Breath Biopsy Assessment of Liver Disease Using an Exogenous Volatile Organic Compound-Toward Improved Detection of Liver Impairment.

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).

Faecal gas analysis by electronic nose as novel, non-invasive method for assessment of active and quiescent paediatric inflammatory bowel disease: Proof of principle study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) and its two phenotypes ulcerative colitis (UC) and Crohn's disease (CD) are essentially assessed by endoscopy, both in initial diagnostic work-up and during follow-up. This carries a high burden, especially on paediatric patients. Faecal volatile organic compounds (VOCs) are considered potential non-invasive biomarkers for intestinal diseases linked to gut microbiota alterations. We hypothesized that faecal VOC analysis by electronic nose allows discrimination of children with CD, UC and controls during active disease and remission. METHODS: Faecal VOC patterns of children with newly diagnosed IBD and controls were studied by an electronic nose (Cyranose 320®), at baseline and upon achieving remission at 6-weeks of follow-up. Disease activity was assessed by global physician's assessment, substantiated by serum C-reactive protein and faecal calprotectin. Internally cross-validated receiver-operator-characteristic curves and corresponding sensitivity and specificity for detection of IBD were calculated RESULTS: Faecal VOC profiles of patients with UC (26) and CD (29) differed from controls (28); in active disease (AUC±95% CI, p-value, sensitivity, specificity: 1.00±0.00; p<0.001, 100%, 100%) and (0.85±0.05, p<0.001, 86%, 67%) and in clinical remission (0.94±0.06, p<0.001, 94%, 94%) and (0.94±0.06, p<0.001, 94%, 94%), respectively. Furthermore, CD-patients differed from UC-patients during active disease (0.96±0.03; p<0.001, 97%, 92%), and upon achieving clinical remission (0.81±0.08, p=0.002, 88%, 72%). CONCLUSION: Faecal VOC analysis allowed discrimination of paediatric patients with IBD from controls, both during active disease and remission. It therefore has potential as non-invasive test, in both diagnostic work-up and assessment of disease activity in IBD.