Utilization of animal models to investigate nonalcoholic steatohepatitis-associated hepatocellular carcinoma.
Utilization of animal models to investigate nonalcoholic steatohepatitis-associated hepatocellular carcinoma.
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利用动物模型研究非酒精性脂肪性肝炎相关肝细胞癌
DOI：
10.18632/oncotarget.8641
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发表时间：
2016-07-05
期刊：
影响因子：
--
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Wu J
非酒精性脂肪性肝病（NAFLD）包括一系列肝脏疾病，其中脂肪蓄积来自单纯性脂肪肝、非酒精性脂肪性肝炎（NASH）、纤维化/肝硬化和NAFLD/NASH相关肝细胞癌（HCC）。NASH是NAFLD的一种进展形式，需要医疗护理。5-10例NASH患者中有1例可能在5-10年内进展为终末期肝病（ESLD或肝硬化）;同时，危及生命的ESLD和HCC并发症是主要死亡原因。NAFLD在临床上日益加重的负担，阐明其发病机制和进展，以及评估潜在治疗方法的疗效，需要可靠的动物模型。大多数NASH相关的HCC发生在肝硬化受试者中;然而，HCC确实出现在没有肝硬化的NASH患者中。脂毒性、氧化应激、胰岛素抵抗、内质网应激、脂肪因子和淋巴因子谱改变以及肠道微生物组变化影响NAFLD进展并构成关键的病理生物学相互作用。这些因子如何在脂肪性炎症和纤维化/肝硬化的微环境中促进恶性转化，并导致肿瘤的发展是肝病学领域面临的关键问题之一。本文综述了啮齿类动物NASH-HCC模型的特点，并讨论了利用这些模型揭示NASH相关HCC发展的奥秘所面临的挑战。
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver disorders with fat accumulation from simple fatty liver, nonalcoholic steatohepatitis (NASH), fibrosis/cirrhosis and NAFLD/NASH-associated hepatocellular carcinoma (HCC). NASH is a progressive form of NAFLD and requires medical attention. One of 5-10 NASH patients may progress to end-state liver disease (ESLD or cirrhosis) in 5-10 years; meanwhile, life-threatening complications of ESLD and HCC account for major mortality. An increasing burden of NAFLD in clinics, elucidation of its pathogenesis and progression, and assessment of the efficacy of potential therapeutics demand reliable animal models. Most NASH-associated HCC occurs in cirrhotic subjects; however, HCC does appear in NASH patients without cirrhosis. Lipotoxicity, oxidant stress, insulin resistance, endoplasmic reticulum stress, altered adipokine and lymphokine profiles and gut microbiome changes affect NAFLD progression and constitute key pathobiologic interplays. How these factors promote malignant transformation in a microenvironment of steatotic inflammation and fibrosis/cirrhosis, and lead to development of neoplasms is one of critical questions faced in the hepatology field. The present review summarizes the characteristics of emerging rodent NASH-HCC models, and discusses the challenges in utilizing these models to unveil the mysteries of NASH-associated HCC development.
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影响因子：
5.6
作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
3.1
作者：
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通讯作者：
Wu, Jian
影响因子：
25.7
作者：
Fuchs, Michael;Sanyal, Arun J.
通讯作者：
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