First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece.
Pharmacol Res. 2022 Jul;181:106261. doi: 10.1016/j.phrs.2022.106261. Epub 2022 May 16.
Hepatocellular carcinoma (HCC) occurs in the setting of prolonged liver inflammation, hepatocyte necrosis and regeneration in patients with cirrhosis. Despite the progress made in the medical management of the disorder during the past decades, the available pharmacological options remain limited, leading to poor survival rates and quality of life for patients with HCC. Sodium-glucose cotransporter 2 inhibitors (SGLT2) originally emerged as drugs for the treatment of hyperglycemia; however, they soon demonstrated important extra-glycemic properties, which led to their evaluation as potential treatments for a wide range of non-metabolic disorders. Evidence from animal studies suggests that SGLT2i have the potential to modulate molecular pathways that affect hallmarks of HCC, including inflammatory responses, cell proliferation, and oxidative stress. The impressive benefits of neurohormonal modulation observed with SGLT2i in congestive heart failure set the stage for human trials in cirrhotic ascites. However, future studies need to evaluate several aspects of the benefit to risk ratio of such a therapeutic strategy, including the co-administration with antineoplastic agents and diuretics, infections, use in hospitalized individuals, renal safety and hypovolemia. In this narrative review, we discuss the putative role of SGLT2i in the treatment of patients with HCC, starting with the mechanisms that could justify a possible benefit and ending with potential clinical implications and areas for future research.
肝细胞癌（HCC）发生于肝硬化患者的长期肝脏炎症、肝细胞坏死和再生的背景下。尽管在过去几十年中，该疾病的医学管理取得了进展，但现有的药物选择仍然有限，导致 HCC 患者的生存率和生活质量较差。钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）最初作为治疗高血糖的药物出现；然而，它们很快表现出重要的非血糖特性，这促使人们评估它们作为治疗广泛非代谢疾病的潜在治疗方法。来自动物研究的证据表明，SGLT2i 有可能调节影响 HCC 特征的分子途径，包括炎症反应、细胞增殖和氧化应激。SGLT2i 在充血性心力衰竭中观察到的神经激素调节的显著益处为肝硬化腹水的人体试验奠定了基础。然而，未来的研究需要评估这种治疗策略的获益与风险比的几个方面，包括与抗肿瘤药物和利尿剂联合使用、感染、在住院患者中的使用、肾脏安全性和血容量不足。在这篇叙述性综述中，我们讨论了 SGLT2i 在 HCC 患者治疗中的潜在作用，从可能证明有益的机制开始，最后讨论潜在的临床意义和未来研究的领域。
