Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2403
Revised: December 31, 2013
Accepted: January 19, 2014
Published online: March 7, 2014
Processing time: 168 Days and 3.5 Hours
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.
Core tip: Massive hepatic cell death is a key characteristic of liver failure. Enzyme-linked immunosorbent assay was used to measure M65 and M30 in a chronic hepatitis B (CHB) infection cohort which included healthy controls, CHB and acute-on-chronic liver failure (ACLF) patients. Elevated M65 and M30 differentiated CHB or ACLF patients from healthy controls and gradually increased with disease severity. M30/M65 was significantly increased in ACLF patients with spontaneous recovery (P = 0.032), and the AUC of this ratio at the 3-mo survival period was 0.661 (sensitivity: 52.9%) with a high specificity (92.6%) compared with the Model for End-Stage Liver Disease and Child-Pugh scores.