Abstracts Division 2
40. The lysosomal enzyme cathepsin D as a new diagnostic indicator for alcoholic liver disease
Mengying Li1, Tom Houben1, Mad Egerod Israelsen2, Maria Kjærgaard2, Marit Westerterp3, Aleksander Ahm Krag2, Maja Thiele2, Ronit Shiri-Sverdlov1
1 Department of Genetics and Cell Biology, School of Nutrition and Translational Research in Metabolism, Maastricht University, the Netherlands
2 Center for Liver Research, Odense University Hospital and University of Southern Denmark, Kloevermarken 10, entrance 112, DK-5000 Odense, Denmark.
3 Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Background
Alcohol is the seventh leading cause of premature death worldwide, many of whom die from alcohol-related liver disease (ALD). However, underlying pathological mechanisms causing the early stages of ALD are currently under-investigated. Lysosomal cathepsin D (CTSD) was previously shown to detect early stages of NAFLD, and circulating CTSD is known to be elevated in advanced liver disease. We therefore investigated plasma CTSD in relation to different histological stages of ALD.
Methods
We conducted a cross-sectional study of 305 asymptomatic ALD patients with a liver biopsy scored according to the NAS CRN system, and compared their plasma CTSD levels with 40 healthy controls, matched for age, gender and BMI. We excluded patients with decompensation at baseline. Next, we determined the correlations between plasma CTSD levels and histology scored for fibrosis, ballooning, lobular inflammation and steatosis. Areas under the receiver operating characteristic curve (AUC) were generated to investigate the accuracy of plasma CTSD levels alone or in combination with known non-invasive markers to predict ALD.
Results
Plasma CTSD levels were significantly higher in ALD patients compared to matched healthy controls (37.7 vs 22.9 ng/mL; AUC 0.838). While hepatic diagnostic parameters (AST/ALT ratio and Telimedian levels) were linked to advanced ALD stages based on the NAS scores, plasma CTSD levels were highest at early ALD stages and declined upon more advanced ALD stages. Further, plasma CTSD levels exhibited a weak negative correlation with the ELF test and transient elastography and hepatic diagnostic determinants independently correlated with plasma CTSD levels. Furthermore, combining plasma CTSD levels with transient elastography and AST/ALT ratio resulted in a high diagnostic accuracy (ROC-AUC: 0.893) for predicting ALD. Finally, plasma CTSD levels were increased in drinking individuals and remained elevated even after abstinence.
Conclusion
Lysosomal leakage of CTSD into the circulation may be a sensitive marker of early stages of ALD.
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