r=0.70, P<0.0001), SMA-PI (r=-0.49, P=0.02), RRA-RI (r=0.66, P=0.0002) was observed only for HVPG values <12 mmHg. HVPG but not DUS correlated with the presence of esophageal varices (P<0.0001). CONCLUSIONS: Superior mesenteric artery pulsatility index, intraparenchymal splenic and right interlobar renal artery resistance indices do not adequately predict severe portal hypertension.     

Hepatic Venous Pressure Gradient: Worth Another Look?

Portal hypertension is one of the most important complications of chronic liver disease and accounts for significant morbidity and mortality. Measurement of the hepatic venous pressure gradient (HVPG) is a simple, invasive, and reproducible method of assessing portal venous pressure. Measurement of HVPG provides the clinician an estimate of the degree of intrahepatic portal flow resistance, guides therapy for variceal bleeding (primary and secondary prophylaxis), assesses feasibility of resection in patients with hepatocellular cancer, and predicts response to therapy of patients with chronic hepatitis C. Achieving hemodynamic targets of reducing the HVPG to <10 mmHg or a 20% reduction from baseline virtually eliminates complications related to portal hypertension from chronic liver disease. This review explores the role of HVPG measurement in the contemporary treatment of patients with cirrhosis and portal hypertension.     

Hepato-systemic gradient of carbon monoxide in cirrhosis

Background and aims

Experimental data suggest that in liver cirrhosis splanchnic and systemic vasculature exhibit marked endothelial Carbon monoxide (CO) overproduction, while recent data demonstrated heme oxygenase (HO) hyperactivity in the liver of rats with cirrhosis. No data are so far available on CO levels in the hepatic veins of cirrhotic patients. We aimed at evaluating whether plasma CO levels differ between systemic (peripheral vein) and hepatic (hepatic vein) circulation in patients with viral cirrhosis with and without ascites.

Methods

We enrolled 31 consecutive non-smoking in- or outpatients with liver cirrhosis. We measured wedge (occluded, WHVP) and free hepatic venous pressures (FHVP) and hepatic-vein pressure gradient (HVPG) was the calculated. Plasma level of NO and plasma CO concentration were determined both in peripheral vein and in the hepatic vein in cirrhotics.

Results

In cirrhotic patients plasma CO levels were significantly higher in the hepatic vein (16.66 ± 10.71 p.p.m.) than in the peripheral vein (11.71 ± 7.00 p.p.m). Plasma NO levels were significantly higher in peripheral vein (97.02 ± 21.11 μmol/ml) than in the hepatic vein (60.76 ± 22.93 μmol/ml).

Conclusions

In patients with liver cirrhosis we documented a hepato-systemic CO gradient as inferred by the higher CO values in the hepatic vein than in the peripheral vein. In cirrhotic patients, CO and NO exhibit opposite behavior in the liver, while both molecules show increased values in the systemic circulation. It can be speculated that increased intra-hepatic CO levels might represent a counterbalancing response to reduced NO intra-hepatic levels in human liver cirrhosis.     

Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension

Background and Aim: To evaluate hepatic hemodynamics in patients with nodular regenerative hyperplasia of the liver (NRH) with portal hypertension (PHT). Methods: We retrospectively reviewed the charts of 24 patients referred for PHT related to biopsy‐proven NRH. Hemodynamic measurements included wedged hepatic vein (WHVP) and inferior vena cava (IVCP), and, in 12 patients, portal vein pressure (PVP). Hepatic vein pressure gradient (HVPG: WHVP–IVCP) and portal vein pressure gradient (PVPG: PVP–IVCP) were calculated. Results: Nodular regenerative hyperplasia was associated in 24 patients with various diseases (oxaliplatin chemotherapy, treatment with purine antagonists, post liver transplantation, hematologic and rheumatologic conditions and HIV infection). Liver function parameters were either completely normal or slightly impaired. Patients were referred for gastroesophageal varices (n = 18), and/or ascites (n = 11), and/or splenomegaly (n = 20). In patients with varices or ascites, HVPG was lower than 10 mmHg (a cut‐off point for the presence of varices and/or ascites) in 15/21, suggesting a pre‐sinusoidal component to their PHT confirmed by a PVP higher than 12 mmHg in 12/12 patients. The mean difference between HVPG and PVPG was 8.7 mmHg in these patients. Ten patients were treated by transjugular intrahepatic portosystemic shunt. None of them re‐bled, and one presented transient hepatic encephalopathy. Conclusions: Presinusoidal PHT associated with NRH is probably related to compression of portal venules by the regenerative nodules. In patients with HTP and a HVPG < 10 mmHg, the diagnosis of NRH must be suspected and PVP measured, which is important in the management of these patients.     

Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study.

BACKGROUND AND AIMS: Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis. MATERIAL AND METHODS: In 76 patients with cirrhosis (69 men and seven women), both DI of Doppler HV waveform and HVPG were measured, and the relationship between them was analysed. DI was calculated by the minimum velocity/maximum velocity of the HV waveform. An HVPG>12 mmHg was defined as severe portal hypertension. In a subgroup of 19 patients receiving propranolol, changes in both DI and HVPG were evaluated after propranolol administration for 3 months. One author (S. K. B.) performed all DI of Doppler HV waveform studies. RESULTS: Abnormal HV waveforms were seen in 66 of 76 patients (86.8%). DI significantly correlated with the grade of HVPG, i.e. with higher HVPG increased DI was observed (P<0.01). By logistic regression analysis, DI>0.6 was significantly more likely to be severe portal hypertension (odds ratio: 14.19, 95% confidence interval: 4.07-49.55). Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9% and a specificity of 81.8% for the presence of severe portal hypertension. In 19 patients of the propranolol subgroup, change of DI following propranolol treatment also significantly correlated with that of HVPG (P<0.01). CONCLUSIONS: Damping index of the HV waveform by Doppler ultrasonography might be a non-invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis.     

Comparison between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis

Portal vein pressure and wedged hepatic vein pressure were measured simultaneously in 21 patients with hepatitis B-related cirrhosis of the liver and were compared to pressure measured in six patients with idiopathic portal hypertension. No significant difference in the portal venous pressure gradient was found between patients with cirrhosis and those with idiopathic portal hypertension (17.3 +/- 4.3 mmHg (mean +/- S.D.) vs. 19.7 +/- 3.1 mmHg, P greater than 0.05). However, the difference between the portal and the hepatic venous pressure gradient was significantly smaller in patients with cirrhosis than in idiopathic portal hypertension patients (1.3 +/- 1.7 vs. 10.8 +/- 2.1 mmHg, P less than 0.001). An excellent correlation was found between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis (r = 0.94, P less than 0.001). There was no linear relationship between the portal venous pressure gradient and varix size or bleeding episodes. We concluded that a close agreement existed between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related liver cirrhosis. Therefore, measurement of wedged hepatic vein pressure reliably reflects portal vein pressure in these patients.     

Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer‐assisted digital image analysis (DIA) of Sirius Red‐stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively‐transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty‐two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 5–10). Portal hypertension (HVPG ≥ 6 < 10 mmHg) was present in 30 (69.8%), and HVPG ≥ 10 mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.75–23.25). Median Child–Pugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.3–12.4) versus 23% in stage 6 (IQR 17–33.7, P < 0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically‐significant portal hypertension (HVPG ≥ 10 mmHg, odds ratio: 1.085, confidence interval: 1.004–1.172, P = 0.040). A CPA of 14% was the best cut‐off value for clinically‐significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event‐free survival was significantly shorter in patients with CSPH or with a CPA value ≥ 14%, or with a combination of both. Conclusion: In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing “early” from “late” severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG ≥ 10 mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification.