Microvascular Thrombosis and Liver Fibrosis Progression: Mechanisms and Clinical Applications

Airola, Carlo; Pallozzi, Maria; Cerrito, Lucia; Santopaolo, Francesco; Stella, Leonardo; Gasbarrini, Antonio; Ponziani, Francesca Romana

doi:10.3390/cells12131712

Cited by 7 publications

(3 citation statements)

References 158 publications

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“…The imbalance of vWF/ADAMTS-13 exacerbates the low specificity of vWF proteolysis by ADAMTS-13 in patients with LC [ 16 ]. The expression of thrombogenic ultrahigh-molecular-weight vWF multimers (VWF-HMWMs) is increased in the portal venous endothelium in LC [ 33 ]. Thus, the vWF/ADAMTS-13 imbalance may facilitate a local persistence of vWF-HMWMs but not VWF levels in patients with LC and PVT [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis

Suzuki,

Namisaki,

Takya

et al. 2024

IJMS

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Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21–3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC.

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Section: Discussionmentioning

confidence: 99%

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis

Suzuki,

Namisaki,

Takya

et al. 2024

IJMS

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“…No recommendation can be made about the use of anticoagulation to prevent PVT in PSVD, and this remains an unmet need [ 66 ]. Currently, whether PVT occurrence leads to the worsening of natural history of chronic liver disease is debated; however, on the other hand, as previously described, growing evidence suggests a direct role of anticoagulants in the prevention of liver fibrosis and parenchymal extinction acting on microthrombosis with a reduction in hepatic decompensation risk [ 107 , 159 , 160 , 161 , 162 , 163 , 164 , 165 ]. Indeed, a study conducted in rats with carbon tetrachloride (CCL4) induced liver damage demonstrated a reduction in fibrosis after low weight molecular heparin (LWMH) administration associated with an improvement in liver regeneration [ 166 ].…”

Section: Discussion and Future Perspectives: The Role Of Anticoagulationmentioning

confidence: 99%

Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis

Giuli

Pallozzi

Venturini

et al. 2023

IJMS

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Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow’s triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients.

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“…In cirrhosis, reduced ADAMTS13 activity leads to the accumulation of ultra-large VWF multimers that paradoxically induce abnormal angiogenesis. 38 Studies suggest VWF processing could be a valuable prognostic marker in advanced chronic liver disease. In cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt procedures, those with PVT had significantly higher VWF antigen levels.…”

Section: Understanding Disease Mechanismsmentioning

confidence: 99%

Transforming Screening, Risk Stratification, and Treatment Optimization in Chronic Liver Disease Through Data Science and translational Innovation

Addissouky

2024

InaJGHE

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Background: Chronic liver diseases continue to face challenges in prognosis, treatment selection, disease mechanisms, screening, and therapeutic optimization. Promising innovations could address these gaps through data integration and novel analytic approaches.Main Body: MAPS-CRAFITY integrating clinical variables, AFP, and CT/MRI findings, and transformer modeling of RFA data improve HCC outcome prediction to guide management. Analyses revealing IL21R as a PBC susceptibility gene and implicating dysfunctional VWF processing in portal hypertension deliver mechanistic insights. Quantifying childhood MAFLD informs screening needs, while supporting use of G6PD deficient liver donors enables transplantation access expansion through risk stratification. Updating Baveno criteria enhances PBC prognosis, and an HCC prognostic score identifies optimal RFA candidates to maximize treatment efficacy.Conclusion: Recent research leverages diverse data types, genetics, imaging, and machine learning to develop integrated predictive systems that allow more personalized therapy selection. Elucidating molecular pathways provides therapeutic targets and prognostic biomarkers. Evidence-based screening and risk models facilitate delivering tailored interventions. Optimization of current modalities through prognostic validation and patient selection improves real-world effectiveness. Multifaceted modern research approaches promise to address unmet needs and transform hepatology care.

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Microvascular Thrombosis and Liver Fibrosis Progression: Mechanisms and Clinical Applications

Cited by 7 publications

References 158 publications

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis

Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis

Transforming Screening, Risk Stratification, and Treatment Optimization in Chronic Liver Disease Through Data Science and translational Innovation

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