Non-invasive Predictors of Esophageal Varices and Their Correlation to Upper Endoscopic Findings

Non-invasive Predictors of Esophageal Varices in Pediatric Portal Hypertension and Their Correlation to Upper Endoscopic Findings

The goal of this observational study:

• To evaluate the diagnostic accuracy of non-invasive markers in predicting the presence and grading of esophageal varices in children with portal hypertension.
• To correlate these non-invasive markers with the severity of portal hypertension and the grade of esophageal varices to identify patients at high risk of bleeding.
• To propose a defined protocol for screening esophageal varices in those children.

Study Overview

• Status: Not yet recruiting
• Conditions: Portal Hypertension; Esophageal Varices

Detailed Description

Portal hypertension in children represents a major hepatobiliary disorder characterized by abnormally elevated pressure within the portal venous system, typically defined as a clinically significant increase in portal venous pressure leading to the formation of portosystemic collaterals and complications such as splenomegaly, hypersplenism, gastroesophageal varices, and portal hypertensive gastropathy. Although direct portal pressure measurement is rarely performed in pediatrics, portal hypertension is generally inferred when clinical, laboratory, and radiologic findings indicate increased resistance to portal blood flow. Doppler ultrasonography demonstrating reduced portal vein velocity, increased portal vein diameter, or reversal of flow is widely accepted as a non-invasive surrogate of elevated portal pressure in children.

The true global incidence of pediatric portal hypertension remains difficult to determine, partly because of variations in underlying etiologies across different regions. Nevertheless, portal hypertension is a major cause of upper gastrointestinal bleeding in childhood, accounting for a significant proportion of variceal hemorrhage admissions in tertiary pediatric gastroenterology units. In developing countries, extrahepatic portal vein obstruction (EHPVO) constitutes the leading cause, whereas intrahepatic diseases dominate in high-income nations. With increasing survival of children with chronic liver diseases and improved neonatal care, the burden of pediatric portal hypertension has been rising over the past two decades, underscoring the need for improved strategies for early diagnosis and prevention of complications.

Causes of portal hypertension in children are traditionally divided into extrahepatic and intrahepatic categories. EHPVO is among the most frequent etiologies in many low- and middle-income countries and is commonly associated with neonatal umbilical vein catheterization, sepsis, dehydration, thrombophilia, abdominal surgery, and congenital portal vein malformations. These children often present at a young age with splenomegaly and hypersplenism despite preserved liver synthetic function. Intrahepatic causes include cholestatic liver diseases such as biliary atresia-which remains a leading indication for pediatric liver transplantation-congenital hepatic fibrosis, autoimmune hepatitis, Wilson disease, alpha-1-antitrypsin deficiency, metabolic disorders, and chronic viral hepatitis.

Progressive hepatocellular injury, fibrosis, and architectural distortion increase resistance to portal flow and lead to portal hypertension in these conditions.

Diagnosis of portal hypertension in children relies on a combination of clinical evaluation, laboratory abnormalities, and imaging findings. Splenomegaly is the most common and often earliest clinical manifestation. Laboratory markers such as thrombocytopenia reflect hypersplenism secondary to splenic sequestration. Doppler ultrasound is the first-line diagnostic tool, providing information on portal vein diameter, patency, flow velocity, degree of congestion, presence of cavernous transformation, and detection of portosystemic collaterals. Additional imaging modalities such as contrast-enhanced CT, MR angiography, and elastography may assist in defining the underlying cause and assessing liver stiffness. Endoscopy remains the gold standard for confirming and grading esophageal varices; however, its invasive nature and the need for anesthesia in children limit its use as a routine screening tool. Consequently, numerous non-invasive predictors such as platelet count, spleen size, platelet-to-spleen ratio, APRI, liver stiffness, and composite scores have been investigated to reduce reliance on endoscopy.

Complications of pediatric portal hypertension vary according to etiology and disease stage. Esophageal and gastric varices represent the most feared sequelae, with variceal hemorrhage contributing significantly to morbidity and mortality. Other complications include portal hypertensive gastropathy, hypersplenism, ascites, growth failure, minimal hepatic encephalopathy, and portal biliopathy in cases of long-standing EHPVO. Extrahepatic consequences such as portopulmonary hypertension and hepatopulmonary syndrome are increasingly recognized in children with chronic liver disease and may adversely affect prognosis, transplant eligibility, and overall quality of life.

