Miyagi S, Kawagishi N, Sekiguchi S, Akamatsu Y, Sato K, Takeda I, Kobayashi Y, Tokodai K, Fujimori K, Satomi S
Department of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University, Aoba-ku, Sendai, Japan.
Transplant Proc. 2012 Apr;44(3):797-801. doi: 10.1016/j.transproceed.2012.01.012.
Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the needs for pretransplantation treatments may be eliminated. It is known that negative impacts of immunosuppression are limited among LDLT for HCC, however, we believe that excessive immunosuppression is one of the risk factors for recurrence. We compared the impacts of immunosuppression for LDLT with hepatectomy outcomes for HCC.
From 1991 to 2010, we performed 144 LDLTs including 14 patients with HCC. Seven met the Milan criteria. Immunosuppressive therapies were based on tacrolimus plus methylprednisolone plus CD25 antibody. For ABO-incompatible cases, we also used mycophenolate mofetil and rituximab. Five cases underwent strong imunosuppressive therapy (steroid pulse or rituximab) within 180 days. In addition, we performed hepatectomy for 180 HCC cases from 1997 to 2010.
Overall survival rates of the LDLT cohort and hepatectomy groups were similar, but disease-free 5-year survival rates (DFS) of the LDLT cohort were significantly better than those of the hepatectomy group (total = 54.4% versus 27.4%, within the Milan criteria cases, 71.4% versus 33.8%). Thus, the negative impact of immunosuppression on recurrence was less than the benefit of a whole liver resection. Among strongly immunosuppressed cases, 5-years DFS rates were significantly worse than among other immunosuppressed cases (20.0% versus 76.2%). Upon univariate analysis, the factors associated with HCC recurrence were alpha-fetoprotein levels and steroid doses within 180 days, but multivariate analysis did not show a predictor for recurrence.
Patients who are strongly immunosuppressed may have several negative impacts for recurrences. More careful indications must be selected for ABO-incompatible cases.
活体供肝肝移植（LDLT）为肝细胞癌（HCC）患者提供了及时的肝移植机会。如果ABO血型不相容的LDLT可行，那么可能无需进行移植前治疗。已知免疫抑制对HCC的LDLT患者的负面影响有限，然而，我们认为过度免疫抑制是复发的危险因素之一。我们比较了免疫抑制对LDLT的影响与HCC肝切除术后的结果。
1991年至2010年，我们共进行了144例LDLT，其中14例为HCC患者。7例符合米兰标准。免疫抑制治疗方案为他克莫司联合甲泼尼龙加CD25抗体。对于ABO血型不相容的病例，我们还使用了霉酚酸酯和利妥昔单抗。5例患者在180天内接受了强化免疫抑制治疗（类固醇冲击或利妥昔单抗）。此外，1997年至2010年，我们对180例HCC患者进行了肝切除术。
LDLT队列和肝切除组的总生存率相似，但LDLT队列的5年无病生存率（DFS）显著高于肝切除组（总体分别为54.4%和27.4%，在符合米兰标准的病例中，分别为71.4%和33.8%）。因此，免疫抑制对复发的负面影响小于全肝切除的益处。在接受强化免疫抑制治疗的病例中，5年DFS率显著低于其他免疫抑制治疗的病例（20.0%对76.2%）。单因素分析显示，与HCC复发相关的因素为甲胎蛋白水平和180天内的类固醇剂量，但多因素分析未显示复发的预测因素。
接受强化免疫抑制治疗的患者可能对复发有多种负面影响。对于ABO血型不相容病例，必须选择更谨慎的适应症。
