Effect of portal hypertension caused by chronic high venous pressure on small-intestinal sugar absorption

The purpose of this study was to investigate the vascular contractile and inositol phosphate responses in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL) in Sprague–Dawley rats. Sham-operated rats served as controls. Pressures, vasoconstrictor responses, and inositol phosphate responses were determined at 14 days after surgery. The portal venous pressure was significantly higher, while systemic arterial pressure and heart rate were lower, in PVL rats. Dose-dependent contractile responses were observed for both norepinephrine (1 × 10−8 – 3 × 10−6 M) and vasopressin (3 × 10−10 – 3 × 10−8 M) in the tail artery of both groups. The contractile response to norepinephrine was significantly decreased in PVL rats compared with controls at all doses. The contractile response to vasopressin was significantly decreased in PVL rats at higher doses. After myo-[3H]inositol incorporation in tail artery, the levels of 3H-labelled phosphatidylinositols (cpm/mg) were similar between the two groups. Norepinephrine (10−7 – 10−5 M) and vasopressin (10−10 – 10−8 M) dose dependently stimulated the 3H-labelled inositol phosphate production in the tail artery of both PVL and sham-operated rats. However, the response was significantly lower in PVL rats. The results suggested that the attenuation of vascular contractile responses in portal hypertension was reflected in the phosphoinositide messenger system.Key words: portal hypertension, inositol phosphates, phosphoinositide, tail artery, contractile response.

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Non-invasive methods in the assessment of portal hypertension severity

Gastroenterologie a hepatologie ◽

10.48095/ccgh2021125 ◽

2021 ◽

Vol 75 (2) ◽

pp. 125-133

Author(s):

Soňa Franková ◽

Jan Šperl

Keyword(s):

Portal Hypertension ◽

Liver Fibrosis ◽

Shear Wave ◽

Transient Elastography ◽

Venous Pressure ◽

Liver Stiffness ◽

Invasive Technique ◽

Hepatic Veins ◽

Oesophageal Varices ◽

Non Invasive

Portal hypertension represents a wide spectrum of complications of chronic liver diseases and may present by ascites, oesophageal varices, splenomegaly, hypersplenism, hepatorenal and hepatopulmonary syndrome or portopulmonary hypertension. Portal hypertension and its severity predicts the patient‘s prognosis: as an invasive technique, the portosystemic gradient (HPVG – hepatic venous pressure gradient) measurement by hepatic veins catheterisation has remained the gold standard of its assessment. A reliable, non-invasive method to assess the severity of portal hypertension is of paramount importance; the patients with clinically significant portal hypertension have a high risk of variceal bleeding and higher mortality. Recently, non-invasive methods enabling the assessment of liver stiffness have been introduced into clinical practice in hepatology. Not only may these methods substitute for liver biopsy, but they may also be used to assess the degree of liver fibrosis and predict the severity of portal hypertension. Nowadays, we can use the quantitative elastography (transient elastography, point shear-wave elastrography, 2D-shear-wave elastography) or magnetic resonance imaging. We may also assess the severity of portal hypertension based on the non-invasive markers of liver fibrosis (i.e. ELF test) or estimate clinically signifi cant portal hypertension using composite scores (LSPS – liver spleen stiff ness score), based on liver stiffness value, spleen diameter and platelet count. Spleen stiffness measurement is a new method that needs further prospective studies. The review describes current possibilities of the non-invasive assessment of portal hypertension and its severity.

