Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg (LCCH), University of Heidelberg, Heidelberg, Germany.
Front Immunol. 2020 May 12;11:892. doi: 10.3389/fimmu.2020.00892. eCollection 2020.
Despite increasing awareness of the negative impact of cold ischemia time (CIT) in liver transplantation, its precise influence in different subgroups of liver transplant recipients has not been analyzed in detail. This study aimed to identify liver transplant recipients with an unfavorable outcome due to prolonged cold ischemia. 40,288 adult liver transplantations, performed between 1998 and 2017 and reported to the Collaborative Transplant Study were analyzed. Prolonged CIT significantly reduced graft and patient survival only during the first post-transplant year. On average, each hour added to the cold ischemia was associated with a 3.4% increase in the risk of graft loss (hazard ratio (HR) 1.034, < 0.001). The impact of CIT was strongest in patients with hepatitis C-related (HCV) cirrhosis with a 24% higher risk of graft loss already at 8-9 h (HR 1.24, 95% CI 1.05-1.47, = 0.011) and 64% higher risk at ≥14 h (HR 1.64, 95% CI 1.30-2.09, < 0.001). In contrast, patients with hepatocellular cancer (HCC) and alcoholic cirrhosis tolerated longer ischemia times up to <10 and <12 h, respectively, without significant impact on graft survival ( = 0.47 and 0.42). In HCC patients with model of end-stage liver disease scores (MELD) <20, graft survival was not significantly impaired in the cases of CIT up to 13 h. The negative influence of CIT on liver transplant outcome depends on the underlying disease, patients with HCV-related cirrhosis being at the highest risk of graft loss due to prolonged cold ischemia. Grafts with longer cold preservation times should preferentially be allocated to recipients with alcoholic cirrhosis and HCC patients with MELD <20, in whom the effect of cold ischemia is less pronounced.
尽管人们越来越意识到冷缺血时间(CIT)对肝移植的负面影响,但尚未详细分析其在不同肝移植受者亚组中的具体影响。本研究旨在确定因冷缺血时间延长而导致不良结局的肝移植受者。
分析了 1998 年至 2017 年间在协作移植研究中报告的 40288 例成人肝移植病例。延长冷缺血时间仅在移植后第一年显著降低移植物和患者存活率。平均而言,冷缺血时间每增加 1 小时,移植物丢失的风险增加 3.4%(风险比(HR)1.034,<0.001)。CIT 的影响在丙型肝炎相关(HCV)肝硬化患者中最强,在 8-9 小时时,移植物丢失的风险增加 24%(HR 1.24,95%CI 1.05-1.47,=0.011),在≥14 小时时,风险增加 64%(HR 1.64,95%CI 1.30-2.09,<0.001)。相比之下,肝细胞癌(HCC)和酒精性肝硬化患者可耐受长达<10 小时和<12 小时的较长缺血时间,而移植物存活率没有显著影响(=0.47 和 0.42)。在 MELD 评分(MELD)<20 的 HCC 患者中,CIT 长达 13 小时时,移植物存活率并未受到显著影响。
CIT 对肝移植结局的负面影响取决于基础疾病,HCV 相关肝硬化患者因冷缺血时间延长而导致移植物丢失的风险最高。冷保存时间较长的移植物应优先分配给酒精性肝硬化和 MELD<20 的 HCC 患者,因为冷缺血的影响在这些患者中不太明显。