Liu Teng, Wang Ren-Xue, Han Jun, Qiu Yi-Ling, Borchers Christoph H, Ling Victor, Wang Jian-She
Department of Pediatrics, Fudan University Shanghai Medical College, The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
BC Cancer Agency, Vancouver, British Columbia, Canada.
Ann Transl Med. 2020 Mar;8(5):185. doi: 10.21037/atm.2020.01.103.
We ask if plasma bile acid profiles can be used to monitor the effectiveness of partial internal biliary diversion (PIBD) for treating uncontrolled cholestasis in progressive familial intrahepatic cholestasis type 2 (PFIC2) patients.
Plasma bile acids were profiled in 3 cases of ATP-binding cassette, sub-family B member 11 ()mutated PFIC2 children before and after PIBD compared to healthy controls and 8 PFIC2 patients. The quantitation of bile acids was performed by reversed-phase ultrahigh-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS) with negative ion detection.
Before PIBD, all three patients presented with >50-fold higher levels of total plasma bile acids, 2-7 folds higher ratios of taurine: glycine conjugated primary bile acids, and unchanged secondary bile acids levels compared to healthy controls. After PIBD, only one of the three patients (P3) showed relief of cholestasis. The bile acid profiles of the two nonresponding patients showed little change while that of the responding patient showed a 5-fold reduction in total plasma primary bile acids, a reduced taurine: glycine conjugate ratio, and an unexpected 26- and 12-fold increase in secondary bile acids DCA and LCA respectively. One year later, the responder suffered a recurrence of cholestasis, and the bile acid profile shifted back to a more pre-PIBD-like profile.
Plasma bile acid profiles may potentially be useful as sensitive biomarkers for monitoring the clinical course of PIBD patients. Relief of cholestasis after PIBD appears to be associated with significantly increased circulating toxic secondary bile acids and this may limit the utility of PIBD in PFIC2 patients in the long run.
我们探讨血浆胆汁酸谱是否可用于监测部分肝内胆汁转流术（PIBD）治疗2型进行性家族性肝内胆汁淤积症（PFIC2）患者失控性胆汁淤积的疗效。
对3例三磷酸腺苷结合盒亚家族B成员11（ABCB11）突变的PFIC2患儿在PIBD前后的血浆胆汁酸进行分析，并与健康对照者和8例PFIC2患者进行比较。采用反相超高效液相色谱/多反应监测-质谱联用仪（UPLC/MRM-MS）负离子检测法对胆汁酸进行定量分析。
与健康对照者相比，在PIBD前，所有3例患者的血浆总胆汁酸水平均高出50倍以上，牛磺酸：甘氨酸结合型初级胆汁酸的比例高出2-7倍，次级胆汁酸水平无变化。PIBD后，3例患者中只有1例（P3）胆汁淤积得到缓解。2例无反应患者的胆汁酸谱变化不大，而有反应患者的血浆初级胆汁酸总量降低了5倍，牛磺酸：甘氨酸结合物比例降低，次级胆汁酸脱氧胆酸（DCA）和石胆酸（LCA）分别意外升高了26倍和12倍。1年后，有反应者胆汁淤积复发，胆汁酸谱又恢复到更接近PIBD前的状态。
血浆胆汁酸谱可能作为监测PIBD患者临床病程的敏感生物标志物。PIBD后胆汁淤积的缓解似乎与循环中有毒次级胆汁酸的显著增加有关，从长远来看，这可能会限制PIBD在PFIC2患者中的应用。
