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Inflammation in non-alcoholic fatty liver

More and more people are developing non-alcoholic fatty liver disease (NAFLD), i.e. fatty liver disease that is not caused by increased alcohol consumption. Worldwide, around 25 percent are affected; in Europe, it’s more than 30 percent.

Only a few people living with NAFLD develop advanced liver disease. On the one hand, this is reassuring. On the other hand, it raises a question. How can we identify the few people who are at risk for disease progression to better protect them?

Non-alcoholic Steatohepatitis as an important predictor of disease progression

One of the main roles in predicting disease progression is played by non-alcoholic steatohepatitis (NASH). What is the difference fatty liver disease and steatohepatitis? If the liver has to store more fats than it can release, a condition called fatty liver disease develops. If the presence of fat then leads to inflammation of the liver, the condition is called steatohepatitis.

Yet we know little about why some patients develop steatohepatitis and some do not. But it has been shown: the larger the adipocytes (a group of endocrine-active proteins from adipose tissue), the worse the steatosis. Moreover, in studies of morbidly obese patients, it has been observed that enlargement of subcutaneous adipocytes (hypertrophy) is often associated with fatty liver, steatohepatitis, and hepatic fibrosis.

Non-alcoholic fatty liver disease develops into steatohepatitis: It’s not the adipocyte hypertrophy’s fault

So it’s all about the adipocytes. The larger they are, the worse the steatosis. In overweight individuals, hypertrophy is more often associated with fatty liver, steatohepatitis, and liver fibrosis. So is hypertrophy also to blame for progressive liver disease in non-overweight individuals? It’s not that simple. This has led researchers to investigate the association of adipocyte volume or adipokine expression with features of steatohepatitis or hepatic fibrosis in patients with NAFLD.

What methods did they use? An expert liver pathologist reassessed all biopsies and the activity of the fatty liver (the so called NAFLD activity score) was calculated. After an overnight fast, participants were examined, and they performed biopsies of subcutaneous fat tissue and measurement of fat cells. Using RNA sequencing, they measured subcutaneous adipokines.

Their results show that there is an association between adipocyte hypertrophy and non-alcoholic fatty liver disease, but no association with non-alcoholic steatohepatitis. This supports the theory that adipocyte hypertrophy is an important factor in the pathophysiology of non-alcoholic fatty liver disease. But: Predictive models of subcutaneous adipose tissue gene expression observed in morbidly obese individuals cannot be translated into a typical cohort of patients with nonalcoholic fatty liver disease.

They state:

Our finding demands for further research focusing on the interplay between NAFLD and gene expressions of subcutaneous adipose tissue in large cohorts of patients recruited from clinical settings.
Holmer et al., 2022

Read more about the data, methods and findings here: