Synopsis

Keywords: Cross-organ: Metabolic disease, Body: Liver

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated at 25%. Non-alcoholic steatohepatitis (NASH) affects ~20% of NAFLD patients leading to progressive liver fibrosis and cirrhosis. The incidence of liver decompensation, liver cancer, and death related to NASH cirrhosis is expected to increase 2-3 fold over the next decade. Liver biopsy is the reference for diagnosing NASH and fibrosis, but non-invasive serum tests and imaging tools are increasingly available for the diagnosis of advanced fibrosis. Current medical management for NASH includes lifestyle intervention and treatment of metabolic disease, but there are currently no FDA-approved compounds for NASH.

Non-alcoholic fatty liver disease (NAFLD) is the common liver disease globally, and an estimated 8 million Canadians currently have NAFLD^1,2. This is primarily driven by the epidemic of metabolic conditions such as type 2 diabetes mellitus and obesity. NAFLD includes patients withboth non-alcoholic fatty liver (NAFL) and non-alcoholic steaohepatitis (NASH), defined as a specific pattern of hepatic steatosis and inflammatory histologic changes that affects about 20% of patients with NAFLD, with risks of progressive liver fibrosis, cirrhosis, and associatedcomplications such as hepatoma³. NASH is a multi-organ disease and cardiovascular disease represents the most frequent cause of death in NAFLD patients. The incidence of liver decompensation, liver cancer, and death related to NASH cirrhosis is expected to increase 2-3 fold over the next decade. Liver biopsy is considered the reference standard for diagnosing NASH and liver fibrosis. Several non-invasive tools for the diagnosis of NAFLD and associated liver fibrosis are available, and rely on two different approaches: a biological approach based on the quantification of biomarkers in the serum, and a physical approach based on liver stiffness assessment by either ultrasonography or magnetic resonance- based elastography techniques^2,3. These non-invasive tests are not able to diagnose NASH, but have clinical utility in predicting advanced fibrosis when used in combination in appropriate cohorts. Current medical management for NASH includes lifestyle intervention, treatment of metabolic disease, and in select patients, pharmacotherapy such as Vitamin E and Pioglitazone. There are currently no FDA-approved NASH drugs, but several promising compounds targeting weight-loss, metabolic, inflammatory, or fibrosis pathways, are in late phase clinical trials^2,3

Acknowledgements

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