Portal‐systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt

Everson, Gregory T.; Martucci, Michele; Shiffman, Mitchell L.; Sterling, Richard K.; Morgan, Timothy R.; Hoefs, John C.

doi:10.1111/j.1365-2036.2007.03389.x

Cited by 25 publications

(44 citation statements)

References 35 publications

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“…Other tests measure hepatic circulation using test compounds with flowdependent, high firstpass hepatic extraction such as galactose (galactose elimination capacity 115 and cholate clearances and shunt 116 . Although attractive candidates to assess response to a treatment, the clin ical validity of these parameters has yet to be estab lished and thus the clinical importance of any change remains uncertain.…”

Section: Blood Measures Of Liver Regenerationmentioning

confidence: 99%

Liver regeneration — mechanisms and models to clinical application

Forbes

Newsome

2016

Nat Rev Gastroenterol Hepatol

322

296

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Although the normal liver has a fantastic regenerative capacity, following acute injury or resection this regener ative ability becomes overwhelmed in two important scenarios: in the setting of severe acute liver injury or when there is severe chronic liver injury with aberrant liver architecture and marked liver fibrosis 1,2 . These scenarios are clinically relevant and often result in serious morbidity and mortality 3 . While there have been decades of excellent and clinically informative research into understanding the signals that control regener ation of the normal liver 4 , the mechanisms at play when the abnor mal liver attempts regeneration are less well described 5 . Understanding how regeneration fails or is impaired in the severely damaged liver is an important goal. Lessons learned from relevant animal models might have impor tance in the clinical setting and aid the develop ment of new therapies to either promote regener ation or prevent complications that arise during the period of liver regeneration.A clinical scenario in which an improved understand ing of regeneration of the compromised liver would be of benefit includes liver transplantation, here the increas ingly common use of partial liver grafts such as split livers and living donor transplants relies upon regener ation of the donor graft to reach the correct liver mass 6 .Failure of regeneration in these settings results in poor or delayed graft function, prolonged intensive care stays, occasionally a requirement for retransplantation or, ulti mately, even death of the recipient 7,8 . By understanding the pathological mechanisms driving these adverse con ditions it is hoped that the period of regeneration can be more predictable and the associated clinical complications ultimately preventable. The ability to predict or improve liver regeneration when the liver is compromised -for example, in the setting of cirrhosis when surgical resection of hepatocellular cancer (HCC) is commonly performed, or following the resection of colorectal hepatic metastasis, when the liver has received prior chemotherapy -would enable clinicians to optimize cancer resection approaches. Furthermore, by understanding the mechanisms under lying normal liver regeneration and aberrant liver regener ation in chronic liver injury it is hoped that we will be able to promote 'healthy regeneration' or remodel ling in chronic liver disease. Such a scenario in which this approach could be applied includes liver cirrhosis. Here, the initial insult (such as viral hepatitis or autoimmune hepatitis) can sometimes be directly treated, but the liver tissue is left severely damaged and still susceptible to the clinical consequences of liver failure, portal hypertension and an increased risk of HCC 9 .Abstract | Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsi...

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Section: Blood Measures Of Liver Regenerationmentioning

confidence: 99%

Liver regeneration — mechanisms and models to clinical application

Forbes

Newsome

2016

Nat Rev Gastroenterol Hepatol

322

296

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“…Everson et al [50 ] compared different 'quantitative' liver function tests in the frame of an antiviral hepatitis C treatment (HALT) study. The best test proved to be a 'dual isotope tracer' approach, in which different isotopic variants of the bile acid cholate were given orally and intravenously [51]. Using plasma enrichment values of both tracers, flow rates were quantified for the portovenous perfusion shunt, for the entero-hepatic cycling of bile acids and their excretion.…”

Section: Monitoringmentioning

confidence: 99%

“…To keep the tests as simple and as noninvasive as possible, measurements of the plasma tracer enrichment values or a parallel infusion of different tracer compounds, which all would provide additional, useful information, were abandoned. The power of more extended tracer studies is outlined by Beylot [65] and was demonstrated with the 'cholate-liver function test' [51]. Another extended tracer approach was used to assess amino acid absorption and metabolism [66,67].…”

Section: Joint Determination Of Gastric Emptying and Liver Functionmentioning

confidence: 99%

13CO2 breath tests, a tool to assess intestinal and liver function in the ICU?

Vogt

Radermacher²,

Georgieff³

2010

Current Opinion in Critical Care

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“…Cholates have been safely administered both orally and intravenously 1,9,23,24 . In the dual test, [2,2,4,4-D]cholate (D4-cholate)is administered orally and, [24- 13 C]cholate (13C-cholate) is administered intravenously, simultaneously.…”

Section: Dual Cholate Testmentioning

confidence: 99%

Noninvasive assessment of liver function

Helmke

Colmenero

Everson

2015

Current Opinion in Gastroenterology

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Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy.

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Portal‐systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt

Abstract: SUMMARY BackgroundMeasurement of portal inflow and portal-systemic shunt using cholate clearances could be useful in monitoring patients with liver disease.

Cited by 25 publications

References 35 publications

Liver regeneration — mechanisms and models to clinical application

Liver regeneration — mechanisms and models to clinical application

13CO2 breath tests, a tool to assess intestinal and liver function in the ICU?

Noninvasive assessment of liver function

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