Gamma-glutamyltransferase levels at age 2 stratifies progression of portal hypertension in biliary atresia Open Access
Freeman, Alvin Jay (2016)
Abstract
Background & Aims: Approximately 50% of patients with biliary atresia (BA) will survive with native liver (SNL) past 2 years of age. Most, but not all, BA SNL patients will develop sequelae of portal hypertension during childhood, yet there are no means to accurately predict those who will develop portal hypertension. We sought to determine if serum GGT levels could predict subsequent thrombocytopenia, as a marker of portal hypertension, in BA SNL patients after age 2.
Methods: Retrospective chart review was completed for 46 children diagnosed or cared for with BA SNL and born between November 2010 and January 2013 at three large pediatric liver centers. An association between elevated GGT level (≥ 100 U/L) at age 2 with platelet counts at 4-6 years of age was evaluated using a generalized linear mixed model.
Results: GGT ≥ 100 U/L at 2 years of age has a predictive negative relationship with thrombocytopenia at 4, 5 and 6 years of age (p < 0.01 at each age). BA subjects with a GGT ≥ 100U/L at age 2 have a statistically significant lower median platelet level compared to those patients with a GGT < 100 U/L at 2 years of age (160 vs. 211 x 103/μL, p=0.04). Additionally, patients with a GGT ≥ 100 U/L at 2 years of age exhibited significant yearly worsening of their thrombocytopenia until 6 years of age (median platelet level 109 x 103/ml by age 6, p < 0.01 for median platelet level at each yearly interval from 2 to 6 years of age).
Conclusion: A serum GGT ≥ 100U/L at 2 years of age predicts worsening thrombocytopenia through age 6 in patients with BA. Thus, serum GGT levels may serve as a serum biomarker for the development of portal hypertension in patients with BA SNL patients.
Table of Contents
Introduction………………………………………………………………………….….1
Background……………………………………………………………………………..3
Methods………..………………………………………………………………………..8
Results………………………………………………….……………………………….14
Discussion/Conclusions………………………………………………………….....19
References………………………………………………………………………..…….25
Figure 1: Disease progression in biliary atresia…………………………….....29
Figure 2: Illustration of biliary atresia…………………………………..……...30
Figure 3: Patient anatomy status post Kasai HPE………………..…………...31
Table 1: Inclusion and exclusion criteria…………………………………........32
Figure 4: Study Over view………………………………….............................33
Table 2: Baseline demographics…………………………………....................34
Figure 5: Histograms of GGT and platelets………………………………….....35
Figure 6: GGT at age 2 inversely correlates with platelet counts at each age…36
Figure 7: CART analysis…………………………………................................37
Table 3: Median platelet levels with IQR, maximum, minimum and 95%
confidence intervals stratified by GGT…………………………………............38
Figure 8: ROC curves with AUC for logistic regression models at 4, 5
and 6 years of age ………………………………….........................................39
Figure 9: Stratification of platelet levels by GGT < or ≥ 100 U/L at age 2....40
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