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Noninvasive Methods of Predicting Large Esophageal Varices in Children with Intrahepatic Portal Hypertension

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Noninvasive Methods of Predicting Large Esophageal Varices in Children with Intrahepatic Portal Hypertension ORIGINAL ARTICLE:HEPATOLOGY Noninvasive Methods of Predicting Large Esophageal Varices in Children With Intrahepatic Portal Hypertension ÃMarina Rossato Adami, ÃCarlos Oscar Kieling, yFernando Pereira Schwengber, zVania N. Hirakata, and §Sandra Maria Gonc¸alves Vieira ABSTRACT Objective: Esophageal variceal bleeding is a severe complication of portal What Is Known hypertension. The standard diagnostic screening test and therapeutic proce- dure for esophageal varices (EV) is endoscopy, which is invasive in pediatric patients. This study aimed to evaluate the role of noninvasive parameters as Platelet count, the Clinical Prediction Rule described predictors of large varices in children with intrahepatic portal hypertension. by Gana et al, and the risk score could be used in Methods: Participants included in this cross-sectional study underwent a children with portal hypertension to reduce the num- screening endoscopy. Variceal size, red marks, and portal gastropathy were ber of unnecessary endoscopies. assessed and rated. Patients were classified into two groups: Group 1 (G1) with small or no varices and Group 2 (G2) with large varices. The population consisted What Is New of 98 children with no history of gastrointestinal (GI) bleeding, with a mean age of 8.9Æ 4.7 years. The main outcome evaluated was the presence of large varices. A combined analysis of the Clinical Prediction Rule, Results: The first endoscopy session revealed the presence of large varices risk score, and platelet count/spleen size z score could in 32 children. The best noninvasive predictors for large varices were be helpful as a pre-endoscopy risk assessment to platelets (Area under the ROC Curve [AUROC] 0.67; 95% CI 0.57– select children with intrahepatic portal hypertension 0.78), the Clinical Prediction Rule (CPR; AUROC 0.65; 95% CI 0.54– who may benefit from a surveillance endoscopy. 0.76), and risk score (AUROC 0.66; 95% CI 0.56–0.76). The logistic regression model showed that children with a CPR value under 114 were 8.59 times more likely to have large varices. Risk scores higher than À1.2 also increased the likelihood of large varices (OR 6.09; P ¼ 0.014), as did a platelet count/spleen size z score lower than 25 (OR 3.99; P ¼ 0.043). The pproximately 50% of pediatric patients with chronic liver combination of these three tests showed a high negative predictive value. disease are estimated to present with gastrointestinal (GI) Conclusions: The CPR, the risk score, and the platelet count/spleen size z bleedingA at some point. Such symptoms may require blood score could be helpful in identifying cirrhotic children who may be eligible transfusions and intensive care hospitalization, and may poten- for endoscopy. tially lead to the development of sepsis, ascites, and occasionally, Key Words: esophageal and gastric varices, gastrointestinal endoscopy, death (1,2). liver cirrhosis, pediatrics, portal hypertension Duche´ et al estimated that the prevalence of endoscopic esophageal varices (EV) in children with cirrhosis because of biliary atresia is 70.4%. The first episode of GI bleeding observed (JPGN 2018;66: 442–446) in these children generally occurred before the 2nd year of age and was found to be associated with large EV, gastric varices and/or the presence of red marks on endoscopic examination (3). A study by Received May 29, 2015; accepted September 13, 2017. Miga et al (4) also reported that patients with biliary atresia have a From the ÃPediatric Gastroenterology Unit and Pediatric Liver Transplanta- 50% risk of death or need for liver transplantation at the 6-year mark tion Program, Hospital de Clı´nicas de Porto Alegre, the yMedical School, after their first episode of EV bleeding. Universidade Federal do Rio Grande do Sul, the zResearch and Post Hepatology guidelines recommend that all cirrhotic adult § Graduation Unit, Hospital de Clı´nicas de Porto Alegre, and the Pediatric patients undergo endoscopic screening for EV (5). However, Department, Hospital de Clı´nicas de Porto Alegre, Pediatric Gastroenter- ology Unit and Pediatric Liver Transplantation Program, Universidade due to a lack of evidence for use of primary prophylaxis in Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. pediatric patients, the benefit of endoscopic screening remains Address correspondence and reprint requests to Marina Rossato Adami, controversial (6). MD, MSc, Rua Jari 671/812, 91350-170 Porto Alegre, Rio Grande do Upper endoscopy is the gold standard for diagnosing varices, Sul, Brazil (e-mail: [email protected]). and therapy can be provided as the diagnostic assessment is This article has been developed as a Journal CME Activity by NASPGHAN. performed. However, this procedure is expensive and associated Visit http://www.naspghan.org/content/59/en/Continuing-Medical-Edu- with risks, especially in children. Preliminary data suggest that cation-CME to view instructions, documentation, and the complete noninvasive methods may predict the presence of EV in adult (7– necessary steps to receive CME credit for reading this article. 