Improving Assessment of Fatty Liver Disease

This study evaluates possible genetic reasons for the development of non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ASH) and the progression of fatty liver.

Introduction

What is steatohepatitis?

Steatohepatitis is a liver disease characterized by inflammation of the liver and fat accumulation in the liver at the same time. There are two main types: Alcoholic steatohepatitis (ASH), connected with excess alcohol consumption and Non-alcoholic steatohepatitis (NASH), affecting people who consume no or only low levels of alcohol. The changes seen in the liver look similar for both diseases.

In patients where there is only high levels of fat without inflammation (simple fatty liver) then the condition is less likely to progress to more serious forms of disease and scarring. For patients with NASH or ASH, some can develop more advanced diseases where the liver becomes damaged and scarred.

Why do we want to identify steatohepatitis?

Non-alcoholic steatohepatitis (NASH) is the most common condition we see in those who attend our liver clinics. Although this condition is more common in those who are overweight and patients with diabetes, it also occurs in those who are neither diabetic nor overweight.

The steps involved in progression towards liver damage are currently not clear. It is important to investigate factors that might predispose people to progressive inflammation and scarring of the liver, in order to develop new treatments for the condition

Substances which can be detected non-invasively (eg in blood or urine samples) which indicate the severity of disease would be useful markers for diagnosis and to monitor the disease progression as an alternative to a biopsy.

What factors may be involved in steatohepatitis development?

  1. Individual peoples’ DNA could be responsible in deciding the way the fat is distributed in the organs, and also how the body various factors that cause inflammation.
  2. There are a number of other factors that may contribute to the development of NASH as they can change the chemical composition of blood for example.

Aims of our research study

  1. We aim to determine whether genetic differences in components of pathways involved in processing fat or developing inflammation and scarring in the liver are associated with an increased risk of developing NASH. Genetic differences of patients with steatohepatitis (NASH or ASH) will be compared with those who have ‘simple fatty liver’ and with healthy volunteers. This comparison would identify the genetic differences between different groups of participants and would us to identify factors which might be involved in the progression of liver disease.
  2. Possible new chemical indicators of disease processes have been suggested based on other research studies. Some indicators have been proposed to show liver cell damage in a non-invasive way, such as blood or urine samples. This study aims to find out whether these biomarkers are valuable in diagnosing fatty liver, scarring, NASH and ASH.

Dates open for recruitment (start-finish)

Who can participate?

  • Must be aged over 18 and able to give informed consent
  • Anyone diagnosed with non-alcoholic fatty liver disease (usually by liver biopsy)
  • Anyone diagnosed with alcoholic liver disease (usually by liver biopsy)
  • ‘Healthy volunteers’ – people with no known/diagnosed liver disease

What it involves:

  • Visits – one visit to Nottingham Digestive Diseases Biomedical Research Centre (‘BRU’) in QMC, Nottingham. Lasts about 60-90 minutes
  • Discussion with nurse about your risk factors, that might increase your risk of developing liver disease, and advice on how they can be reduced
  • Invite you to participate in further studies, participant advisory group, receive newsletter or attend research open event

Samples:

  • Blood (up to 36ml)
  • Urine (if possible)
  • Poo (stool – if possible)

Questions – interview with nurse

  • Health overview – height, weight, grip strength etc, age,
  • Medical background details of clinical tests relating to liver diagnosis and medication
  • Diet/lifestyle questions