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All You Need to Know About Non-Alcoholic Fatty Liver Disease

by Federica Parisi PhD, September 27, 2016 at 07:00 AM


Non-Alcoholic Fatty liver disease (NAFLD) is a complex condition where an excessive amount of fat accumulates in the liver, independently from alcohol consumption. It is currently unclear how and why NAFLD develops, although obesity is a clear risk factor. Improved preclinical models are currently needed so that we can gain a better understanding about the pathophysiology of the disease, and develop more effective treatments. CrownBio has recently presented data on our newly developed NAFLD model, which complements our existing resources and technologies for studying the disease.

Fatty liver is a progressive disease that starts with fat built up within the liver, a condition known medically as liver steatosis. Initially fat accumulation is limited to a small proportion of the liver, which otherwise stays healthy and without significant injury.

However while the condition advances the immune system reacts to the excess of fat, mounting an inflammatory response. At this stage the condition is more severe and is known as non-alcoholic steatohepatitis (NASH).

In its final stage the liver starts failing, developing scarring or fibrosis (cirrhosis) which is a high risk factor for liver failure among the obese population.

Individuals affected by metabolic syndrome – a cluster of conditions, including obesity, diabetes, high blood cholesterol, high blood pressure, and high blood fats – are at high risk of developing NAFLD. These patients are also considered at high risk for heart disease.

How Does Obesity Link to Fatty Liver?

Although it is clear that obesity considerably raises the risk of NAFLD, not everyone who is obese develops fatty liver, and not everyone who has fatty liver is obese. These exceptions are one of the reasons why risk factors for the disease are not completely clear.

It is also unclear whether these differences depend on patients’ genetic background but a 2008 study points to excess fat as the only clearly identified risk factor.

Fatty liver has also become the most common form of long-term liver disease in children. According to a June 2016 review published in the International Journal of Molecular Sciences, the problem is "affecting 10 to 20 percent of the general pediatric population, and 50 to 80 percent of those who are obese."

Symptoms and Diagnosis

NAFLD usually has no symptoms, and when it does they are pretty generic manifestations that could be mistaken for a number of other medical problems.

Because of the disease being symptomless at an early stage, it is generally diagnosed when it’s already advanced and while doctors are testing for other conditions.

If blood test liver values are abnormal or doctors believe the liver is slightly bigger than normal (without any long-term heavy alcohol use), then an ultrasound or CAT scan can be used to take a closer look.

A liver biopsy is needed for a definite NAFLD diagnosis, and is also the only way to distinguish between the early stage of harmless fatty liver and the more advanced cases of NASH, showing inflammation and scarring.

However, biopsies are an invasive and time consuming diagnostic methods that rely on the pathologist’s experience and best judgment to give a clear diagnosis.

CrownBio has validated a sonographic screening technique involving liver ultrasound, which is used for unbiased quantification of liver fat content in preclinical models of NAFLD/NASH.

By fine-tuning this technique on our preclinical models we hope to be able to bring a non-invasive screening method to patients to assess their liver fat content, which will no longer rely on liver biopsy.

Understanding the pathophysiology of the disease is key to predict who is at greater risk of developing NAFLD/NASH and will most likely benefit from a particular treatment regimen.

To improve our understanding of the condition CrownBio has developed preclinical models of NAFLD/NASH that present the main liver manifestations observed in the human disease and respond similarly to the same treatments.

Our preclinical models are the most translatable models available to study human metabolic syndrome and all its complication, including NAFLD and NASH.

Contact us today to learn more about our recently presented data on our NAFLD/NASH models and technologies.


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