Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure.
Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure.
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DOI：
10.3748/wjg.v20.i9.2403
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发表时间：
2014-03
影响因子：
4.3
通讯作者：
S. Zheng;Shuang Liu;Mei Liu;M. McCrae;Jun-feng Li;Yuanping Han;Chun Xu;F. Ren;Yu Chen;Z. Duan
中科院分区：
文献类型：
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作者：
S. Zheng;Shuang Liu;Mei Liu;M. McCrae;Jun-feng Li;Yuanping Han;Chun Xu;F. Ren;Yu Chen;Z. Duan
目的探讨循环细胞死亡指标对慢性肝炎B病毒（HBV）感染为单一病因的慢加急性肝衰竭（ACLF）患者预后的价值。方法全长和半胱天冬酶切割的细胞角蛋白18（检测为M65和M30抗原）代表坏死和凋亡的循环指标。采用酶联免疫吸附试验（ELISA）检测169例慢性B肝炎（CHB）患者、33例健康对照者和81例ACLF患者血清中M65和M30。根据3个月生存期，ACLF患者被定义为自发恢复（n = 33）和非自发恢复（包括死亡患者和需要肝移植的患者）（n = 48）。结果两种生物标志物水平随着肝病进展而逐渐显著增加（对于M65：所有P < 0.001;对于M30：对照vs CHB，P = 0.072;其他：所有P < 0.001）。对照组M30/M65比值显著高于慢性乙型肝炎患者（P = 0.010）和急性肝衰竭患者（P < 0.001）。此外，受试者工作特征曲线下面积（AUC）分析表明，这两种生物标志物在识别CHB患者的ACLF方面具有诊断价值（AUC ≥ 0.80）。有趣的是，值得注意的是，ACLF患者自发和非自发恢复之间的M30/M65比值存在显著差异（P = 0.032）。将M30/M65比值与终末期肝病模型（MELD）和Child-Pugh评分比较，其AUC为0.66，敏感性为52.9%，特异性最高为92.6%（MELD：AUC = 0.71;敏感性，79.4%;特异性，63.0%; Child-Pugh：AUC = 0.77;敏感性，61.8%;特异性，88.9%）。结论M65和M30与肝脏疾病严重程度密切相关。M30/M65比值可能是HBV相关ACLF患者自发恢复的潜在预后指标。
AIM To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC ≥ 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF.