Department of Neuroscience, Reproductive Medicine and Dentistry, Section of Pharmacology, Federico II University, Medical School of Naples, 80131 Naples, Italy.
Department of Clinical Medicine and Surgery, Federico II University, Medical School of Naples, 80131 Naples, Italy.
Int J Mol Sci. 2021 Nov 30;22(23):12947. doi: 10.3390/ijms222312947.
Immune checkpoint inhibitors represent one of the most significant recent advances in clinical oncology, since they dramatically improved the prognosis of deadly cancers such as melanomas and lung cancer. Treatment with these drugs may be complicated by the occurrence of clinically-relevant adverse drug reactions, most of which are immune-mediated, such as pneumonitis, colitis, endocrinopathies, nephritis, Stevens Johnson syndrome and toxic epidermal necrolysis. Drug-induced steatosis and steatohepatitis are not included among the typical forms of cancer immunotherapy-induced liver toxicity, which, instead, usually occurs as a panlobular hepatitis with prominent lymphocytic infiltrates. Nonetheless, non-alcoholic fatty liver disease is a risk factor for immunotherapy-induced hepatitis, and steatosis and steatohepatitis are frequently observed in this condition. In the present review we discuss how these pathology findings could be explained in the context of current models suggesting immune-mediated pathogenesis for steatohepatitis. We also review evidence suggesting that in patients with hepatocellular carcinoma, the presence of steatosis or steatohepatitis could predict a poor therapeutic response to these agents. How these findings could fit with immune-mediated mechanisms of these liver diseases will also be discussed.
免疫检查点抑制剂是临床肿瘤学最近的重大进展之一,因为它们显著改善了致命癌症如黑色素瘤和肺癌的预后。这些药物的治疗可能会因发生临床相关的药物不良反应而变得复杂,其中大多数是免疫介导的,如肺炎、结肠炎、内分泌疾病、肾炎、史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症。药物诱导的脂肪变性和脂肪性肝炎不属于癌症免疫治疗引起的肝毒性的典型形式,后者通常表现为全小叶肝炎,伴有明显的淋巴细胞浸润。然而,非酒精性脂肪性肝病是免疫治疗引起肝炎的一个危险因素,在这种情况下,脂肪变性和脂肪性肝炎经常被观察到。在本综述中,我们讨论了如何根据目前的免疫介导的脂肪性肝炎发病机制模型来解释这些病理学发现。我们还回顾了一些证据,表明在肝细胞癌患者中,脂肪变性或脂肪性肝炎的存在可能预示着对这些药物治疗的反应不佳。这些发现如何与这些肝脏疾病的免疫介导机制相吻合也将进行讨论。