University of Utah and Intermountain Primary Children's HospitalSalt Lake CityUT.
University of Colorado School of MedicineAuroraCO.
Hepatology. 2021 Mar;73(3):1061-1073. doi: 10.1002/hep.31560.
Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes.
We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis.
We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.
许多原发性硬化性胆管炎（PSC）患儿接受口服万古霉素治疗（OVT）或熊去氧胆酸（UDCA）。关于这些药物是否能改善预后的数据很少。
我们分析了小儿 PSC 联合会的回顾性数据。根据最近似的倾向评分，对接受 OVT 治疗的患儿进行 1:1:1 匹配，与接受 UDCA 治疗或接受观察（无治疗）的患儿进行匹配，以确保基线特征相似。264 例患儿（88 例分别接受 OVT、UDCA 或观察）具有匹配的倾向评分，且在人口统计学、表型、免疫抑制、基线生化和肝纤维化方面相似。在意向治疗分析中，所有结局指标在治疗组之间均无差异。在 OVT、UDCA 和未治疗组中，γ-谷氨酰转移酶分别正常化 53%、49%和 52%（P 无统计学意义[NS]），肝纤维化分期改善分别为 20%、13%和 18%，恶化分别为 11%、29%和 18%（P 无统计学意义[NS]），5 年肝移植登记概率分别为 21%、10%和 12%（P 无统计学意义[NS]）。良好的结局与 PSC 轻度表型和最小肝纤维化有关。
我们描述了迄今为止最大的关于 PSC 患儿接受 OVT 治疗的结局，并将其与接受 UDCA 或无治疗的精心匹配的患儿进行了比较。与观察策略相比，OVT 和 UDCA 均未显示出改善结局的作用。患者以相似的速度进展为终末期肝病。未接受治疗的患儿常有生化指标自发正常化，尤其是在大多数表型较轻和疾病早期的患儿中。需要进行安慰剂对照治疗试验，以确定小儿 PSC 的有效治疗方法。
