Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
Department of Surgery, University of Missouri, Columbia, MO 65211, USA.
Int J Mol Sci. 2021 Jul 15;22(14):7571. doi: 10.3390/ijms22147571.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved treatment. NAFLD accounts as a major causing factor for the development of hepatocellular carcinoma (HCC), and its incidence rises accompanying the prevalence of obesity and diabetes. Reprogramming of antidiabetic and anti-obesity medicine is a major treatment option for NAFLD and NASH. Liver inflammation and cellular death, with or without fibrosis account for the progression of NAFLD to NASH. Therefore, molecules and signaling pathways involved in hepatic inflammation, fibrosis, and cell death are critically important targets for the therapy of NAFLD and NASH. In addition, the avoidance of aberrant infiltration of inflammatory cytokines by treating with antagonists also provides a therapeutic option. Currently, there is an increasing number of pre-clinical and clinical trials undergoing to evaluate the effects of antidiabetic and anti-obesity drugs, antibiotics, pan-caspase inhibitors, / antagonists, and others on NAFLD, NASH, and liver fibrosis. Non-invasive serum diagnostic markers are developed for fulfilling the need of diagnostic testing in a large amount of NAFLD cases. Overall, a better understanding of the underlying mechanism of the pathogenesis of NAFLD is helpful to choose an optimized treatment.
非酒精性脂肪性肝病 (NAFLD) 是全球最常见的慢性肝病,其谱广泛,从单纯性脂肪变性到非酒精性脂肪性肝炎 (NASH) 的晚期阶段不等。尽管有许多针对 NAFLD 治疗的临床试验正在进行,但目前尚无批准的治疗方法。NAFLD 是肝细胞癌 (HCC) 发展的主要原因之一,其发病率随着肥胖症和糖尿病的流行而上升。抗糖尿病和抗肥胖药物的重新编程是治疗 NAFLD 和 NASH 的主要选择。肝脏炎症和细胞死亡,无论是否伴有纤维化,都导致 NAFLD 向 NASH 的进展。因此,参与肝炎症、纤维化和细胞死亡的分子和信号通路是治疗 NAFLD 和 NASH 的关键靶点。此外,通过用 拮抗剂治疗来避免炎症细胞因子的异常浸润也提供了一种治疗选择。目前,越来越多的临床前和临床试验正在评估抗糖尿病和抗肥胖药物、抗生素、泛半胱天冬酶抑制剂、/拮抗剂等对 NAFLD、NASH 和肝纤维化的影响。正在开发非侵入性血清诊断标志物,以满足大量 NAFLD 病例的诊断检测需求。总的来说,更好地了解 NAFLD 发病机制的潜在机制有助于选择优化的治疗方法。