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.     

Should we routinely measure portal pressure in patients with cirrhosis, using hepatic venous pressure gradient (HVPG) as a guide for prophylaxis and therapy of bleeding and rebleeding? No

Portal hypertension (PH) is a severe complication of liver cirrhosis. Measurement of the degree of portal hypertension is usually performed by measuring the hepatic venous pressure gradient (HVPG) which is the difference between the free hepatic venous pressure (FHVP) and the wedged hepatic venous pressure (WHPG). The HVPG accurately reflects the degree of PH in the majority of liver diseases. PH is defined by an increase of HVPG values above the normal upper limit of 5 mm Hg, while clinically significant PH is defined by an HVPG to ≥ 10 mm Hg. Although measurement of HVPG potentially has several applications, in clinical practice its major use has been related to the assessment of hemodynamic response to pharmacological therapy, in order to evaluate the efficacy of treatment and to predict the risk of rebleeding from esophageal varices. When properly performed, HVPG is a reliable, safe and good predictive tool in the management of portal hypertension. However, the need for appropriate equipment, sufficient and reliable operators and costs, have discouraged its use outside Liver Units specifically devoted to the clinical management of portal hypertension. This has diminished its applicability. Combining its use with transjugular liver biopsy and using the prognostic value of HVPG may help encourage its use.     

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.     

Features of portal hypertension are associated with major adverse events in Fontan patients: The VAST study

Background

Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events.

Methods

A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001 to 2011 was performed. The relationship between features of portal hypertension (VAST score ≥ 2, 1 point each for Varices, Ascites, Splenomegaly or Thrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression.

Results

73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24 ± 11 years, mean interval from Fontan 17 ± 6 years) were included in analysis. Features of portal hypertension (VAST score ≥ 2) were present in 26 (36%), and there were 19 major adverse events: death (n = 12), transplant (n = 6), and HCC (n = 1). A significant relationship was found between VAST score ≥ 2 and major adverse events (OR = 9.8, 95% CI [2.9–32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ≥ 2 remained significant (OR = 9.1, 95% CI [1.4–57.6]).

Conclusion

Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings.     

Quantitation of tissue polypeptide antigen (TPA) in hepatic and systemic circulation in patients with chronic liver diseases

Background and Aim: Abnormal serum tissue polypeptide antigen (TPA) values are commonly found in patients with chronic liver damage and liver cirrhosis even in the absence of malignancies. The aim of this study was to compare serum TPA levels in patients with cirrhosis, to examine correlations between TPA levels and the degree of portal hypertension, and to evaluate TPA concentrations in paired hepatic and peripheral blood samples. Methods: A total of 128 patients with chronic liver disease of various severity were studied prospectively. TPA concentrations in hepatic vein and peripheral blood were determined, and Hepatic Vein Pressure Gradient (HVPG) was measured. Results: TPA levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis, and in systemic circulation than in hepatic vein blood. Peripheral but not hepatic TPA levels did correlate with the HVPG. Subjects with clinically significant portal hypertension (HVPG > 10 mmHg) showed significantly higher peripheral TPA levels than those with HVPG < 10 mmHg. Conclusions: Our data suggest that the increased TPA levels observed in cirrhotic patients and the high systemic‐to‐hepatic blood TPA gradient are probably due to the presence of portal‐systemic shunts rather than to hepatic necro‐inflammatory activity. In clinical practice, TPA determination could help us to identify and to follow up cirrhotic patients with more severe portal hypertension.     

Longitudinal assessment of liver stiffness in patients undergoing antiviral treatment for hepatitis C

Background

Liver stiffness has been suggested as a parameter of fibrosis progression/regression in hepatitis C virus (HCV) patients.

Aim

To evaluate stiffness before and after peginterferon–ribavirin treatment.

Methods

Stiffness was prospectively measured in 74 HCV patients, 32 genotypes 1/4 (43.25%) and 42 genotypes 2/3 (56.75%), before, at end of treatment, and after 3 years of follow-up (49 patients). On the same study day, 21 patients underwent liver biopsy.

