Serum Proteomics Uncovers Biomarkers of Clinical Portal Hypertension in Children With Biliary Atresia

Osborn, Julie B.; Mourya, Reena; Thanekar, Unmesha; Su, Weiji; Lin, Fei; Shivakumar, Pranavkumar; Bezerra, Jorge A.

doi:10.1002/hep4.1878

Cited by 3 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NILDA are best calibrated for chronic viral hepatitis and ALD etiologies but tend to overestimate CSPH risk in patients with obesity and NAFLD. [23] Promising, but small and nonexternally validated, studies have reported good correlation of contrast-enhanced ultrasoundderived, [73] MRI, [74] and serum biomarkers [75][76][77][78] with HVPG. However, as reviewed in the AASLD NILDA Guideline, correlations between blood-based NILDA and CSPH remains inferior to those with imagingbased NILDA.…”

Section: Do Not Use Deep Sedation (Avoid Fentanyl and Propofolmentioning

confidence: 99%

AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis

Kaplan,

Ripoll,

Thiele

et al. 2023

Hepatology

View full text Add to dashboard Cite

Portal hypertension results from a series of maladaptive responses to chronic liver injury and cirrhosis. Initially, structural mechanisms because of accumulation of fibrous tissue, regenerative nodules, microthrombi, parenchymal extinction, and collapse lead to an increase in intrahepatic vascular resistance (1). In addition to architectural distortion, dynamic sinusoidal vasoconstriction contributes to 30% of the total increase in vascular tone. These structural changes lead to an increased portal pressure gradient; when this reaches values of about 10 mm Hg, it gives rise to formation of portal-systemic collaterals and compensatory splanchnic vasodilation, which, in turn, increases portal blood flow and, consequently, portal pressure (2). One of the first consequences of portal hypertension is the development of portosystemic collaterals, for which vascular endothelial growth factor (VEGF)-driven angiogenesis plays an important role (3). Gastroesophageal varices represent the most clinically relevant collaterals because of their increased risk of bleeding. Bleeding is directly dependent on increased wall tension at the varices, determined by portal pressure, variceal diameter, and thin wall thickness. Vasodilation occurs also in the systemic circulation resulting in a hyperdynamic circulatory state, driven by decreased effective arterial blood volume leading to activation of neurohumoral and vasoconstrictive systems, sodium and water retention, and increased cardiac output. This process eventually results in the development of ascites and, at late stages, hepatorenal syndrome because of compensatory renal vasoconstriction. Hepatic encephalopathy represents a multifactorial complication of portal hypertension, resulting from portosystemic shunting, impaired synthetic liver function, increased bacterial translocation, and muscle wasting (sarcopenia). Finally, imbalances on vasoconstrictors and vasodilators in the pulmonary circulation results in hepatopulmonary syndrome (increased vasodilation) and portopulmonary hypertension (increased vasoconstriction). CO, carbon monoxide; H 2 S, hydrogen sulfide; HVR, hepatic vascular resistance; NO, nitric oxide; ET, endothelin.

show abstract

Section: Do Not Use Deep Sedation (Avoid Fentanyl and Propofolmentioning

confidence: 99%

AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis

Kaplan,

Ripoll,

Thiele

et al. 2023

Hepatology

View full text Add to dashboard Cite

show abstract

“…These proteins relate to angiogenesis and lymphangiogenesis, as the adaptive and compensatory mechanisms activated along the PH development [ 9 , 11 , 12 ]. Osborn et al have compared the serum proteomic profiles of children with biliary atresia and identified five protein candidates (SEMA6B, SFRP3, COMMD7, BMX, and VCAM1) in children with clinical signs of CSPH [ 13 ]. Their presumed role in the pathogenesis of PH might be illustrated by the Bone marrow kinase on chromosome X (BMX) protein that is involved in the regulation of proinflammatory cytokines secretion [ 14 ], whereas Vascular cell adhesion molecule 1 (VCAM-1) is involved in endothelial activation and angiogenesis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension

Pastrovic,

Novak,

Grgurevic

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Introduction Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD). Materials and methods Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups. Results We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH. Discussion and conclusion We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD.

show abstract

Cholestatic diseases

Carpino,

Ceci,

Kennedy

et al. 2024

Sinusoidal Cells in Liver Diseases

View full text Add to dashboard Cite

Serum Proteomics Uncovers Biomarkers of Clinical Portal Hypertension in Children With Biliary Atresia

Cited by 3 publications

References 27 publications

AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis

AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis

Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension

Cholestatic diseases

Contact Info

Product

Resources

About