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2021-11-22Zeitschriftenartikel DOI: 10.3389/fphys.2021.757293
Physiologically Based Modeling of the Effect of Physiological and Anthropometric Variability on Indocyanine Green Based Liver Function Tests
dc.contributor.authorKöller, Adrian
dc.contributor.authorGrzegorzewski, Jan
dc.contributor.authorKönig, Matthias
dc.date.accessioned2022-01-14T10:18:57Z
dc.date.available2022-01-14T10:18:57Z
dc.date.issued2021-11-22none
dc.date.updated2021-12-06T14:00:48Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/24580
dc.description.abstractAccurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery. A key challenge in the evaluation of liver function with DLFTs is the large inter-individual variability. Indocyanine green (ICG) is a widely applied test compound used for the evaluation of liver function. After an intravenous administration, pharmacokinetic (PK) parameters are calculated from the plasma disappearance curve of ICG which provide an estimate of liver function. The hepatic elimination of ICG is affected by physiological factors such as hepatic blood flow or binding of ICG to plasma proteins, anthropometric factors such as body weight, age, and sex, or the protein amount of the organic anion-transporting polypeptide 1B3 (OATP1B3) mediating the hepatic uptake of ICG. Being able to account for and better understand these various sources of inter-individual variability would allow to improve the power of ICG based DLFTs and move toward an individualized evaluation of liver function. Within this work we systematically analyzed the effect of various factors on ICG elimination by the means of computational modeling. For the analysis, a recently developed and validated physiologically based pharmacokinetics (PBPK) model of ICG distribution and hepatic elimination was utilized. Key results are (i) a systematic analysis of the variability in ICG elimination due to hepatic blood flow, cardiac output, OATP1B3 abundance, liver volume, body weight and plasma bilirubin level; (ii) the evaluation of the inter-individual variability in ICG elimination via a large in silico cohort of n = 100,000 subjects based on the NHANES cohort with special focus on stratification by age, sex, and body weight; (iii) the evaluation of the effect of various degrees of cirrhosis on variability in ICG elimination. The presented results are an important step toward individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectindocyanine greeneng
dc.subjectmathematical modeleng
dc.subjectcomputational modeleng
dc.subjectpharmacokineticseng
dc.subjectliver functioneng
dc.subjectICGeng
dc.subjectPBPKeng
dc.subjectliver cirrhosiseng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titlePhysiologically Based Modeling of the Effect of Physiological and Anthropometric Variability on Indocyanine Green Based Liver Function Testsnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/24580-6
dc.identifier.doi10.3389/fphys.2021.757293none
dc.identifier.doihttp://dx.doi.org/10.18452/23949
dc.type.versionpublishedVersionnone
local.edoc.container-titleFrontiers in physiologynone
local.edoc.pages17none
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionLebenswissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameFrontiers Research Foundationnone
local.edoc.container-publisher-placeLausannenone
local.edoc.container-volume12none
dc.description.versionPeer Reviewednone
local.edoc.container-articlenumber757293none
dc.identifier.eissn1664-042X
local.edoc.affiliationKöller, Adrian; Institute for Theoretical Biology, Institute of Biology, Humboldt University, Berlin, Germanynone
local.edoc.affiliationGrzegorzewski, Jan; Institute for Theoretical Biology, Institute of Biology, Humboldt University, Berlin, Germanynone
local.edoc.affiliationKönig, Matthias; Institute for Theoretical Biology, Institute of Biology, Humboldt University, Berlin, Germanynone

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