Scientists have identified a biomarker that could form the basis of a breath test for the detection of early-stage liver disease.

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The researchers believe their study is important because, for the first time, it opens a potential route to noninvasive, real-time detection of early-stage liver disease.

In the journal EBioMedicine, a study led by the University of Birmingham in the UK suggests that high levels of a natural compound called limonene in the breath could be a sign of early-stage cirrhosis of the liver.

Lead investigator and molecular physics researcher Dr. Margaret O'Hara says we already know that the breath of people with liver disease has a very distinct smell, and they wanted to find out what causes it. She adds:

"Now that we have found a biomarker for the disease in limonene, we can continue to verify how good it is for diagnosing liver disease."

Limonene is a natural compound found in fruits and vegetables and in abundance in citrus fruits like oranges and lemons. It is also found in cosmetics, perfume and cleaning products and is used to flavor candies.

Because symptoms tend to be vague and often mild during the early stages, patients with liver disease do not usually seek medical advice until the condition is advanced and the liver is more damaged. Even then, symptoms can be mistaken for other diseases. They can include fatigue, jaundice, bleeding, swelling, bruising easily, confusion and nausea.

Cirrhosis is where continuous, long-term damage causes the liver to become so scarred it cannot function properly. The disease can lead to liver failure and cancer. Currently, the only treatment option for advanced cirrhosis of the liver is organ transplant.

In the US, liver cirrhosis is the 12th leading cause of death overall and the fifth leading cause of death for people aged 45-54.

Earlier this year, a study led by the Loyola University Chicago Stritch School of Medicine found that liver cirrhosis is more common in the US than previously thought. The researchers suggest the disease affects 633,000 adults in the US population and not 400,000 as previously thought, and that 69% of Americans with the disease do not realize they have it.

In the UK, where the new study took place, liver disease has risen sharply in recent decades to become the third biggest cause of early death, with 75% of deaths being alcohol related.

Breath levels of limonene higher in patients with liver cirrhosis

Dr. O'Hara and colleagues carried out their study in two phases. First, they compared breath samples from 31 patients with liver cirrhosis with those from 30 healthy controls.

In the second phase, they compared breath samples taken before and after liver transplants. The before samples came from the same 31 patients as in the first phase, and the after samples came from 11 of those patients who went on to have liver transplants.

The breath samples were analyzed with a mass spectrometer. For phase 1, this showed that the level of limonene in the patients with liver cirrhosis were much higher than in the healthy controls.

The researchers say this is probably because a diseased liver cannot fully metabolize limonene.

The phase 2 analysis showed that the levels of limonene gradually dropped in the transplant patients in the days following receipt of their new organ.

Limonene is 'unambiguously associated with diseased liver'

Dr. O'Hara says there have been previous attempts to find possible biomarkers for liver disease but these have suggested compounds like isoprene and acetone, which are not specific enough since they can also be indicative of other diseases or even arise naturally from normal metabolic activity.

"We wanted to find a biomarker that is unambiguously associated with diseased liver," she notes, and concludes:

"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."

Senior author Dr. Chris Mayhew, who heads the molecular physics group that includes Dr. O'Hara and some of the other authors, says their findings are "astounding because they link limonene to the diseased liver rather than simply the diseased patient," and notes:

"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 study is important, he says, because for the first time it opens a potential route to noninvasive, real-time detection of early-stage liver disease. He concludes:

"If that is possible, then the disease could be reversed by drugs and lifestyle change which would lead to major socioeconomic impacts."

The group is now pursuing additional funding to take the research to the next stage - evaluating the diagnostic accuracy of their breath analysis method for early-stage liver disease.

Meanwhile, Medical News Today has also learned that stem cell therapy could replace liver transplants in the treatment of liver failure. In the journal Nature Cell Biology, scientists describe how, for the first time, they restored organ function in a severely damaged liver in a live animal by transplanting lab-grown stem cells.