Evidence for alcohol-mediated masked hemolysis in ALD patients and a vicious cycle of hemolysis and iron-mediated liver damage

Background and Aims Our recent study indicates that red blood cells (RBC) are also an important target in alcohol-related injury. We here studied the injury of hematologic system in ALD patients and its translational relation with liver injury.

Methods Based on a large prospectively patient cohort of heavy drinkers, we identify a subgroup of 25% with high ferritin and low hemoglobin levels that show the worst outcome. RBC fragility in the ALD patients with the normal people by the hemolytic agent phenyl hydrazine (PHZ). The ALD mouse model was applied to observe the damage caused by alcohol in bone marrow and erythropoiesis. In addition, hemolysis and iron overload models were used to verify the vicious effect of iron accumulation on liver function.

Results In the subgroup with high ferritin and low hemoglobin, the large erythrocytes, elevated unconjugated bilirubin and LDH are highly suggestive of enhanced hemolysis. This is further confirmed by the high expression of CD163. Moreover, despite iron overload in these patients, serum levels of the iron master switch hepcidin were suppressed ultimately causing further iron uptake. ALD mouse showed less hematopoietic cells, and acute ethanol binge even caused quick erythroid inhibition. In both iron overload model and hemolytic model, serum iron and hepcidin were increased, while the hemolytic and iron overloading combined mouse model showed no further hepcidin upregulation with even higher serum iron.

Conclusion Our translational findings suggest a novel role of heme turnover in hemolytic damage of patients with ALD.

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Artikel online veröffentlicht:
26. Januar 2022