Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut–liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.

非酒精相关性脂肪肝/脂肪性肝炎（NAFL/NASH）已成为全球肝病的主要原因。NASH 是 NAFL 的一种晚期形式，可能呈进展性，并且更容易发展为肝硬化和肝细胞癌。目前，生活方式干预是预防和控制NAFL而不发生纤维化的最重要和最有效的策略。虽然专门治疗 NAFL/NASH 的合适药物仍然有限，但在阐明发病机制和确定治疗靶点方面正在取得不断进展。在这篇综述中，我们讨论了病因学和前瞻性治疗靶点的最新进展，以及前/临床试验和专利中的候选药理学，重点关注糖尿病、肝脂质代谢、炎症和纤维化。重要的是，越来越多的证据表明，肠-肝轴的破坏和微生物衍生的代谢产物驱动了 NAFL/NASH 的发病机制。细胞外囊泡（EV）作为信号传导介质，导致脂质积累、巨噬细胞和肝星状细胞活化，进一步促进 NAFL/NASH 发生过程中的炎症和肝纤维化进展。针对肠道微生物群或 EV 可能作为治疗 NAFL/NASH 的新策略。最后，其他机制，例如细胞疗法和遗传方法，也具有巨大的治疗潜力。结合不同机制的药物和个体化医疗可能会提高疗效，更好地造福NAFL/NASH患者。