Dongiovanni Paola, Meroni Marica, Longo Miriam, Fargion Silvia, Fracanzani Anna Ludovica
General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pad. Granelli, 20122 Milan, Italy.
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy.
Biomedicines. 2021 Oct 23;9(11):1524. doi: 10.3390/biomedicines9111524.
Nonalcoholic fatty liver disease (NAFLD) is the leading contributor to the global burden of chronic liver diseases. The phenotypic umbrella of NAFLD spans from simple and reversible steatosis to nonalcoholic steatohepatitis (NASH), which may worsen into cirrhosis and hepatocellular carcinoma (HCC). Notwithstanding, HCC may develop also in the absence of advanced fibrosis, causing a delayed time in diagnosis as a consequence of the lack of HCC screening in these patients. The precise event cascade that may precipitate NASH into HCC is intricate and it entails diverse triggers, encompassing exaggerated immune response, endoplasmic reticulum (ER) and oxidative stress, organelle derangement and DNA aberrancies. All these events may be accelerated by both genetic and environmental factors. On one side, common and rare inherited variations that affect hepatic lipid remodeling, immune microenvironment and cell survival may boost the switching from steatohepatitis to liver cancer, on the other, diet-induced dysbiosis as well as nutritional and behavioral habits may furtherly precipitate tumor onset. Therefore, dietary and lifestyle interventions aimed to restore patients' health contribute to counteract NASH progression towards HCC. Even more, the combination of therapeutic strategies with dietary advice may maximize benefits, with the pursuit to improve liver function and prolong survival.
非酒精性脂肪性肝病（NAFLD）是导致全球慢性肝病负担的主要因素。NAFLD的表型范围从简单且可逆的脂肪变性到非酒精性脂肪性肝炎（NASH），后者可能恶化为肝硬化和肝细胞癌（HCC）。尽管如此，HCC也可能在没有晚期纤维化的情况下发生，由于这些患者缺乏HCC筛查，导致诊断延迟。可能促使NASH发展为HCC的确切事件级联是复杂的，它涉及多种触发因素，包括过度的免疫反应、内质网（ER）和氧化应激、细胞器紊乱和DNA异常。所有这些事件都可能因遗传和环境因素而加速。一方面，影响肝脏脂质重塑、免疫微环境和细胞存活的常见和罕见遗传变异可能会促进从脂肪性肝炎向肝癌的转变，另一方面，饮食引起的生态失调以及营养和行为习惯可能会进一步促使肿瘤发生。因此，旨在恢复患者健康的饮食和生活方式干预有助于抵消NASH向HCC的进展。更重要的是，治疗策略与饮食建议的结合可能会使益处最大化，以追求改善肝功能和延长生存期。
