Coagulation, Microenvironment and Liver Fibrosis

Bitto, Niccolò; Liguori, Eleonora; Mura, Vincenzo La

doi:10.3390/cells7080085

Cited by 47 publications

(35 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High VWF levels indicate endothelial dysfunction and liver sinusoidal endothelial cells (LSEC) likely contribute to the increased VWF levels in these patients 39 . LSEC dysfunction impacts intrahepatic resistance, and thus, aggravates portal hypertension, which may further increase bacterial translocation 40 .…”

Section: Discussionmentioning

confidence: 99%

The impact of ABO blood type on the prevalence of portal vein thrombosis in patients with advanced chronic liver disease

Scheiner

Gruber

Semmler

et al. 2020

Liver International

View full text Add to dashboard Cite

Background and aims: Non-O blood type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non-O-BT is a risk factor for PVT and (II) whether non-O-BT impacts VWF/factor VIII in patients with ACLD. Methods: Retrospective analysis comprising two cohorts: (I) "US" including all adult liver transplantations in the US in the MELD era and (II) "Vienna" comprising patients with a hepatic venous pressure gradient (HVPG) ≥6 mmHg. Results: (I) The "US cohort" included 84 947 patients (non-O: 55.43%). The prevalence of PVT at the time of listing (4.37% vs 4.56%; P = .1762) and at liver transplantation (9.56% vs 9.33%; P = .2546) was similar in patients with O-and non-O-BT. (II) 411 patients were included in the "Vienna cohort" (non-O: 64%). Mean HVPG was 18(9) mmHg and 90% had an HVPG ≥10 mmHg. Patients with non-O-BT had slightly increased VWF levels (318(164)% vs 309(176)%; P = .048; increase of 23.8%-23.9%in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non-O-BT explained only 1% of the variation in VWF and had no effect on FVIII. Conclusions:Although non-O-BT impacts VWF in patients with early stage ACLD, its contribution to VWF variation is considerably smaller than in the general population.Moreover, non-O-BT had no impact on FVIII. These findings may explain the absence of an association between non-O-BT and PVT in patients with advanced cirrhosis.

show abstract

Section: Discussionmentioning

confidence: 99%

The impact of ABO blood type on the prevalence of portal vein thrombosis in patients with advanced chronic liver disease

Scheiner

Gruber

Semmler

et al. 2020

Liver International

View full text Add to dashboard Cite

show abstract

“…The activation of hepatic stellate cells (HSC) is the key pathogenic mechanism of hepatic fibrogenesis. Experimental animal models support a biological link between coagulation and fibrosis showing that thrombin and FXa can activate HSC [62,63] and, conversely, their inhibition by anticoagulants may prevent or reduce fibrogenesis [57].…”

Section: Potential Role Of Coagulation System On the Development Of Tmentioning

confidence: 99%

“…While currently available direct-acting antivirals will probably erase the burden of chronic viral hepatitis, effective antifibrotic drugs for CLD are still lacking [62]. Patients with metabolic disease (NAFLD/NASH) with indication to anticoagulation are continuously rising and would represent the ideal candidates for future studies evaluating the effect of long-term anticoagulation, including DAOCs, on fibrogenesis and portal hypertension.…”

Section: Potential Role Of Coagulation System On the Development Of Tmentioning

confidence: 99%

Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review

Ballestri¹,

Capitelli²,

Fontana³

et al. 2020

Adv Ther

View full text Add to dashboard Cite

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent and relevant healthcare issues. Direct oral anticoagulants (DOACs) are now the first-choice for anticoagulant treatment of these conditions displaying a better efficacy/safety profile than vitamin-K antagonists, mainly due to significantly reduced risk of major bleeding, especially of intracranial haemorrhage. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries showing a continuously growing prevalence. Nonalcoholic steatohepatitis (NASH), its evolutive form, will be the leading cause for liver transplantation by 2020. NAFLD is independently associated with an increased risk of abnormalities of cardiac structure and function, including cardiac rhythm disorders (mainly AF). Moreover, data suggest an increased risk of unprovoked VTE associated with NAFLD/NASH. Therefore, a growing number of patients with chronic liver disease (CLD) will be candidate for anticoagulant therapy in the near future. Cirrhosis of any etiology is characterized by an unstable thrombosis/bleeding haemostatic balance, making anticoagulant therapy particularly challenging in this condition. Given that patients with significant active liver disease and cirrhosis were excluded from all pivotal randomized controlled trials on DOACs, this comprehensive review aims at critically discussing real-world evidence, including the latest population studies, regarding the use of DOACs in patients with CLD/cirrhosis.

show abstract

“…255 The cellular responses of thrombin are mediated by receptors with proteolytic activity-protease-activated receptors (PAR), expressed by endothelium, platelets, and HSCs enable crosstalk between these cells. 256,257 Thrombin exerts vasoconstricting, proinflammatory, and prohemostatic effects and also promotes proliferation and a profibrotic phenotype of HSCs. 258,259 Thus, inhibition of PARs is a promising therapeutic target in liver fibrosis and PHT, since experimental studies showed that inhibition of PARs prevents the fibrogenic response of HSCs in animal models of liver diseases.…”

Section: Anticoagulationmentioning

confidence: 99%

Vascular Targets for the Treatment of Portal Hypertension

et al. 2019

View full text Add to dashboard Cite

Portal hypertension is the main driver for severe complications in patients with liver cirrhosis. With improved understanding of molecular pathways that promote hepatic vascular remodeling, vasoconstriction, and sinusoidal capillarization potential vascular targets for the treatment of portal hypertension have been identified. Inhibition of vascular endothelial and platelet-derived growth factors–driven angiogenesis has been shown to reduce portal pressure and decrease hepatic inflammation. Angiopoietin/Tie signaling represents additional promising vascular targets in liver disease. The eNOS-NO-sGC-cGMP pathway modulates sinusoidal vasoconstriction and capillarization. Nuclear farnesoid X receptor (FXR) agonists decrease intrahepatic vascular resistance by inhibition of fibrogenesis and sinusoidal remodeling. Statins ameliorate endothelial dysfunction, decrease portal pressure, and reduce fibrogenesis. Anticoagulation with low-molecular heparin or anti-Xa inhibitors improved portal hypertension by deactivation of hepatic stellate cells and potentially via reduction of sinusoidal microthrombosis. This review summarizes important vascular targets for treatment of portal hypertension that have shown promising results in experimental studies.

show abstract

Coagulation, Microenvironment and Liver Fibrosis

Cited by 47 publications

References 141 publications

The impact of ABO blood type on the prevalence of portal vein thrombosis in patients with advanced chronic liver disease

The impact of ABO blood type on the prevalence of portal vein thrombosis in patients with advanced chronic liver disease

Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review

Vascular Targets for the Treatment of Portal Hypertension

Contact Info

Product

Resources

About