Novel insights into alcoholic liver disease: Iron overload, iron sensing and hemolysis

[摘要] The liver is the major target organ of continued alcohol consumption at risk and resultingalcoholic liver disease (ALD) is the most common liver disease worldwide. The underlyingmolecular mechanisms are still poorly understood despite decades of scientific effort limitingour abilities to identify those individuals who are at risk to develop the disease, to developappropriate screening strategies and, in addition, to develop targeted therapeutic approaches.ALD is predestined for the newly evolving translational medicine, as conventional clinical andhealth care structures seem to be constrained to fully appreciate this disease. This concept paperaims at summarizing the 15 years translational experience at the Center of Alcohol Researchin Heidelberg, namely based on the long-term prospective and detailed characterization ofheavy drinkers with mortality data. In addition, novel experimental findings will be presented. Aspecial focus will be the long-known hepatic iron accumulation, the somewhat overlooked roleof the hematopoietic system and novel insights into iron sensing and the role of hepcidin. Ourpreliminary work indicates that enhanced red blood cell (RBC) turnover is critical for survivalin ALD patients. RBC turnover is not primarily due to vitamin deficiency but rather to ethanoltoxicity directly targeted to erythrocytes but also to the bone marrow stem cell compartment.These novel insights also help to explain long-known aspects of ALD such as mean corpuscularvolume of erythrocytes (MCV) and elevated aspartate transaminase (GOT/AST) levels. Thiswork also aims at identifying future projects, naming unresolved observations, and presentingnovel hypothetical concepts still requiring future validation.

[关键词] alcoholic liver disease;iron overload;hemolysis;erythrophagocytosis;hepcidin;cd163;red blood cell