Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH. Given the disease burden, there is an important unmet need for pharmacologic treatment options for this patient population. The underlying pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex and reflected by the myriad of therapies, with different targets, currently under investigation. In broad strokes, drug development has focused on modulation of metabolic pathways, inflammatory cascades, and/or mechanisms impacting fibrosis. Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. The compounds in phase IIa have provided promising results in terms of potential benefits on various aspects of histopathology. Agents in later stages of development have shown fairly modest results in terms of reduction of hepatic steatosis, necroinflammation and fibrosis. If longer term safety and efficacy are established among heterogeneous cohorts, these medications may help mitigate potential morbidity and mortality for this burgeoning patient population.

中文翻译：

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NASH 药物治疗：当前和新兴

非酒精性脂肪性肝病 (NAFLD) 已成为全球最突出的慢性肝病形式之一，反映了全球肥胖症的流行。那些患有 NAFLD 进行性变异的非酒精性脂肪性肝炎 (NASH) 的多系统发病率和死亡率风险显着增加。然而，目前没有批准的 NASH 药物疗法。鉴于疾病负担，对于该患者群体的药物治疗选择存在重要的未满足需求。导致 NAFLD 和 NASH 发生和进展的潜在病理生理机制是复杂的，目前正在研究的具有不同靶点的无数疗法反映了这一点。从广义上讲，药物开发的重点是调节代谢途径、炎症级联反应、和/或影响纤维化的机制。尽管在增强我们对 NAFLD 发病机制的理解方面取得了很大进展，但临床试验注册方面的挑战和临床试验设计的复杂性阻碍了药物治疗的发展。IIa 期化合物在组织病理学各个方面的潜在益处方面提供了有希望的结果。处于开发后期的药剂在减少肝脂肪变性、坏死性炎症和纤维化方面显示出相当温和的结果。如果在异质队列中建立长期安全性和有效性，这些药物可能有助于降低这一新兴患者群体的潜在发病率和死亡率。临床试验注册方面的挑战和临床试验设计的复杂性阻碍了药物治疗的发展。IIa 期化合物在组织病理学各个方面的潜在益处方面提供了有希望的结果。处于开发后期的药剂在减少肝脂肪变性、坏死性炎症和纤维化方面显示出相当温和的结果。如果在异质队列中建立长期安全性和有效性，这些药物可能有助于降低这一新兴患者群体的潜在发病率和死亡率。临床试验注册方面的挑战和临床试验设计的复杂性阻碍了药物治疗的发展。IIa 期化合物在组织病理学各个方面的潜在益处方面提供了有希望的结果。处于开发后期的药剂在减少肝脂肪变性、坏死性炎症和纤维化方面显示出相当温和的结果。如果在异质队列中建立长期安全性和有效性，这些药物可能有助于降低这一新兴患者群体的潜在发病率和死亡率。IIa 期化合物在组织病理学各个方面的潜在益处方面提供了有希望的结果。处于开发后期的药剂在减少肝脂肪变性、坏死性炎症和纤维化方面显示出相当温和的结果。如果在异质队列中建立长期安全性和有效性，这些药物可能有助于降低这一新兴患者群体的潜在发病率和死亡率。IIa 期化合物在组织病理学各个方面的潜在益处方面提供了有希望的结果。处于开发后期的药剂在减少肝脂肪变性、坏死性炎症和纤维化方面显示出相当温和的结果。如果在异质队列中建立长期安全性和有效性，这些药物可能有助于降低这一新兴患者群体的潜在发病率和死亡率。