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Noninvasive Evaluation of Portal Hypertension Using a Supervised Learning Technique

Journal of Healthcare Engineering ◽

10.1155/2017/6183714 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Mindaugas Marozas ◽

Romanas Zykus ◽

Andrius Sakalauskas ◽

Limas Kupčinskas ◽

Arūnas Lukoševičius

Keyword(s):

Portal Hypertension ◽

Supervised Learning ◽

Evaluation Method ◽

Clinical Laboratory ◽

Transient Elastography ◽

Venous Pressure ◽

Noninvasive Evaluation ◽

Noninvasive Methods ◽

Supervised Learning Algorithms ◽

Clinically Significant

Portal hypertension (PHT) is a key event in the evolution of different chronic liver diseases and leads to the morbidity and mortality of patients. The traditional reliable PHT evaluation method is a hepatic venous pressure gradient (HVPG) measurement, which is invasive and not always available or acceptable to patients. The HVPG measurement is relatively expensive and depends on the experience of the physician. There are many potential noninvasive methods to predict PHT, of which liver transient elastography is determined to be the most accurate; however, even transient elastography lacks the accuracy to be a perfect noninvasive diagnostic method of PHT. In this research, we are focusing on noninvasive PHT assessment methods that rely on selected best-supervised learning algorithms which use a wide set of noninvasively obtained data, including demographical, clinical, laboratory, instrumental, and transient elastography measurements. In order to build the best performing classification meta-algorithm, a set of 21 classification algorithms have been tested. The problem was expanded by selecting the best performing clinical attributes using algorithm-specific filtering methods that give the lowest error rate to predict clinically significant PHT. The suggested meta-algorithm objectively outperforms other methods found in literature and can be a good substitute for invasive PHT evaluation methods.

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Hepatic venous-portal gradient (HVPG) measurement: pearls and pitfalls

British Journal of Radiology ◽

10.1259/bjr.20210061 ◽

2021 ◽

pp. 20210061

Author(s):

Qiqi Lu ◽

Sum Leong ◽

Kristen Alexa Lee ◽

Ankur Patel ◽

Jasmine Ming Er Chua ◽

...

Keyword(s):

Portal Hypertension ◽

Hepatic Encephalopathy ◽

Risk Stratification ◽

Variceal Bleeding ◽

Gold Standard ◽

Crucial Role ◽

Venous Pressure ◽

Common Cause ◽

Life Threatening ◽

Selection And Assessment

Hepatic venous pressure gradient (HVPG) is the gold-standard for measurement of portal hypertension, a common cause for life-threatening conditions such as variceal bleeding and hepatic encephalopathy. HVPG also plays a crucial role in risk stratification, treatment selection and assessment of treatment response. Thus recognition of common pitfalls and unusual hepatic venous conditions is crucial. This article aims to provide a radiographical and clinical guide to HVPG with representative clinical cases.

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Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation

Digestive Diseases ◽

10.1159/000500115 ◽

2019 ◽

Vol 37 (6) ◽

pp. 498-508 ◽

Cited By ~ 1

Author(s):

Carolina A. Serrano ◽

Simon C. Ling ◽

Sofia Verdaguer ◽

Miguel León ◽

Nicolás Jarufe ◽

...

Keyword(s):

Liver Transplantation ◽

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Venous Pressure ◽

Portal Pressure ◽

Peripheral Circulation ◽

Chronic Liver ◽

Noninvasive Markers ◽

Collateral Formation

Background/Aims: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. Methods: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. Results: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-β, PDGFsRα, PDGF-AB and BB, CD163, TGF-β VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

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The study of hepatic hemodynamics: research activity or clinical tool?

Italian Journal of Medicine ◽

10.4081/itjm.2010.201 ◽

2013 ◽

pp. 201-206

Author(s):

Claudio Puoti ◽

Lia Bellis

Keyword(s):

