Mendler Michel, Kwok Hansen, Franco Edson, Baron Pedro, Weissman Jill, Ojogho Okechukwu
Division of Gastrointestinal and Liver Diseases, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
Liver Transpl. 2008 Sep;14(9):1313-22. doi: 10.1002/lt.21529.
Peripheral blood CD4+ adenosine triphosphate [ATP (ng/mL)] release [ImmuKnow Immune Cell Function Assay (ATP)] correlates to immunoreactivity. We hypothesized that ATP levels could provide insight into hepatitis C virus (HCV) infection and recurrent liver disease in liver transplantation (LT). We studied our center's LT cohort, in which ATP levels had been measured off protocol from February 2005 through July 2006. Of the 280 LTs performed since 1993, 114 (58.2%) fit the selection criteria, with a mean age of 49 +/- 10 years. LT (alone/combination) indications included HCV (58%), alcoholic liver disease (41%), hepatocellular carcinoma (16%), and other (33%). Four hundred seventy-seven ATP levels were obtained: 3 (1-17) per patient 25 months (4 days to 19 years) from the time from transplantation. Final diagnoses were normal allograft function (n = 166, 35%), recurrent disease (n = 199, 42%), septic event (n = 34, 7%), other (n = 51, 11%), and undetermined (n = 27, 6%). Two hundred eighty-one ATP levels were obtained [3 (1-18) per patient] in 66 HCV(+) patients. Forty-five (68%) developed biopsy-proven recurrent liver disease [188/281 (67%) ATP levels]. The median ATP level (ng/mL) was 162 (1-761); it was lower in HCV(+) patients (151 +/- 109) versus HCV(-) patients (211 +/- 139; P < 0.0001). ATP ranges in HCV(+) patients were stable from the time from transplantation. In HCV(-) patients, ATP ranges were initially high and eventually decreased to HCV(+) levels (P = 0.01). Immunosuppressant levels were low in 62% of HCV(-) patients versus 38% of HCV(+) patients (P = 0.04). In HCV(+) patients, ATP was lower in disease recurrence (139 +/- 97) versus none (181 +/- 141; P = 0.01) with similar immunosuppression, and ATP decreased with grade (P = 0.05) but not stage. Time from transplantation, aspartate aminotransferase/alanine aminotransferase >1, and low ATP were independently associated with recurrent HCV. In conclusion, after LT, global cellular immune function appears depressed at baseline in HCV(+) patients versus HCV(-) patients and more so in HCV(+) recurrent disease.
外周血CD4⁺三磷酸腺苷[ATP（纳克/毫升）]释放量[免疫状态检测免疫细胞功能分析（ATP）]与免疫反应性相关。我们推测ATP水平可为肝移植（LT）中丙型肝炎病毒（HCV）感染及复发性肝病提供见解。我们研究了本中心的肝移植队列，自2005年2月至2006年7月期间对该队列进行了非方案性ATP水平检测。自1993年以来进行的280例肝移植中，114例（58.2%）符合入选标准，平均年龄为49±10岁。肝移植（单独/联合）适应证包括HCV（58%）、酒精性肝病（41%）、肝细胞癌（16%）及其他（33%）。共获得477个ATP水平数据：每位患者从移植时间起25个月（4天至19年）内获取3个（1 - 17个）数据。最终诊断为移植肝功能正常（n = 166，占35%）、复发性疾病（n = 199，占42%）、脓毒症事件（n = 34，占7%）、其他（n = 51，占11%）及未明确（n = 27，占6%）。66例HCV阳性患者共获得281个ATP水平数据[每位患者3个（1 - 18个）]。45例（占68%）出现经活检证实的复发性肝病[188/281个（占67%）ATP水平数据]。ATP水平中位数（纳克/毫升）为162（1 - 761）；HCV阳性患者（151±109）低于HCV阴性患者（211±139；P < 0.0001）。HCV阳性患者的ATP范围自移植后保持稳定。在HCV阴性患者中，ATP范围最初较高，最终降至HCV阳性患者水平（P = 0.01）。62%的HCV阴性患者免疫抑制剂水平较低，而HCV阳性患者中这一比例为38%（P = 0.04）。在HCV阳性患者中，疾病复发时ATP水平（139±97）低于无疾病复发时（181±141；P = 0.01），免疫抑制情况相似，且ATP水平随分级降低（P = 0.05）但不随分期降低。移植时间、天冬氨酸氨基转移酶/丙氨酸氨基转移酶 >1及低ATP水平与HCV复发独立相关。总之，肝移植后，与HCV阴性患者相比，HCV阳性患者的整体细胞免疫功能在基线时似乎受到抑制，在HCV阳性复发性疾病患者中更为明显。
