Fisher R A, Bu D, Thompson M, Tisnado J, Prasad U, Sterling R, Posner M, Strom S
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0254, USA.
Transplantation. 2000 Jan 27;69(2):303-7. doi: 10.1097/00007890-200001270-00018.
A practical method of monitoring engraftment by transplanted hepatocytes for the purpose of bridging human liver failure to native regeneration is described.
A previously healthy 37-year-old female with a 2-week history of a febrile illness presented with fulminant liver failure. Findings on admission included the following: illicit drug use, serum hepatitis B surface antigen positive, grade 1 encephalopathy, prothrombin time (pt) >100 sec, F7<1%, NH3 150 micromol/L, alanine aminotransferase 4079 U/L, total bilirubin level 11.4 mg/dl, and glucose 70 mg/dl (on IV D10). With immunosuppression, 8.8x10(8), 96% viable human hepatocytes were intraportally infused. Clinical chemistries, total sHLA class I, and ELISA to measure donor-specific sHLA-A1 and -B8 were recorded. Serial transjugular liver biopsies were performed and pooled for histological examination, DNA extraction, and HLA DNA typing.
The patient fully recovered. At months 3 and 4 with donor biopsy specimen class I HLA DNA no longer detectable, immunosuppression was tapered off. The patient is clinically normal, serum hepatitis B surface antigen negative at 10 months of follow-up.
Bridging liver failure with donor hepatocytes with HLA class I antigen disparate from recipients is clinically feasible, and allows for a marker, combined with serial graft histology, to safely wean immunosuppression when native liver regeneration succeeds.
描述了一种通过移植肝细胞监测植入情况的实用方法，目的是将人类肝衰竭过渡到肝脏自然再生阶段。
一名此前健康的37岁女性，有2周发热病史，出现暴发性肝衰竭。入院时的检查结果如下：有非法药物使用史，血清乙肝表面抗原阳性，1级肝性脑病，凝血酶原时间（pt）>100秒，F7<1%，NH3 150微摩尔/升，丙氨酸转氨酶4079 U/L，总胆红素水平11.4毫克/分升，葡萄糖70毫克/分升（静脉输注10%葡萄糖溶液）。在免疫抑制的情况下，经门静脉输注了8.8×10⁸个、活力为96%的人肝细胞。记录临床化学指标、总sHLA I类以及用于测量供体特异性sHLA - A1和 - B8的酶联免疫吸附测定（ELISA）结果。进行了系列经颈静脉肝活检，并将样本合并用于组织学检查、DNA提取和HLA DNA分型。
患者完全康复。在第3个月和第4个月时，供体活检标本中I类HLA DNA不再可检测到，免疫抑制逐渐减少。在随访10个月时，患者临床情况正常，血清乙肝表面抗原阴性。
将与受体I类HLA抗原不同的供体肝细胞用于桥接肝衰竭在临床上是可行的，并且当肝脏自然再生成功时，结合系列移植组织学检查，该方法可提供一个标志物以安全地逐渐减少免疫抑制。
