Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease

Sinha, Rohit; Lockman, K. A.; Homer, Natalie; Bower, Edward K M; Brinkman, Paul; Knobel, Hugo H.; Fallowfield, Jonathan; Jaap, Alan J.; Hayes, Peter; Plevris, John

doi:10.1016/j.jhepr.2020.100137

Cited by 24 publications

(26 citation statements)

References 45 publications

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“…In this study, we have significantly expanded on this concept by showing that limonene correlates with established blood metrics of liver function, but not with ALT, a biomarker of liver damage. In agreement with our results, Sinha et al ( 30 ) also mentioned a negative correlation between breath limonene and serum albumin. A difference can be observed with a study by Friedman et al ( 15 ) that showed a correlation between lung air limonene and prothrombin time, but not with serum bilirubin and albumin.…”

Section: Discussionsupporting

confidence: 94%

“…Our results confirm and expand on previous findings by O'Hara et al ( 17 ) who demonstrated that limonene levels are elevated in subjects with HCC and cirrhosis and a study by Fernandez Del Rio et al ( 14 ) which showed that restoring hepatic function by liver transplant brings breath limonene levels to baseline in the following weeks. Similarly, Sinha et al ( 30 ) found high levels of limonene in the breath of patients with non-alcoholic steatohepatitis (NASH) cirrhosis, compared with those of patients with non-alcoholic fatty liver disease, further supporting our conclusion that cirrhosis is the primary driver for the elevation of breath limonene levels.…”

Section: Discussionsupporting

confidence: 88%

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

Ferrandino

Orf

Smith

et al. 2020

Clin Transl Gastroenterol

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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 2 = 0.25, P value = 0.0016, r = 0.51), albumin ( R 2 = 0.58, P value = 5.3e-8, r = −0.76), and international normalized ratio ( R 2 = 0.29, P value = 0.0003, r = 0.51), but not with alanine aminotransferase ( R 2 = 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 ).

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 88%

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

Ferrandino

Orf

Smith

et al. 2020

Clin Transl Gastroenterol

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“… 40 Measurement of volatile organic compounds, such as erpinene, dimethyl sulfide, and D-limonene, in breath is another approach that may prove useful in diagnosing and managing some liver diseases. 41 , 42 These approaches have also been termed volatomics or breath biopsy. Although many of these tests do show reasonable correlation with other tests of liver function, they are not indicated for the diagnosis of disease and are of limited value in measuring degrees of fibrosis, steatosis or inflammation.…”

Section: Limitations Of Liver Biopsymentioning

confidence: 99%

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

Neuberger

Cain

2021

HMER

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Histology remains essential for the diagnosis and management of many disorders affecting the liver. However, the biopsy procedure itself is associated with a low risk of harm to the patient and cost to the health services; samples may not be adequate and are subject to sampling variation. Furthermore, interpretation often depends on the skill of the pathologist. Increasingly, new techniques are becoming available that are altering the indications for liver biopsy. Many diseases of the liver can be diagnosed and managed using serological and radiological techniques; the degree of fibrosis and fat can often be assessed by serological or imaging techniques and the nature of space occupying lesions defined by serology, imaging and use of liquid biopsy. However, these techniques, too, are subject to limitations: sensitivity and specificity is not always adequate for diagnosis or management; some techniques are expensive and often also require expert interpretation. Although there may be less need for liver biopsy today, histology remains the gold standard as well as an essential tool for the diagnosis and management of many conditions, especially where there are multiple pathologies, or where a diagnosis cannot or has not been made by alternative approaches. Until less invasive techniques become more reliable and accessible, liver histology will remain a key investigation.

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“…Therefore, there has been an increasing interest in nutrigenomics, proteomics, and metabolomics to monitor metabolism from a wider perspective. Volatomic analysis of exhaled breath, used mainly for searching noninvasive biomarkers for diseases [ 19 , 20 , 21 ], could be used to characterize volatile organic compounds (VOCs) relating to various diets or specific foods, such as WG cereals. This research could lead to new information on the metabolic effects of WG foods and their association with health effects.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Two-Dimensional Gas Chromatography–Mass Spectrometry Analysis of Exhaled Breath Compounds after Whole Grain Diets

et al. 2021

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Exhaled breath is a potential noninvasive matrix to give new information about metabolic effects of diets. In this pilot study, non-targeted analysis of exhaled breath volatile organic compounds (VOCs) was made by comprehensive two-dimensional gas chromatography–mass spectrometry (GCxGC-MS) to explore compounds relating to whole grain (WG) diets. Nine healthy subjects participated in the dietary intervention with parallel crossover design, consisting of two high-fiber diets containing whole grain rye bread (WGR) or whole grain wheat bread (WGW) and 1-week control diets with refined wheat bread (WW) before both diet periods. Large interindividual differences were detected in the VOC composition. About 260 VOCs were detected from exhaled breath samples, in which 40 of the compounds were present in more than half of the samples. Various derivatives of benzoic acid and phenolic compounds, as well as some furanones existed in exhaled breath samples only after the WG diets, making them interesting compounds to study further.

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Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease

Cited by 24 publications

References 45 publications

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

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

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

Comprehensive Two-Dimensional Gas Chromatography–Mass Spectrometry Analysis of Exhaled Breath Compounds after Whole Grain Diets

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