Roeb Elke
Gastroenterology, Justus Liebig University Giessen, Giessen, Germany.
Visc Med. 2022 Apr;38(2):126-132. doi: 10.1159/000519611. Epub 2021 Oct 26.
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing and strongly associated with the metabolic syndrome, especially with obesity. A subtype, nonalcoholic steatohepatitis (NASH), might progress to advanced fibrosis and cirrhosis. NASH patients have an increased all-cause mortality. First and foremost are malignancies, followed by cardiovascular diseases.
The NAFLD fibrosis score and noninvasive liver stiffness measurement (transient hepatic elastography) are essential components for the diagnostic risk assessment of NAFLD patients. Other steatoses (alcohol, genetic disorders, drugs, toxins, malnutrition, etc.) must be considered in the differential diagnosis. So far, there is no approved liver-specific drug therapy with a proven effect on NAFLD for patients without diabetes mellitus. Obeticholic acid (FXR agonist), cenicriviroc (a dual inhibitor of the chemokine receptors (CCR), CCR2 and CCR5), acetyl-CoA carboxylase inhibitors, and several thyroid hormone analogs are the most advanced substances in clinical development in ongoing phase 2 and 3 studies.
Weight loss, physical training, and the screening and treatment of risk factors represent the cornerstones of NAFLD therapy. Treatment with glucagon-like peptide 1 analogs (e.g., liraglutide, semaglutide) and sodium-dependent glucose transporter 2 inhibitors can be recommended in patients with diabetes and NASH.
非酒精性脂肪性肝病(NAFLD)的患病率正在上升,且与代谢综合征密切相关,尤其是与肥胖相关。其一种亚型,非酒精性脂肪性肝炎(NASH),可能会进展为晚期纤维化和肝硬化。NASH患者的全因死亡率增加。首要死因是恶性肿瘤,其次是心血管疾病。
NAFLD纤维化评分和非侵入性肝脏硬度测量(瞬时弹性成像)是NAFLD患者诊断风险评估的重要组成部分。在鉴别诊断中必须考虑其他脂肪变性(酒精、遗传疾病、药物、毒素、营养不良等)。到目前为止,对于无糖尿病的NAFLD患者,尚无经批准的对NAFLD有确切疗效的肝脏特异性药物治疗。奥贝胆酸(FXR激动剂)、西尼莫德(趋化因子受体(CCR)CCR2和CCR5的双重抑制剂)、乙酰辅酶A羧化酶抑制剂以及几种甲状腺激素类似物是正在进行的2期和3期临床研究中最先进的物质。
体重减轻、体育锻炼以及危险因素的筛查和治疗是NAFLD治疗的基石。对于患有糖尿病和NASH的患者,可推荐使用胰高血糖素样肽1类似物(如利拉鲁肽、司美格鲁肽)和钠依赖性葡萄糖转运蛋白2抑制剂进行治疗。