Researchers of the Molecular Physics Group at the University of Birmingham have developed a new breath test for detecting early-stage liver disease. The test makes use of a naturally occurring compound limonene, found in lemons and oranges, which could indicate the presence of liver disease early-on.

Limonene And Liver Disease

Liver disease is the third leading cause of premature deaths in the UK, out of which a three-fourth of liver-related deaths are attributed to alcohol. The disease is often asymptomatic until it reaches advanced stages. Even when signs and symptoms begin to appear, they are generally mistaken for other pathological disorders. In severe cases, such as liver cirrhosis, transplant is the only remaining option.

The compound limonene is present abundantly in citrus fruits, followed by various fruits and vegetables. Being a common food additive, it can easily be ingested or inhaled. Other uses include adding limonene in fruit flavorings, cosmetics, cleaning products and perfumes.

According to the study published in EBioMedicine, researchers investigated the effectiveness of limonene as a biomarker for early-stage liver disease. The study was performed in two phases: breath samples from 31 patients of cirrhosis were compared with a healthy control group. This was followed by comparing breath samples of pre-transplant patients with a sub-cohort of 11 patients who were yet to have a liver transplant.

The breath samples were collected using the sampling protocol developed by Ms. Raquel Fernandez del Rio, a Marie Curie Early Stage Researcher in the Molecular Physics Group. The samples were stored in an extremely sensitive analytical instruments capable of measuring the intensity of ‘aroma molecules’ (molecules that emit smells).

Establishing The Efficacy Of The Biomarker

Breath samples from patients who had yet to have a liver transplant showed extremely high levels of limonene as compared to normal individuals. This demonstrated their inability to efficiently metabolize the compound.

However, the levels of limonene in breathe of patients after having a liver transplant gradually decreased over many days. This led researchers to deduce that un-metabolized limonene had been stored in the body fat of patients with liver cirrhosis.

Previous research has found significant biomarkers for liver disease, including isoprene and acetone, but they are not very specific and can stand out for various normal metabolic processes, explained primary investigator Dr Margaret O’Hara from the Molecular Physics Group. The aim of this study was to discover a biomarker that could be used to detect liver disease unambiguously.

Dr O’Hara added that the team wanted to find what caused the distinct smell on the breath of patients with liver disease. How that limonene has proved to be an important biomarker, its efficacy can be further put to test in diagnosing liver-related complications.

Future Prospects

If the research is successful, Dr O’Hara envisions the creation of a portable breath analyzer that GP’s and health professionals could use to detect early signs of liver disease. This would significantly improve treatment and mortality rates.

“These results are amazing since they associate limonene to the diseased liver instead of the diseased patient. Moreover, breath tests are significant and more accurate since they provide an opportunity to evaluate the overall function of the liver, rather than a localized test, such as biopsy”, Dr Chris Mayhew, Head of the Molecular Physics Group stated.

“These findings could provide, for the first time, a prospective conduit for ‘non-invasive real-time detection’ of early-stage cirrhosis. With this made possible, the disease could be reversed via drugs and lifestyle changes, leading to major socio-economic impacts”.