Narrative review explores immunometabolic networks in MASH and MASLD

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Frontiers in Medicine Published May 27, 2026 Medically reviewed May 27, 2026 Study authors: Jiang Yu, Yong Peng DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that immunometabolic profiling may guide future individualized treatment in MASH/MASLD, but evidence is preliminary.

This narrative review examines the role of immunometabolic networks in metabolic dysfunction-associated steatohepatitis (MASH) and metabolic dysfunction-associated steatotic liver disease (MASLD). The authors synthesize current understanding of the complex interplay between immune and metabolic pathways in disease progression. They argue that traditional single-target approaches may be insufficient given the heterogeneity of these conditions.

The review emphasizes that precision stratification based on immunometabolic profiles could enable more individualized treatment. Multi-target interventions that address both metabolic and inflammatory components are proposed as promising directions for future drug development. However, the review does not report specific study populations, sample sizes, interventions, or outcomes.

Limitations are not explicitly stated in the source, but as a narrative review, it provides a qualitative synthesis rather than a systematic analysis. The authors do not present pooled effect sizes or comparative data. The practice relevance is conceptual, suggesting that future research should focus on personalized strategies.

Clinicians should interpret these findings as exploratory. The review offers a framework for understanding disease mechanisms but does not provide actionable clinical recommendations. Further research, including clinical trials, is needed to validate these concepts.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Metabolic dysfunction-Associated Steatohepatitis (MASH) is a progressive subtype of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis, which may evolve to cirrhosis and hepatocellular carcinoma. Despite its growing global burden, no widely approved pharmacotherapy is available, highlighting the need to elucidate immunometabolic mechanisms and identify effective therapeutic targets. This review summarizes the epidemiology and clinical features of MASH and focuses on key pathogenic pathways, including insulin resistance, lipotoxicity, mitochondrial dysfunction, and gut-liver axis disturbance. Immune dysregulation mediated by Kupffer cell activation, macrophage polarization, inflammasome signaling, and cytokine networks is discussed in depth. The critical role of immunometabolic crosstalk in disease progression is emphasized. Current and emerging therapeutic targets—such as PPARs, FXR, THR-β, the GLP-1/FGF21 axis, DGAT2, and CCR2/CCR5—are systematically reviewed, together with advances in oligonucleotide therapy, cell-based interventions, and combination strategies. MASH results from the complex coupling of metabolic imbalance and immune-driven inflammation, making single-target therapy insufficient. Precision stratification based on immunometabolic networks and multi-target interventions represent promising directions for future drug development and individualized treatment.