Rapid "breath-print" of liver cirrhosis by Proton Transfer Reaction Time of Flight Mass Spectrometry

Background & Aim: Being rapid and non-invasive, breath analysis is a promising diagnostic tool although difficulties related to data interpretation, reproducibility and sensibility have limited its application. The aim of the present work was to investigate whether a recently realized direct injection mass spectrometric technique (Proton Transfer Reaction Time of Flight Mass Spectrometry, PTR-ToF-MS) allows the direct and noninvasive diagnosis of cirrhosis as well as the assessment of the disease severity by direct analysis of exhaled breath. Methods: Twelve patients (M/F 8/4, mean age 70.5, range 42-80 years) with liver cirrhosis of different etiologies and status and 14 healthy subjects (M/F 5/9, mean age 52.3, range 35-77 years) were enrolled in the study. The etiology of cirrhosis was viral in 9 (8 HCV and 1 HBV) and metabolic in 3. The Child-Pugh class was A in 6 patients, B in 3, and C in the remaining 3 patients. Real time breath analysis was performed using a buffered end-tidal (BET) on-line sampler coupled to a PTR-ToF-MS. Spectra were acquired using the data acquisition software TOF-DAQ (Tofwerk AG, Switzerland) with a mass/charge range of 10–400 Th. The data were analyzed by non-parametric ANOVA (Kruskal-Wallis test) using the Statistica 9.1 (StatSoft, USA) software. Results: Eight peaks resulted significantly different in cirrhotic patients compared to healthy controls: two related to ketones, (2-pentanone, C8-ketone), two to terpenes and four to sulfur compounds. Three peaks resulted significantly different between Child-Pugh A cirrhotic patients and Child-Pugh B+C cirrhotic patients and precisely: C8-ketone, a monoterpene and a NS-compound. Conclusion: In conclusion, real time analysis of breath allows to distinguish cirrhotic from healthy subjects and well compensated liver disease from more advanced liver stage. The proposed method can be used to identify the stage and severity of liver disease in real time with a safe and non-invasive procedure