Isoprene in exhaled breath may be an option for diagnosing fibrosis in liver disease

Last Updated: 2015-10-07

By Larry Hand

NEW YORK (Reuters Health) - Breath testing for volatile organic compounds (VOCs) such as isoprene could be a "promising option" for helping to diagnose advanced fibrosis in patients with chronic liver disease (CLD), according to a new study.

"This was a pilot study that included 61 patients with only 20 patients with advanced fibrosis or cirrhosis," Dr. Naim Alkhouri of the Digestive Disease Institute at the Cleveland Clinic Foundation in Ohio told Reuters Health by email.

"We are working on developing small and cheap sensors that can determine the breath levels of isoprene and other volatile organic compounds. The goal is to develop a hand-held device (similar to an alcohol breathalyzer) that can be used in real time by clinicians to risk-stratify their patients with chronic liver disease," he explained.

Dr. Alkhouri and colleagues used selective ion flow tube mass spectrometry (SIFT-MS) to analyze exhaled breath samples from 61 CLD patients undergoing liver biopsy at the Cleveland Clinic.

Patients used a mouth wash to rinse before collection of the breath samples to reduce contamination from VOCs produced in the mouth. The collections took place following an eight-hour fast.

Patients exhaled at a rate of 50 ml/s through a mouth filter until emptying their lungs. Researchers collected the breath samples in Mylar bags, capped them, then analyzed the samples within four hours, according to an article online September 17 in Clinical and Translational Gastroenterology.

Most patients had CLD due to hepatitis (44.3%) and a number of others had it due to nonalcoholic fatty liver disease (29.5%).

The researchers tested for 21 VOCs and found six compounds to have statistically significant concentration differences between mild and advanced fibrosis.

Levels were lower in advanced fibrosis at 224.2 ppb versus 117.8 ppb for acetone, 8.0 versus 1.9 for benzene, 3.2 versus 1.6 for carbon disulfide, 40.4 versus 13.5 for isoprene, 19.5 versus 12.3 for pentane, and 75.6 versus 63.0 for ethane (Bonferroni-corrected p<0.002 for all).

Isoprene, after further analysis, had the highest area under the curve for predicting advanced fibrosis. Probability of advanced fibrosis decreases 10% for every unit increase in isoprene (odds ratio, 0.9; p<0.001).

The researchers calculated that isoprene levels below 14.1 ppb would provide for 93% specificity, 60% sensitivity, 80% positive predictive value, and 83% negative predictive value. They set a cut-off value of 29 ppb to rule out advance fibrosis and 14.1 ppb to rule it in.

"Of all the compounds, isoprene can most reliably diagnose advanced fibrosis," the researchers wrote. "Isoprene is a marker of cholesterol biosynthesis and our results suggest that this pathway may be impaired in patients with advanced liver fibrosis and compensated liver disease well before the development of low plasma cholesterol level that is characteristic of patients with end-stage liver disease."

"Further validation in a larger number of patients is required before breath testing to determine if isoprene level can be recommended to diagnose advanced fibrosis. The effect of different diets and medications on isoprene levels needs further clarification," Dr. Alkhouri said.

The Ohio Department of Development partially supported this research. The authors reported no disclosures.

SOURCE: http://bit.ly/1Md59d3

Clin Transl Gastroenterol 2015.