Breath biomarkers and non-alcoholic fatty liver disease: Preliminary observations

Solga, Steven F.; Alkhuraishe, Amir R.; Cope, Keary A.; Tabesh, Alireza; Clark, Jeanne M.; Torbenson, Michael; Schwartz, Patrick B.; Magnuson, Thomas; Diehl, Anna Mae; Risby, Terence H.

doi:10.1080/13547500500421070

Cited by 57 publications

(34 citation statements)

References 28 publications

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“…Each of these pathways may generate different oxidation products that potentially could be quantifi ed. Based on the importance of oxidative stress in the pathogenesis of NASH, several groups have attempted to elucidate whether measurement of systemic markers of OS may be used as biomarkers (16)(17)(18)28 ). However, three key questions have remained unanswered: Which specifi c oxFA are enriched in the livers during NASH development?…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Feldstein

López

Tamimi

et al. 2010

Journal of Lipid Research

257

207

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This article is available online at http://www.jlr.org S. L. Hazen. Mass spectrometric profi ling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J. Lipid Res. 2010. 51: 3046-3054.Supplementary key words oxidized fatty acids • mass spectrometry • chiral mass spectrometry Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease affecting both adults and children, and it is strongly associated with obesity and insulin resistance ( 1, 2 ). One in three adults and one in ten children or adolescents in the United States have hepatic steatosis, a stage within the spectrum of NAFLD that is characterized by triglyceride accumulation in liver cells and follows a benign, nonprogressive clinical course ( 3, 4 ). Nonalcoholic steatohepatitis (NASH) is defi ned as lipid accumulation with evidence of cellular damage, infl ammation, and different degrees of scarring or fi brosis ( 5 ). NASH is a serious condition as approximately 25% of these patients progress to cirrhosis and its feared complications of portal hypertension, liver failure, and hepatocellular carcinoma ( 6-8 ).At present, the available noninvasive markers for NAFLD include a set of clinical signs and symptoms, nonspecifi c laboratory and radiological imaging tests, and combinations of clinical and blood test results ( 9 ). Although several of these markers are generally useful for the diagnostic evaluation of a patient with suspected Abstract Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the pathways that contribute to oxidative damage in vivo are poorly understood. Our aims were to defi ne the circulating profi le of lipid oxidation products in NAFLD patients, the source of these products, and assess whether their circulating levels refl ect histological changes in the liver. The levels of multiple structurally specifi c oxidized fatty acids, including individual hydroxy-eicosatetraenoic acids (HETE), hydroxy-octadecadenoic acids (HODE), and oxo-octadecadenoic acids (oxoODE), were measured by mass spectrometry in plasma at time of liver biopsy in an initial cohort of 73 and a validation cohort of 49 consecutive patients. Of the markers monitored, 9-and 13-HODEs and 9-and 13-oxoODEs, products of free radical-mediated oxidation of linoleic acid (LA), were signifi cantly elevated in patients with nonalcoholic steatohepatitis (NASH), compared with patients with steatosis. A strong correlation was revealed between these oxidation products and liver histopathology (infl ammation, fi brosis, and steatosis). Further analyses of HODEs showed equivalent R and S chiral distribution. A risk score for NASH (oxNASH) was developed in the initial clinical cohort and shown to have high diagnostic accuracy for NASH versus steatosis in the independent validation cohort. Subjects with elevated oxNASH levels (top tertile) were 9.7-fold ( P < 0.0001) more likely to have NASH than those with low levels (b...

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Section: Discussionmentioning

confidence: 99%

Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Feldstein

López

Tamimi

et al. 2010

Journal of Lipid Research

257

207

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“…Elevated breath nitric oxide (NO) concentrations (>16 ppbv) are found in asthmatic patients [29] and increased sulfides are present in those with cystic fibrosis (net uptake of 110 pptv carbonyl sulfide vs 250 pptv for controls)[30]. A separate panel of 5 VOCs (2-propanol, 2,3-dihydro-1-phenyl-4(1H)-quinazolinone, 1-phenyl-ethanone, heptanal, and isopropyl myristate) is associated with breast cancer[31], acetone with non-alcoholic steatohepatitis (919 nmol/l with stage 2–3 steatosis vs 675 nmol/l in stage 0–1)[32], and dimethyl sulfide with cirrhosis and fetor hepaticus (29.02 ppbv vs 13.79 ppbv in controls)[33]. Many more biomarkers are likely to be reported in the near future.…”

Section: B Gases In the Human Bodymentioning

confidence: 99%

The clinical potential of exhaled breath analysis for diabetes mellitus

Minh

Blake

Galassetti

2012

Diabetes Research and Clinical Practice

166

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“…Elevated levels of ethanol have been shown to be associated with hepatic steatosis, while increased breath acetone with nonalcoholic steatohepatitis. At the same time acetone levels were correlated to transaminase values in blood [120]. Other reports combine breath gas and liver enzyme data to propose a model for screening and discrimination of alcoholic fatty liver disease, nonalcoholic fatty liver disease, cirrhosis and cancer based on acetaldehyde and isoprene in combination with three other compounds [121].…”

Section: Key Termmentioning

confidence: 95%

Detection of Volatile Malodorous Compounds in Breath: Current Analytical Techniques and Implications in Human Disease

Calenic

Amann

2014

Bioanalysis

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For the last few decades intense scientific research has been placed on the relationship between trace substances found in exhaled breath such as volatile organic compounds (VOC) and a wide range of local or systemic diseases. Although currently there is no general consensus, results imply that VOC have a different profile depending on the organ or disease that generates them. The association between a specific pathology and exhaled breath odor is particularly evident in patients with medical conditions such as liver, renal or oral diseases. In other cases the unpleasant odors can be associated with the whole body and have a genetic underlying cause. The present review describes the current advances in identifying and quantifying VOC used as biomarkers for a number of systemic diseases. A special focus will be placed on volatiles that characterize unpleasant breath 'fingerprints' such as fetor hepaticus; uremic fetor; fetor ex ore or trimethylaminuria.

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Breath biomarkers and non-alcoholic fatty liver disease: Preliminary observations

Cited by 57 publications

References 28 publications

Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

The clinical potential of exhaled breath analysis for diabetes mellitus

Detection of Volatile Malodorous Compounds in Breath: Current Analytical Techniques and Implications in Human Disease

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