Saunders Emily A, Engel Bastian, Höfer Anne, Hartleben Björn, Vondran Florian W R, Richter Nicolas, Potthoff Andrej, Zender Steffen, Wedemeyer Heiner, Jaeckel Elmar, Taubert Richard
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Institute for Pathology, Hannover Medical School, Hannover, Germany.
Am J Transplant. 2022 Feb;22(2):519-531. doi: 10.1111/ajt.16817. Epub 2021 Sep 13.
Graft survival beyond year 1 has not changed after orthotopic liver transplantation (OLT) over the last decades. Likewise, OLT causes comorbidities such as infection, renal impairment and cancer. We evaluated our single-center real-world individualized immunosuppression program after OLT, based on 211 baseline surveillance biopsies (svLbx) without any procedural complications. Patients were classified as low, intermediate and high rejection risk based on graft injury in svLbx and anti-HLA donor-specific antibodies. While 32% of patients had minimal histological inflammation, 57% showed histological inflammation and 23% advanced fibrosis (>F2), which was not predicted by lab parameters. IS was modified in 79% of patients after svLbx. After immunosuppression reduction in 69 patients, only 5 patients showed ALT elevations and three of these patients had a biopsy-proven acute rejection, two of them related to lethal comorbidities. The rate of liver enzyme elevation including rejection was not significantly increased compared to a svLbx control cohort prior to the initiation of our structured program. Immunosuppression reduction led to significantly better kidney function compared to this control cohort. In conclusion, a biopsy guided personalized immunosuppression protocol after OLT can identify patients requiring lower immunosuppression or patients with graft injury in which IS should not be further reduced.
在过去几十年中，原位肝移植（OLT）术后1年以上的移植物存活率并未改变。同样，OLT会引发感染、肾功能损害和癌症等合并症。我们基于211例无任何手术并发症的基线监测活检（svLbx），评估了我们单中心实际应用的OLT术后个体化免疫抑制方案。根据svLbx中的移植物损伤和抗HLA供体特异性抗体，将患者分为低、中、高排斥风险组。32%的患者组织学炎症轻微，57%表现出组织学炎症，23%有进展性纤维化（>F2），实验室参数无法预测这种情况。79%的患者在svLbx后调整了免疫抑制方案。在69例患者免疫抑制减量后，只有5例患者出现ALT升高，其中3例经活检证实为急性排斥反应，2例与致命合并症有关。与我们结构化方案启动前的svLbx对照队列相比，包括排斥反应在内的肝酶升高率没有显著增加。与该对照队列相比，免疫抑制减量使肾功能显著改善。总之，OLT术后活检指导的个性化免疫抑制方案可以识别需要较低免疫抑制的患者或存在移植物损伤且不应进一步降低免疫抑制的患者。
