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The presence of interferon affects the progression of non-alcoholic fatty liver disease

Genes & Immunity volume 23, pages 157–165 (2022)Cite this article

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Abstract

Inflammation and metabolic dysfunction are hallmarks of the progression of non-alcoholic fatty liver disease (NAFLD), which is the fastest-growing liver disease worldwide. Emerging evidence indicates that innate immune mechanisms are essential drivers of fibrosis development in chronic inflammatory liver diseases, including NAFLD. In this study, 142 NAFLD patients were genotyped for three IFNL4 single-nucleotide variants in order to investigate the genetic relationship between IFNL4 and fibrosis in NAFLD patients. We observed an overrepresentation of the non-functional IFNL4 allele in patients with significant fibrosis (>F2). Next, we investigated the potential protective role of interferon (IFN) in relation to the development of liver fibrosis in an animal model of non-alcoholic steatohepatitis (NASH). In contradiction to our hypothesis, the results showed an increase in fibrosis in IFN treated animals. Our study clearly indicates that IFN is able to affect the development of liver fibrosis, although our clinical and experimental data are conflicting.

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Fig. 1: Interferon response to different dosages of rIFNα.
Fig. 2: Body weight changes during the 16-week experiment.
Fig. 3: Interferon response during the 16-week experiment.
Fig. 4: Blood and tissue evaluation.

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Data availability

The data that support the findings of this study are available on request from the corresponding author, MM, upon reasonable request. The data are not publicly available due to the privacy of the human participants.

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Funding

This study was supported by Danmarks Frie Forskningsfond (7016-00331B), Novo Nordisk Fonden (NNF19OC0055039), and Fabrikant Vilhelm Pedersen og hustrus mindelegat. The funding sources had no role in the study design, collection, analysis, and interpretation of data, writing of the paper or the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark

    Michelle Møhlenberg & Rune Hartmann

  2. Department of Biomedicine, Aarhus University, Aarhus C, Denmark

    Michelle Møhlenberg

  3. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark

    Peter Lykke Eriksen, Tea Lund Laursen, Henning Grønbæk & Karen Louise Thomsen

  4. Department of Pathology, Aarhus University Hospital, Aarhus N, Denmark

    Mette Bak Nielsen & Stephen Jacques Hamilton Dutoit

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  1. Michelle Møhlenberg
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Contributions

MM, KLT, HG, and RH contributed to study design, data collection, data analysis, data interpretation. PLE and TLL contributed with patient inclusion. SJHD and MBN performed histopathological analyses. MM wrote the paper draft. MM performed the literature search, created figures and tables. The final version of this paper was reviewed and approved by all authors.

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Correspondence to Michelle Møhlenberg.

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Møhlenberg, M., Eriksen, P.L., Laursen, T.L. et al. The presence of interferon affects the progression of non-alcoholic fatty liver disease. Genes Immun 23, 157–165 (2022). https://doi.org/10.1038/s41435-022-00176-6

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