Immune mechanisms of alcoholic hepatitis

  • Research type

    Research Study

  • Full title

    Immune mechanisms of acute alcoholic hepatitis

  • IRAS ID

    186252

  • Contact name

    Ashwin Dhanda

  • Contact email

    ashwin.dhanda@nhs.net

  • Sponsor organisation

    Plymouth Hospitals NHS Trust

  • Duration of Study in the UK

    4 years, 0 months, 1 days

  • Research summary

    Alcoholic hepatitis (AH) is a serious complication of alcohol misuse with up to half dying from the severe form. With the growing affordability and consumption of alcohol this condition is becoming increasingly prevalent in the UK and it is been identified as a research priority by the European Association for the Study of the Liver.

    Alcohol stimulates the immune system leading to an influx of immune cells (particularly monocytes) into the liver which drives inflammation and liver damage. Glucocorticoids (steroids) improve short term survival in this condition but up to 40% of the population is steroid resistant and will continue to deteriorate and die from this disease. Unfortunately, no other treatment has a proven benefit in this condition. Therefore it is important firstly, to be able to identify steroid resistant patients early after presentation to hospital and secondly, to develop novel therapies based on a clearer understanding of the liver immune system.

    We have previously demonstrated that a laboratory based test can accurately predict steroid resistance in patients with AH and here we intend to confirm these findings and develop a new test that can easily be applied to everyday clinical practice.

    We have also been investigating the role of monocytes (a type of immune cell) in the development and resolution of AH and have found that a subtype of monocyte, which may play a role in reducing inflammation, is increased in blood from these patients. In this study we intend to study the monocyte in more detail to investigate whether they can be manipulated to improve liver healing.
    Lay summary of study results: Lay summary Alcohol-related hepatitis (AH) is a serious complication of harmful alcohol use with up to half dying from the severe form within a year. With the growing affordability and consumption of alcohol this condition is becoming increasingly common in the UK and it is been identified as a research priority by the European Association for the Study of the Liver.

    Alcohol stimulates the immune system leading to an influx of immune cells (particularly monocytes) into the liver which drives inflammation and liver damage. Glucocorticoids (steroids) improve short term survival in this condition but up to 40% of the population does not respond to this treatment (termed steroid resistant) and will continue to deteriorate and die from this disease. Unfortunately, no other treatment has a proven benefit in this condition. Therefore it is important firstly, to be able to identify steroid resistant patients early after presentation to hospital and secondly, to develop novel therapies based on a clearer understanding of the liver immune system.

    We have previously demonstrated that a laboratory based test can accurately predict steroid resistance in patients with AH and here we intend to confirm these findings and develop a new test that can easily be applied to everyday clinical practice. We have also been investigating the role of monocytes (a type of immune cell) in the development and resolution of AH and have found that a subtype of monocyte, which may play a role in reducing inflammation, is increased in blood from these patients. In this study we intend to study the monocyte in more detail to investigate whether they can be manipulated to improve liver healing.

  • REC name

    London - Queen Square Research Ethics Committee

  • REC reference

    15/LO/1501

  • Date of REC Opinion

    14 Oct 2015

  • REC opinion

    Further Information Favourable Opinion