Search

Background & Aims: Von Willebrand factor antigen (vWFAg), a protein measured to test the level of vWF released from the vascular endothelium has gained much attention as a marker for portal hypertension (PHT) severity. The objectives of this study were to investigate the use of vWFAg as a biomarker along with liver and spleen stiffness measurements by transient elastography as potential predictors of clinically significant varices (CSV), variceal bleeding (VB) and decompensation in children with PHT. Methods: This observational prospective cohort study included 117 children (median age 10 [IQR 6-14] years) who underwent oesophagogastroduodenoscopy between January’2012 to November’2021 and a validation group of 33 children who underwent the same procedure between December’2021 to March’2023. Measurements of vWFAg and glycoprotein Ib binding activity of VWF (GPIbR) were available in 97 patients in the study group and in all patients in the validation group.Results: vWFAg and GPIbR were significantly higher in children with CSV (223 IU/dl and 166 IU/dl; p = 0.015 and p = 0.04, respectively) and VB (218 IU/dl and 174 IU/dl; p = 0.077 and p = 0.03, respectively) than in those without CSV or VB, respectively. Ninety-six patients had liver and spleen stiffness measurements. Spleen stiffness was significantly higher in patients with CSV compared to those without CSV (p = 0.003). In a chronic liver disease subgroup, a predictive scoring tool based on vWFAg, GPIbR, platelet count, and spleen/liver stiffness measurements could predict CSV with an AUROC of 0.76 (p = 0.04). Conclusions: This study suggests the predictive value of vWF for CSV and VB increases when combined with spleen stiffness, with AUROCs of 0.88 and 0.82, respectively. Hence, a combination of biomarkers could assist clinicians in diagnosing CSV, preventing unnecessary invasive procedures. Impacts and implications: Surveillance endoscopies in children with portal hypertension (PHT) have their own risks and non-invasive markers, such as von Willebrand factor antigen, glycoprotein Ib binding activity of VWF (GPIbR), and transient elastography could be used to predict clinically significant varices, variceal bleeding and disease compensation in children with PHT. Such non-invasive markers for PHT and varices are lacking in the paediatric population. The results show that von Willebrand factor and GPIbR along with transient elastography can be used to formulate a scoring system which can be used as a clinical tool by paediatric hepatologists to monitor the progression of PHT and risk of bleeding, and hence to stratify the performance of invasive endoscopic procedures under general anaesthesia. However, there is a need to validate the scoring system in children with portal vein thrombosis and for hepatic decompensation in a multi-centre registry in the future.

In children, fatty liver disease is a group of disorders that often overlaps with inherited metabolic disorders (IMDs), which requires prompt diagnosis and specific management. Metabolic dysfunction–associated fatty liver disease (MAFLD) or, formerly, non-alcoholic fatty liver disease (NAFLD) is the hepatic component of a multisystemic disease that requires a positive criteria in metabolic dysfunction for diagnosis. However, in children, the diagnosis of MAFLD is one of the exclusions of an IMD [paediatric fatty liver disease (PeFLD) type 1] including the possibility that an IMD can be identified in the future following investigations that may be negative at the time. Therefore, while children with fatty liver with metabolic dysfunction could be classified as MAFLD (PeFLD type 2) and managed that way, those who do not fulfil the criteria for metabolic dysfunction should be considered separately bearing in mind the possibility of identifying a yet undiagnosed IMD (PeFLD type 3). This concept is ever more important in a world where MAFLD is the most common cause of liver disease in children and adolescents in whom about 7% are affected. The disease is only partially understood, and awareness is still lacking outside hepatology and gastroenterology. Despite its increasing pervasiveness, the management is far from a one-size-fits-all. Increasing complexities around the genetic, epigenetic, non-invasive modalities of assessment, psychosocial impacts, therapeutics, and natural history of the disease have meant that an individualised approach is required. This is where the challenge lies so that children with fatty liver are considered on their own merits. The purpose of this review is to give a clinical perspective of fatty liver disease in children with relevance to metabolic dysfunction.