Breath testing for human liver function assessment

Armuzzi, Alessandro; Candelli, Marcello; Zocco, Maria Assunta; Andréoli, A.; Lorenzo, Antonino De; Nista, Enrico Celestino; Miele, Luca; Cremonini, Filippo; Cazzato, I.A.; Grieco, Antonio; Gasbarrini, Giovanni; Gasbarrini, Antonio

doi:10.1046/j.1365-2036.2002.01374.x

Cited by 100 publications

(92 citation statements)

References 168 publications

(209 reference statements)

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“…diet) may cause variations in the natural occurrence of 13 CO 2. Therefore, the final results are expressed as delta-over-baseline (DOB) values [114][115][116].…”

Section: Exhaled Breathmentioning

confidence: 99%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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Interindividual variability in the expression and function of drug metabolizing cytochrome P (CYP) 450 enzymes, determined by a combination of genetic, non-genetic and environmental parameters, is a major source of variable drug response. Phenotyping by administration of a selective enzyme substrate, followed by the determination of a specific phenotyping metric, is an appropriate approach to assess the in vivo activity of CYP450 enzymes, as it takes into account all influencing factors. A phenotyping protocol should be as simple and convenient as possible. Typically, phenotyping metrics are determined in traditional matrices, such as blood, plasma or urine. Several sampling strategies have been proposed as an alternative for these traditional sampling techniques.In this review, we provide a comprehensive overview of available methods using dried blood spots, hair, oral fluid, exhaled breath and sweat for in vivo CYP450 phenotyping. We discuss the relation between phenotyping metrics measured in these samples and those in conventional matrices, along with the advantages and limitations of the alternative sampling techniques. Reliable phenotyping procedures for several clinically relevant CYP450 enzymes, including CYP1A2, CYP2C19 and CYP2D6, are currently available for oral fluid, breath or dried blood spots, while additional studies are needed for other CYP450 isoforms, such as CYP3A4. The role of hair analysis for this purpose remains to be established. Being non-or minimally invasive, these sampling strategies provide convenient and patient-friendly alternatives for classical phenotyping procedures, which may contribute to the implementation of CYP450 phenotyping in clinical practice. 4 Key Points Phenotyping by administration of a selective probe drug, followed by determination of a specific phenotyping metric, allows to assess the in vivo enzyme activity of CYP450 enzymes, taking into account genetic, non-genetic and environmental influencing factors. In addition to classical sampling techniques, such as blood or urine collection, reliable phenotyping procedures for several clinically relevant CYP450 enzymes are currently available for oral fluid, breath and dried blood spots.

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“…diet) may cause variations in the natural occurrence of 13 CO 2. Therefore, the final results are expressed as delta-over-baseline (DOB) values [114][115][116].…”

Section: Exhaled Breathmentioning

confidence: 99%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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“…Continuous research work has brought about considerable progress and nowadays it is possible to assess by means of 13 C breath tests the microsomal, the cytosolic, and the mitochondrial function of the liver [1][2][3][4] . A look at pertinent literature shows that during the past decade, from among the compounds applied for microsomal 13 C breath tests, 13 C-methacetin has steadily been making its way to be recognized as the most frequently used substrate.…”

Section: Brief Articlementioning

confidence: 99%

“…A look at pertinent literature shows that during the past decade, from among the compounds applied for microsomal 13 C breath tests, 13 C-methacetin has steadily been making its way to be recognized as the most frequently used substrate. A number of features support its usefulness as a functional liver probe: a fast metabolism to acetaminophen and 13 CO2 by cytochrome P450 1A2 (CYP 1A2), safety at low doses applied for a breath test, and a low cost [1][2][3][4] . Accordingly very promising results on its diagnostic usefulness were obtained in patients with chronic hepatitis C virus infection [5,6] , primary biliary cirrhosis [7,8] , non-alcoholic steatohepatitis [9] , and various stages of liver cirrhosis [10][11][12][13][14] , including those awaiting a liver transplantation [15] .…”

Section: Brief Articlementioning

confidence: 99%

¹³C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

Kasicka-Jonderko

A²,

Jonderko³

et al. 2011

WJG

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METHODS:Twenty healthy volunteers (10 female, 10 male) underwent the 13 C-MBT after intake of 75 mg 13 C-methacetin p.o. on three occasions. Short-and medium-term reproducibility was assessed with paired examinations taken at an interval of 2 and 18 d (medians), respectively. RESULTS:The reproducibility of the 1-h cumulative 13 C recovery (AUC0-60), characterized by a coefficient of variation of 10%, appeared to be considerably better than the reproducibility of the maximum momentary 13 C recovery or the time of reaching it. Remarkably, as opposed to the short gap between consecutive examinations, the capacity of the liver to handle 13 C-methacetin increased slightly but statistically significantly when a repeat dose was administered after two to three weeks.Regarding the AUC0-60, the magnitude of this fixed bias amounted to 7.5%. Neither the time gap between the repeat examinations nor the gender of the subjects affected the 13 C-MBT reproducibility. CONCLUSION:13 C-MBT is most reproducibly quantified by the cumulative 13 C recovery, but the exactitude thereof may be modestly affected by persistent stimulation of CYP1A2 on repeat examinations.

