Physiological and Biochemical Basis of Clinical Liver Function Tests

Hoekstra, Lisette T.; Graaf, Wilmar de; Nibourg, Geert A. A.; Heger, Michal; Bennink, Roelof J.; Stieger, Bruno; Gulik, Thomas M. van

doi:10.1097/sla.0b013e31825d5d47

Cited by 281 publications

(200 citation statements)

References 87 publications

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“…In the case of planned liver resections, information on the liver function of individual segments is needed to successfully improve the outcome of this procedure (de Graaf et al, 2010a;Hoekstra et al). Noninvasive methods such as scintigraphy or MRI are already under clinical investigation and have demonstrated to predict the remaining functional liver mass in patients scheduled for resection (de Graaf et al, 2010c).…”

Section: Perspectivementioning

confidence: 99%

The emerging role of transport systems in liver function tests

Stieger

Heger

Graaf

et al. 2012

European Journal of Pharmacology

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Liver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified that also transport substances employed in liver function tests. Such substances include endogenous bilirubin or exogenously administered indocyanine green, agents for magnetic resonance imaging, agents for single photon emission computed tomography or agents for breath tests. The increasing functional and molecular information on the respective transport systems should improve the management and as a result the outcome of patients scheduled for liver surgery or transplantation. To achieve the latter goal, clinical studies that assess individual patients' liver function over the course of their disease with liver function tests are needed to firmly establish and validate recently introduced and novel liver function markers. The emerging role of transport systems in liver function tests Bruno Stieger is supported by grant # 31003A_124652 from the Swiss National Science foundation. AbstractLiver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified, that also transport substances employed in liver function tests. Such substances include endogenous bilirubin or exogenously administered indocyanine green, agents for magnetic resonance imaging, agents for single photon emission computed tomography or agents for breath tests. The increasing functional and molecular information on the respective transport systems should improve the management and as a result the outcome of patients scheduled for liver surgery or transplantation. To achieve the latter goal, clinical studies that assess individual patients liver function over the course of their disease with liver function testes are needed to firmly establish and validate recently introduced and novel liver function markers.

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Section: Perspectivementioning

confidence: 99%

The emerging role of transport systems in liver function tests

Stieger

Heger

Graaf

et al. 2012

European Journal of Pharmacology

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“…Such agents are taken up by normal hepatocytes (but not neoplasms), and appear in the biliary tree. Quantitation of their uptake and biliary excretion provides an assessment of liver function [17,18], and (through imaging) a functional liver volume. These tracers and contrast agents were optimized iteratively by medicinal chemists.…”

Section: Hepatobiliary Imaging Modalities and Tracersmentioning

confidence: 99%

Noninvasive Preclinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury

Kenna

Waterton

Baudy

et al. 2018

Methods in Pharmacology and Toxicology

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Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and druginduced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug-drug interactions mediated via hepatobiliary transporter perturbation.

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“…The effect of hepatic I/R injury on the basolateral OATP1B1, 1B3 and 2B1 transporters is best documented, mainly because these proteins are responsible for uptake of indocyanine green (ICG) and 99m Tc-mebrofenin (64), which are used to quantitatively assess liver function (65). Functionality and expression of the rat homologs of these transporters (OATP1A1, 1A4, and 2B1, respectively [19]) was investigated in a rat model of partial liver ischemia combined with resection of the nonischemic liver lobes.…”

Section: Hypothermia and Glucose Metabolismmentioning

confidence: 99%

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

Olthof

Reiniers

Dirkes

et al. 2015

Mol Med

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Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided.

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Physiological and Biochemical Basis of Clinical Liver Function Tests

Cited by 281 publications

References 87 publications

The emerging role of transport systems in liver function tests

The emerging role of transport systems in liver function tests

Noninvasive Preclinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

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