First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, Athens, Greece.
Semin Cancer Biol. 2023 Aug;93:20-35. doi: 10.1016/j.semcancer.2023.04.010. Epub 2023 May 4.
Hepatocellular carcinoma (HCC) is estimated to be the third leading cause of cancer-related mortality and is characterized by low survival rates. Nonalcoholic fatty liver disease (NAFLD) is emerging as a leading cause of HCC, whose rates are increasing, owing to the increasing prevalence of NAFLD. The pathogenesis of NAFLD-associated HCC is multifactorial: insulin resistance, obesity, diabetes and the low-grade hepatic inflammation, which characterizes NAFLD, seem to play key roles in the development and progression of HCC. The diagnosis of NAFLD-associated HCC is based on imaging in the presence of liver cirrhosis, preferably computerized tomography or magnetic resonance imaging, but liver biopsy for histological confirmation is usually required in the absence of liver cirrhosis. Some preventive measures have been recommended for NAFLD-associated HCC, including weight loss, cessation of even moderate alcohol drinking and smoking, as well as the use of metformin, statins and aspirin. However, these preventive measures are mainly based on observational studies, thus they need validation in trials of different design before introducing in clinical practice. The treatment of NAFLD should be tailored on an individual basis and should be ideally determined by a multidisciplinary team. In the last two decades, new medications, including tyrosine kinase inhibitors and immune checkpoints inhibitors, have improved the survival of patients with advanced HCC, but trials specifically designed for patients with NAFLD-associated HCC are scarce. The aim of this review was to overview evidence on the epidemiology and pathophysiology of NAFLD-associated HCC, then to comment on imaging tools for its appropriate screening and diagnosis, and finally to critically summarize the currently available options for its prevention and treatment.
肝细胞癌 (HCC) 估计是癌症相关死亡率的第三大原因，其特点是生存率低。非酒精性脂肪性肝病 (NAFLD) 正成为 HCC 的主要原因，由于 NAFLD 的患病率不断增加，其发病率也在增加。NAFLD 相关 HCC 的发病机制是多因素的：胰岛素抵抗、肥胖、糖尿病和低级别肝炎症，这些似乎在 HCC 的发展和进展中起关键作用。NAFLD 相关 HCC 的诊断基于存在肝硬化的影像学检查，最好是计算机断层扫描或磁共振成像，但在没有肝硬化的情况下通常需要肝活检进行组织学确认。已经为 NAFLD 相关 HCC 推荐了一些预防措施，包括减肥、停止甚至适量饮酒和吸烟，以及使用二甲双胍、他汀类药物和阿司匹林。然而，这些预防措施主要基于观察性研究，因此在引入临床实践之前，需要在不同设计的试验中进行验证。NAFLD 的治疗应根据个体情况量身定制，最好由多学科团队确定。在过去的二十年中，包括酪氨酸激酶抑制剂和免疫检查点抑制剂在内的新药物改善了晚期 HCC 患者的生存率，但专门为 NAFLD 相关 HCC 患者设计的试验很少。本综述的目的是概述 NAFLD 相关 HCC 的流行病学和病理生理学证据，然后对其适当筛查和诊断的影像学工具进行评论，最后对其预防和治疗的现有选择进行批判性总结。
