Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction–associated steatotic liver disease (MASLD), including metabolic dysfunction–associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction–associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.

中文翻译：

---

代谢功能障碍相关的脂肪肝病相关的肝细胞癌的表型

肝细胞癌 (HCC) 通常是肝硬化的结果，但近年来 HCC 的流行病学发生了巨大变化。代谢功能障碍相关的脂肪肝病 (MASLD)，包括代谢功能障碍相关的脂肪性肝炎，已成为全世界最常见的慢性肝病，也是 HCC 的主要原因。相当一部分 MASLD 相关 HCC (MASLD-HCC) 也可能发生在没有肝硬化的患者中。在这种情况下引发癌变的具体途径尚未完全阐明，对 MASLD 患者 HCC 监测的建议也具有挑战性。在精准医疗时代，了解在 MASLD 环境中定义 HCC 风险增加患者概况的过程至关重要，包括心脏代谢危险因素和可以有效解决的分子靶标。理想情况下，定义包含关键病理生理学特征的类别，并与定制的诊断和治疗策略相关，应有助于识别特定的 MASLD-HCC 表型。在这篇综述中，我们讨论了 MASLD-HCC，包括其流行病学和医疗保健负担、促进 MASLD 的机制数据、代谢功能障碍相关的脂肪性肝炎和 MASLD-HCC。作为风险分层的潜在策略，MASLD-HCC 的代谢表型的作用对其自然史、预后和治疗进行了专门讨论。还讨论了识别高危患者和筛查策略的挑战，以及 MASLD-HCC 预防和治疗的潜在方法。