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Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure
Su-Jun Zheng1, Shuang Liu1, Mei Liu1
1Su-Jun Zheng, Shuang Liu, Mei Liu, Jun-Feng Li, Feng Ren, Yu Chen, Zhong-Ping Duan, Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
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.
Insights
Circulating cell death indicators, M65 and M30, correlate with liver disease severity in chronic hepatitis B patients. The M30/M65 ratio shows potential for predicting spontaneous recovery in acute-on-chronic liver failure (ACLF).
Area of Science:
- Hepatology
- Biomarker Discovery
- Liver Disease Pathophysiology
Background:
- Acute-on-chronic liver failure (ACLF) in chronic hepatitis B virus (HBV) infection presents a significant clinical challenge.
- Circulating biomarkers indicating hepatocyte death, specifically cytokeratin 18 fragments (M65 and M30), are being investigated for their role in liver disease.
Purpose of the Study:
- To evaluate the prognostic significance of M65 and M30 in patients with HBV-related ACLF.
- To assess the diagnostic and prognostic capabilities of these biomarkers in comparison to established scoring systems.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure M65 and M30 levels in healthy controls, chronic hepatitis B (CHB) patients, and ACLF patients.
- ACLF patients were categorized based on 3-month survival into spontaneous recovery and non-spontaneous recovery groups.
Main Results:
- M65 and M30 levels increased with liver disease severity (P < 0.001).
- The M30/M65 ratio was significantly lower in CHB and ACLF patients compared to controls (P < 0.001).
- The M30/M65 ratio differentiated between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032), showing high specificity (92.6%) for predicting outcomes.
Conclusions:
- M65 and M30 are strongly linked to the severity of liver disease.
- The M30/M65 ratio emerges as a promising prognostic marker for spontaneous recovery in HBV-related ACLF patients.
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