Evidences supporting the concept that the liver is a lymphoid
organ are available since the early sixties, but only in the last few
years we started to dissect the underlying mechanisms that
makes the liver an unique organ in the human body for its ability
to balance between immune tolerance and overreaction. This
critical and complex function of the liver is obtained thanks to a
peculiar anatomy and microanatomy, unique features of hepatic
parenchymal cells and a large number of resident immune and
immune-related cells. One of the area which is more benefiting
from these advances, it is that related to ALD, liver diseases due
to a loss of tolerance. Liver autoimmunity is indeed a great
paradox for an organ with peculiar tolerizing properties. Growing
amount of evidences are dissecting the complex mechanisms
which coordinate immune responses between the liver and gut,
and the role of gut bacteria in ALD. As for many other complex
diseases, genome wide association studies are providing important
information on the ethiopathogenesis of ALD. Of course, the
accumulating knowledge from these generic studies needs to be
confirmed and explored in the context of functional studies with
the ultimate goal of developing novel therapeutic approaches for
ALD. There is no doubt that we are witnessing the birth of a new
era of clinical opportunities, but the real challenge is now to
transfer these “basic” knowledge to the clinical arena with a
beneficial impact to our patients.