Sepsis-Induced Liver Dysfunction Mechanisms

Sepsis-induced liver dysfunction arises from an intricate interplay between systemic inflammation, microcirculatory derangements and intrinsic hepatic responses. Endothelial barrier disruption and impaired sinusoidal perfusion precipitate hypoxic injury in hepatocytes, while activated Kupffer cells and recruited neutrophils release cytokines, reactive oxygen species and proteases. Concomitant metabolic reprogramming in hepatocytes and non-parenchymal cells alters bile acid transport, impairs bilirubin conjugation and disrupts lipid and glucose homeostasis. Dysregulated innate immune signalling engages inflammasomes and pyroptotic pathways in hepatocytes, amplifying cell death and inflammation. Organelle stress, including endoplasmic reticulum and Golgi fragmentation, further contributes to hepatocellular apoptosis and cytokine overproduction via NF-κB and PI3K–AKT cascades. Gut-liver crosstalk, mediated by bacterial translocation and altered microbial metabolites, exacerbates liver injury by perpetuating systemic endotoxaemia. Collectively, these mechanisms underlie early cholestasis and biochemical disturbances in sepsis, highlight potential biomarkers in bile acids and identify targets for modulating immune-metabolic circuits to preserve hepatic function and improve clinical outcomes.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Sepsis-Induced Liver Dysfunction Mechanisms publication trend

The graph below shows the total number of articles in sepsis-induced liver dysfunction mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Kupffer cells: Resident macrophages of the liver sinusoids that clear pathogens and release cytokines during inflammation.

Liver sinusoidal endothelial cells (LSECs): Fenestrated endothelial cells lining hepatic sinusoids, crucial for microcirculatory exchange and immune surveillance.

Pyroptosis: A form of programmed cell death driven by inflammatory caspases and characterised by gasdermin-mediated membrane pore formation.

Cholestasis: Impairment of bile flow leading to accumulation of bilirubin and bile acids in liver and circulation.

Golgi stress: Disruption of Golgi structure and function under pathological conditions, triggering stress responses and apoptosis.

References

1. Single‐cell RNA sequencing reveals the effects of capsaicin in the treatment of sepsis‐induced liver injury. MedComm (2023).
2. GOLPH3 promotes endotoxemia-induced liver and kidney injury through Golgi stress-mediated apoptosis and inflammatory response. Cell Death & Disease (2023).
3. Gut-liver crosstalk in sepsis-induced liver injury. Critical Care (2020).
4. Advances in sepsis-associated liver dysfunction. Burns & Trauma (2014).
5. HSPA12A attenuates lipopolysaccharide-induced liver injury through inhibiting caspase-11-mediated hepatocyte pyroptosis via PGC-1α-dependent acyloxyacyl hydrolase expression. Cell Death & Differentiation (2020).