A theoretical examination of the effects of gut wall metabolism, hepatic elimination, and enterohepatic recycling on estimates of bioavailability and of hepatic blood flow

1978 ◽  
Vol 6 (5) ◽  
pp. 355-367 ◽  
Author(s):  
K. Sandy Pang ◽  
James R. Gillette
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Enterohepatic Recycling ◽  
Hepatic Elimination ◽  
Theoretical Examination

scholarly journals Physiologically based modeling of the effect of physiological and anthropometric variability on indocyanine green based liver function tests

2021 ◽  
Author(s):  
Adrian Köller ◽  
Jan Grzegorzewski ◽  
Matthias König
Keyword(s):  
Blood Flow ◽  
Body Weight ◽  
Liver Function ◽  
Indocyanine Green ◽  
Hepatic Blood Flow ◽  
Liver Function Tests ◽  
Individual Variability ◽  
Hepatic Elimination ◽  
Function Tests ◽  
Physiologically Based

Accurate 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 towards 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=100000 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 towards individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.

scholarly journals Physiologically Based Modeling of the Effect of Physiological and Anthropometric Variability on Indocyanine Green Based Liver Function Tests

2021 ◽  
Vol 12 ◽  
Author(s):  
Adrian Köller ◽  
Jan Grzegorzewski ◽  
Matthias König
Keyword(s):  
Blood Flow ◽  
Body Weight ◽  
Liver Function ◽  
Indocyanine Green ◽  
Hepatic Blood Flow ◽  
Liver Function Tests ◽  
Individual Variability ◽  
Hepatic Elimination ◽  
Function Tests ◽  
Physiologically Based

Accurate 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.

Hepatic Blood Flow in Patients with Tumors of the Liver

1963 ◽  
Vol 44 (6) ◽  
pp. 733-739 ◽  
Author(s):  
Kathleen M. Wartnaby ◽  
I.A.D. Bouchier ◽  
C.E. Pope ◽  
Sheila Sherlock
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Tumors Of The Liver

External Recording Method for Estimating Hepatic Blood Flow With the Use of Radiogold

1959 ◽  
Vol 36 (1) ◽  
pp. 112-119 ◽  
Author(s):  
Joseph S. Burkle ◽  
Marvin L. Gliedman
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Recording Method

The Clearance of 133Xenon from the Liver Intraportal Injection in Man

1965 ◽  
Vol 05 (03) ◽  
pp. 241-245 ◽  
Author(s):  
K.-F. Aronsen ◽  
B. Ericsson ◽  
A. Fajgelj ◽  
S.-E. Lindell
Keyword(s):  
Blood Flow ◽  
Portal Vein ◽  
Hepatic Blood Flow ◽  
Scintillation Detectors ◽  
Disappearance Rate ◽  
Simultaneous Measurements

Summary 133Xe dissolved in saline was injected into the portal vein in man. Hepatic blood flow was calculated from the disappearance rate of 133Xe recorded with scintillation detectors placed over the liver. The results are discussed and related to simultaneous measurements of the pressure in the portal vein.

Hepatic Blood Flow with Colloidal 198Au in the Diagnosis of Chronic Hepatitis in Children

1975 ◽  
Vol 14 (02) ◽  
pp. 158-162
Author(s):  
Viorica Szantay ◽  
Lidia Marian
Keyword(s):  
Blood Flow ◽  
Chronic Hepatitis ◽  
Hepatic Blood Flow ◽  
Hepatitis A ◽  
Clinical Findings ◽  
Active Chronic Hepatitis ◽  
Normal Children ◽  
Function Tests ◽  
Biochemical Function ◽  
Diagnostic Criterion

SummaryTracer quantities of colloidal 198Au were used to estimate the hepatic blood flow in normal children and in children with active or progressive chronic hepatitis and also to obtain scintigrams of the liver.In active chronic hepatitis a significant decrease in HBF values was observed, suggesting that the method may be used as a diagnostic criterion which is superior to hepatic scintigraphy.In progressive chronic hepatitis HBF values even lower than those in active hepatitis were observed. Together with more characteristic clinical findings and abnormal results of biochemical function tests, they underline the value of the method in estimating the severity and the evolution of the disease.

Clinical Application of Radiofrequency Ablation for Malignant Liver Tumor during Interruption of Hepatic Blood Flow

2000 ◽  
Vol 18 ◽  
pp. 121-125
Author(s):  
Takashi Shibata ◽  
Takahiro Niinobu ◽  
Masashi Kitada ◽  
Takashi Shimano ◽  
Motohisa Takami ◽  
...  
Keyword(s):  
Blood Flow ◽  
Radiofrequency Ablation ◽  
Clinical Application ◽  
Hepatic Blood Flow ◽  
Liver Tumor ◽  
Malignant Liver Tumor ◽  
Malignant Liver
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