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Clin Transl Gastroenterol

Title:		Breath Biopsy Assessment of Liver Disease Using an Exogenous Volatile Organic Compound-Toward Improved Detection of Liver Impairment
Author(s):		Ferrandino G; Orf I; Smith R; Calcagno M; Thind AK; Debiram-Beecham I; Williams M; Gandelman O; de Saedeleer A; Kibble G; Lydon AM; Mayhew CA; Allsworth M; Boyle B; van der Schee MP; Allison M; Hoare M; Snowdon VK;
Address:		"Owlstone Medical, Cambridge, UK. Current affiliation: Human Metabolome Technologies, Leiden, the Netherlands. Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK. Institute for Breath Research, Leopold-Franzens-Universitat Innsbruck, Dornbirn, Austria. Molecular Physics Group, School of Physics and Astronomy, University of Birmingham, Birmingham, UK. Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Addenbrooke's Hepatology and Liver Transplantation Unit, Addenbrooke's Hospital, Cambridge, UK. CRUK Cambridge Institute, Cambridge, UK. Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK"
Journal Title:		Clin Transl Gastroenterol
Year:		2020
Volume:		11
Issue:		9
Page Number:		e00239 -
DOI:		10.14309/ctg.0000000000000239
ISSN/ISBN:		2155-384X (Electronic) 2155-384X (Linking)
Abstract:		"INTRODUCTION: Liver cirrhosis and its complication - hepatocellular carcinoma (HCC) - have been associated with increased exhaled limonene. It is currently unclear whether this increase is more strongly associated with the presence of HCC or with the severity of liver dysfunction. METHODS: We compared the exhaled breath of 40 controls, 32 cirrhotic patients, and 12 cirrhotic patients with HCC using the Breath Biopsy platform. Breath samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. Limonene levels were compared between the groups and correlated to bilirubin, albumin, prothrombin time international normalized ratio, and alanine aminotransferase. RESULTS: Breath limonene concentration was significantly elevated in subjects with cirrhosis-induced HCC (M: 82.1 ng/L, interquartile range [IQR]: 16.33-199.32 ng/L) and cirrhosis (M: 32.6 ng/L, IQR: 6.55-123.07 ng/L) compared with controls (M: 6.2 ng/L, IQR: 2.62-9.57 ng/L) (P value = 0.0005 and 0.0001, respectively) with no significant difference between 2 diseased groups (P value = 0.37). Levels of exhaled limonene correlated with serum bilirubin (R = 0.25, P value = 0.0016, r = 0.51), albumin (R = 0.58, P value = 5.3e-8, r = -0.76), and international normalized ratio (R = 0.29, P value = 0.0003, r = 0.51), but not with alanine aminotransferase (R = 0.01, P value = 0.36, r = 0.19). DISCUSSION: Exhaled limonene levels are primarily affected by the presence of cirrhosis through reduced liver functional capacity, as indicated by limonene correlation with blood metrics of impaired hepatic clearance and protein synthesis capacity, without further alterations observed in subjects with HCC. This suggests that exhaled limonene is a potential non-invasive marker of liver metabolic capacity (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A388)"
Keywords:		"Adult Aged Aged, 80 and over Biomarkers/analysis Breath Tests Carcinoma, Hepatocellular/*diagnosis/pathology/physiopathology Case-Control Studies Cross-Sectional Studies Female Humans Limonene/*analysis Liver/pathology/physiopathology Liver Cirrhosis/*dia;"
Notes:		"MedlineFerrandino, Giuseppe Orf, Isabel Smith, Rob Calcagno, Marzia Thind, Anita Kaur Debiram-Beecham, Irene Williams, Megan Gandelman, Olga de Saedeleer, Alexandra Kibble, Graham Lydon, Anne Marie Mayhew, Chris A Allsworth, Max Boyle, Billy van der Schee, Marc P Allison, Michael Hoare, Matthew Snowdon, Victoria K eng 26813/CRUK_/Cancer Research UK/United Kingdom Observational Study Research Support, Non-U.S. Gov't 2020/10/24 Clin Transl Gastroenterol. 2020 Sep; 11(9):e00239. doi: 10.14309/ctg.0000000000000239"