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Researchers find breath biomarkers may help diagnose early-stage cirrhosis

New research data published in EBioMedicine showed that limonene, methanol and 2-pentanone were useful breath biomarkers for diagnosing cirrhosis.

“Previous studies have found potential biomarkers for liver disease, such as isoprene and acetone, but they are not specific enough because they are possible biomarkers for other diseases or can arise from numerous normal metabolic processes,”  Margaret O'Hara, BSc (Hons), PGCE, MSc, DipIPEM, PhD, of the Molecular Physics Group, University of Birmingham, UK, said in a press release. “We wanted to find a biomarker that is unambiguously associated with diseased liver.”

Margaret O'Hara

O’Hara and colleagues, including Chris Mayhew, BSc, DIC, PhD, FInsP, head of the Molecular Physics Group, and Raquel Fernández del Río, a Marie Curie early-stage researcher working with the Molecular Physics Group, conducted a two-part biomarker procedure that consisted of analyzing and comparing alveolar breath samples of 31 patients with cirrhosis to breath samples of 30 healthy controls. Among these patients, 12 had their breath samples assessed after liver transplantation and five were followed as “in-patients” post-transplant, according to the research.

Overall, the researchers observed seven volatiles higher in patients with cirrhosis compared with the controls. Of these seven, limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide decreased post-transplant.

Limonene was found to have the best diagnostic capability, according to an area under the receiver operating characteristic curve (AUROC) of 0.91. However, this improved after combining limonene with methanol and 2-pentanone (AUROC = 0.95), which had a sensitivity of 97% and a specificity of 70%.

Five patients participated in a longitudinal study to determine if any of the five volatiles’ volume mixing ratios (VMR) changed over time post-transplant. What the researchers found was that only limonene’s VMR decreased following transplant.

“The group's results are astounding because they link limonene to the diseased liver rather than simply the diseased patient,” Mayhew said in the release. “A particularly important advantage of breath tests is that they offer the opportunity to assess the global function of the liver, rather than a localized test such as biopsy.”

The researchers concluded: “Our study raises the possibility of a pharmacokinetic-based test for assessing liver function which could be used for diagnosing liver disease, i.e. where a known quantity of limonene is administered and its wash-out in breath is assessed over time. Importantly, this study provides a set of biomarkers which can be used in future studies to assess the potential of breath analysis for the diagnosis of early-stage liver disease.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.