Randomised clinical study: acute effects of metformin versus placebo on portal pressure in patients with cirrhosis and portal hypertension

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

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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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Mo1533 – Portal Pressure Gradient Measured Immediately After Transjugular Intrahepatic Portosystemic Shunt Placement: Poor in Predicting Rebleeding in Patients with Portal Hypertension

Gastroenterology ◽

10.1016/s0016-5085(19)40353-3 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1334

Author(s):

Xiaolong Qi ◽

Lei Wang ◽

Fangze Huang ◽

Chuan Liu ◽

Xinlong Lin ◽

...

Keyword(s):

Portal Hypertension ◽

Pressure Gradient ◽

Transjugular Intrahepatic Portosystemic Shunt ◽

Portal Pressure ◽

Portosystemic Shunt ◽

Shunt Placement ◽

Intrahepatic Portosystemic Shunt

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Failure of Splenectomy to Ameliorate Portal Hypertension in Myeloproliferative Disorders

Canadian Journal of Gastroenterology ◽

10.1155/1994/632862 ◽

1994 ◽

Vol 8 (2) ◽

pp. 97-100

Author(s):

Samuel S Lee ◽

Guido Van Rosendaal ◽

Thomas E Lay ◽

James K Kelly ◽

Graham F Pineo

Keyword(s):

Portal Hypertension ◽

Portal Pressure ◽

Myeloproliferative Disorders ◽

Myeloproliferative Disorder ◽

Correct Treatment ◽

Forward Flow ◽

Optimum Treatment ◽

Flow Component ◽

Significant Amelioration

The correct treatment of portal hypertension associated with myeloproliferative disorders remains uncertain. Splenectomy has been advocated by some to eliminate the forward flow component of the portal hypertension and thus reduce portal pressure. The authors describe three recent cases of myeloproliferative disorder in whom splenectomy failed to achieve any significant amelioration of portal hypertension, with in-depth hemodynamic studies in one patient. Based on these experiences, the authors suggest that splenectomy is not the optimum treatment of the portal hypertension associated with myeloproliferative disorders.

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