New Breath Test Shows Possible Biomarker for Early-Stage Liver Disease Diagnosis

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A natural compound, limonene, found in oranges and lemons, could be indicative in early-stage diagnosis of liver disease. Patients with this illness do not often present with symptoms until the disease is advanced. Even then diagnosis is difficult and the symptoms and signs are often general and can be mistaken for other pathologies. For advanced cirrhosis liver,transplant is the only treatment.

In the UK liver disease has risen sharply over the past few decades and is the 3rd biggest cause of premature mortality, with 3/4 of liver deaths due to alcohol. Patients do not often present with symptoms until the disease is advanced.

The R enantiomer of limonene smells like oranges. The S enantiomer smells like lemons.

The R enantiomer of limonene smells like oranges. The S enantiomer smells like lemons. Credit: https://jahschem.wikispaces.com/stereochem+in+biology

The Molecular Physics Group’s study was carried out in 2 phases – breath samples from a group of 31 patients suffering from cirrhosis were first compared with a healthy control group. Then pre-transplant samples of the liver disease sufferers were compared with a sub-cohort of 11 patients who went on to have a liver transplant.

When the patients were tested before transplant surgery, the level of limonene in the breath was found to be very high as patients could not fully metabolize limonene. When the team tested the same patients who had received a new liver, the tests showed that the limonene levels gradually dropped over several days as unmetabolized limonene had been stored in the body fat of people suffering with cirrhosis.

Schematic of the breath sampling device. Breath samples are only drawn into the glass syringe once the capnograph shows that the alveolar phase of the exhaled breath has been reached.

Schematic of the breath sampling device. Breath samples are only drawn into the glass syringe once the capnograph shows that the alveolar phase of the exhaled breath has been reached. Typically 3–4 breaths are needed to fill a syringe to 100 ml. Credit http://www.ebiomedicine.com/action/showFullTextImages?pii=S2352-3964%2815%2930079-7

 

“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.” said Dr Margaret O’Hara ‘We already knew that people with liver disease have a very distinct smell on the breath and we wanted to find out what caused that smell.”

‘If our further research is successful, in the future we can envisage a small portable breath analyser that can be used by GPs and other health professionals to screen for early stage liver disease , leading to earlier treatment and better survival rates.’ http://www.eurekalert.org/pub_releases/2015-08/uob-nbt081115.php

Longitudinal changes in volume mixing ratios (VMRs) in nmol/mol for limonene at given days after liver transplant for patients F2, F4, F5, M3, and M7. The data point at day 0 for F2 was taken just before transplant surgery. Credit: http://dx.doi.org/10.1016/j.ebiom.2015.07.027

Longitudinal changes in volume mixing ratios (VMRs) in nmol/mol for limonene at given days after liver transplant for patients F2, F4, F5, M3, and M7. The data point at day 0 for F2 was taken just before transplant surgery. Credit: http://dx.doi.org/10.1016/j.ebiom.2015.07.027