Serum keratin 18‐M65 levels detect progressive forms of alcohol‐associated liver disease in early noncirrhotic stages
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Background and Aims: The progression of alcohol‐associated liver disease (ALD) in its early precirrhotic stages can be a silent process. Serum keratin 18 levels (K18‐M65) predict severe events and mortality in advanced stages of ALD, but data on this biomarker in early stages are scarce. We evaluated the diagnostic accuracy of K18‐M65 levels in identifying early forms of ALD. Methods: We prospectively evaluated two cohorts of actively drinking patients with alcohol use disorder (AUD) following a rehabilitation program (training (n = 162) and validation (n = 78)) and matched healthy controls (n = 21). Clinical, laboratory, and imaging data were used to distinguish AUD patients with simple steatosis (minimal ALD) and steatohepatitis/fibrosis (early ALD). We measured serum K18‐M65 levels and assessed their ability to predict early ALD. Results: High levels of K18‐M65 characterized AUD patients with early ALD, while levels in the minimal ALD group were similar to those in healthy controls. K18‐M65 levels distinguished minimal liver disease from early ALD (AUROC = 0.8704; p < 0.0001) with an optimal cutoff at 265.9 U/L. K18‐M65 levels strongly correlated with transaminases and predicted early ALD (OR 25.81; 95% CI 3.166–336.1; p < 0.0001), controlled attenuation parameter, and liver stiffness independently from transaminases and other potential confounders. K18‐M65 levels did not discriminate between fibrosis and steatohepatitis but correlated with histological signs of hepatocellular injury and inflammation (all p < 0.05). The K18‐M65 cutoff detected early ALD in the validation cohort with high accuracy (sensitivity 86.67%, specificity 96.67%) and a very high positive likelihood ratio (28.6; 95% CI 4.14–197.73). Conclusions: Serum K18‐M65 levels can be used as a biomarker to detect early ALD stages with excellent predictive value.
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Human ALD patients show significant downregulation of gene sets related to T cell selection and adaptive immunity, with CD8A among the leading downregulated genes.
“Patients with ALD26 had a significant down-regulation of gene sets linked to T cell selection and adaptive immunity, with CD8A being one of the leading downregulated genes (Fig.4B, C, supplementary Table 3).”
From Opposite regulation of intestinal and intrahepatic CD8 <sup>+</sup> T cells controls alcohol-associated liver disease progression (2025) · cites this paper as [26]
The Results section describes a cohort of patients with alcohol-associated liver disease, but reports K18-M65 measurements and limited liver-tissue mRNA correlations, not gene-set analysis. Searches for CD8A, T-cell selection, and adaptive immunity found no passage in our copy reporting the claimed downregulation. (LLM, conf=0.76)
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- Authors
- Maccioni, L., Horsmans, Y., Leclercq, I., Schnabl, B., & Stärkel, P.
- Affiliations
- UCLouvain (BE)
- Cliniques Universitaires Saint-Luc (BE)
- University of California San Diego (US)
- Corresponding author
- Stärkel, Peter
- Venue
- Alcohol: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2023-04-27
- Volume
- 47
- Issue
- 6
- Pages
- 1079-1087
- ISSN
- 0145-6008 (ISSN-L)
- 2993-7175
- PMC
- PMC10803128
- OpenAlex
- W4365811052
- Cited by
- 10
- References
- 26
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Funders
- Biocodex Microbiota Foundation
- Biomedical Laboratory Research and Development, VA Office of Research and Development (BX004594)
- Fonds De La Recherche Scientifique - FNRS (J.0146.17, T.0217.18)
- Waalse Gewest (ARC 2018)
- National Institutes of Health (R01 AA24726, R37 AA020703, U01 AA026939, U01 AA026939‐04S1, DK120515, AA011999)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- alcoholic liver disease, alcoholism, biomarkers, steatohepatitis, liver fibrosis, simple steatosis, diagnostic accuracy, controlled attenuation parameter, liver stiffness, transaminases, hepatocyte injury
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