IgA-autoantibodies to histone 2B allow to differentiate between alcohol- and metabolic dysfunction-associated...

The diagnosis of alcohol-associated liver disease (ALD), and especially the differential diagnosis with metabolic dysfunction-associated steatotic LD (MASLD) remains challenging and is primarily dependent on the patient's medical history. Several autoantibodies have been described in ALD but they are not specific to this condition. Preliminary studies provided evidence that antibodies to histone 2B (H2B) of the IgA-type are strongly associated with ALD. This retrospective study demonstrates that they may serve as a novel biomarker for the disease and correlate with liver cirrhosis.

Sera from 985 patients with different chronic LD (ALD n = 171, toxic LD n = 51, MASLD n = 138, cryptogenic cirrhosis n = 17, autoimmune LD n = 518) were tested for anti-H2B-IgA-antibodies using an in-house ELISA. Laboratory parameters were available for all patients and histological data for 718 patients.

Prevalence and reactivity of anti-H2B-IgA-antibodies were significantly higher in patients with ALD than in all other groups except those with cryptogenic cirrhosis. The antibodies were predominantly found in patients with advanced LD, but did not correlate with patient-reported amount of alcohol intake. The presence of anti-H2B-IgA antibodies increases the risk of suffering from ALD by 29 times.

Anti-H2B-IgA-antibodies in sera from patients with chronic LD are strongly indicative of an alcoholic/toxic process and facilitate differentiation from MASLD.