Hepatic Urea Nitrogen Handling in Patients With NASH

  • days left to enroll
  • participants needed
  • sponsor
    University of Aarhus
Updated on 24 January 2021
liver disease
fatty liver
bariatric surgery
other liver diseases


The aim of the project is to investigate the metabolic regulation of the hepatic urea nitrogen handling and various cognitive functions measured by psychometric and neurophysiological tests before and after bariatric surgery in patients with non-alcoholic fatty liver disease (NAFLD).


NAFLD is the most common cause of chronic liver disease in the western world affecting 10-30% of the general population. It is strongly associated with the metabolic syndrome caused by overweight and obesity. NAFLD is a spectrum of liver disease ranging from steatosis (hepatocytic fat accumulation occurs without hepatocellular injury), to non-alcoholic steatohepatitis (NASH) (steatosis is accompanied by inflammation and hepatocyte injury with or without fibrosis) and to cirrhosis in patients that are not consuming excessive alcohol. The prognosis of patients with simple steatosis appears benign whereas NASH often has a progressive course with increased liver-related morbidity and mortality.

Patients with liver disease often have impairment of metabolic liver functions. The liver has numerous functions, which are essential for maintenance of life e.g. urea synthesis. This function is central in whole body nitrogen (N) homeostasis and removes ammonia, which is produced during N conversion and is extremely toxic especially for brain functions. Impairment of urea synthesis causes increased ammonia concentrations in the blood, which is taken up by the brain and contributes to development of hepatic encephalopathy in patients with liver disease. This condition is one of the most debilitating complications of liver disease as it affects cognitive functions and with increasing severity also behaviour and motor function. The mild stage (termed minimal hepatic encephalopathy) causes subtle cognitive dysfunction, which can only be detected by means of special tests. The more severe stages (manifest hepatic encephalopathy) are accompanied by manifest dysfunction of sleep pattern and orientation eventually leading to liver coma. The condition is reversible and no structural brain damage occurs.

We seek to investigate the consequences of bariatric surgery on liver and brain function with a special focus on NASH patients. The investigations will comprise examination of the capacity for urea synthesis and various psychometric and neurophysiological tests to evaluate the patient's cognitive functions before and 18 months after surgery.

A liver biopsy will be availed at the time of surgical intervention and genetic and functional characterization of urea cycle enzymes will be performed to correlate with histological scores, clinical disease staging and ammonia/capacity for urea synthesis. A further liver biopsy will be performed after 18 months to determine if there has been any change in NAFLD disease stage and urea cycle enzymes after intervention.

Condition NAFLD, Non-alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis (NASH), Nonalcoholic Fatty Liver Disease, Non Alcoholic Fatty Liver Disease, Non-alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis (NASH), non-alcoholic fatty liver
Clinical Study IdentifierNCT03260036
SponsorUniversity of Aarhus
Last Modified on24 January 2021


Yes No Not Sure

Inclusion Criteria

Age 18 years
Referred for bariatric surgery (BMI > 40 kg/m2 or BMI > 35 kg/m2 and obesity-related complications
Steatosis on ultrasound (US)
Alcohol intake < 40g/day
Exclusion of other liver diseases

Exclusion Criteria

Chronic inflammatory diseases
Acute severe bacterial infection (sepsis, pneumonia, urinary tract infection etc.)
Neurological diseases
Prednisolone treatment within the last 8 weeks
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note