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“…

Arq Gastroenterol 41

ARTIGO ORIGINAL / ORIGINAL ARTICLE

ARQGA/1206 INTRODUÇÃODiferentes testes têm sido empregados no estudo da função hepática e na avaliação das alterações estruturais das doenças hepáticas crônicas (1,9,12,14) . No entanto, são limitados ao que se propõem, visto que a função hepática é medida complexa que envolve síntese, metabolismo, estoque e secreção de substâncias para sangue e/ou bile, detoxificação de xenobióticos, como algumas das importantes funções do fígado.

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“…Os testes respiratórios com diferentes substratos exógenos têm sido utilizados com esse fim e têm as vantagens de serem não-invasivos, de fácil execução e baixa ou nenhuma toxicidade (1,9) . Dentre os substratos utilizados, a metacetina marcada com carbono 13 ( 13 C-metacetina), tem sido empregada nas doenças hepáticas crônicas (1,6,8,9,13) , particularmente em portadores de cirrose hepática e de hepatite crônica C (2,3,7,10,11) . Essa substância seria rapidamente absorvida no duodeno e metabolizada pelo sistema microssomal hepático, dependente do citocromo P450.…”

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Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C

Oliveira¹,

Reber²,

Lanzoni

et al. 2006

Arq. Gastroenterol.

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Arq Gastroenterol 41 ARTIGO ORIGINAL / ORIGINAL ARTICLE ARQGA/1206 INTRODUÇÃODiferentes testes têm sido empregados no estudo da função hepática e na avaliação das alterações estruturais das doenças hepáticas crônicas (1,9,12,14) . No entanto, são limitados ao que se propõem, visto que a função hepática é medida complexa que envolve síntese, metabolismo, estoque e secreção de substâncias para sangue e/ou bile, detoxificação de xenobióticos, como algumas das importantes funções do fígado. Isso explica a dificuldade de se obter um teste único para medidas dessas diferentes vias metabólicas.Na tentativa de vencer essas limitações, vários testes dinâmicos explorando determinada função específica do fígado, têm sido propostos na última década. O princípio básico desses testes é fundamentado na administração de uma dada substância exógena, que é, principalmente ou quase exclusivamente, metabolizada pelo fígado, permitindo a determinação da capacidade do órgão em metabolizar e eliminar tal substância, refletindo a chamada massa funcional hepática (1,3,9) . Os testes respiratórios com diferentes substratos exógenos têm sido utilizados com esse fim e têm as vantagens de serem não-invasivos, de fácil execução e baixa ou nenhuma toxicidade (1,9) . Dentre os substratos utilizados, a metacetina marcada com carbono 13 ( 13 C-metacetina), tem sido empregada nas doenças hepáticas crônicas (1,6,8,9,13) , particularmente em portadores de cirrose hepática e de hepatite crônica C (2,3,7,10,11) . Essa substância seria rapidamente absorvida no duodeno e metabolizada pelo sistema microssomal hepático, dependente do citocromo P450. Nos microssomos a metacetina sofre uma O-dealquilação em sua estrutura, sendo convertida em acetaminofem e 13 CO 2 , que será medido no ar expirado, RESUMO -Racional -O teste respiratório da metacetina marcada com carbono 13 ( 13 C-metacetina) é método não-invasivo que permite examinar a função hepática microssomal, permitindo avaliação quantitativa da massa hepática funcional. ObjetivoAvaliar a utilidade clinica do teste respiratório da 13 C-metacetina na avaliação de pacientes com doença crônica do fígado pelo vírus da hepatite C. Casuística e métodos -Setenta e oito pacientes com hepatite crônica C e 13 indivíduos saudáveis pareados por sexo e idade foram estudados. Pacientes infectados cronicamente pelo vírus C foram classificados como portadores de hepatite crônica (n = 51) ou cirrose hepática (n = 27, sendo 7 deles classificados como descompensados pela presença de ascite, icterícia e/ou encefalopatia). Pacientes co-infectados HbsAg/HIV, em uso crônico de álcool, com outras doenças crônicas ou em uso de medicamentos que pudessem interferir com a atividade do citocromo P450, foram excluídos. O estádio e a atividade da doença nos fragmentos de biopsia foram determinados de acordo com os critérios da Sociedade Brasileira de Hepatologia. O teste respiratório da C-metacetina 120 min foram significantemente mais reduzidos nos grupos cirróticos (19,2 ± 7,1% para cirróticos compensados e 14,7 ± 4,0% para os cir...

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Breath testing for human liver function assessment

Cited by 100 publications

References 168 publications

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

¹³C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C

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Breath testing for human liver function assessment

Cited by 100 publications

References 168 publications

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

13C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C

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¹³C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations