Animal Models for Liver Disease Research

Investigations show that liver diseases threatening human health include liver parenchymal cell damage, viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis (NASH), liver cirrhosis, and liver cancer. As is known to all, animal disease models are indispensable for the research and development of effective drugs for various liver diseases.

Liver injury

Liver injury mainly refers to the functional damage or necrosis of liver parenchymal cells. Clinical liver injury is mainly caused by drinking, food poisoning, drug toxicity, viral hepatitis, fatty liver, liver cirrhosis, and cholestasis. Severe acute liver injury may develop into liver failure, which is life-threatening. Chronic liver injury may develop to the end-stage of liver cirrhosis and liver cancer.

The mouse model of liver injury can be used to study the mechanism of liver injury-repair and liver regeneration, as well as screen and evaluate liver protection and treatment of liver injury, which is of great research significance.

Hepatitis B and C virus

Hepatitis B virus (HBV) can cause acute and chronic liver infections, among which chronic infection is the main cause of severe liver disease.

Commonly used HBV models include:

• Transgenic mouse
• Hydrodynamic injection model
• AAV vector transfection model
• human-murine chimeric liver mouse models

Hepatitis C virus (HCV) is also a hepatocyte-specific virus that can only infect humans and non-human primates (NHPs). There is no suitable animal model for a long time.

Fatty liver, NASH, liver fibrosis, liver cirrhosis, and liver cancer

Non-alcoholic fatty liver disease (NAFLD) is a world-wide chronic disease. The incidence of NAFLD exploded in the past 20 years. If not effectively treated, it will gradually develop into non-alcoholic steatohepatitis (NASH) and fibrosis. Through timely intervention at this stage, the liver can still return to normal. Once it progresses to cirrhosis, the incidence rate of hepatocellular carcinoma (HCC) will reach 1~4%.

Development progress of NASH drugs

At present, the medical community believes that NASH is the result of multiple factors, including genetics, obesity, metabolic syndrome (such as high blood pressure, high blood sugar, abdominal fat accumulation, and related cardiovascular diseases), and diabetes.

The complex pathogenesis of NASH results in multiple drug targets. The current in-progress drugs mainly target fat, inflammation, and fibrosis. The metabolic targets can be subdivided into lipids, glucose, and bile acids. The inflammation targets include oxidative stress, inflammation, and immune system targets in many aspects.

According to the model making method and pathological characteristics, the commonly used disease models can be divided into four categories, which are diet induced models, chemical and diet induced models, genetically engineered and diet induced models, and humanized composite models. The NASH animal models can be established through dietary induction, genetic modification, or joint intervention by multiple methods.

The phenotypes and formation mechanisms of liver animal models prepared by different methods vary. Choosing the most suitable animal model will help speed up the drug screening process, validate new therapies, and solve the biological pathogenesis of NASH and HCC more quickly. Many biotechnology companies take the development and provision of various liver disease animal models as one of the strategic layouts and have developed a variety of liver disease models to meet the various needs of scientific research institutions and pharmaceutical R&D entities for animal models.

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