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For some diseases, the doctor needs a tissue biopsy to fully classify a diagnosis, estimate prognosis and install a treatment. Classical examples are cancer and inflammatory bowel disease. Fatty liver disease (FLD) is another disease entity where imprecise indications such as nonspecific liver enzymes, ultrasound examination or magnetic resonance imaging (MRI) will estimate the stages of the pathology.

Fatty liver is marked by the presence of excessive hepatic steatosis, defined as 5% or more liver fat by weight. From the benign stage of excessive hepatic steatosis, fatty liver disease can progress to steatohepatitis, i.e. the hepatocytes react to the excess fat with inflammation. This inflammatory process includes several stages of fibrosis, ultimately leading to cirrhosis, i.e. the development of actual scar tissue. Some patients may develop an associated hepatocellular carcinoma, or cancer of the bile duct.

In terms of prevalence, various methods estimate that 15-46% of the European and US population have fatty liver disease, and approximately 20% are estimated likely to develop progressive liver disease leading to fibrosis and cirrhosis. However, the actual prevalence of steatohepatitis is uncertain due to the lack of non-invasive clinical biomarkers and the protracted asymptomatic nature of the disease. A liver biopsy is essentially the only procedure that reliably differentiates between simple fatty liver and steatohepatitis, including the assessment of the various stages of fibrosis mentioned above. Liver biopsies are rarely available in population-based cohorts, thus actual measures of annual incidence and knowledge of disease trajectories are based on estimates of imprecise ultrasound examination, or magnetic resonance imaging.

Far from all individuals with simple steatosis develop steatohepatitis or end-stage liver disease. In our project we will seek answers to the inter-individual differences in prognosis. So far, there is very limited knowledge on how we might stratify the patient population according to their risk of fast progression, including risk of cirrhosis, liver transplant and greater mortality risk, versus those who may remain in the state of benign steatosis for years or even may revert back to normal liver. To this end we will reanalyse biopsies indicating fatty liver disease as an example of a disease continuum where further tissue examination may help further stratify the patient population according to prognosis.