We investigated simple, reproducible, and routinely available noninvasive parameters for esophageal varies in pediatric LC. Our study indicated platelet count <111,000 platelets per microliter, risk score >-0.82, platelet count to spleen size <6.95, and APRI >0.45 can be the significant predictors for the presence of EV. Spleen size, platelet count, INR, APRI, platelet count to spleen size ratio, and the risk score differed significantly between patients with and without EV on univariate analysis, however, the logistic regression analysis did not show any differences, which also indicates that none of these parameters were independently associated with the presence of the EV. The differences in the age, sex, and the etiology of the disease are possible indicators of these findings [
12]. Several studies have been performed to identify noninvasive markers of EV in children, such as hypoalbuminemia, the Child-Pugh score, spleen diameter, thrombocytopenia, the platelet to spleen diameter ratio, Clinical Prediction Rule (CPR), and the APRI [
13-
15]. Other modalities, such as computed tomography scan, transient elastography, and endoscopic capsule imaging are also found useful for detecting the large EVs; though they are expensive and are not commonly available [
16]. Gana et al. [
17], indicated that platelet count, with a cutoff point of 115,000, is the best predictor of EV, with an AUROC curve of 0.79 (95% CI, 0.690–0.900). Our study is in line with their findings, we indicated that the platelet count with a cutoff of 111,000, can predict the EV, with an AUROC curve of 0.833 (95% CI, 0.754–0.912). In the adult population with advanced fibrosis, Park et al. [
11] assessed the laboratory variables for predicting the presence of EV. They combined variables, including the platelets and bilirubin, to form a risk score. They indicated that the score had a good sensitivity and specificity with the cutoff point of -1.0. However, this study was conducted in adults. The current study found that the risk score is a good predictor of EV in children, where, the cutoff point with best sensitivity and specificity was -0.82 (sensitivity, 83.7%; specificity, 70.9%; odds ratio [OR], 12.54). According to the study performed by Adami et al. [
18] in 2018 on 98 children with portal hypertension, 3 markers, including CPR (OR, 8.59), the risk score (OR, 6.09), and the platelet/spleen size
z score below 25 (OR, 3.99) were reported to be good predictors of large EV. The CRP was not investigated in the current study, but our findings were in accord with their findings, in addition to risk score (OR, 12.54) and platelet/spleen size z score (OR, 7.89), we found that the APRI (OR, 6.78) and platelet count (OR, 10.57) are also good predictors. Fagundes et al. [
15] evaluated 111 children in 2007 (age range, 0.7–17.6 years) and demonstrated that splenomegaly, Platelet count below the 130,000/mm
3 and prehepatic and presinusoidal causes of portal hypertension could predict the presence of EV. Due to a high risk of bleeding, Molleston [
19] recommended close monitoring of children with portal hypertension associated with splenomegaly and low platelets, which in association with the aforementioned factors with EV, was indicated by Fagundes et al. [
15] splenomegaly via physical examination has high sensitivity and specificity for the diagnosis of EV. Being an important sign of cirrhosis and portal hypertension, splenomegaly raises the risk of EV up to 14.62 folds, which was indicated by Fagundes et al. [
15]; as well as hypoalbuminemia which shows portal hypertension and a higher risk of EV (OR, 4.17). Splenomegaly was present in 96.7% of our patients, but our results did not indicate it as a predictor of EV in cirrhotic children, moreover, the mean albumin level in our study did not differ between the patients with and without EV.
Thrombocytopenia can occur in these patients as a result of several etiologies, such as immune-mediated mechanisms, lower thrombopoietin synthesis, or platelets pooled by spleen as a result of portal hypertension [
20]. Without any intermediated factors associated with the pathogenesis, it has been indicated that thrombocytopenia is related directly to portal hypertension, in addition to the presence of EV [
21]. Unlike adults [
22], isolated platelet count could predict EV in pediatrics [
23]; however, different cutoff points for platelet count have been described up to present, ranging from 100,000 mm
3 to 130,000 mm
3. Giannini et al. [
24] suggested a platelet count to the spleen diameter ratio as a novel predictor of EV. A ratio below the 909 was indicated to be associated with EV where, the diagnostic accuracy of this parameter was 86% and the negative predictive value was 87%. In this regard, Sezer et al. [
25] also demonstrated that platelet count and platelet to spleen diameter are unsuitable for detecting the EV in cirrhotic children. Adami et al. [
14] reported that children with EV had lower platelet count (with cutoff 115,000) and greater spleen diameter. They also found that platelet to spleen ratio below the 1.0 discriminates patients with EV from those without EV. Although logistic regression was not statistically significant, which was explained by the authors as the differences in the age and gender, we found that it is a significant predictor of EV, with AUROC curve of 0.794, sensitivity of 76.2%, specificity of 71.2%, positive predictive value of 68.1%, and negative predictive value of 78.7%.
Our study has some limitations; a larger sample size should be evaluated for identifying the definite noninvasive marker of EV, which could be able to replace the routine endoscopic evaluations performed by experienced hepatologists. We did not divide our patients in age subgroups that might have provided greater specificity to our findings. Furthermore, unlike adults, liver failure in cirrhotic children derives from a variety of causes. It seems better if the accuracy of the markers is evaluated in a group of patients with the same cause of LC.
In conclusion, the findings of our study suggest that platelet count, platelet count to spleen size, and APRI can be the significant predictors for the presence of EV. Additionally, spleen size, platelet count, INR, APRI, platelet count to spleen size ratio, and the risk score differed significantly between patients with and without EV. These factors might reduce the need of invasive methods like EGD.