Yassin Woroud, Nasser Roni, Veitsman Ella, Saadi Tarek
Israel Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Department of Liver, Rambam Health Care Campus, Haifa, Israel.
Turk J Gastroenterol. 2024 Jan 17;35(3):232-238. doi: 10.5152/tjg.2024.22838.
The thiopurine drugs-azathioprine and mercaptopurine-are purine antimetabolites used for the treatment of autoimmune hepatitis. These drugs undergo metabolism through genetically determined pathways, which influences their effectiveness and toxicity. There is scarce information regarding the clinical effects of measuring drug metabolites in these patients. The goal of the study is to test the clinical significance of measuring thiopurine metabolites in patients unsuccessfully treated with thiopurines. Clinical and laboratory data collected for patients who were treated for autoimmune hepatitis between 2015 and 2018, and did not achieve full remission under thiopurine therapy and had thiopurine metabolite levels measured due to lack of response and suspicious side effects were chosen. We compared clinical and laboratory data before and after the therapy change. The study included 25 tests of thiopurine metabolites in 21 patients. Six tests had therapeutic levels. Three tests showed high levels leading to lowering the drug dose. In 11 cases, levels of 6-thioguanine nucleotide were low; the dose was not changed in 3 of these, and the dose was increased in the remaining 8. Shunting was observed in 5 cases, 2 of which were mild and the dose was not changed. In the remaining 3, the dose was decreased, and allopurinol was added. Significant improvements in liver enzymes were observed following dose adjustments. We showed that, in cases of suboptimal response to thiopurine treatment, measuring thiopurine metabolites had an important role in optimizing therapy. In most patients, changing the dose led to a significant improvement with no need to switch to secondline therapies.
硫唑嘌呤和巯嘌呤这两种硫嘌呤类药物是用于治疗自身免疫性肝炎的嘌呤抗代谢物。这些药物通过基因决定的途径进行代谢，这会影响它们的疗效和毒性。关于在这些患者中测量药物代谢物的临床效果的信息很少。本研究的目的是测试在硫嘌呤治疗效果不佳的患者中测量硫嘌呤代谢物的临床意义。选取了2015年至2018年间接受自身免疫性肝炎治疗、在硫嘌呤治疗下未实现完全缓解且因缺乏反应和可疑副作用而测量了硫嘌呤代谢物水平的患者的临床和实验室数据。我们比较了治疗方案改变前后的临床和实验室数据。该研究包括对21例患者进行的25次硫嘌呤代谢物检测。6次检测达到治疗水平。3次检测显示水平较高，导致药物剂量降低。在11例中，6-硫鸟嘌呤核苷酸水平较低；其中3例未改变剂量，其余8例增加了剂量。5例观察到代谢途径改变，其中2例为轻度，未改变剂量。在其余3例中，降低了剂量，并添加了别嘌醇。剂量调整后观察到肝酶有显著改善。我们表明，在硫嘌呤治疗反应欠佳的情况下，测量硫嘌呤代谢物在优化治疗中具有重要作用。在大多数患者中，改变剂量导致显著改善，无需改用二线治疗。
