Alcohol-Related Liver Disease: Insights From Clinical, Histological, and Molecular Profiling

Patients with alcohol-related hepatitis (AH) exhibit a more profound deregulation of gene expression compared with patients with never-decompensated alcohol-related liver disease (ndALD). These were among other study findings published in Gut.

Many forms of alcohol-related liver disease (ALD) are known to be clinically silent, which may affect the opportunity for early diagnosis. Since a life-threatening decompensated AH episode can develop at any stage of ALD, researchers hypothesized that a clinical, histological, and molecular characterization of ndALD and AH could help clarify critical biomarkers and pathways of disease progression. The ultimate goal was to lead to early diagnosis and new drug targets.

In an international, observational multicenter study, a clinical, analytical, immunohistochemistry, and hepatic RNA microarray analysis was performed on a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225).

Compared with ndALD patients, AH patients had a greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels. Patients with AH vs ndALD also demonstrated profound liver failure and increased mortality (1-year mortality; 50% vs 10%). However, histologically, ballooning, pericellular fibrosis, and steatosis were similar in both groups.

Conversely, Mallory-Denk bodies, bilirubinostasis, advanced fibrosis, ductular reaction, and severe neutrophil infiltration were more frequent among patients with AH. A transcriptome analysis revealed a significant gene dysregulation within both phenotypes when compared with control participants. AH development led to a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism, and ndALD demonstrated deregulated gene expression regarding matrisome and immune response.

“This study might contribute to increased awareness of the analytical and histological features of early compensated forms of ALD,” the researchers wrote. “The molecular characterization of ndALD could favor the development of novel pathophysiological-based targeted therapies.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Ventura-Cots M, Argemi J, Jones PD, et al. Clinical, histological and molecular profiling of different stages of alcohol-related liver disease. Gut. Published online January 6, 2022. doi:10.1136/gutjnl-2021-324295