非侵入性血清学标志物在肝移植受者早期移植物排斥反应管理中的应用。

The utility of noninvasive serologic markers in the management of early allograft rejection in liver transplantation recipients.

作者信息

Dickson R C, Lauwers G Y, Rosen C B, Cantwell R, Nelson D R, Lau J Y

机构信息

Section of Hepatobiliary Diseases, University of Florida, Gainesville, USA.

出版信息

Transplantation. 1999 Jul 27;68(2):247-53. doi: 10.1097/00007890-199907270-00015.

DOI:10.1097/00007890-199907270-00015

PMID:10440396

Abstract

BACKGROUND

Early allograft rejection after orthotopic liver transplantation (OLT) currently requires a biopsy for diagnosis. Alpha-glutathione S-transferase (alpha-GST) and Pi-glutathione S-transferase (Pi-GST) are potential noninvasive markers of hepatocyte and biliary epithelial cell injury. Our aim was to determine the utility of noninvasive serologic markers in the management of early hepatic allograft rejection.

METHODS

Forty-four of 52 consecutive adult patients undergoing primary OLT at the University of Florida were included in the study. All had protocol liver biopsies between days 6 and 8 after OLT. Serum alpha-GST and plasma Pi-GST were determined using a sandwich enzyme immunoassay (Biotrin International, Dublin, Ireland). All biopsy specimens were retrospectively reviewed and scored for rejection and cholestasis.

RESULTS

The biopsy specimens were scored for rejection as moderate to severe in 14 patients (group 1) or none to mild in 30 patients (group 2). Group 1 had statistically higher mean levels than group 2 for alpha-GST on days 6, 7, and 9; alanine aminotransferase on days 6 and 9; aspartate aminotransferase (AST) on days 6 and 7; alkaline phosphate (AP) on days 3 through 7, 9, and 10; and gamma-glutamyl transferase on day 3. No differences between groups were seen with Pi-GST or total bilirubin. Between days 6 and 8, the following values were found more frequently in group 1 than group 2: alpha-GST level >15 ng/ml (11/14 vs. 14/30; P<0.01); AST >100 U/L (8/14 vs. 2/30; P=0.002); and AP >120 U/L (14/14 vs. 17/30). Combining AP with either alpha-GST or AST led to improved detection of rejection over any single marker alone. In the first week after the initiation of rejection treatment, alpha-GST was the only marker that accurately predicted response.

CONCLUSION

Serum alpha-GST may be useful in the management of early hepatic allograft rejection. A combination of noninvasive markers may be beneficial to diagnose early hepatic allograft rejection.

摘要

背景

目前原位肝移植（OLT）后早期移植物排斥反应需要通过活检来诊断。α-谷胱甘肽S-转移酶（α-GST）和π-谷胱甘肽S-转移酶（π-GST）是肝细胞和胆管上皮细胞损伤的潜在非侵入性标志物。我们的目的是确定非侵入性血清学标志物在早期肝移植排斥反应管理中的效用。

方法

佛罗里达大学连续52例接受初次OLT的成年患者中有44例纳入本研究。所有患者在OLT后第6至8天进行了常规肝脏活检。采用夹心酶免疫测定法（爱尔兰都柏林的Biotrin International公司）测定血清α-GST和血浆π-GST。所有活检标本均进行回顾性审查，并对排斥反应和胆汁淤积进行评分。

结果

活检标本的排斥反应评分为14例患者为中度至重度（第1组），30例患者为无至轻度（第2组）。第1组在第6、7和9天的α-GST平均水平、第6和9天的丙氨酸转氨酶、第6和7天的天冬氨酸转氨酶（AST）、第3至7天、9和10天的碱性磷酸酶（AP）以及第3天的γ-谷氨酰转移酶在统计学上均高于第2组。π-GST或总胆红素在两组之间未见差异。在第6至8天，第1组中以下值出现的频率高于第2组：α-GST水平>15 ng/ml（11/14对14/30；P<0.01）；AST>100 U/L（8/14对2/30；P=0.002）；以及AP>120 U/L（14/14对17/30）。将AP与α-GST或AST联合使用比单独使用任何一种标志物能更好地检测排斥反应。在开始排斥反应治疗后的第一周，α-GST是唯一能准确预测反应的标志物。