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A unique set of cytokine and chemokine markers could serve as biomarkers to differentiate non-alcoholic steatohepatitis from non-alcoholic fatty liver disease.

A unique set of cytokine and chemokine markers could serve as biomarkers to differentiate non-alcoholic steatohepatitis (NASH [MASH]) from non-alcoholic fatty liver disease (NAFLD [MASLD]), according to an observational cross-sectional study published in Inflammation.

Nadella Mounika and colleagues wrote, “Hepatic inflammation plays a key role in the pathophysiology of NAFLD. Inflammatory mediators such as cytokines and chemokines contribute to NAFLD development and progression. In the present study, we aimed to investigate the inflammatory protein signatures as predictive disease-specific markers for NAFLD.”

Serum concentrations of various cytokines and chemokines were assessed utilizing sensitive multiplex assays, and principal component analysis (PCoA) was used to reveal distinct variances in cytokine and chemokine levels between study groups. Additionally, a random forest classification model identified disease-predictive markers and protein-protein network analysis was conducted to ascertain the various signaling pathways correlated with the disease-specific panel of markers.

The study cohort included 233 patients between 20 and 65 years old. Patients were divided into three groups: 64 healthy individuals (control group), 109 patients with fatty liver confirmed by ultrasound (NAFL group), and 60 patients with fatty liver and inflammation, with or without fibrosis, confirmed by biopsy or fibro scan (NASH group). Participants had non-alcoholic fatty liver disease (NAFLD), limited alcohol consumption, and no other liver or chronic diseases, pregnancy, or history of abdominal surgery.

Results revealed that non-invasive markers such as APRI, AST/ALT, HSI, FIB-4, and NFS were statistically significant among the study groups. APRI, HSI, FIB-4, and NFS scores were higher in patients in the NASH group than in the control and NAFL groups.

“PCoA results demonstrated statistically significant differences in cytokines and chemokines between each of the study groups.” wrote the authors, “Our protein-protein network revealed that these markers are involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, TNF, chemokine, JAK/STAT, P13K/Akt, TLR, NOD-like receptor, NF-kB, and adipocytokine signaling pathways which might be responsible for disease pathogenesis.”

The authors concluded that distinct cytokine and chemokine markers could be employed as biomarkers in differentiating NASH from NAFL; however, additional larger multicenter studies are needed to ascertain the potential usefulness of these panels of markers.

Lastly, the authors wrote, “Future studies are recommended focusing on the various molecular pathways that are identified in our study for therapeutic decision-making.”