Cano Luis, Foucher Fabien, Musso Orlando
Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'environnement (INRAE), Univ Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Front Oncol. 2025 May 16;15:1565692. doi: 10.3389/fonc.2025.1565692. eCollection 2025.
Liver cancers show high interindividual and intratumor heterogeneity. Among them, hepatocellular carcinoma (HCCs) represents approximately 90% of liver cancers, followed by intrahepatic cholangiocarcinoma (iCCA; ~10 to 15%), childhood hepatoblastoma, angiosarcoma and hemangioendothelioma (< 1%). More than 80% of HCCs arise in a backdrop of chronic inflammatory liver diseases of diverse etiologies. These underlying liver diseases are major determinants of geographic diversity of HCCs. Across the world, substantial differences in the prevalence of chronic viral hepatitides, alcohol misuse, Metabolic Disfunction-Associated Steatotic Liver Disease (MASLD) and exposure to toxic substances are frequently related to social and economic inequalities. Vulnerable populations are more frequently exposed to infections such as hepatitis B and C viruses that, combined with other risk factors, lead to both vertical and horizontal transmission and, in turn, impact on age and sex-related diversity. In this review, we describe the global landscape of risk factors leading to HCC: MASLD, chronic hepatitis B and C infections, alcohol misuse, exposure to other toxic substances and genetic predispositions. We describe their combined effects on the clinical and epidemiological features of HCCs around the globe. Clinical presentation, incidence and mortality rates of HCCs show therefore great geographic heterogeneity, which is also related to the inequalities in the gross domestic product , the socio-demographic index, the access to health care resources and to the implementation of policies for surveillance and screening of patients at risk. Awareness of the biological and geopolitical sources of HCC diversity will hopefully lead to more efficient international cooperation in the prevention and early management of chronic liver diseases and HCC.
肝癌表现出高度的个体间和肿瘤内异质性。其中，肝细胞癌（HCC）约占肝癌的90%，其次是肝内胆管癌（iCCA；约10%至15%）、儿童肝母细胞瘤、血管肉瘤和血管内皮瘤（<1%）。超过80%的HCC发生在多种病因的慢性炎症性肝病背景下。这些潜在的肝脏疾病是HCC地理多样性的主要决定因素。在全球范围内，慢性病毒性肝炎、酒精滥用、代谢功能障碍相关脂肪性肝病（MASLD）和接触有毒物质的患病率存在显著差异，这往往与社会和经济不平等有关。弱势群体更频繁地接触乙型和丙型肝炎病毒等感染，这些感染与其他风险因素相结合，导致垂直和水平传播，进而影响与年龄和性别相关的多样性。在本综述中，我们描述了导致HCC的全球风险因素格局：MASLD、慢性乙型和丙型肝炎感染、酒精滥用、接触其他有毒物质和遗传易感性。我们描述了它们对全球HCC临床和流行病学特征的综合影响。因此，HCC的临床表现、发病率和死亡率存在很大的地理异质性，这也与国内生产总值、社会人口指数、获得医疗资源的机会以及对高危患者进行监测和筛查政策的实施方面的不平等有关。认识到HCC多样性的生物学和地缘政治根源有望在慢性肝病和HCC的预防及早期管理方面带来更有效的国际合作。
