Limonene in exhaled breath is elevated in hepatic encephalopathy

M E O’Hara,T Shah,C A Mayhew,P Pemberton,A Holt,R Fernández Del Río,T Whitehouse

doi:10.1088/1752-7155/10/4/046010

M E O’Hara, T Shah + Show 5 more

Open Access

https://doi.org/10.1088/1752-7155/10/4/046010

Copy DOI

Abstract

Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol−1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol−1, respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10–44) and 42 (32–58) nmol mol−1.

Highlights

alcoholic liver disease (ALD) GC HE hepatocellular cancer (HCC) ITU lower quartile (LQ) MS Minimal HE (MHE) Overt HE (OHE) OPU ppbv proton transfer reaction mass spectrometer (PTR-MS) UKELD upper quartile (UQ) volatile organic compounds (VOCs) volume mixing ratios (VMR)Alcoholic liver disease Gas chromatography Hepatic encephalopathy Hepatocellular cancer Intensive treatment unit Lower quartile Mass spectrometry Minimal hepatic encephalopathy Overt hepatic encephalopathy Out-patient clinic Parts per billion by volume Proton transfer reaction mass spectrometry United Kingdom model for End-stage Liver Disease Upper quartile Volatile organic compounds Volume mixing ratioVolatile organic compounds (VOCs) are produced in the body as a result of various metabolic processes and endogenous VOC analysis in the breath has been proposed as a potential diagnostic tool in human disease
Methanol and 2-pentanone have previously been shown to be elevated in the breath of cirrhotic patients compared with controls and in patients pre-transplant compared with the same patients after transplant [7]
Patients with HCC had lower levels of limonene than those without HCC but this may be a reflection of the fact that patients with HCC are usually considered for transplant at an earlier stage of liver decompensation

Summary

Introduction

Alcoholic liver disease Gas chromatography Hepatic encephalopathy Hepatocellular cancer Intensive treatment unit Lower quartile Mass spectrometry Minimal hepatic encephalopathy Overt hepatic encephalopathy Out-patient clinic Parts per billion by volume Proton transfer reaction mass spectrometry United Kingdom model for End-stage Liver Disease Upper quartile Volatile organic compounds Volume mixing ratio. Volatile organic compounds (VOCs) are produced in the body as a result of various metabolic processes and endogenous VOC analysis in the breath has been proposed as a potential diagnostic tool in human disease. Breath VOCs have been measured in patients with liver disease in a number of studies [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21] and several VOCs have been suggested as biomarkers for cirrhosis.

Methods

Results

Conclusion