**6. Conclusions**

MCs are important immune cells of the myeloid lineage present in healthy liver, and to a larger degree in diseased liver. In particular, experimental models of hepatic fibrosis have shown that the overall quantities of MCs significantly increase in all kinds of liver insults. In humans, first evidence has connected elevated numbers of MCs to the pathogenesis of PBC, PSC, bile duct obstruction, hepatitis, alcohol-induced liver injury, steatosis, steatohepatitis, congenital and non-congenital liver fibrosis, liver cancer, liver rejection upon liver transplant, and liver aging. Although the impact of MCs in the initiation or progression of these disease entities is still poorly understood, it was suggested that they contribute to the liver's fibrotic response to chronic inflammation. However, MCs possess favorable immunomodulatory properties on other immune cells and act as a first effector cell in the innate response when encountering antigens. In this regard, the role of MCs in hepatic fibrosis is unclear and merits particular interest. Potential therapeutic MC-targeted strategies are the blockade of MC activity by MC stabilizers, inhibition of MC-selective enzymes, and the application of antagonists binding to receptors associated with an MC function. However, none of these approaches has been systematically tested in appropriate models and further experimental, translational, and clinical studies are urgently needed to explore whether the different compounds are beneficial in the therapy of hepatic fibrosis or its progression to cirrhosis or hepatocellular carcinoma.

**Author Contributions:** Writing-original draft preparation, R.W., S.K.M., C.L., and M.H.; writing-review and editing, R.W., S.K.M., C.L., and M.H.; funding acquisition, R.W., C.L., and M.H.; visualization, R.W., and S.K.M.

**Funding:** R.W., C.L., and M.H. are supported by the German Research Foundation (DFG, SFB/TRR57, Projects P04, P13, and Q3; HU794/12-1) and by the Interdisciplinary Centre for Clinical Research (IZKF) within the Faculty of Medicine at the RWTH Aachen University (Projects O3-1, O3-4, and O3-5). None of the funding sources exerted influence on content or decision to submit this review for publication. This research received no external funding.

**Acknowledgments:** The authors are grateful to Sabine Weiskirchen (Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, University Hospital Aachen, Aachen) for kindly preparing the figures and the graphical abstract for this review.

**Conflicts of Interest:** The authors declare no conflict of interest.
