Title: Targeting Complement to Treat Fatty Liver Disease
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Frequently found in people with obesity and diabetes, non-alcoholic fatty liver disease (NALFD) is rapidly becoming a major public health concern: affecting 25% of the UK’s population, including up to 30% of the Welsh population. The disease is characterised by an increased build-up of fat in the liver that may progress to inflammation, liver cancer, and liver failure. Despite its soaring healthcare cost (estimated £7,804 annual cost per NAFLD patient care), there is currently no approved treatment for NAFLD. As the leading cause of liver transplantation, the disease is indeed a big problem for maintaining longer, healthier, and happier lives towards ‘A Healthier Wales’. Responding to this challenge, our long-term goal is to find an effective way to treat the disease. Complement component 3, often called C3, is an essential protein in our body’s immune system, providing the first line of defence against diseases. Using the state-of-the-art biological technologies, we recently found that after ‘deleting’ C3 protein, the mice had much less amount of fat in their liver. Based on the preliminary data, the objective of this proposal is to define whether targeting C3 is a potential way to treat NAFLD. By combining expertise in liver diseases, immunity and ‘big data’ technologies, we aim to: (i) determine ways in which C3 can enhance fat accumulation and drive inflammation in the liver (ii) how C3 works together with its partners during the disease progression. Achieving the proposed aims will create a novel foundation to understand how C3 controls onset and progression of fatty liver disease, the first step toward developing a new strategy to treat NAFLD.

Lay abstract: Frequently found in people with obesity and diabetes, non-alcoholic fatty liver disease (NALFD) is rapidly becoming a major public health concern: affecting 25% of the UK’s population, including up to 30% of the Welsh population. The disease is characterised by an increased build-up of fat in the liver that may progress to inflammation, liver cancer, and liver failure. Despite its soaring healthcare cost (estimated £7,804 annual cost per NAFLD patient care), there is currently no approved treatment for NAFLD. As the leading cause of liver transplantation, the disease is indeed a big problem for maintaining longer, healthier, and happier lives towards ‘A Healthier Wales’. Responding to this challenge, our long-term goal is to find an effective way to treat the disease. Complement component 3, often called C3, is an essential protein in our body’s immune system, providing the first line of defence against diseases. Using the state-of-the-art biological technologies, we recently found that after ‘deleting’ C3 protein, the mice had much less amount of fat in their liver. Based on the preliminary data, the objective of this proposal is to define whether targeting C3 is a potential way to treat NAFLD. By combining expertise in liver diseases, immunity and ‘big data’ technologies, we aim to: (i) determine ways in which C3 can enhance fat accumulation and drive inflammation in the liver (ii) how C3 works together with its partners during the disease progression. Achieving the proposed aims will create a novel foundation to understand how C3 controls onset and progression of fatty liver disease, the first step toward developing a new strategy to treat NAFLD.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL