a Department M3/Internal Medicine IV , University of Medicine and Pharmacy , Târgu Mureş , Romania.
b Diabetes, Nutrition and Metabolic Diseases Outpatient Unit , Emergency County Clinical Hospital , Târgu Mureş , Romania.
Expert Rev Clin Pharmacol. 2017 May;10(5):535-547. doi: 10.1080/17512433.2017.1300059. Epub 2017 Mar 6.
The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) is high and it is associated with poor prognosis. Hepatic steatosis results as a consequence of excessive hepatic lipid accumulation which correlates with insulin resistance and lipotoxicity, with subsequent oxidative stress, inflammation, apoptosis and fibrosis. Areas covered: This article presents the main pathophysiologic mechanisms and currently available drugs evaluated for their therapeutic effects on NAFLD/nonalcoholic steatohepatitis (NASH) and drugs under development that target relevant pathogenetic pathways. However, to date there is no particular drug approved for treatment of NAFLD in patients with T2D. Expert commentary: Early recognition and intervention are essential to ameliorate disease progression. Specific recommendations are still needed for NAFLD/NASH screening and diagnosis and therapeutic algorithm in patients with T2D. Lifestyle optimization with significant weight loss is a key intervention in patients with NAFLD and T2D. Pioglitazone, liraglutide, vitamin E, OCA and pentoxifylline have proven some histological improvements in NASH and omega 3-PUFAs were shown to decrease liver fat, but no specific recommendation can be made for treatment of NASH. Perhaps a combination of agents that target different pathogenic pathways are needed to better control disease progression, but more robust evidence for these agents is still needed.
非酒精性脂肪性肝病(NAFLD)在 2 型糖尿病(T2D)患者中的患病率很高,且与预后不良相关。肝脂肪变性是由于肝内脂质过度积累而导致的,这与胰岛素抵抗和脂毒性相关,继而导致氧化应激、炎症、细胞凋亡和纤维化。
本文介绍了主要的病理生理机制,以及目前评估用于治疗 NAFLD/非酒精性脂肪性肝炎(NASH)的疗效的药物,以及针对相关发病途径的正在开发的药物。然而,迄今为止,尚无专门用于治疗 T2D 患者 NAFLD 的药物获得批准。
早期识别和干预对于改善疾病进展至关重要。对于 T2D 患者的 NAFLD/NASH 筛查、诊断和治疗方案,仍需特定的建议。生活方式优化和显著减轻体重是 NAFLD 和 T2D 患者的关键干预措施。吡格列酮、利拉鲁肽、维生素 E、奥贝胆酸和己酮可可碱已被证明对 NASH 的组织学改善有一定效果,而 ω-3-PUFAs 则可降低肝脂肪,但对于 NASH 的治疗尚无特定推荐。或许需要联合使用针对不同发病途径的药物来更好地控制疾病进展,但仍需要这些药物的更有力证据。