Aziz Bishoi, Kok Beverley, Cheah Matthew, Lytvyak Ellina, Moctezuma-Velazquez Carlos, Wasilenko Shawn, Tsochatzis Emmanuel, Ravikumar Reena, Jose Sophie, Allison Michael, Gunson Bridget, Manas Derek, Monaco Andrea, Mirza Darius, Fusai Giuseppe, Owen Nicola, Thorburn Douglas, Roberts Keith, Srinivasan Parthi, Wigmore Stephen, Athale Anuja, Creamer Felicity, Fernando Bimbi, Iyer Vikram, Madanur Mansoor, Sen Gourab, Montano-Loza Aldo J, Hansen Bettina, Mason Andrew L
Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada.
Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
Am J Gastroenterol. 2025 Feb 1;120(2):459-468. doi: 10.14309/ajg.0000000000002977. Epub 2024 Jul 25.
Primary sclerosing cholangitis (PSC) may reoccur following liver transplantation (LT), and the diagnosis established once imaging studies demonstrate the diagnostic cholangiographic appearance. To evaluate whether the development of recurrent PSC (rPSC) is associated with cholestasis soon after LT, we studied whether changes in hepatic biochemistry within the first 12 months were linked with the development of rPSC and graft loss.
We conducted a retrospective cohort analysis of 158 transplant recipients with PSC in Canada and 549 PSC transplant recipients from the United Kingdom. We evaluated serum liver tests within 12 months after LT and the subsequent development of a cholangiographic diagnosis of rPSC as a time-dependent covariate using Cox regression. Severe cholestasis was defined as either alkaline phosphatase > 3× upper limit of normal or total bilirubin > 100 μmol/L.
Patients who developed rPSC were more likely to have severe cholestasis vs those without at 3 months (20.5% vs 8.2%, P = 0.011), at 6 months (17.9% vs 10.0%, P = 0.026), and 12 months (15.4% vs 7.8%, P = 0.051) in the Canadian cohort and at 12 months in the UK cohort (27.9% vs 12.6%, P < 0.0001). By multivariable analysis, development of severe cholestasis in the Canadian cohort at 3 months (hazard ratio [HR] = 2.41, P = 0.046) and in the UK cohort at 12 months (HR = 3.141, P < 0.0001) was both associated with rPSC. Severe cholestasis at 3 months in the Canadian cohort was predictive of graft loss (HR = 3.88, P = 0.0001).
The development of cholestasis within 3-12 months following LT was predictive of rPSC and graft loss.
原发性硬化性胆管炎（PSC）在肝移植（LT）后可能复发，一旦影像学检查显示出诊断性胆管造影表现即可确诊。为了评估复发性PSC（rPSC）的发生是否与LT后不久的胆汁淤积有关，我们研究了术后12个月内肝脏生化指标的变化是否与rPSC的发生及移植物丢失有关。
我们对加拿大的158例PSC移植受者和英国的549例PSC移植受者进行了回顾性队列分析。我们使用Cox回归评估LT后12个月内的血清肝功能检查以及随后经胆管造影诊断为rPSC的情况，并将其作为时间依赖性协变量。严重胆汁淤积定义为碱性磷酸酶>正常上限的3倍或总胆红素>100μmol/L。
在加拿大队列中，发生rPSC的患者在3个月时（20.5%对8.2%，P = 0.011）、6个月时（17.9%对10.0%，P = 0.026）和12个月时（15.4%对7.8%，P = 0.051）比未发生rPSC的患者更易出现严重胆汁淤积；在英国队列中，12个月时（27.9%对12.6%，P < 0.0001）也是如此。多变量分析显示，加拿大队列中3个月时出现严重胆汁淤积（风险比[HR]=2.41，P = 0.046）以及英国队列中12个月时出现严重胆汁淤积（HR = 3.141，P < 0.0001）均与rPSC相关。加拿大队列中3个月时的严重胆汁淤积可预测移植物丢失（HR = 3.88，P = 0.0001）。
LT后3 - 12个月内胆汁淤积的发生可预测rPSC和移植物丢失。