Results

In 55 patients with sustained virological response (74.32%), liver stiffness decreased significantly at end of therapy (6.8 ± 4.9 kPa) vs. baseline (9.5 ± 6.9 kPa, p = 0.04). The decrease vs. baseline was maintained in 30 sustained virological response patients after 3 years follow-up (6.8 ± 4.6 kPa vs. 10.8 ± 8.5 kPa, p = 0.0141). No difference was found at end of treatment vs. baseline (10.1 ± 4.7 kPa vs. 9.7 ± 4.2 kPa, p = 0.825) and after 3 years of follow-up vs. baseline (10.2 ± 3.4 kPa vs. 9.7 ± 4.2 kPa, p = 0.765) in null responders. Similar results were found in relapsers at end of treatment vs. baseline (13.7 ± 7.7 kPa vs. 15.2 ± 8.2 kPa, p = 0.74), and after 3 years of follow-up vs. baseline (16.9 ± 10.0 kPa vs. 15.2 ± 8.2 kPa, p = 0.734). Pre-treatment stiffness >12 kPa was significantly associated with no SVR (p < 0.025), RR = 2.44 (95% C.I. 1.17–5.07).

Conclusion

Liver stiffness may be useful to assess long-term antiviral treatment response.     

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.     

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.     

Correlation of HVPG Level with CTP Score,MELD Score,Ascites, Size of Varices,and Etiology in Cirrhotic Patients

Background/Aim:

This study intends to determine the correlation of a patient''s hepatic venous pressure gradient (HVPG) measurement with six factors: Child–Turcotte–Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients.

Patients and Methods:

Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient''s HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements.

Results:

The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 ± 7.3 vs 15.2 ± 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 ± 5.3 vs 10.7 ± 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 ± 5.8 vs 11.7 ± 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 ± 4.7 vs 11 ± 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 ± 5.5 mmHg) as compared with those in CTP class B (16.9 ± 2.9 mmHg) and CTP class A (10.5 ± 4.1 mmHg; P ≤ 0.001).

Conclusion:

HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis.     

Non-invasive aspartate aminotransferase to platelet ratio index correlates well with invasive hepatic venous pressure gradient in cirrhosis

Background

Hepatic venous pressure gradient (HVPG) is the best recommended tool to measure portal pressure, but is invasive. HVPG helps in prognosticating cirrhosis and predict its complications. Aminotransferase to platelet ratio index (APRI) is a simple non-invasive marker of hepatic fibrosis. We aimed to correlate APRI with HVPG and to determine the usefulness of APRI in predicting complication of cirrhosis.

Methods

APRI and HVPG were measured in consecutive patients of cirrhosis aged 18 to 70 years. Spearman’s rho was used to estimate their correlation; a cut-off value of APRI to predict severe portal hypertension (HVPG >?12 mmHg) was determined.

Results

This study, conducted between August 2011 and December 2014, included 277 patients, median age 51 (range: 16–90) years, 84% males. Etiology of cirrhosis was alcohol in 135 (49%), cryptogenic/nonalcoholic steatohepatitis (NASH) in 104 (38%), viral in 34 (12%), and others in 4 (1%). Median Child-Turcott-Pugh (CTP) and model for end-stage liver disease (MELD) scores were 7 (5–11) and 11 (6–33), respectively. Median HVPG was 17.0 (1.5–33) mmHg and median APRI was 1.09 (0.21–12.22). There was positive correlation between APRI and HVPG (Spearman’s rho 0.450, p?<?0.001). The area under the receiver operating characteristic (ROC) curve of APRI for predicting severe portal hypertension was 0.763 (p?<?0.01). Youden’s index defined the cut-off of APRI for predicting HVPG >?12 mmHg was 0.876 with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 71%, 78%, 94%, 38%, and 73%, respectively. APRI also correlated well with CTP, variceal size, bleeding status, ascites but not with MELD.

Conclusions

APRI score of 0.876 has an acceptable accuracy to predict severe portal hypertension (HVPG >?12 mmHg). High APRI also correlated with severity of cirrhosis and its complications. Thus, APRI may be used as a simple, bedside, non-invasive, and inexpensive tool for evaluating portal hypertension and complications of cirrhosis.

     

Non-selective β-blockers improve the correlation of liver stiffness and portal pressure in advanced cirrhosis

Background

Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated.

Methods

One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6?weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG?≤?12?mmHg.

Results

Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4?±?16.5 vs. 70.3?±?7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21?±?5 vs. 26?±?5 vs. 26?±?4?mmHg). The correlation of LS and HVPG was stronger in controls with HVPG?≤?12?mmHg (R?=?0.951; P??12?mmHg (R?=?0.538; P?=?0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS (R?=?0.930; P?R?=?0.864), but not in nonresponders (R?=?0.535), whereas changes in LS, heart rate, and MAP were similar in responders and nonresponders.

