Noninvasive Technique Quantifies Nonalcoholic Fatty Liver Disease Progression

A new, noninvasive method of quantifying the progression of nonalcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis could prove crucial in charting the disease's prospective course, according to researchers.

Noting a need to "identify patients with more rapidly progressing disease and to demonstrate early response to treatment," University of California San Diego School of Medicine investigators conducted a study in which they describe "a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and non-invasively in blood."
________________________________________________________________________________________________________________________________________________________________________

RELTED CONTENT
How Much Exercise is Best for Nonalcoholic Fatty Liver Disease?
Nonalcoholic Fatty Liver Disease: Update on Evaluation and Treatment
________________________________________________________________________________________________________________________________________________________________________

For this study, 21 patients with suspected NAFLD ingested heavy water (a form of water containing deuterium, a heavier form of hydrogen) 2 to 3 times daily for a period of 3 to 5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on ²H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). The authors also used magnetic resonance elastography to measure liver stiffness.

The investigators found that hepatic collagen FSR in NAFLD increased with advancing disease stage (getting higher in NASH than NAFL), positively correlated with fibrosis score and liver stiffness, and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR, according to the authors.

"Approximately 20% of patients who progress to cirrhosis among those with NASH have a rapid progression," says Rohit Loomba, MD, MHSc, director of the NAFLD Research Center, director of hepatology and a professor of medicine at the University of California at San Diego, and co-author of the study.

"Until now, we did not have a way to detect those [patients]," says Loomba. "We believe that this technology, if validated, can help us identify rapid progressors efficiently, so we can act on their disease earlier."

With only a small percentage of NAFLD patients progressing to advanced liver disease, and the years or even decades that progression may take, "the key clinical questions are, which NAFLD patients will progress and are they responding to an intervention?" adds Marc Hellerstein, MD, PhD, a professor of nutritional science and toxicology at the University of California at Berkeley, and another study co-author.

This study presents a new clinical diagnostic test, or biomarker, that tells the doctor how actively fibrogenic an NAFLD/NASH patient's liver is, in real time," says Hellerstein.

"If further validated in large cohorts, this test could allow selection of NAFLD patients who are most likely to progress for initiation of treatment, and may also allow rapid and personalized evaluation of the efficacy of new agents."

—Mark McGraw

Reference:

Decaris ML, Li KW, Emson CL, et al. Identifying NAFLD patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood [published online October 5, 2016]. Hepatology. doi:10.1002/hep.28860.