The new research published today in Science Translational Medicine is by Newcastle University researchers, as part of the EPoS and LITMUS consortia, which bring clinicians, scientists and academic experts from universities across Europe with scientists from the leading pharmaceutical companies.

NAFLD is a disease which affects approximately 25% of the adult population worldwide and at present the diagnosis of the disease requires a liver biopsy, which can only be done in specialist hospitals, and it remains a challenge to identify those people that will be most severely affected and are going to progress to end-stage liver disease.

The global increase in obesity has led to a dramatic rise in the prevalence of NAFLD, affecting approximately 25% of the adult population worldwide. NAFLD is caused by a build-up of fat in the liver, which leads to inflammation, scarring and ultimately cirrhosis or liver cancer in some people. The disease is associated with a substantial socioeconomic burden, which, coupled with rising prevalence, is a growing public health challenge.

The research reveals a better understanding of the mechanisms of the disease progression and identifies a better diagnostic test which can identify why some people are affected more severely than others.

In the study, the team examined the mRNA profile (which genes are actively expressed and which are not) in the livers of patients with different severities of the disease using advanced RNA sequencing methods. Over 400 liver biopsies were included in this multicentre study being one of the largest studies of its kind performed for NAFLD to date.

They observed changes in genes controlling liver metabolism, inflammation and tissue scaring. In addition, one of the key findings was the identification of a core “gene expression signature” of 25 different genes that consistently changed as the disease got worse. This 25 gene signature gives new insights that are relevant to a number of different key processes in the liver disease.

In addition, they show that many of the changes in expression of the 25 genes lead to alterations in proteins that can be detected in the blood. The team believe that at least two of these proteins have great potential as new diagnostic tests for NAFLD severity. Others may offer some new insights into treatment targets. Work to explore and validate these findings is still ongoing but the results so far are promising.

The new publication has 29 collaborating authors from institutions across Europe and USA. The first author, Dr Olivier Govaere, and the senior authors Prof Ann Daly and Prof Quentin Anstee are from Newcastle University Translational and Clinical Research Institute. The work was done in Newcastle as part of the EPoS project which was funded by the EU-Horizon 2020 research funding programme. The promising new biomarkers identified by this research will go forward for further detailed evaluation within the EU-IMI2 LITMUS project, coordinated by Prof Quentin Anstee.

This project has received funding from the European Union’s Horizon 2020 research funding programme and the Innovative Medicines Initiative 2 Joint Undertaking. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

Reference: Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis. Science Translational Medicine