Efficacy of measuring natural killer-activating receptor ligands to predict the pathogenesis of metabolic dysfunction-associated steatotic liver disease

Objective: The proportion of metabolic dysfunction-associated steatotic liver disease (MASLD) in chronic liver diseases is increasing. The degree of intrahepatic natural killer (NK) cell infiltration has been reported to correlate with MASLD progression. We aimed to investigate the involvement of NK cell-activating receptor ligands in MASLD pathogenesis.
Methods: This study cohort comprised 69 patients with biopsy-proven MASLD. The concentrations of major histocompatibility complex class I polypeptide-related sequences A and B (MICA and MICB, respectively) and B7H6 in patient sera were measured.
Results: The metabolic dysfunction-associated steatohepatitis (MASH, n=44) group had a higher level of the ligands than the metabolic-associated steatotic liver (MASL, n=25) group. Interestingly, concentrations of B7H6 were significantly correlated with portal inflammation (P<0.001), rather than lobular inflammation. For the unadjusted analysis to predict MASH, the AUC scores for MICA, MICB, and B7H6 were 0.560, 0.609, and 0.648, respectively. After adjusting for gender, age, and BMI, the scores were 0.573, 0.791, and 0.750, respectively.
Conclusion: The three NK-activating receptor ligands were higher in the sera of the MASH group than those of the MASL group and strongly correlated with tumor markers, indicating the potential for hepatocarcinogenesis. Higher concentrations of serum B7H6 were correlated with advanced fibrosis and the degree of portal inflammation, which is a potential biomarker for predicting the pathogenesis of MASH.