Conclusions

Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HVPG?>?12?mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT.     

Hepatopulmonary syndrome in patients with Schistosoma mansoni periportal fibrosis

Hepatopulmonary syndrome (HPS) is characterized by the presence of liver disease, arterial hypoxemia and intrapulmonary vascular dilatation (IPVD). IPVD includes diffused or localized dilated pulmonary capillaries and, less commonly, pleural and pulmonary arteriovenous communications. The aim of the present study was to investigate the occurrence of HPS in patients with Schistosoma mansoni periportal fibrosis in treatment at a university hospital in northeastern Brazil.

Patients and methods

Eighty-four patients were enrolled in the study between April and July 2007 and underwent arterial blood gas analysis. Patients with an alveolar-arterial oxygen gradient (DA-aO₂) ≥15 mmHg were submitted to contrast-enhanced transthoracic echocardiogram (CE-TTE) with saline microbubbles. The diagnostic criterion for HPS was DA-aO₂ ≥ 15 mmHg associated to IPVD, as identified through CE-TTE. Patients with HPS underwent contrast-enhanced 16-channel multidetector-row computed tomography (MDCT) of the thorax.

Results

Twenty-two patients (26.19%) had DA-aO₂ ≥ 15 mmHg (mean value = 20.86 ± 7.91). CE-TTE was positive for IPVD in five of the 22 patients with DA-aO₂ ≥ 15 mmHg and all these patients had hepatosplenic disease, revealing a 6% prevalence of HPS (CI: 1.96-13.35) in the overall population of 84 patients, with a 10.2% prevalence in the group with hepatosplenic disease. The following were the 16-channel MDCT findings in these five patients: dilated peripheral pulmonary vasculature (100%); ratio of segmental arterial diameter to adjacent bronchial diameter equal to or greater than 2:1 (100%); higher number of visible terminal vessel branches in lung dependent regions (40%); and micronodules associated with subpleural surface centrilobular vessels (40%). No patient had evidence of arteriovenous fistula. These findings reveal that HPS occurs (usually in a mild form) in patients with Schistosoma mansoni periportal fibrosis and portal hypertension seems to be an important factor related to the occurrence of HPS in such cases.     

Diagnosing and monitoring cirrhosis: Liver biopsy, hepatic venous pressure gradient and elastography

In this review we summarize the role of liver biopsy, transient elastography and hepatic venous pressure gradient (HVPG) in the diagnosis and monitoring of patients with liver cirrhosis. Transient elastography is useful for the non-invasive diagnosis of cirrhosis, but relevant information is lost if it is used as a dichotomous test. The development of clinically significant portal hypertension (defined as a hepatic venous pressure gradient ≥ 10 mmHg) is associated with the development of varices and decompensation and it is something that it is worth testing for. Transient elastography has some value for the prediction of clinically significant portal hypertension, but a large proportion of patients have non-diagnostic values. It has also some value for the diagnosis of varices, but non-invasive markers cannot substitute endoscopic screening in cirrhosis. Better dynamic, easily repeatable non-invasive tools are needed to monitor compensated cirrhosis.     

Adding banding ligation is effective as rescue therapy to prevent variceal rebleeding in haemodynamic non-responders to pharmacological therapy

Background

It is unknown which is the best therapy to treat haemodynamic non-responders to pharmacological therapy after variceal bleeding.

Aim

To evaluate the efficacy of adding banding ligation to drugs to prevent variceal rebleeding in haemodynamic non-responders to drugs.

Methods

Fifty-three cirrhotic patients with variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were then titrated to maximum tolerated doses. A second HVPG was taken 14 days later. Responders (HVPG ≤12 mm Hg or ≥20% decrease from baseline) were maintained on drugs and non-responders had banding ligation added to drugs.

Results

Mean follow-up was 28 months. In 5 patients the second HVPG could not be performed because of early rebleeding. The remaining 48 patients were classified as responders (n = 24) and non-responders (n = 24), who had banding added. No baseline differences were observed between groups. Variceal rebleeding occurred in 12% of the 48 patients whose haemodynamic response was assessed. Responders on drug therapy presented a 16% rebleeding rate, whilst non-responders rescued with banding showed an 8% rebleeding rate. Rebleeding-related mortality was not different between groups.

