Serum GRP78 as a potential biomarker for early liver injury and active fibrogenesis in alcohol-associated liver disease

Alcohol-associated liver disease(ALD) is an important cause of liver-related lesions and death, mainly caused by long-term or excessive alcohol consumption.Reactive oxygen species (ROS) produced during alcohol metabolism induce an oxidative stress response, which GRP78 playing an important regulatory role. This study aims to investigate the relationship between serum GRP78 levels and liver fibrosis/cirrhosis in ALD patients. A case control study was conducted, involving ALD patients (n = 122) and healthy participants (n = 28). Liver steatosis and fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum GRP78 was measured by sandwich ELISA based on two monoclonal anti-GRP78 antibodies and calibrated with a standard of recombinant GRP78. Serum GRP78 levels increased in alcohol-associated steatohepatitis and alcoholic hepatitis patients correlated with early fibrosis severity (F1 fibrosis stage), but were significantly downregulated in patients with cirrhosis (F4 fibrosis stage). Furthermore, serum GRP78 levels showed a weak negative correlation with liver stiffness measurements (LSM; r = - 0.2064, p = 0.0365) and demonstrated a notable association with the severely advanced fibrotic stage in ALD patients, while showing no significant correlation with the controlled attenuation parameter (CAP) associated with liver steatosis. This study suggests that serum GRP78 is a potential noninvasive biomarker for early liver injury and active fibrogenesis in ALD patients. When combined with LSM, it improves diagnostic accuracy for advanced fibrosis and cirrhosis.