Investigating Alcoholic Hepatitis Using Serum Keratin 18 (M60 and M35) as Diagnostic and Prognostic Biomarkers (Code-T0069)

Background: Alcoholic Liver Disease (ALD) is a major cause of chronic liver disease worldwide, progressing from simple steatosis to more severe forms such as alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. The pathogenesis of ALD is multifactorial, involving genetic predispositions, alcohol-induced hepatocyte damage, and inflammation. Cytokeratin 18 (CK18), a biomarker released from necrotic and apoptotic cells, is emerging as a valuable tool in diagnosing AH.

Aim and Objectives:

1. Primary objective is to compare aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the AST:ALT ratio with K18M65 and M30 levels in determining the diagnosis of Alcoholic Hepatitis and severity of liver disease as assessed by MELD in chronic heavy alcohol users.
2. Secondary objective is to compare serum K18 concentrations with commonly used biomarkers of Alcoholic Hepatitis in predicting 3- month mortality.

Methods: A cohort of chronic heavy alcohol users was enrolled, and their serum levels of CK18 fragments (K18M65 and K18M30), AST, ALT, and AST/ALT ratio were measured. Participants were categorized into mild, moderate, and severe groups based on their Model for End-Stage Liver Disease (MELD) scores. Serum levels of K18M65 and K18M30 were quantified using ELISA and analyzed in relation to disease severity, liver function, and mortality outcomes.

Results: Both K18M65 and K18M30 levels were significantly higher in patients with severe alcoholic hepatitis. K18M65 levels increased from 1423 U/L in mild cases to 2884 U/L in severe cases (p=0.004), while K18M30 levels rose from 634 U/L to 1542 U/L (p=0.009). The K18M65/ALT ratio showed a significant correlation with disease severity (p=0.029). Moreover, higher levels of K18M65 and K18M30 were strongly associated with mortality risk, with deceased patients showing significantly elevated levels (K18M65: 4732 U/L vs. 2094 U/L; p=0.002, K18M30: 2624 U/L vs. 1052 U/L; p=0.002). The K18M65/ALT ratio was also higher in deceased patients (p=0.021). Receiver operating characteristic (ROC) analysis demonstrated that K18M65 had excellent diagnostic accuracy, with an area under the curve (AUC) of 0.927 and 100% sensitivity at a cut-off of 2580 U/L.

Conclusion: Serum CK18 fragments, particularly K18M65 and K18M30, are promising biomarkers for diagnosing and predicting the prognosis of alcoholic hepatitis. These biomarkers are superior to traditional liver enzymes in correlating with disease severity. Their integration into clinical practice could improve management and outcomes for patients with alcoholic hepatitis.

Keywords: Alcoholic Liver Disease (ALD), Alcoholic Hepatitis (AH), Cytokeratin 18 (CK18), Biomarkers, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Liver Disease Severity, M65 Assay, M30 Assay.Bottom of Form