Role of autoimmune phenomena in nonalcoholic fatty liver disease: Insights and limitations

Metabolic dysfunction-associated steatotic liver disease, previously known as nonalcoholic fatty liver disease (NAFLD), is becoming increasingly common and is associated with significant morbidity and mortality related to both liver and non-liver issues. In its early stages, NAFLD is characterized by immune cell dysregulation, which suggests that immune-targeted therapies could be a viable treatment option for nonalcoholic steatohepatitis. A recent study by Zhu <i>et al</i>. investigated the role of autoantibodies in metabolic dysfunction-associated steatotic liver disease at various histological stages. While the research provided valuable insights, several methodological concerns are noted, which include the study's retrospective design, a limited panel of autoantibodies, and a lack of a prospective study design that adequately controls for confounding factors such as age, comorbidities and lifestyle. Furthermore, the interpretation of positive antinuclear antibodies as evidence of autoimmune involvement in NAFLD is questioned due to the possibility of nonspecific immune responses. Recommendations to improve the study's design include conducting prospective studies, implementing more detailed antibody profiling, and adjusting for demographic and clinical factors. Future studies should address these issues to improve the clinical relevance and credibility of findings related to autoimmunity in NAFLD.