Salama Hosny, Zekri Abdel-Rahman, Zern Mark, Bahnassy Abeer, Loutfy Samah, Shalaby Sameh, Vigen Cheryl, Burke Wendy, Mostafa Mohamed, Medhat Eman, Alfi Omar, Huttinger Elizabeth
Hepatology Department, Cairo University Hospital, Cairo, Egypt.
Cell Transplant. 2010;19(11):1475-86. doi: 10.3727/096368910X514314. Epub 2010 Jun 29.
The only presently viable treatment for end-stage liver disease is whole organ transplantation. However, there are insufficient livers available. The aim of the present study is to provide autologous bone marrow-derived stem cells as a potential therapeutic for patients with end-stage cirrhosis. This is a retrospective chart review of autologous stem cell treatment in 48 patients, 36 with chronic end-stage hepatitis C-induced liver disease and 12 with end-stage autoimmune liver disease. For all patients, granulocyte colony-stimulating factor was administered to mobilize their hematopoietic stem cells. Following leukapheresis, CD34(+) stem cells were isolated, amplified, and partially differentiated in culture, then reinjected into each subject via their hepatic artery or portal vein. Treatment was generally well tolerated with the expected moderate but transient bone pain from G-CSF in less than half of the patients. Three patients had serious treatment-related complications, and only 20.8% of these end-stage liver disease patients died during 12 months of follow up. For all patients there was a statistically significant decrease in ascites. There was clinical and biochemical improvement in a large percentage of patients who received the transplantation. In the viral group, there were marked changes in albumin (p = 0.0003), bilirubin (p = 0.04), INR (p = 0.0003), and ALT levels (p = 0.02). In the autoimmune group, values also improved significantly for albumin (p = 0.001), bilirubin (p = 0.002), INR (p = .0005), and ALT levels (p = 0.003). These results suggest that autologous CD34(+) stem cell transplantation may be safely administered and appears to offer some therapeutic benefit to patients with both viral and autoimmune-induced end-stage liver disease.
目前,终末期肝病唯一可行的治疗方法是全器官移植。然而,可用肝脏数量不足。本研究的目的是提供自体骨髓来源的干细胞,作为终末期肝硬化患者的一种潜在治疗方法。这是一项对48例患者进行自体干细胞治疗的回顾性病历审查,其中36例患有慢性丙型肝炎引起的终末期肝病,12例患有终末期自身免疫性肝病。对于所有患者,均给予粒细胞集落刺激因子以动员其造血干细胞。白细胞分离术后,分离、扩增并在培养中部分分化CD34(+)干细胞,然后通过肝动脉或门静脉将其重新注入每个受试者体内。治疗一般耐受性良好,不到一半的患者出现了G-CSF预期的中度但短暂的骨痛。3例患者出现了严重的治疗相关并发症,在12个月的随访期间,这些终末期肝病患者中只有20.8%死亡。所有患者的腹水均有统计学意义的减少。接受移植的大部分患者在临床和生化方面都有改善。在病毒组中,白蛋白(p = 0.0003)、胆红素(p = 0.04)、国际标准化比值(INR,p = 0.0003)和谷丙转氨酶(ALT)水平(p = 0.02)有显著变化。在自身免疫组中,白蛋白(p = 0.001)、胆红素(p = 0.002)、INR(p = 0.0005)和ALT水平(p = 0.003)的值也显著改善。这些结果表明,自体CD34(+)干细胞移植可以安全进行,并且似乎对病毒和自身免疫引起的终末期肝病患者都有一定的治疗益处。