Inflammation links liver fibrosis development to diastolic myocardial function in early alcohol-associated liver disease
C Grander, M Riederer, C Wenter, P Strobl, L Gatterer, S Zagitzer-Hofer, Y Aysar, J Seneca, P Pjevac, I Graziadei, H Tilg, J Marksteiner, W GranderAbstract
Background/Introduction
Chronic alcohol consumption induces persistent low-grade systemic inflammation, contributing to organ dysfunction. While hepatic injury is well characterized, early myocardial involvement in alcohol use disorder (AUD) remains poorly understood. Growth differentiation factor-15 (GDF-15), a stress-induced cytokine, regulates metabolism and inflammation and may link hepatic and cardiac injury.
Purpose
To investigate mechanisms and biomarkers underlying concurrent liver and myocardial dysfunction in early AUD, with a focus on GDF-15 as a potential hepato-cardiac marker.
Methods
The study integrated data from a murine model of alcohol-associated liver disease with a human cohort comprising patients with alcohol use disorder (AUD; n = 50) undergoing inpatient detoxification to test the proposed hypothesis.
Results
In mice fed an ethanol-containing diet, histological liver injury, myocyte thickening, and elevated circulating growth differentiation factor 15 (GDF-15) levels were observed. Patients with early stage of alcohol use disorder (AUD) exhibited impaired myocardial function characterized by elevated E/e′ ratios and reduced global myocardial strain. Circulating GDF-15 levels were increased in AUD and correlated positively with myocardial strain parameters, and systemic inflammatory markers, including LPS-binding protein, TNF, and IL-10. During alcohol abstinence, myocardial strain improved and GDF-15 levels decreased. Notably, higher baseline GDF-15 levels predicted a subsequent improvement in myocardial contractility after sustained abstinence, supporting a potential cardioprotective role of GDF-15. Finally, gut microbiota alterations appeared to be linked to myocardial and inflammatory changes, as the commensal bacterium Parasutterella excrementihominis was inversely associated with GDF-15 levels.
Conclusions
Alcohol induced myocardial alterations are more likely influenced by microbiota driven inflammation and GDF-15 than toxic effects of ethanol.