Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, 39011 Santander, Spain.
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain.
Int J Mol Sci. 2023 Jun 27;24(13):10718. doi: 10.3390/ijms241310718.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.
非酒精性脂肪性肝病(NAFLD)涵盖了一系列疾病谱,从单纯性脂肪变性到非酒精性脂肪性肝炎(NASH)。肝脂肪变性可能源于多种途径的功能障碍,因此,与该疾病相关的多种分子触发因素已被描述。NASH 的发展涉及炎症和纤维化过程的激活。此外,NAFLD 还与多种肝外合并症密切相关,即代谢综合征、2 型糖尿病、肥胖症、高血压、心血管疾病和慢性肾脏病。由于 NAFLD 表现的异质性和疾病的多因素病因,NAFLD 的临床试验正在测试广泛的干预措施和药物,但收效甚微。在这里,我们提出了对 NAFLD 患者不同表型特征的叙述性综述,其疾病可能由不同的药物引发,并沿着不同的病理生理途径发展。因此,对 NAFLD 患者进行正确的表型分型和个体化治疗是一种创新的治疗方法,可能会带来更好的治疗效果。