Liver disease
What is liver disease?
The term liver disease includes over 100 different diseases which affect the liver, which together affect at least 2 million people in the UK. Liver disease is the third leading cause of premature death in the UK.
Liver disease and liver cancer together caused 2.5% of deaths in England in 2020 and on average, 40 people die from liver disease every day in the country.
Despite being 90% preventable, liver diseases have been on the rise for the last few decades. Since 1970, deaths due to liver disease have increased by 400%, in contrast with other major diseases, such as heart disease and cancer, where deaths have either remained stable or decreased.
Understanding the liver
The liver is the second largest organ in the body and is just as vital an organ as the heart. It works hard, performing hundreds of complex functions. These include :
- Processing and breaking down digested food
- fighting infections and illness
- removing toxins (poisons), such as alcohol, from the body
- controlling cholesterol levels
- helping blood clot
- releasing bile, a liquid that breaks down fats and aids digestion
Common liver diseases
This means that a number of different things can go wrong with the liver, most of which don’t even cause obvious signs or symptoms until the disease is fairly advanced and the liver is damaged. Here are some common liver diseases :
Alcohol-related liver diseases
Excessive alcohol consumption over multiple years damages the liver and can lead to scarring of the liver, also known as cirrhosis. Alcohol-related liver disease accounts for 60% of all liver disease.
Non-alcoholic fatty liver disease
Fat builds up within liver cells, usually in overweight or obese people, and damages them. 63% of UK adults are now classed as obese and overweight, and an estimated 1 in 3 have early-stage non-alcohol related fatty liver disease (NAFLD). Losing 10% of body weight is usually enough to improve liver function in those with NAFLD. Experts predict that over the next decade, NAFLD will become the leading cause of endstage liver disease and transplantation.
Hepatitis
A viral infection or the exposure to harmful substances such as alcohol can cause inflammation or swelling of the liver. 180,000 people are chronically infected with hepatitis B and 143,000 are estimated to carry the hepatitis C virus.
Liver cancer
Liver cancer is the fastest rising cause of cancer death in the UK, with only 13% of patients surviving past 5 years. Around 6,000 cases of primary liver cancer are diagnosed each year in the UK, which means almost 16 people per day get the bad news. The vast majority of them will have underlying advanced liver disease.
Haemochromatosis
A genetic disorder that causes the gradual build-up of iron in the body, usually around the liver
Primary biliary cirrhosis
A rare, long-term type of liver disease that damages the bile ducts in the liver
How animals are used to model liver disease
Considering the high prevalence of liver disease worldwide, and the lack of non-animal alternatives for preclinical testing, animal models are crucial to understanding the causes and effects of liver disease, identifying therapeutic targets, potential drug and biomarkers, and testing novel medication. Further elucidating the progression of alcohol-related (AFLD) and non-alcoholic fatty liver disease (NAFLD) but also alcohol-related (ASH) and non-alcoholic (NASH) steatohepatitis, to advanced chronic liver disease (ACLD) will help a great number of patients.
To reflect this diversity, researchers have engineered just as many animal models to represent the spectrum of symptoms. Here, we have a quick summary of how animals have been used to research the most common liver diseases.
Animals have been used to study many of the different liver diseases including:
- Alcohol related liver disease
- Steatosis (both alcohol-related and non-alcoholic)
- Non-alcoholic fatty liver disease (NAFLD)
- Advanced chronic liver disease
- Primary liver cancer
Because there are many different types of liver disease, there is no single animal species or animal model that represents all liver diseases. In most cases, scientists will use different animal models to study different symptoms or aspects of the disease. For example, non-alcoholic fatty liver disease can be induced in mice and other rodents by feeding them a special diet, the mice then develop aspects of non-alcoholic fatty liver disease and are considered an 'animal models of NAFLD'.
The animal species that have been commonly used to research liver disease are:
- Mice
- Rats
For detailed information on the animal models that have been used to study liver disease and the methods employed by the studies, see animalresearch.info
Organoid models
Although animal models are still the best approach to comprehensively study of the causes and effects of liver diseases, and to develop new drugs, sometimes translating the findings from animals to humans can be challenging.
3D human cell cultures have been developed to complement animal studies. These organoids remove the confounding variables that might be introduced by animal models and are more complex than homogenized cell cultures. They allow researchers to study specific cellular functions and regulation, as well as drug efficacy and toxicity, in a liver-centered environment. They have already been applied in the context of NAFLD/NASH studies.
Animal welfare
Many countries, including the UK, regulate laboratory animal welfare by law and demand that the severity of animal experiments are evaluated and considered when performing biomedical research. The welfare of the animals must be considered alongside the scientific questions, especially when researchers have no choice between different animal models.
When pursuing animal experiments, scientists have to balance two goals: animal welfare and the potential benefit of research. As such they try to choose animal models that answer the scientific reasoning with the least possible distress on the animals.
Treatments for liver disease
Most of the time, liver disease can be reversed with lifestyle modifications such as changes in diet and alcohol consumption. However, when the disease progresses, medical assistance might be required.
Treatment for liver disease depends on the type of liver disease and how far it has progressed. However, there are currently no medications approved for NAFLD, though some are in clinical trials. Various medicines can be used to manage the problems associated with the condition, such as medicine to treat high blood pressure, treat high cholesterol, treat type 2 diabetes and treat obesity. Liver failure may ultimately require a liver transplant.
As liver disease affects more and more people, it is important that research continues to ultimately better understand the variety of conditions that affect the liver and find new ways to treat them.
