Abstract：
Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease characterized by acute attacks and accumulation of the porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Patients with AIP have a high risk of primary liver cancer (PLC). We aimed to assess the association between porphyrin precursor excretion and the risk for PLC in patients with AIP. We studied 48 patients with AIP who developed PLC between 1987 and 2015 and 140 age and sex matched controls with AIP but no PLC. Data on all available urinary PBG and ALA samples collected from 1975 until 1 year before PLC diagnosis were analyzed and compared between cases and controls using logistic regression. Porphyrin precursor excretion was higher in patients with PLC (PBG median 7.9 [IQR 4.4-21.9] mmol/mol creatinine) than in controls (3.8 [1.2-9.8]) (adjusted odds ratio 1.07, 95% confidence interval: 1.02-1.12). None of the 28 patients with all registered samples below the upper limit of normal (ULN) developed PLC, and only one of the 45 patients with all samples <2× ULN developed PLC. Among non-PLC controls, ALA and PBG levels decreased after age 50-60 while an increasing trend was observed after age 65 among those who developed PLC. Increased urinary porphyrin precursors are associated with a high risk of developing PLC. Patients with normal levels appear to have a low risk while high or increasing ALA and PBG after age 65 indicates high risk, which should be considered in surveillance decisions.
摘要：
急性间歇性卟啉病（AIP）是一种罕见的遗传性代谢疾病，其特征是卟啉前体5-氨基乙酰丙酸（ALA）和胆色素原（PBG）的急性发作和积累。AIP患者患原发性肝癌（PLC）的风险很高。我们旨在评估AIP患者卟啉前体排泄与PLC风险之间的关系。我们研究了1987年至2015年之间发生PLC的48例AIP患者，以及140例年龄和性别匹配的AIP对照，但没有PLC。分析了从1975年到PLC诊断前一年收集的所有可用尿液PBG和ALA样本的数据，并使用逻辑回归在病例和对照之间进行了比较。PLC患者的卟啉前体排泄（PBG中位数7.9（IQR4.4-21.9）mmol/mol肌酐）高于对照组（3.8（1.2-9.8））（调整后的比值比1.07，95％置信区间：1.02-1.12）。所有注册样本均低于正常上限（ULN）的28例患者均未出现PLC，所有样本<2xULN的45例患者中只有1例发生PLC。在非PLC控制中，在50-60岁后，ALA和PBG水平下降，而在65岁后，在患有PLC的人群中观察到增加的趋势。尿中卟啉前体的增加与发展PLC的高风险相关。正常水平的患者似乎具有低风险，而65岁后高或增加的ALA和PBG表明高风险。这应该在监控决策中考虑。本文受版权保护。保留所有权利。
