Veterans Affairs Puget Sound Healthcare System, USA; University of Washington, Seattle, WA, USA.
J Hepatol. 2021 Dec;75(6):1476-1484. doi: 10.1016/j.jhep.2021.08.012. Epub 2021 Aug 25.
Non-alcoholic fatty liver disease (NAFLD) is projected to become the leading cause of hepatocellular carcinoma (HCC) in many countries. Many risk factors for NAFLD are also independently associated with HCC, including obesity, diabetes, Hispanic ethnicity and genetic polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13. Steatosis-related lipotoxicity and oxidative DNA damage can induce hepatocarcinogenesis. These factors may explain the association between NAFLD and HCC, especially in the absence of cirrhosis. In fact, NAFLD/NASH is a leading cause of HCC in the absence of cirrhosis. Identifying patients with pre-cirrhotic NAFLD who have a high enough HCC risk to justify HCC screening represents one of the greatest clinical challenges in NAFLD. Validated models that combine multiple risk factors and fibrosis stage into "HCC risk calculators" are not yet available for patients with NAFLD. Development of such tools would enable risk stratification, identification of high-risk patients even in the absence of cirrhosis, and individualised (risk-based) surveillance strategies.
非酒精性脂肪性肝病（NAFLD）预计将成为许多国家肝细胞癌（HCC）的主要病因。NAFLD 的许多危险因素也与 HCC 独立相关，包括肥胖、糖尿病、西班牙裔和 PNPLA3、TM6SF2、GCKR、MBOAT7 和 HSD17B13 中的基因多态性。脂肪变性相关的脂毒性和氧化 DNA 损伤可诱导肝癌发生。这些因素可能解释了 NAFLD 与 HCC 之间的关联，尤其是在没有肝硬化的情况下。事实上，在没有肝硬化的情况下，NAFLD/NASH 是 HCC 的主要病因。确定具有足够高 HCC 风险的处于肝硬化前期的 NAFLD 患者，以便对其进行 HCC 筛查，这是 NAFLD 面临的最大临床挑战之一。对于 NAFLD 患者，目前尚无将多种危险因素和纤维化阶段结合起来的“HCC 风险计算器”等经过验证的模型。开发此类工具将能够进行风险分层，即使在没有肝硬化的情况下，也能识别出高危患者，并制定个体化（基于风险）的监测策略。
