Patients who develop chronic fibrotic liver disease, caused by viral or metabolic aetiologies, are at a high risk of developing hepatocellular carcinoma (HCC). Even after complete HCC tumour resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent de novo HCC tumours, which progress into incurable, advanced-stage disease in most patients. Thus, early detection and prevention of HCC development is, in principle, the most impactful strategy to improve patient prognosis. However, a "one-size-fits-all" approach to HCC screening for early tumour detection, as recommended by clinical practice guidelines, is utilised in less than 20% of the target population, and the performance of screening modalities, including ultrasound and alpha-fetoprotein, is suboptimal. Furthermore, optimal screening strategies for emerging at-risk patient populations, such as those with chronic hepatitis C after viral cure, or those with non-cirrhotic, non-alcoholic fatty liver disease remain controversial. New HCC biomarkers and imaging modalities may improve the sensitivity and specificity of HCC detection. Clinical and molecular HCC risk scores will enable precise HCC risk prediction followed by tailoured HCC screening of individual patients, maximising cost-effectiveness and optimising allocation of limited medical resources. Several aetiology-specific and generic HCC chemoprevention strategies are evolving. Epidemiological and experimental studies have identified candidate chemoprevention targets and therapies, including statins, anti-diabetic drugs, and selective molecular targeted agents, although their clinical testing has been limited by the lengthy process of cancer development that requires long-term, costly studies. Individual HCC risk prediction is expected to overcome the challenge by enabling personalised chemoprevention, targeting high-risk patients for precision HCC prevention and substantially improving the dismal prognosis of HCC.

中文翻译：

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精准医疗时代肝癌危险因素及预防

由病毒或代谢病因引起的慢性纤维化肝病患者罹患肝细胞癌 (HCC) 的风险很高。即使在完全切除或消融 HCC 肿瘤后，残余肝脏中的致癌组织微环境也可能引起复发性 HCC 肿瘤，在大多数患者中进展为无法治愈的晚期疾病。因此，原则上，早期发现和预防 HCC 发展是改善患者预后的最有效策略。然而，根据临床实践指南的建议，只有不到 20% 的目标人群采用了一种用于早期肿瘤检测的“一刀切”的 HCC 筛查方法，并且筛查方式（包括超声和甲胎蛋白，是次优的。此外，针对新出现的高危患者群体（例如病毒治愈后患有慢性丙型肝炎的患者或患有非肝硬化、非酒精性脂肪肝的患者）的最佳筛查策略仍然存在争议。新的 HCC 生物标志物和成像方式可能会提高 HCC 检测的灵敏度和特异性。临床和分子 HCC 风险评分将实现精确的 HCC 风险预测，然后对个体患者进行量身定制的 HCC 筛查，最大限度地提高成本效益并优化有限医疗资源的分配。几种针对特定病因和通用的 HCC 化学预防策略正在不断发展。流行病学和实验研究已经确定了候选化学预防靶点和疗法，包括他汀类药物、抗糖尿病药物和选择性分子靶向药物，尽管它们的临床测试受到癌症发展漫长过程的限制，需要长期、昂贵的研究。个体 HCC 风险预测有望通过个性化化学预防、针对高危患者进行精准 HCC 预防并大幅改善 HCC 的不良预后来克服这一挑战。