20) and pediatric patients (21–23). Noninvasive pediatric markers Source of Support: Fundac¸a˜o de Incentivo a Pesquisa e Eventos do Hospital such as the Clinical Prediction Rule (CPR) presented good diag- de Clı´nicas de Porto Alegre: FIPE-HCPA. No other financial disclosures are reported. nostic accuracy in identifying children with EV, but they were not The other authors report no conflicts of interest. superior to upper endoscopy for patients who may have varices Copyright # 2017 by European Society for Pediatric Gastroenterology, (22,23). Recently, we also observed that platelet count, the CPR as Hepatology, and Nutrition and North American Society for Pediatric described by Gana et al (22,23), and the risk score (20) could be Gastroenterology, Hepatology, and Nutrition used in children with portal hypertension to reduce the number of DOI: 10.1097/MPG.0000000000001841 unnecessary endoscopies (24). 442 JPGN Volume 66, Number 3, March 2018 Copyright © ESPGHAN and NASPGHAN. All rights reserved. JPGN Volume 66, Number 3, March 2018 Noninvasive Methods of Predicting Large Esophageal Varices It is well known that the risk of EV bleeding is related to TABLE 1. Demographic characteristics of the sample variceal size, the presence of red signs on varices as assessed by endoscopy, and to the degree of liver dysfunction determined by the G1 G2 Child-Pugh classification (5). Although the Child-Pugh classifica- (F1 or no varices) (F2 or F3) tion is not validated in children, a higher Child-Pugh score has been Variables (n ¼ 66) (n ¼ 32) previously associated with a higher rate of complications and mortality in children waiting for liver transplantation (25). Methods Age 8.8 (Æ4.8) 9.1 (Æ4.7) such as CT scans, transient elastography and endoscopic capsule Sex imaging seem to be promising tools for detecting large EV, but their Man 29 (44%) 17 (53%) cost-effectiveness is questionable (26). To the best of the authors’ Woman 37 (56%) 15 (47%) knowledge, few studies have investigated the use of noninvasive Diagnosis methods to predict large EV in pediatric populations. Biliary aresia 18 (27%) 8 (25%) The aim of the present study was to assess the role of Autoimmune hepatitis 12 (18%) 9 (28%) noninvasive methods in predicting large EV in pediatric patients Idiopathic biliary cirrhosis 10 (15%) 2 (6%) with intrahepatic portal hypertension. Sclerosing cholangitis 5 (7%) 1 (3%) Cystic fibrosis 6 (9%) 0 Other causes 15 (23%) 12 (37%) MATERIALS AND METHODS The study was conducted on patients younger than 18 years G1 ¼ Group 1; G2 ¼ Group 2. with a diagnosis of chronic liver disease who had undergone esophagogastroduodenoscopy (EGD) between 2000 and 2011 at the Hospital de Clı´nicas de Porto Alegre, a tertiary care medical center in southern Brazil. All patients were retrospectively evalu- To assess the performance of the variables evaluated for EV ated, and those who met the following criteria were excluded from prediction, a receiver operator characteristic (ROC) curve was the analysis: active or previous variceal bleeding; any kind of constructed, and the area under the curve (AUROC) was calculated. variceal treatment or variceal bleeding prophylaxis (such as nonse- This analysis determined the following cut-off values for each 3 lective b-blocker use, endoscopic variceal ligation/sclerotherapy, variable assessed: platelet count, 115 (10 /mL); platelets/spleen surgical portosystemic shunt, or transjugular intrahepatic portosys- size z score, 25; CPR, 114; risk score, À1.2; platelets/spleen size, temic shunt insertion); or previous liver transplants or malignancies. 1; and APRI test, 1.4 (24). The primary variable assessed was the presence of EV in the Independent predictors for large EV were assessed by includ- endoscopy. Clinical and demographic patient data, as well as ing variables that reached statistical significance in the univariate information regarding diagnosis, medication use, and previous analyses (P < 0.05) into subsequent multivariate analyses. In order physical examinations, were collected. The results of any labor- to enhance the prediction of large EV, a combined analysis of these atorial tests and ultrasound scans performed within 3 months of the variables was performed. We categorized them into three classes: EGD were also included in the analysis. all variables positive, at least one variable positive, and none The endoscopy procedures were carried out as part of a positive. clinical care routine by 4
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