Helmke Steve, Kittelson John, Imperial Joanne C, McRae Michael P, Everson Gregory T
Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
HepQuant LLC, Denver, Colorado.
Gastro Hep Adv. 2024 Jul 14;3(7):944-953. doi: 10.1016/j.gastha.2024.07.005. eCollection 2024.
We quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis.
Forty-seven patients had baseline testing, and 40 were retested after 1 year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test), and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT). Disease severity index (DSI), hepatic reserve (HR%), and portal-systemic shunting (SHUNT%) were calculated.
Three subgroups with low, moderate, and high disease severity were defined from the age-adjusted results for DSI, HR%, and SHUNT%. Standard laboratory tests, clinical scores, cytokine levels, and clinical outcome correlated with these subgroups. In univariate analysis of baseline tests, SHUNT% was a strong predictor of clinical outcome (n = 13 of 47; areas under the receiver operating characteristic curve, 0.84, 0.90). A model combining SHUNT%, DSI (or HR%), platelet count, and changes from baseline was most predictive of outcome (n = 10 of 40; areas under the receiver operating characteristic curve, 0.95, 0.96).
DSI, HR%, and SHUNT% identified subgroups of primary sclerosing cholangitis based on the age-related severity of hepatic impairment that predicted risk for liver-related clinical outcome. Further study is warranted to confirm and validate these intriguing findings both in studies of natural progression of primary sclerosing cholangitis and in clinical trials. DuO enhances the utility of quantitative liver function testing.
我们使用定量功能测试对肝功能损害进行量化,并将功能损害的严重程度与原发性硬化性胆管炎的肝脏相关并发症及预后相关联。
47例患者进行了基线测试,40例在1年后再次进行测试。对于每项测试,口服(DuO、分流试验)和静脉注射(分流试验)用冷的、非放射性同位素标记的胆酸盐,分别在20分钟和60分钟(DuO)或0、5、20、45、60和90分钟(分流试验)采集血液进行分析。计算疾病严重程度指数(DSI)、肝脏储备(HR%)和门体分流(SHUNT%)。
根据DSI、HR%和SHUNT%的年龄校正结果定义了疾病严重程度低、中、高的三个亚组。标准实验室检查、临床评分、细胞因子水平和临床结局与这些亚组相关。在基线测试的单因素分析中,SHUNT%是临床结局的有力预测指标(47例中有13例;受试者操作特征曲线下面积为0.84、0.90)。结合SHUNT%、DSI(或HR%)、血小板计数以及与基线相比的变化的模型对结局的预测性最强(40例中有10例;受试者操作特征曲线下面积为0.95、0.96)。
DSI、HR%和SHUNT%根据与年龄相关的肝损害严重程度确定了原发性硬化性胆管炎的亚组,这些亚组可预测肝脏相关临床结局的风险。有必要进一步研究以在原发性硬化性胆管炎自然病程研究和临床试验中证实和验证这些有趣的发现。DuO提高了定量肝功能测试的效用。