Verkade Henkjan J, Thompson Richard J, Arnell Henrik, Fischler Björn, Gillberg Per-Göran, Mattsson Jan P, Torfgård Kristina, Lindström Erik
Department of Pediatrics, University of Groningen, Beatrix Children's Hospital/University Medical Center Groningen, Groningen, The Netherlands.
Institute of Liver Studies, King's College London, London, United Kingdom.
J Pediatr Gastroenterol Nutr. 2020 Aug;71(2):176-183. doi: 10.1097/MPG.0000000000002789.
We assessed available data on impact of partial external biliary diversion (PEBD) surgery on clinical outcomes in patients with progressive familial intrahepatic cholestasis (PFIC).
We performed a systematic literature review (PubMed) and meta-analysis to evaluate relationships between liver biochemistry parameters (serum bile acids, bilirubin, and alanine aminotransferase [ALT]) and early response (pruritus improvement) or long-term outcomes (need for liver transplant) in patients with PFIC who underwent PEBD.
Searches identified 175 publications before September 2018; 16 met inclusion criteria. Receiver operating characteristic (ROC) analysis examined ability of liver biochemistry parameters to discriminate patients who demonstrated early and long-term response to PEBD from those who did not. Regarding pruritus improvement in 155 included patients in aggregate, 104 (67%) were responders, 14 (9%) had partial response, and 37 (24%) were nonresponders. In ROC analyses of individual patient data, post-PEBD serum concentration of bile acids, in particular, could discriminate responders from nonresponders for pruritus improvement (area under the curve, 0.99; P < 0.0001; n = 42); to a lesser extent, this was also true for bilirubin (0.87; P = 0.003; n = 31), whereas ALT could not discriminate responders from nonresponders for pruritus improvement (0.74; P = 0.06; n = 28). Reductions from pre-PEBD values in serum bile acid concentration (0.89; P = 0.0003; n = 32) and bilirubin (0.98; P = 0.002; n = 18) but not ALT (0.62; P = 0.46; n = 18) significantly discriminated decreased aggregate need for liver transplant.
Changes in bile acids seem particularly useful in discriminating early and long-term post-PEBD outcomes and may be potential biomarkers of response to interruption of enterohepatic circulation in patients with PFIC.
我们评估了部分体外胆汁转流术（PEBD）对进行性家族性肝内胆汁淤积症（PFIC）患者临床结局影响的现有数据。
我们进行了一项系统的文献综述（PubMed）和荟萃分析，以评估接受PEBD的PFIC患者的肝脏生化参数（血清胆汁酸、胆红素和丙氨酸转氨酶[ALT]）与早期反应（瘙痒改善）或长期结局（肝移植需求）之间的关系。
检索在2018年9月之前共识别出175篇出版物；16篇符合纳入标准。受试者工作特征（ROC）分析检查了肝脏生化参数区分对PEBD有早期和长期反应的患者与无反应患者的能力。关于总共155例纳入患者的瘙痒改善情况，104例（67%）有反应，14例（9%）有部分反应，37例（24%）无反应。在个体患者数据的ROC分析中，尤其是PEBD术后胆汁酸血清浓度能够区分瘙痒改善的有反应者与无反应者（曲线下面积，0.99；P<0.0001；n=42）；胆红素在较小程度上也如此（0.87；P=0.003；n=31），而ALT不能区分瘙痒改善的有反应者与无反应者（0.74；P=0.06；n=28）。血清胆汁酸浓度（0.89；P=0.0003；n=32）和胆红素（0.98；P=0.002；n=18）相对于PEBD术前值的降低显著区分了肝移植总需求的减少，但ALT（0.62；P=0.46；n=18）没有。
胆汁酸变化似乎对区分PEBD术后早期和长期结局特别有用，可能是PFIC患者对肠肝循环中断反应的潜在生物标志物。
