van Vorstenbosch Robert, van Munster Kim, Stavropoulos Georgios, Pachen Daniëlle, van Schooten Frederik-Jan, Ponsioen Cyriel, Smolinska Agnieszka
Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research, Maastricht University, Maastricht, The Netherlands.
Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Academic Medical Center, Amsterdam, The Netherlands.
JHEP Rep. 2024 Apr 27;6(8):101103. doi: 10.1016/j.jhepr.2024.101103. eCollection 2024 Aug.
BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. PSC is a complex disease of largely unknown aetiology that is strongly associated with inflammatory bowel disease (IBD). Diagnosis, especially at an early stage, is difficult and to date there is no diagnostic biomarker. The present study aimed to assess the diagnostic potential of volatile organic compounds (VOCs) in exhaled breath to detect (early) PSC in an IBD population.
Breath samples were obtained from 16 patients with PSC alone, 47 with PSC and IBD, and 53 with IBD alone during outpatient clinic visits. Breath sampling was performed using the ReCIVA breath sampler and subsequently analysed by gas chromatography mass spectrometry. Random forest modelling was performed to find discriminatory VOCs and create a predictive model that was tested using an independent test set.
The final model to discriminate patients with PSC, with or without IBD, from patients with IBD alone included twenty VOCs and achieved a sensitivity, specificity, and area under the receiver-operating curve on the test set of 77%, 83%, and 0.84 respectively. Three VOCs (isoprene, 2-octanone and undecane) together correlated significantly with the Amsterdam-Oxford score for PSC disease prognosis. A sensitivity analysis showed stable results across early-stage PSC, including in those with normal alkaline phosphatase levels, as well as further progressed PSC.
The present study demonstrates that exhaled breath can distinguish PSC cases from IBD and has potential as a non-invasive clinical breath test for (early) PSC.
Primary sclerosing cholangitis is a complex chronic liver disease, which ultimately results in cirrhosis, liver failure, and death. Detection, especially in early disease stages, can be challenging, and therefore therapy typically starts when there is already some irreversible damage. The current study shows that metabolites in exhaled breath, so called volatile organic compounds, hold promise to non-invasively detect primary sclerosing cholangitis, including at early disease stages.
原发性硬化性胆管炎（PSC）是一种慢性胆汁淤积性肝病，其特征为胆管进行性炎症和纤维化。PSC是一种病因 largely unknown 的复杂疾病，与炎症性肠病（IBD）密切相关。诊断，尤其是早期诊断困难，迄今为止尚无诊断生物标志物。本研究旨在评估呼出气中挥发性有机化合物（VOCs）检测IBD人群中（早期）PSC的诊断潜力。
在门诊就诊期间，从16例单纯PSC患者、47例PSC合并IBD患者和53例单纯IBD患者中采集呼气样本。使用ReCIVA呼气采样器进行呼气采样，随后通过气相色谱 - 质谱联用仪进行分析。进行随机森林建模以寻找具有鉴别性的VOCs并创建预测模型，该模型使用独立测试集进行测试。
用于区分有或无IBD的PSC患者与单纯IBD患者的最终模型包含20种VOCs，在测试集上的灵敏度、特异性和受试者操作特征曲线下面积分别为77%、83%和0.84。三种VOCs（异戊二烯、2 - 辛酮和十一烷）共同与PSC疾病预后的阿姆斯特丹 - 牛津评分显著相关。敏感性分析显示，在早期PSC患者（包括碱性磷酸酶水平正常者）以及病情进展更严重的PSC患者中结果均稳定。
本研究表明，呼出气可将PSC病例与IBD区分开来，具有作为（早期）PSC非侵入性临床呼气测试的潜力。
原发性硬化性胆管炎是一种复杂的慢性肝病，最终会导致肝硬化、肝衰竭和死亡。检测，尤其是在疾病早期阶段，可能具有挑战性，因此治疗通常在已经出现一些不可逆损伤时才开始。当前研究表明，呼出气中的代谢物，即所谓的挥发性有机化合物，有望非侵入性地检测原发性硬化性胆管炎，包括在疾病早期阶段。
