Krishnan A, Mukherjee D. Role of autoimmune phenomena in nonalcoholic fatty liver disease: Insights and limitations. World J Hepatol 2025; 17(3): 103835 [DOI: 10.4254/wjh.v17.i3.103835]
Corresponding Author of This Article
Arunkumar Krishnan, MD, Assistant Professor, Department of Supportive Oncology, Atrium Health Levine Cancer, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Mar 27, 2025; 17(3): 103835 Published online Mar 27, 2025. doi: 10.4254/wjh.v17.i3.103835
Role of autoimmune phenomena in nonalcoholic fatty liver disease: Insights and limitations
Arunkumar Krishnan, Diptasree Mukherjee
Arunkumar Krishnan, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States
Arunkumar Krishnan, Department of Supportive Oncology, Atrium Health Levine Cancer, Charlotte, NC 28204, United States
Diptasree Mukherjee, Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar 751019, Odisha, India
Co-first authors: Arunkumar Krishnan and Diptasree Mukherjee.
Author contributions: Krishnan A contributed to the concept of the study; Mukherjee D and Krishnan A were involved in critically revising the manuscript for important intellectual content, drafting the manuscript, and participating in the review and editing, they contributed equally to this article, they are the co-first authors of this manuscript; and all authors reviewed and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arunkumar Krishnan, MD, Assistant Professor, Department of Supportive Oncology, Atrium Health Levine Cancer, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Received: December 2, 2024 Revised: February 21, 2025 Accepted: March 5, 2025 Published online: March 27, 2025 Processing time: 114 Days and 6.5 Hours
Abstract
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 et al. 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.
Core Tip: A study by Zhu et al investigated the presence of autoantibodies across different histological stages of nonalcoholic fatty liver disease (NAFLD). The findings suggest that autoantibodies may play a role in the immune dysregulation observed in NAFLD. We recommend further refinement by incorporating prospective methods and controlling for additional confounding factors such as body mass index and metabolic comorbidities. Expanding the antibody panel and measuring antibody titers with greater granularity could enhance the accuracy. Moreover, stratifying data by age and sex and exploring cytokine profiles may provide a better understanding of the immunological mechanisms involved in NAFLD progression.
