Case control study evaluating the genetic factors associated with the development of non-alcoholic steatohepatitis (NASH 2002)

1st January 2012 - ongoing

Status: In Recruitment

Specialism: Liver.

Team: Professor Guruprasad Aithal.

The term non-alcoholic steatohepatitis, (NASH), describes a disease in which liver has excess fat leading to inflammation and scarring. Samples taken from the liver of patients with NASH look similar to the livers damaged by excess alcohol consumption. However, this condition affects people drinking little or no alcohol. Although this condition is more common in those who are over weight and patients with diabetes, NASH affects both men and women equally and can occur in those who are neither diabetic nor obese. In recent years, NASH is the commonest condition we see in those who attend our liver clinics. Although this condition is largely benign, a proportion of patients with inflammation in the liver in addition to fat progress to develop more advanced forms of liver disease. The mechanisms involved in the process which leads to the progressive liver damage are not clear. Identifying factors that predispose to progressive inflammation and scarring, is an essential step in developing treatment for this condition.

Genetic make up of an individual may be responsible in determining the way the fat is distributed in the organs as well as the way body responds to various factors that cause inflammation. We aim to study the pattern of genes involved in handling of fat by the liver as well as those involved in the inflammation and scarring in the liver in three groups of subjects. Genetic variations of patients with NASH will be compared with those who have simple fatty liver and with healthy volunteers. Such comparison would identify the genetic differences between different groups of subjects and hence, would allow identification of factors which might be involved in the progression of liver disease.

We would recruit 100 subjects to each group, aged between 30 and 70 with an equal ratio of males to females. Patient group would include those with a histological diagnosis of NASH and the control group with a histological diagnosis of simple fatty liver. Second control group would consist of healthy caucasian volunteers. Subjects would be included if they are competent to give informed consent. There are already about 100 patients each with simple fatty liver and NASH identified in the liver clinic at QMC. A `Patient Information Sheet’ has been designed to accompany the consent form signed by all subjects participating in the study. Dr GP Aithal, Dr SD Ryder or the research nurse would be responsible for obtaining consent to take extra blood samples required. Twenty ml of blood would be collected at the same time as doing routine blood tests. To protect confidentiality, patients will be identified by a unique number on a database. Names will not be used.

We are conducting this study in collaboration with Prof CP Day, Newcastle upon Tyne. The study has received ethical approval from the Joint Ethics Committee at Newcastle upon Tyne.

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guruprasad-aithal Professor Guruprasad Aithal Professor Aithal has been a Consultant Hepatobiliary Physician at Nottingham University Hospitals NHS trust since 2001. He is the Head of the NIHR Nottingham Digestive Diseases Biomedical Research Centre, and the Head of Division for the Nottingham…
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