慢性肝病通常由不同的病因导致肝纤维化和肝硬化。其中非酒精性脂肪性肝病（NAFLD）影响着全球大约四分之一的人口，因此是一个重要且日益增加的公共卫生负担。慢性肝细胞损伤、炎症（非酒精性脂肪性肝炎，NASH）和肝纤维化是原发性肝癌的诱因，尤其是肝细胞癌（HCC），是全球癌症相关死亡的第三个最常见原因。尽管近年来肝病的认识有了很大进展，但在癌前和癌后阶段的治疗选择仍然有限。因此，急需确定可靶向的肝病驱动机制以开发新的治疗方法。单核细胞和巨噬细胞是炎症反应的核心但多才多艺的组成部分，推动慢性肝病的发生和发展。最近在单个细胞水平上进行的蛋白质组学和转录组学研究揭示了一种先前被忽视的巨噬细胞亚群和功能的多样性。实际上，包括肝脏驻留的巨噬细胞（也称Kupffer细胞）和单核细胞来源的巨噬细胞在内的肝巨噬细胞可以根据微环境信号获得各种表型，从而发挥多种有时相互矛盾的功能。这些功能范围从调节和加重组织炎症到促进和夸大组织修复机制（即实质再生、癌细胞增殖、血管生成、纤维化）。由于这些核心功能，肝巨噬细胞成为治疗肝病的一个有吸引力的靶点。在本综述中，我们讨论肝巨噬细胞在慢性肝病中的多方面和相反的作用，特别关注NAFLD / NASH和HCC。此外，我们还讨论了针对肝巨噬细胞的潜在治疗方法。版权所有©2023 Kohlhepp，Liu，Tacke和Guillot。

Chronic liver diseases from varying etiologies generally lead to liver fibrosis and cirrhosis. Among them, non-alcoholic fatty liver disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major and increasing public health burden. Chronic hepatocyte injury, inflammation (non-alcoholic steatohepatitis, NASH) and liver fibrosis are recognized soils for primary liver cancer, particularly hepatocellular carcinoma (HCC), being the third most common cause for cancer-related deaths worldwide. Despite recent advances in liver disease understanding, therapeutic options on pre-malignant and malignant stages remain limited. Thus, there is an urgent need to identify targetable liver disease-driving mechanisms for the development of novel therapeutics. Monocytes and macrophages comprise a central, yet versatile component of the inflammatory response, fueling chronic liver disease initiation and progression. Recent proteomic and transcriptomic studies performed at singular cell levels revealed a previously overlooked diversity of macrophage subpopulations and functions. Indeed, liver macrophages that encompass liver resident macrophages (also named Kupffer cells) and monocyte-derived macrophages, can acquire a variety of phenotypes depending on microenvironmental cues, and thus exert manifold and sometimes contradictory functions. Those functions range from modulating and exacerbating tissue inflammation to promoting and exaggerating tissue repair mechanisms (i.e., parenchymal regeneration, cancer cell proliferation, angiogenesis, fibrosis). Due to these central functions, liver macrophages represent an attractive target for the treatment of liver diseases. In this review, we discuss the multifaceted and contrary roles of macrophages in chronic liver diseases, with a particular focus on NAFLD/NASH and HCC. Moreover, we discuss potential therapeutic approaches targeting liver macrophages.Copyright © 2023 Kohlhepp, Liu, Tacke and Guillot.