Scientists have identified a biomarker that could form the basis of a
breath test for the detection of early-stage liver disease.
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
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
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
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
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
“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.
Written by Catharine Paddock PhD
Copyright: Medical News Today
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