Minder Anna-Elisabeth, Schneider-Yin Xiaoye, Zulewski Henryk, Minder Christoph E, Minder Elisabeth I
Division of Endocrinology, Diabetology, Porphyria and Clinical Nutrition, Stadtspital Zürich, Triemli, 8063 Zurich, Switzerland.
Swiss Reference Centre for Porphyrias, Stadtspital Zürich, Triemli, 8063 Zurich, Switzerland.
Life (Basel). 2023 Apr 21;13(4):1066. doi: 10.3390/life13041066.
In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide.
In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation.
Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant ( < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days ( = 0.012, = 0.0299, respectively). Global radiation only influenced PPIX ( = 0.0113).
These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner.
在动物模型中，促黑素细胞激素（MSH）可保护肝脏免受各种损伤。红细胞生成性原卟啉病（EPP）是一种代谢紊乱疾病，会导致原卟啉（PPIX）积累。除了使人丧失能力的光毒性皮肤反应这一最突出症状外，20%的EPP患者肝功能出现紊乱，4%的患者因肝胆系统清除过量PPIX而出现终末期肝功能衰竭。通过每60天应用控释植入剂阿法美拉肽（一种α-MSH类似物）可减轻皮肤症状。最近，我们发现与治疗前相比，阿法美拉肽治疗期间肝功能检查（LFT）有所改善。本研究调查了这种效果是否具有剂量依赖性，因为剂量依赖性的证据将支持阿法美拉肽的有益影响。
在这项回顾性观察研究中，我们纳入了70例EPP患者的2933次肝功能检查、1186次PPIX浓度检测和1659次阿法美拉肽植入剂应用情况。我们调查了自上次阿法美拉肽给药后的天数或前365天内的给药次数是否对LFT和PPIX水平有影响。此外，我们评估了全球辐射的影响。
患者间差异对PPIX和LFT的影响最为显著。此外，自上次阿法美拉肽植入后，PPIX随着天数增加而显著升高（<0.0001）。在前365天内，随着阿法美拉肽给药次数增加，丙氨酸转氨酶（ALAT）和胆红素显著降低（分别为=0.012，=0.0299）。全球辐射仅影响PPIX（=为0.0113）。
这些发现表明，阿法美拉肽以剂量依赖的方式改善EPP患者的PPIX浓度和LFT。
