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Study reveals biomarker for advanced liver fibrosis in patients with NAFLD

Saras Ramiya
19 Sep 2018

The non-invasive biomarker PRO-C3 can determine the presence of advanced liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), a study shows.

A score based on PRO-C3—a marker of type III collagen formation—was developed by an international research team whose paper has been published in the Hepatology journal. [https://doi.org/10.1002/hep.30163]

The team, led by Professor Jacob George and Associate Professor Mohammed Eslam from the Westmead Institute for Medical Research (WIMR) as well as Professor Leon Adams from the University of Western Australia, found that PRO-C3 progressively increases with fibrosis stage (rho 0.50 p<0.0001) and is independently associated with advanced fibrosis (OR=1.05, 95% CI 1.02–1.08, p=0.03).

The team combined the data on PRO-C3 with routine clinical information including patients’ age, presence of diabetes and platelet count to develop a highly accurate algorithm called ADAPT to detect advanced fibrosis in NAFLD.

The study involved 431 patients from across Australia, the UK and Japan—150 in the derivation and 281 in the validation cohort. These cohorts had extensive clinical phenotyping and liver biopsy. The team measured their PRO-C3 levels using enzyme-linked immunosorbent assay (ELISA).

Using ADAPT, the team showed the areas under the receiver operating characteristics curve (AUROC) of 0.86 in the derivation (95% CI 0.79 to 0.91) and 0.87 in the validation cohort (95% CI 0.83 to 0.91) for advanced fibrosis. These findings were better than the existing fibrosis scores such as aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS).

“Given the high global prevalence of non-alcoholic fatty liver disease, we need a non-invasive clinical tool to accurately measure fibrosis,” said George.

“Our tool will help identify advanced fibrosis in patients, which is crucial, as these are the people who are most likely to develop future health complications,” said Eslam.

“If NAFLD and fibrosis are detected and treated early, permanent liver damage and other life- threatening diseases can be avoided,” he said.

George and his team now plan to validate the score in the general community first and then following up with widespread application and clinical availability.

The research was completed in collaboration with colleagues from WIMR, WIMR’s Storr Liver Centre, University of Sydney and Westmead Hospital in Australia as well as researchers in Denmark, Egypt, Japan and the UK.

NAFLD, well known as ‘fatty liver,’ is a term accorded to a liver consisting of more than five percent of fatty tissue. NAFLD affects people who are physically inactive and obese even though they drink little to no alcohol.

Physical inactivity and obesity are key risk factors for the increased worldwide prevalence in NAFLD. NAFLD, in turn, increases the risk of developing type 2 diabetes mellitus and cardiovascular diseases.

NAFLD begins with the accumulation of fat in the liver and can progress to scarring in the liver, also known as fibrosis. Fibrosis causes the liver to eventually shrink and increases the risk of liver failure and cancer.

NAFLD is the leading cause of chronic liver disease and affects approximately 1-in-4 people, including children, worldwide.

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