Conclusion

In a HVPG-guided strategy, adding banding ligation to drugs is an effective rescue strategy to prevent rebleeding in haemodynamic non-responders to drug therapy.     

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.     

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.METHODS: A cohort of 154 patients with confirmed liver cirrhosis(112 ethylic, 108 men, age 34-72 years)were enrolled in the study. Hepatic venous pressure gradient(HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay(ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.RESULTS: The mean value of HVPG was 16.18 ± 5.6 mm Hg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher(P 0.001). The plasma levels of osteopontin were positively related to HVPG(P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/m L osteopontin distinguished patients with significant portal hypertension(HVPG above 10 mm Hg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG 10 mm Hg and 65% for those with HVPG ≤ 10 mm Hg(P = 0.0086, odds ratio(OR), 2.92, 95% confidence interval(CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/m L had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/m L(37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.     

Non-invasive diagnosis and follow-up of portal hypertension

Compensated advanced chronic liver disease (cACLD) describes the spectrum of advanced fibrosis/cirrhosis in asymptomatic patients at risk of developing clinically significant portal hypertension (CSPH, defined by a hepatic venous pressure gradient (HVPG) ≥10 mmHg). Patients with cACLD are at high risk of liver-related morbidity and mortality. In patients at risk of chronic liver disease, cACLD is strongly suggested by a liver stiffness (LSM) value >15 kPa or clinical/biological/radiological signs of portal hypertension, and ruled out by LSM <10 kPa, or Fibrotest® ≤0.58, or Fibrometer® ≤0.786. Patients with chronic liver disease (excluding vascular diseases) with a LSM <10 kPa are at low risk of developing portal hypertension complications. The presence of CSPH can be strongly suspected when LSM is ≥20 kPa. In a patient without clinical, endoscopic or radiological features of portal hypertension, measurement of the HVPG is recommended before major liver or intra-abdominal surgery, before extra-hepatic transplantation and in patients with unexplained ascites.Endoscopic screening for oesophageal varices can be avoided in patients with LSM <20 kPa and a platelet count >150 G/L (favourable Baveno VI criteria) at the time of diagnosis. There is no non-invasive method alternative for oeso-gastroduodenal endoscopy in patients with unfavourable Baveno criteria (liver stiffness ≥20 kPa or platelet count ≤50 G/l). Platelet count and liver stiffness measurements must be performed once a year in patients with cACLD with favourable Baveno VI criteria at the time of diagnosis. A screening oeso-gastroduodenal endoscopy is recommended if Baveno VI criteria become unfavourable.     

Dénervation rénale dans le traitement de l’hypertension artérielle résistante : expérience du CHU de Lyon

Aim

We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension.

Patients and methods

Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5 ± 11.5 years, BMI 33 ± 5 kg/m² and ambulatory blood pressure 157 ± 16/87 ± 13 mmHg with 4.2 ± 1.5 anti-hypertensive treatment.

Results

We did not observe per procedural and early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20 ± 15 (P < 0.001) and 10 ± 13 mmHg (P = 0.014) (n = 17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5 ± 14.9 mmHg (P = 0.027) for SBP and of 10.5 ± 9.6 mmHg (P = 0.029) for DBP (n = 6). Among these patients, five of them were controlled (ABPM inferior to 130/80 mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4 ± 3 mm (P = 0.031), Sokolow index of 3 ± 3 mm (P = 0.205), Cornell voltage criterion of 9 ± 7 mm (P = 0.027) and Cornell product of 1310 ± 1104 (P = 0.027).

Conclusion

Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe.     

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.     

Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: A randomized,controlled, crossover study

Background

The Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH).

Methods

Using a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5 μg) and intravenous fasudil (30 mg over 30 min). Hemodynamic data were collected at baseline and during acute drug exposure.

Results

Comparable decreases were observed in mean pulmonary artery pressure (− 4.6 ± 4.3 mm Hg vs. − 4.8 ± 4.2 mm Hg) and pulmonary vascular resistance (− 3.0 ± 3.0 Wood U vs. − 2.2 ± 2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7 ± 17.1% vs. 6.9 ± 15.0%; p = 0.044 and 4.5 ± 5.3% vs. 2.7 ± 8.2%; p = 0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8 ± 3.6%), infused fasudil resulted in a non-significant reduction (− 0.6 ± 1.1%).

Conclusion

Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.