Breath biomarkers for detection of human liver diseases: preliminary study

Abstract

Chronic liver disease is initially occult, has multiple aetiologies, involves complex diagnostic questions, and requires follow-up because progression is likely. Blood tests and biopsies are generally used, but have disadvantages. We have developed a new test for liver disease based on abnormal concentrations of metabolic products detected in exhaled breath. This test can be used, in conjunction with other clinically accepted diagnostic protocols, to detect and classify chronic liver diseases. Samples of breath collected from spontaneously breathing human subjects (86 patients presenting with 13 liver diseases and 109 subjects with normal liver function) were concentrated cryogenically and analysed by wide-bore capillary gas chromatography using various detectors. The concentrations of various molecules in exhaled breath were examined for potential use as biomarkers of liver function. Subjects with chronic liver diseases could be differentiated from those with normal liver function by comparing levels of breath carbonyl sulphide, carbon disulphide and isoprene; these differences were confirmed and correlated by comparing the levels with standard clinical blood markers of liver damage. The presence of chronic liver failure can thus be detected with sensitivity and specificity by quantifying sulphur-containing compounds arising from the abnormal metabolism associated with liver disease. The breath test we have developed appears to distinguish between hepatocellular and biliary tract aetiologies, and allows staging for severity. This approach may provide the clinician with a simple, non-invasive technique for use in the screening of large populations and follow-up for patients with chronic liver disease.

Effects of ventilation on the collection of exhaled breath in humans

“…It has previously been shown that both oral and gut bacteria may be significant sources of the volatile sulfur species in breath (44). Moreover, specific sulfur compounds such as carbonyl sulfide and dimethyl sulfide are known markers of liver disease pathogenesis and carbonyl sulfide has been suggested to be an early marker of acute rejection in lung transplant patients (37,43). Because the profile for the total sulfur-containing compounds tracked end-tidal carbon dioxide output, these molecules are probably generated systemically and not derived from the mouth.…”

“…In addition, a new protocol has also been developed for the analysis of total volatile sulfur-containing molecules in exhaled breath. Sulfur-containing molecules have been identified as breath markers of liver pathogenesis, lung transplant rejection, colonic fermentation, and nutrient disposition (20,37,43,44).…”

The therapeutic potential of hydrogen sulfide: separating hype from hope

“…COS is the only volatile sulfur that is increased in exhaled air of patients with cystic fibrosis (69) or of lung transplant patients during the acute rejection phase (150). COS is also exhaled by patients with chronic liver disease (135). COS has been demonstrated to be produced by porcine coronary arteries in vitro, and the rate of COS production is enhanced by stimulating the vessels with ACh or the calcium ionophore, A23187 (7).…”

Trace gas monitoring with infrared laser-based detection schemes

“…Exhaled human breath is a complex gas mixture containing hundreds of different species [47][48][49][50]. The most prominent ones are nitrogen, oxygen, carbon dioxide and water vapor, yet there are traces of numerous other gases and volatile organic compounds (VOCs) present.…”