Acute versus chronic liver disease drives different cardiac injury programmes, review proposes

The authors, Zheng Zhang, Yi Duan, Hongyu Huo and Zhifeng Gao, propose a conceptual framework that contrasts an “acute storm” with a “chronic siege” to organise what is known about liver-associated myocardial injury.

The review, published on 26 October 2026 as an open-access article, is explicitly a framework paper rather than a report of new experimental data. Its authors state that acute and chronic liver disease are associated with differing cardiac phenotypes and recovery trajectories, and they set out to compare the underlying signalling networks, immune-cell programming and injury mechanisms across these two settings, while allowing for overlap and transition between them.

In the acute scenario, the framework describes damage-associated molecular patterns and endotoxin as triggers of rapid, high-intensity activation of the TLR4/NF-κB signalling pathway, alongside mitochondrial oxidative stress. The review notes that ferroptosis and pyroptosis, two forms of regulated cell death, have been implicated as prominent programmes in preclinical models of acute cardiac injury. It is important to note that these are findings drawn from preclinical work, not from human clinical trials.

According to the proposed framework, the cardiac phenotype associated with this acute injury programme is predominantly functional depression, meaning the heart’s pumping performance is impaired, but with greater potential for recovery once the acute insult resolves. This contrasts with the chronic setting, where the authors argue the damage accumulates more slowly and is harder to reverse.

The chronic “siege” is described as sustained disruption of the gut-liver-heart axis, delivering persistent low-grade lipopolysaccharide, metabolic stressors and microbial metabolites to the cardiovascular system. The review suggests these sustained exposures may favour profibrotic macrophage states, contribute to impaired β-adrenergic reserve, and promote TGF-β-dependent fibroblast activation. The authors frame this as a self-reinforcing intercellular communication loop that culminates in progressive structural remodelling of the heart, with variable and often incomplete reversibility.

Between the two extremes, the review identifies a transitional grey zone. The authors present this boundary as a risk continuum rather than a fixed line separating acute from chronic injury.

The framework carries implications for future research priorities. The authors suggest that rapid control of acute inflammatory and injury pathways should be the focus for the storm scenario, while sustained metabolic and anti-fibrotic approaches would be more appropriate for the siege. They stress that these are suggested priorities for research rather than established therapeutic recommendations.

In other words, the central claims of the framework remain hypotheses to be verified, not confirmed clinical findings.

For readers following the field, the value of the paper lies less in new data than in its organising logic: it proposes that the timing and persistence of liver-derived inflammatory signals shape which signalling networks and cell death programmes dominate in the heart, and that this distinction should guide how researchers design the next generation of studies on liver-associated cardiac injury.

Subject of Research: How acute and chronic liver disease may injure the heart through distinct signalling and cell death pathways

Article Title: Acute storm versus chronic siege: divergent signalling networks and cell death programmes in liver-associated myocardial injury

Article References: Zhang, Z., Duan, Y., Huo, H., & Gao, Z. (2026). Acute storm versus chronic siege: divergent signalling networks and cell death programmes in liver-associated myocardial injury. Cell Communication and Signaling. https://doi.org/10.1186/s12964-026-03329-6

Image Credits: AI Generated

DOI: 10.1186/s12964-026-03329-6

Keywords: liver disease, myocardial injury, cardiac injury, inflammation, ferroptosis, pyroptosis, fibrosis, gut-liver-heart axis, TLR4, NF-kB, trained immunity, review