Portal Hypertension ◽

Venous Pressure ◽

Preoperative Assessment ◽

Clinical Tool ◽

Research Activity ◽

Acute Variceal Bleeding ◽

Routine Work ◽

Hepatic Hemodynamics ◽

Pros And Cons ◽

Cirrhotic Patients

Portal hypertension is a progressive complication of cirrhosis. Therefore, the management of a patient with cirrhosis and gastrointestinal bleeding depends largely on the stage of the portal hypertension. The patient may be in the pre-variceal stage or present with acute variceal bleeding, in which case the objectives are to control the current hemorrhage and prevent recurrence. In clinical practice, the severity of portal hypertension can be estimated, reliably and safely, by transjugular measurement of the hepatic venous pressure gradient (HVPG). After a brief review of the pathophysiology of portal hypertension in cirrhosis, the authors describe the technique used to measure transjugular HVPG, its prognostic value in patients with cirrhosis, the pros and cons of including this procedure in routine work-ups of these patients, and its potential roles in monitoring responses to treatment and in the preoperative assessment of cirrhotic patients undergoing hepatic resection.

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Idiopathic refractory ascites after allogeneic stem cell transplantation: a previously unrecognized entity

Blood Advances ◽

10.1182/bloodadvances.2019000638 ◽

2020 ◽

Vol 4 (7) ◽

pp. 1296-1306

Author(s):

Ankur Varma ◽

Susan C. Abraham ◽

Rohtesh S. Mehta ◽

Neeraj Y. Saini ◽

Medhavi Honhar ◽

...

Keyword(s):

Stem Cell ◽

Portal Hypertension ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Venous Pressure ◽

Idiopathic Portal Hypertension ◽

Refractory Ascites ◽

Survival Duration ◽

Hematopoietic Stem ◽

Clinical Criteria

Abstract At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)–related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients’ median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.

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Noninvasive Diagnostics for Portal Hypertension: A Comprehensive Review

Seminars in Liver Disease ◽

10.1055/s-0040-1708806 ◽

2020 ◽

Vol 40 (03) ◽

pp. 240-255 ◽

Cited By ~ 4

Author(s):

Mattias Mandorfer ◽

Virginia Hernández-Gea ◽

Juan Carlos García-Pagán ◽

Thomas Reiberger

Keyword(s):

Portal Hypertension ◽

Beta Blockers ◽

Venous Pressure ◽

Target Population ◽

Diagnostic Value ◽

Clinical Settings ◽

Hepatic Decompensation ◽

Noninvasive Methods ◽

Noninvasive Diagnostics ◽

Clinically Significant

AbstractNoninvasive diagnostics for portal hypertension include imaging and functional tests, as well as blood-based biomarkers, and capture different features of the portal hypertensive syndrome. Definitive conclusions regarding their clinical utility require assessment of their diagnostic value in specific clinical settings (i.e., diagnosing a particular hemodynamic condition within a well-defined target population). Several noninvasive methods are predictive of clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥ 10 mm Hg; the threshold for complications of portal hypertension); however, only a minority of them have been evaluated in compensated advanced chronic liver disease (i.e., the target population). Importantly, most methods correlate only weakly with HVPG at high values (i.e., in patients with CSPH). Nevertheless, selected methods show promise for diagnosing HVPG ≥ 16 mm Hg (the cut-off for increased risks of hepatic decompensation and mortality) and monitoring HVPG changes in response to nonselective beta-blockers or etiological treatments. Finally, we review established and potential future clinical applications of noninvasive methods.

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Effect of portal hypertension on splenic blood flow, intrasplenic extravasation and systemic blood pressure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00516.2002 ◽

2003 ◽

Vol 284 (6) ◽

pp. R1580-R1585 ◽

Cited By ~ 16

Author(s):

Susan Kaufman ◽

Jody Levasseur

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Portal Hypertension ◽

Portal Vein ◽

Venous Pressure ◽

Splenic Vein ◽

Systemic Blood Pressure ◽

Portal Venous Pressure ◽

Systemic Blood ◽

Fluid Extravasation

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 ± 0.5 to 12.0 ± 0.9 mmHg ( n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 ± 0.3 to 1.2 ± 0.1 ml/min ( n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 ± 5.5 to 95 ± 4 mmHg). Splenic afferent nerve activity increased (5.6 ± 0.9 to 16.2 ± 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 ± 0.1 to 1.0 ± 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.

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