University of Utah, Salt Lake City, UT.
University of Manitoba, Winnipeg, Manitoba, Canada.
Hepatology. 2017 Aug;66(2):518-527. doi: 10.1002/hep.29204. Epub 2017 Jun 26.
There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome.
PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).
描述儿童原发性硬化性胆管炎（PSC）的疾病特征和长期预后。
我们从 36 家参与机构中收集了所有儿童 PSC 病例，并对 PSC 诊断日期至门静脉高压或胆管并发症、胆管癌、肝移植或死亡日期进行了生存分析。我们根据疾病表型和诊断时的实验室研究对患者进行分组，以确定长期预后的客观预测因素。我们共确定了 781 例患者，中位年龄为 12 岁，随访时间为 4277 人年；33%的患者合并自身免疫性肝炎，76%的患者合并炎症性肠病，13%的患者合并小胆管 PSC。10 年后，分别有 38%和 25%的患者发生门静脉高压和胆管并发症。一旦发生这些并发症，在无肝源的情况下中位生存时间分别为 2.8 年和 3.5 年。胆管癌的发生率为 1%。5 年和 10 年时的无事件生存率分别为 70%和 53%。诊断时总胆红素、γ-谷氨酰转肽酶和天冬氨酸氨基转移酶与血小板比值指数最高的患者组预后最差。多变量分析显示，PSC-炎症性肠病和小胆管表型与较好的预后相关（风险比分别为 0.6、95%置信区间为 0.5-0.9 和 0.7、95%置信区间为 0.5-0.96）。年龄、性别和自身免疫性肝炎重叠对长期预后没有影响。
PSC 在儿童中呈慢性、进行性病程，近一半的患者在疾病 10 年后出现不良肝脏结局；诊断时胆红素、γ-谷氨酰转肽酶和天冬氨酸氨基转移酶与血小板比值指数升高可识别出风险最高的患者；小胆管 PSC 和 PSC-炎症性肠病是更有利的疾病表型。
