Utilization of animal models to investigate nonalcoholic steatohepatitis-associated hepatocellular carcinoma

Jian Wu _

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Oncotarget. 2016; 7:42762-42776. https://doi.org/10.18632/oncotarget.8641

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Jian Wu1,2

1 Key Laboratory of Molecular Virology, Fudan University Shanghai Medical College, Shanghai, China

2 Shanghai Institute of Liver Diseases, Fudan University, Shanghai, China

Correspondence to:

Jian Wu, email:

Keywords: nonalcoholic fatty liver disease; end-stage liver disease; nonalcoholic steatohepatitis (NASH); NASH-associated hepatocellular carcinoma (NASH-HCC)

Received: January 25, 2016 Accepted: March 29, 2016 Published: April 07, 2016


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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