Kakde Shradha P, Mushtaq Maham, Liaqat Maryyam, Ali Husnain, Mushtaq Muhammad Muaz, Sarwer Muhammad Asad, Ullah Sami, Hassan Muhammad Wali, Khalid Asma, Bokhari Syed Faqeer Hussain
Internal Medicine, Mahatma Gandhi Mission Institute of Health Sciences, Aurangabad, IND.
Medicine and Surgery, King Edward Medical University, Lahore, PAK.
Cureus. 2024 Sep 10;16(9):e69129. doi: 10.7759/cureus.69129. eCollection 2024 Sep.
Non-alcoholic steatohepatitis (NASH) has emerged as a significant global health concern, closely linked to the obesity epidemic and metabolic syndrome. This review explores emerging therapies for NASH that go beyond traditional lifestyle modifications. The complex pathophysiology of NASH, involving insulin resistance, lipotoxicity, oxidative stress, and chronic inflammation, offers multiple targets for therapeutic intervention. While lifestyle changes remain fundamental, their limitations in achieving sustained improvements highlight the need for effective pharmacological and interventional therapies. This review discusses novel pharmacological approaches, including farnesoid X receptor (FXR) agonists, peroxisome proliferator-activated receptor (PPAR) agonists, and agents addressing metabolic dysfunction, inflammation, and fibrosis. Promising candidates such as obeticholic acid, lanifibranor, and semaglutide are highlighted, along with combination therapies targeting multiple pathways simultaneously. Non-pharmacological interventions, including bariatric surgery, endoscopic bariatric and metabolic therapies, and innovative exercise regimens, are also examined for their potential in NASH management. Despite significant advancements, NASH drug development faces challenges due to the disease's complexity, patient heterogeneity, and stringent regulatory requirements. This review also addresses these limitations and explores future directions, including personalized medicine approaches, non-invasive diagnostic tools, and the potential of microbiome modulation and regenerative therapies. The evolving landscape of NASH research emphasizes the need for multidisciplinary approaches integrating advances in diagnostics, therapeutics, and digital health technologies. As the field progresses, the focus remains on developing more effective, personalized, and accessible strategies for preventing, diagnosing, and treating NASH, with the ultimate goal of improving outcomes for patients affected by this increasingly prevalent liver disease.
非酒精性脂肪性肝炎（NASH）已成为一个重大的全球健康问题，与肥胖流行和代谢综合征密切相关。本综述探讨了NASH的新兴疗法，这些疗法超越了传统的生活方式改变。NASH复杂的病理生理学涉及胰岛素抵抗、脂毒性、氧化应激和慢性炎症，为治疗干预提供了多个靶点。虽然生活方式改变仍然是基础，但它们在实现持续改善方面的局限性凸显了有效药物和介入治疗的必要性。本综述讨论了新型药物方法，包括法尼酯X受体（FXR）激动剂、过氧化物酶体增殖物激活受体（PPAR）激动剂以及针对代谢功能障碍、炎症和纤维化的药物。重点介绍了诸如奥贝胆酸、lanifibranor和司美格鲁肽等有前景的候选药物，以及同时针对多种途径的联合疗法。还研究了非药物干预措施，包括减肥手术、内镜减肥和代谢疗法以及创新的运动方案在NASH管理中的潜力。尽管取得了重大进展，但由于该疾病的复杂性、患者异质性和严格的监管要求，NASH药物开发面临挑战。本综述还讨论了这些局限性，并探索了未来方向，包括个性化医疗方法、非侵入性诊断工具以及微生物群调节和再生疗法的潜力。NASH研究不断发展的格局强调了整合诊断、治疗和数字健康技术进展的多学科方法的必要性。随着该领域的发展，重点仍然是开发更有效、个性化和可及的策略来预防、诊断和治疗NASH，最终目标是改善受这种日益普遍的肝脏疾病影响的患者的预后。
