P34 Alterations in plasma neurofilament light chain in acute and chronic liver failure syndromes

<h3>Introduction</h3> Hepatic encephalopathy (HE) is a neuropsychiatric complication of both chronic and acute liver failure syndromes. Hyperammonaemia and systemic inflammation have been identified as key triggers for HE, but current diagnostic approaches imperfect. Neurofilament light chain (NfL) has emerged as a promising biomarker in various neurological disorders due to its correlation with neuroaxonal damage, as reflected in cerebrospinal fluid and blood levels. This study investigates the potential of NfL as a circulating marker of neuronal dysfunction in cirrhosis and acute liver failure (ALF). <h3>Methods</h3> We studied pre-defined chronic and acute liver disease cohorts [stable cirrhosis (SC, n=44), decompensated cirrhosis (DC, n=61), acute-on-chronic liver failure (ACLF, n=43)] and ALF (n=29), in comparison with 25 non-liver sepsis patients (NLS) as ‘positive disease’ controls, and 19 healthy controls (HC). The severity of HE was graded at the time of blood sampling using the West Haven criteria. Plasma NfL and IL-6 levels were quantified using electrochemiluminescence assays (MSD). Clinical data, including ammonia levels, were retrieved from patients’ records. <h3>Results</h3> Median NfL levels showed a stepwise increase systemically with cirrhosis severity (SC/DC/ACLF 41/74/161 pg/mL), irrespective of HE presence, compared to HC (13 pg/mL, p&lt;0.0001) (figure.1). Plasma NfL concentrations were significantly higher in cirrhosis patients diagnosed with clinically-significant HE compared to those without (124 vs 63 pg/mL, p&lt;0.0001). In cirrhosis, NfL levels effectively discriminated between HE grade 0 and grades 1/2, which is clinically challenging due to subtlety in symptoms at these lower grades (AUC=0.69, p=0.003). ALF patients, characterised by high grade HE (3/4), had NfL levels comparable to SC and DC patients. Notably, NLS patients had the highest NfL levels (400 pg/mL) (figure 1). In cirrhosis, but not in ALF, spontaneous survivors had lower plasma NfL levels compared to non-survivors at 30 days post-sampling (p&lt;0.0001). Correlation analysis revealed that plasma NfL is closely associated with IL-6 in SC and DC (r=0.69, p=0.001), but not with ammonia; no significant correlations were observed in ACLF and ALF patients. <h3>Conclusion</h3> NfL has biomarker potential as an adjunct in the diagnosis and grading of HE in cirrhosis patients, and may have additional prognostication value for survival outcome. Systemic inflammation seems to be associated with neuronal dysfunction in SC and DC, whilst the lack of correlation with IL-6 or ammonia levels suggest novel neuroinflammatory pathways contribute to the pathophysiology of HE in ACLF and ALF.