Rathi Sahaj, Hussaini Trana, Yoshida Eric M
Division of Gastroenterology, University of British Columbia and Vancouver General Hospital, Canada.
Division of Gastroenterology, University of British Columbia and Vancouver General Hospital, Canada.
Ann Hepatol. 2021 Jan-Feb;20:100211. doi: 10.1016/j.aohep.2020.04.011. Epub 2020 Jun 6.
Liver cirrhosis accounts for over 2 million deaths annually worldwide. A subset of these patients - those with alcoholic hepatitis and decompensated cirrhosis, have abysmal short-term survival. Liver transplant is the only intervention of proven survival benefit; however organ availability is a major limitation. It is thus imperative to assess potential benefit of experimental therapies as a bridge to transplant. Stem cell therapies have shown some promise in patients with end-stage liver disease. Of these, bone-marrow derived hematopoietic stem cells have generated the most interest. Animal as well as human data suggest biological plausibility of stem cell translocation from bone marrow to liver, giving credence to cytokine therapies based on bone marrow stimulation. Granulocyte colony stimulating factor has been the most frequently used cytokine for this purpose. This intervention has shown encouraging results in terms of safety as well as survival benefits in small clinical trials. The evidence, however, is sparse and heterogeneous. In this review we describe the biological plausibility, mechanisms of action, and clinical evidence of the use of cytokine based stem cell therapy in patients with end-stage liver disease.
肝硬化每年在全球导致超过200万人死亡。其中一部分患者——患有酒精性肝炎和失代偿性肝硬化的患者，短期生存率极低。肝移植是唯一经证实具有生存获益的干预措施；然而，器官供应是一个主要限制因素。因此，评估实验性疗法作为移植桥梁的潜在益处至关重要。干细胞疗法在终末期肝病患者中已显示出一些前景。其中，骨髓来源的造血干细胞最受关注。动物和人类数据表明干细胞从骨髓转移至肝脏具有生物学合理性，这为基于骨髓刺激的细胞因子疗法提供了可信度。粒细胞集落刺激因子是最常用于此目的的细胞因子。在小型临床试验中，这种干预措施在安全性和生存获益方面均显示出令人鼓舞的结果。然而，证据稀少且参差不齐。在本综述中，我们描述了基于细胞因子的干细胞疗法在终末期肝病患者中应用的生物学合理性、作用机制及临床证据。
