Hepatic clearances of antipyrine, indocyanine green, and galactose in normal subjects and in patients with chronic liver diseases

Kawasaki, Seiji; Sugiyama, Yuichi; Iga, Tatsuji; Hanano, Manabu; Beppu, Tomoe; Sugiura, Mitsuo; Sanjo, Kensho; Idezuki, Yasuo

doi:10.1038/clpt.1988.140

Cited by 59 publications

(36 citation statements)

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“…Orally administered antipyrine, a model low-extraction drug with a low intrinsic clearance, is fully absorbed and metabolized slowly by hepatic microsomal P450 enzymes [19]. Therefore, its clearance reflects exclusively the activity of drug-metabolizing enzyme, and is not influenced by hepatic blood flow [20, 21]. In this particular point, we have measured the functional liver mass by antipyrine clearance in the present study, in which hemodynamics of the liver is considered to change after operation.…”

Section: Discussionmentioning

confidence: 99%

Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy

Kobayashi

Imamura²,

Aoki³

et al. 2006

Dig Surg

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Background/Aims: Liver has a remarkable ability to regenerate after major resection. However, little is known about the process of morphological regeneration and hepatic functional recovery in human. Methods: Sixteen donors who underwent right hemihepatectomy were enrolled in this prospective clinical study. The preoperative liver volume and remnant liver volume on postoperative days 5, 12 and 28 were calculated from serial transverse computed tomography images. Liver function was evaluated by measuring the intrinsic clearance of antipyrine before and on postoperative days 5 and 12 days, as well as the biochemical and coagulation assay. Results: A smaller residual liver tended to regenerate faster in 28 days. Operative factors, including intraoperative blood loss, inflow occlusion time, liver transection time and duration of operation were not significantly correlated with postoperative liver regeneration. The intrinsic clearances of antipyrine on postoperative days 5 and 12 days were significantly reduced compared to the respective values before the operation (p < 0.001 and p < 0.05, respectively). On the contrary, the intrinsic clearance values per unit liver volume significantly increased on postoperative 12 days (p < 0.05). Conclusion: The microsomal function of individual hepatocytes may be upregulated after right liver resection perhaps in order to compensate for the reduced functional mass of the liver.

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Section: Discussionmentioning

confidence: 99%

Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy

Kobayashi

Imamura²,

Aoki³

et al. 2006

Dig Surg

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“…A direct comparison of ICG clearance with galactose clearance in healthy volunteers resulted in a mean liver blood flow of 1.2 Llmin with ICG and of 1.5 Llmin with galactose.l 231 ] Comparisons with physical liver blood flow quantification confirmed that ICG is not a good probe for liver blood flow in cirrhoSiS. [232][233][234] Still, ICG may be a sensitive empirical parameter of impairment of certain liver cell functions. It was shown that at early stages of septicaemia ICG clearance was decreased even before a decrease of liver blood flow could be measured with other parameters.…”

Section: Measurement Of Liver Blood Flowmentioning

confidence: 88%

Assessment of Liver Metabolic Function

Brockmöller

Roots

1994

Clinical Pharmacokinetics

132

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Inter- and intraindividual variability in pharmacokinetics of most drugs is largely determined by variable liver function as described by parameters of hepatic blood flow and metabolic capacity. These parameters may be altered as a result of disease affecting the liver, genetic differences in metabolising enzymes, and various types of drug interactions, including enzyme induction, enzyme inhibition or down-regulation. With the now known large number of drug metabolising enzymes, their differential substrate specificity, and their differential induction or inhibition, each test substance of liver function should be used as a probe for its specific metabolising enzyme. Thus, the concept of model test-substances providing general information about liver function has severe limitations. To test the metabolic activity of several enzymes, either several test substances may be given (cocktail approach) or several metabolites of a single test substance may be analysed (metabolic fingerprint approach). The enzyme-specific analysis of liver function results in a preference for analysis of the metabolites rather than analysis of the clearance of the parent test substance. There are specific methods to quantify the activity of cytochrome P450 enzymes such as CYP1A2, CYP2C9, CYP2C19MEPH, CYP2D6, CYP2E1, and CYP3A, and phase II enzymes, such as glutathione S-transferases, glucuronyl-transferases or N-acetyltransferases, in vivo. Interactions based on competitive or noncompetitive inhibition should be analysed specifically for the cytochrome P450 enzyme involved. At least 5 different types of cytochrome P450 enzyme induction may result in major variability of hepatic function; this may be quantified by biochemical parameters, clearance methods, or highly enzyme-specific methods such as Western blot analysis or molecular biological techniques such as mRNA quantification in blood and tissues. Therapeutic drug monitoring is already implicitly used for quantification of the enzyme activities relevant for a specific drug. Selective impairment of hepatic enzymes due to gene mutations may have an effect on the pharmacokinetics of certain drugs similar to that caused by cirrhosis. Assessment of this heritable source of variability in liver function is possible by in vivo or ex vivo enzymological methods. For genetically polymorphic enzymes and carrier proteins involved in drug disposition, molecular genetic methods using a patient's blood sample may be used for classification of the individual into: (i) the impaired or poor metaboliser (homozygous deficient); (ii) the extensive (homozygous active) metaboliser group; and (iii) the moderately extensive metaboliser (heterozygous) group. For hepatic blood flow determinations, galactose or sorbitol given at relatively low doses may be much better indicators than the indocyanine green.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The individual evaluation requires the results of not only usual blood tests, such as Child-Turcotte-Pugh score 32 or model for end-stage liver disease score 33,34 , but also load tests, which assess the degree of liver tolerance under metabolic burden. One of the most popular liver load tests is the indocyanine green (ICG) retention test 35,36 . When discrepancy between the results of the ICG test and other static laboratory data is found, an additional examination (e.g., scintigraphy using 99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin 37-39 ) is recommended.…”

Section: Two Aspects Of Hepatectomy For Precision Liver Surgerymentioning

confidence: 99%

Precision surgery for primary liver cancer

Takamoto

Makuuchi

2019

Cancer Biol Med

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Liver resection remains the best curative option for primary liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. In particular, in liver resection for HCC, anatomical resection of the tumor-bearing segments is highly recommended to eradicate the intrahepatic metastases spreading through portal venous branches. Anatomical liver resection, including anatomical segmentectomy and subsegmentectomy using the dye-injection method, is technically demanding and requires experience for completion of a precise procedure. The recent development of imaging studies and new computer technologies has allowed for the preoperative design of the operative procedure, intraoperative navigation, and postoperative quality evaluation of the anatomical liver resection. Although these new technologies are related to the progress of artificial intelligence, the actual operative procedure is still performed as human-hand work. A precise anatomical liver resection still requires meticulous exposure of the boundary of hepatic venous tributaries with deep knowledge of liver anatomy and utilization of intraoperative ultrasonography.

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Hepatic clearances of antipyrine, indocyanine green, and galactose in normal subjects and in patients with chronic liver diseases

Cited by 59 publications

References 0 publications

Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy

Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy

Assessment of Liver Metabolic Function

Precision surgery for primary liver cancer

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