The early diagnosis of portal hypertension and timely identification of esophageal varices are crucial components of pediatric care. Early screening enables risk stratification, facilitates timely initiation of primary prophylaxis, and significantly reduces the incidence of first variceal bleeding episodes-events associated with substantial morbidity in children. In addition, early detection of the underlying cause allows for more effective medical, surgical, or interventional radiologic management and may prevent long-term complications. Improved non-invasive models and imaging markers continue to support safer, more accessible strategies for monitoring children at risk and reducing dependence on endoscopy. Given the lifelong implications of chronic portal hypertension and the potential for life-threatening bleeding, establishing reliable early predictors of esophageal varices remains a central goal in pediatric hepatology and is essential for optimizing long-term outcomes in affected children.

• Study Type: Observational
• Enrollment (Estimated): 51

Contacts and Locations

• Study Contact: Name: Mennat-Allah H Abdelraheem, MD; Phone Number: +201061811080; Email: menna128hesham1712@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Portal hypertension in children will be defined using non-invasive clinical, laboratory, and Doppler-ultrasound criteria, in the context of clinical presentation, without invasive pressure measurements.

Patients with portal hypertension will be classified as:

patients with hepatic causes and patients with extrahepatic causes

All patients included in this study will be subjected to:

• 1. Full Clinical History
• 2. Detailed Clinical Examination
• 3. Laboratory Investigations
• 4. Abdominal Ultrasound
• 5. Doppler Ultrasound
• 6.Non-invasive predictive scores for esophageal varices

The following parameters will be assessed:

• Platelet count (PLT)
• Spleen size z-score
• Platelet count to spleen size ratio:
• CPR (Calculated Platelet Ratio)
• APRI (AST to Platelet Ratio Index)
• FIB-4
• King score
• MELD and PELD scores will be analyzed as secondary variables and not as primary predictors of esophageal varices -7. Esophagogastroduodenoscopy (EGD)

Description

Inclusion Criteria:

• Patients aged less than 18 years diagnosed with portal hypertension either due to hepatic or extrahepatic causes

Exclusion Criteria:

• Active variceal bleeding at presentation (hemodynamic instability affects platelet/spleen parameters).
• Previous history of variceal bleeding or endoscopic intervention (band ligation/sclerotherapy).
• Prior surgical portosystemic shunts or Transjugular Intrahepatic Portosystemic Shunt (TIPS).
• Current use of vasoactive drugs for primary prophylaxis (e.g., Non-selective beta-blockers).
• Systemic infections or hematological disorders causing independent thrombocytopenia or splenomegaly (to avoid confounding the platelet/spleen ratio).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Receiver Operating Characteristic (AUROC) Curve of non-invasive markers for predicting esophageal varices in children with portal hypertension	The AUROC will be used as the aggregate reported value to represent the diagnostic performance of the following markers: platelet count, spleen size z-score, platelet-to-spleen ratio, AST-to-Platelet Ratio Index (APRI), FIB-4 score, and King score. Using the AUROC combines sensitivity and specificity across all possible cut-off values into a single statistical measure of diagnostic accuracy for predicting the presence and grade of esophageal varices. Esophagogastroduodenoscopy (EGD) will serve as the reference (gold standard) method for detecting and grading esophageal varices.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between non-invasive markers and endoscopic grade of esophageal varices in children with portal hypertension	The relationship between non-invasive markers (platelet count, spleen size z-score, platelet-to-spleen size ratio, CPR, APRI, FIB-4 score, and King score) and the endoscopic grade of esophageal varices (Grade I-III) will be analyzed using Spearman correlation analysis to determine the strength of association between marker values and variceal grade.	Baseline

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): March 20, 2026
• Primary Completion (Estimated): March 20, 2028
• Study Completion (Estimated): May 20, 2028

Study Registration Dates

• First Submitted: March 2, 2026
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hypertension, Portal; Esophageal and Gastric Varices
• Other Study ID Numbers: Non-invasive predictors of O.V

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No