Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis.
Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis.
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DOI：
10.1002/hep4.1251
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发表时间：
2018-11
影响因子：
5.1
通讯作者：
Miloh T
中科院分区：
文献类型：
--
作者：
Deneau MR;Mack C;Abdou R;Amin M;Amir A;Auth M;Bazerbachi F;Marie Broderick A;Chan A;DiGuglielmo M;El-Matary W;El-Youssef M;Ferrari F;Furuya KN;Gottrand F;Gupta N;Homan M;Jensen MK;Kamath BM;Mo Kim K;Kolho KL;Konidari A;Koot B;Iorio R;Martinez M;Mohan P;Palle S;Papadopoulou A;Ricciuto A;Saubermann L;Sathya P;Shteyer E;Smolka V;Tanaka A;Valentino PL;Varier R;Venkat V;Vitola B;Vos MB;Woynarowski M;Yap J;Miloh T
原发性硬化性胆管炎（PSC）的不良临床事件发生太慢，无法在临床试验期间捕获。需要替代终点，但PSC儿童不存在此类经验证的终点。我们评估了γ-谷氨酰转移酶（GGT）降低与儿科PSC患者长期结局之间的相关性。我们在一个多中心的PSC儿童队列中评估了1年时GGT正常化（< 50 IU/L），这些儿童接受或未接受熊去氧胆酸（UDCA）治疗。我们比较了5年时的无事件生存率（无门静脉高压或胆道并发症、胆管癌、肝移植或肝脏相关死亡）。在287名平均年龄为11.4岁的儿童中，81%的儿童使用UDCA，平均剂量为17 mg/kg/天。治疗组和未治疗组在诊断时的GGT相似（314 vs 300，P=不显著[NS]）。两组的平均GGT在1年时均降低，治疗组（与未治疗组相比）患者的值较低（99 vs 175，P= 0.002），但5年无事件生存率相似（74% vs 77%，P= NS）。在1年时GGT正常化（与未正常化相比）的患者中，无论UDCA治疗状态如何，5年无事件生存率均更好（91% vs 67%，P< 0.001）。同样，1年内GGT的较大降低（> 75% vs < 25%降低）也与结局改善相关（5年无事件生存率88% vs 61%，P= 0.005）。结论：在PSC诊断后1年，GGT < 50和/或GGT降低> 75%预示着儿童的5年预后良好。GGT有望在未来的儿科PSC临床试验中作为潜在的替代终点。
Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.
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