Poulsen Kyle L, Cajigas-Du Ross Christina K, Chaney Jarod K, Nagy Laura E
Center for Liver Disease Research, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA.
Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Dig Med Res. 2022 Jun;5. doi: 10.21037/dmr-21-87. Epub 2022 Jun 30.
Liver fibrosis is a disease with characteristics of an aberrant wound healing response. Fibrosis is commonly the end-stage for chronic liver diseases like alcohol-associated liver disease (ALD), metabolic-associated liver disease, viral hepatitis, and hepatic autoimmune disease. Innate immunity contributes to the progression of many diseases through multiple mechanisms including production of pro-inflammatory mediators, leukocyte infiltration and tissue injury. Chemokines and their receptors orchestrate accumulation and activation of immune cells in tissues and are associated with multiple liver diseases; however, much less is known about their potential roles in liver fibrosis. This is a narrative review of current knowledge of the relationship of chemokine biology to liver fibrosis with insights into potential future therapeutic opportunities that can be explored in the future.
A comprehensive literature review was performed searching PubMed for relevant English studies and texts regarding chemokine biology, chronic liver disease and liver fibrosis published between 1993 and 2021. The review was written and constructed to detail the intriguing chemokine biology, the relation of chemokines to tissue injury and resolution, and identify areas of discovery for fibrosis treatment.
Chemokines are implicated in many chronic liver diseases, regardless of etiology. Most of these diseases will progress to fibrosis without appropriate treatment. The contributions of chemokines to liver disease and fibrosis are diverse and include canonical roles of modulating hepatic inflammation as well as directly contributing to fibrosis via activation of hepatic stellate cells (HSCs). Limited clinical evidence suggests that targeting chemokines in certain liver diseases might provide a therapeutic benefit to patients with hepatic fibrosis.
The chemokine system of ligands and receptors is a complex network of inflammatory signals in nearly all diseases. The specific sources of chemokines and cellular targets lend unique pathophysiological consequences to chronic liver diseases and established fibrosis. Although most chemokines are pro-inflammatory and contribute to tissue injury, others likely aid in the resolution of established fibrosis. To date, very few targeted therapies exist for the chemokine system and liver disease and/or fibrosis, and further study could identify viable treatment options to improve outcomes in patients with end-stage liver disease.
肝纤维化是一种具有异常伤口愈合反应特征的疾病。纤维化通常是酒精性肝病（ALD）、代谢相关肝病、病毒性肝炎和自身免疫性肝病等慢性肝病的终末期表现。固有免疫通过多种机制促进许多疾病的进展，包括促炎介质的产生、白细胞浸润和组织损伤。趋化因子及其受体协调免疫细胞在组织中的聚集和激活，并与多种肝脏疾病相关；然而，它们在肝纤维化中的潜在作用却鲜为人知。本文是一篇叙述性综述，阐述了趋化因子生物学与肝纤维化关系的现有知识，并探讨了未来可能探索的潜在治疗机会。
进行了全面的文献综述，在PubMed上搜索1993年至2021年间发表的关于趋化因子生物学、慢性肝病和肝纤维化的相关英文研究及文献。撰写并构建该综述，以详细阐述有趣的趋化因子生物学、趋化因子与组织损伤及修复的关系，并确定纤维化治疗的发现领域。
无论病因如何，趋化因子都与许多慢性肝病有关。如果没有适当的治疗，这些疾病中的大多数都会进展为纤维化。趋化因子对肝病和纤维化的作用是多方面的，包括调节肝脏炎症的典型作用以及通过激活肝星状细胞（HSC）直接促进纤维化。有限的临床证据表明，在某些肝病中靶向趋化因子可能对肝纤维化患者有益。
配体和受体的趋化因子系统是几乎所有疾病中炎症信号的复杂网络。趋化因子的特定来源和细胞靶点赋予慢性肝病和已形成的纤维化独特的病理生理后果。虽然大多数趋化因子具有促炎作用并导致组织损伤，但其他趋化因子可能有助于已形成的纤维化的消退。迄今为止，针对趋化因子系统以及肝病和/或纤维化的靶向治疗非常少，进一步的研究可能会确定可行的治疗方案，以改善终末期肝病患者的预后。
