Galactose elimination capacity as a prognostic marker in patients with severe acetaminophen-induced hepatotoxicity: 10 years’ experience

doi:10.1016/S1542-3565(04)00128-4

Clinical Gastroenterology and Hepatology

Volume 2, Issue 5, May 2004, Pages 418-424

https://doi.org/10.1016/S1542-3565(04)00128-4 Get rights and content

Abstract

$Background & Aims:$ Patients with acetaminophen-induced fulminant hepatic failure may have the capacity for recovery if sufficient liver cell mass remains to allow regeneration. We investigated the prognostic potential of the galactose elimination capacity (GEC) as a noninvasive measurement of functioning liver cell mass in severe acetaminophen-induced hepatotoxicity. $Methods:$ All patients admitted with acetaminophen poisoning during a 10-year period were studied retrospectively. A total of 220 patients who had at least one GEC performed were included in the study. $Results:$ The GEC was lower in patients with than without hepatic encephalopathy (14.5 ± 5.6 μmol/min/kg vs. 23.2 ± 6.7 μmol/min/kg; P < 0.0001). Among patients with hepatic encephalopathy, the GEC was significantly higher in spontaneous survivors than in nonsurvivors (16.8 ± 5.6 μmol/min/kg vs. 12.2 ± 4.7 μmol/min/kg; P < 0.0001). In a logistic regression analysis, GEC was associated independently with mortality (odds ratio: 1.28 per 1 μmol/min/kg decrease in GEC; 95% confidence interval: 1.14–1.45). A threshold GEC of 16.5 μmol/min/kg to identify nonsurvivors had a sensitivity of 90%, a specificity of 72%, a positive predictive value of 49%, and a negative predictive value of 96%. None of 14 patients with hepatic encephalopathy and a GEC less than 10 μmol/min/kg survived. $Conclusions:$ The GEC was strongly associated with development of hepatic encephalopathy and death from acetaminophen-induced fulminant hepatic failure. The GEC was too unspecific to be used alone for identification of transplantation candidates, but it may be useful as a supplement to other selection criteria.

Section snippets

Patients and methods

The medical records of all patients admitted to Rigs-hospitalet, Copenhagen, Denmark, with acetaminophen poisoning between 1992 and 2001 were reviewed. Patients who had at least one GEC performed were included in the study. The following information was recorded for each case: age, sex, quantity of acetaminophen ingested, time from acetaminophen ingestion to initiation of N-acetylcysteine (NAC) treatment (time to NAC), regular alcohol abuse, acute co-ingestion of alcohol, biochemistry including

Results

During the 10-year study period, 871 patients were admitted with acetaminophen poisoning. A total of 288 GECs were performed in the 220 patients (25%) who were included in the study. Table 1 shows the anamnestic, biochemical, and clinical data of the 220 included patients in comparison with the 651 patients who were not included. A GEC was performed in 70% of patients (102 of 146) who developed HE and in 68% of patients (50 of 74) who died or were transplanted, showing the select nature of the

Discussion

Spontaneous recovery from FHF may occur, provided that the remaining liver cell mass is sufficient to allow time for hepatic regeneration, that the patient has the capacity for regeneration, and that fatal nonhepatic complications are avoided. Thus, a measure of functioning liver cell mass would be expected to identify a subgroup of patients without chance of spontaneous recovery despite supportive treatment. Functioning liver cell mass can be estimated directly from determination of hepatocyte

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The capacity of the liver to remove intravenously injected galactose is measured with the galactose elimination capacity (GEC) test [6,7]. The GEC test yields a measure of global metabolic liver function and provides prognostic information for patients with acute [8,9] and chronic [10,11] liver disease, as well as for patients undergoing hepatic resection [12]. However, the GEC test does not provide any information on potential intrahepatic metabolic heterogeneity.
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Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick’s principle. From blood measurements, hepatic systemic clearance (K_syst, L blood/min) and hepatic intrinsic clearance (V_max/K_m, L blood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (K_met, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of K_met.
Mean approximation of K_syst to V_max/K_m was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean K_met was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (p <0.001), in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for K_met in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p <0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p <0.05).
A 20-min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring.
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Plus de 50 ans après sa mise sur le marché, le paracétamol demeure impliqué dans un nombre significatif d’intoxications et de décès chaque année. Nous disposons de plusieurs outils pour nous aider à évaluer le risque d’hépatotoxicité suite à une exposition au paracétamol de même que des modèles prédictifs pour l’indication de greffe hépatique une fois la toxicité installée. Malgré des décennies d’expérience, ces outils restent en revanche limités à plusieurs égards et la recherche à ce niveau demeure très active. Le but de cet article est de revoir l’historique des outils à notre disposition et de discuter de la littérature relative à de nouveaux moyens nous permettant de prédire avec plus de précision le développement d’une hépatotoxicité suite à une intoxication au paracétamol.
More than 50 years after its marketing, acetaminophen remains linked to a significant number of intoxications and deaths each year. We have at our disposal many tools to allow an assessment of the risk of hepatotoxicity following an acetaminophen exposure and predictive models regarding the need for liver transplantation once toxicity is installed also exist. Even with decades of experience, these tools remain limited in many ways. The aim of this article is to trace the history of the tools at our disposal and to review the literature concerning the new methods of risk assessment regarding the development of hepatotoxicity following an acetaminophen intoxication.
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Few admissions to the ICU present a greater clinical challenge than the patient with acute liver failure (ALF), the syndrome of abrupt loss of liver function in a previously unaffected individual. Although advances in the intensive care management of patients with ALF have improved survival, the prognosis of ALF remains poor, with a 33% mortality rate and a 25% liver transplant rate in the United States. ALF adversely affects nearly every organ system, with most deaths occurring from sepsis and subsequent multiorgan system failure, and cerebral edema, resulting in intracranial hypertension (ICH) and brainstem herniation. Unfortunately, the optimal management of ALF remains poorly defined, and practices are often based on local experience and case reports rather than on randomized, controlled clinical trials. The paramount question in any patient presenting with ALF remains defining an etiology, since specific antidotes can save lives and spare the liver. This article will consider recent advances in the assignment of an etiology, the administration of etiology-specific treatment to abate the liver injury, and the management of complications (eg, infection, cerebral edema, and the bleeding diathesis) in patients with ALF. New data on the administration of N-acetylcysteine to patients with non-acetaminophen ALF, the treatment of ICH, and assessment of the need for liver transplantation will also be presented.
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Original articleGalactose elimination capacity as a prognostic marker in patients with severe acetaminophen-induced hepatotoxicity: 10 years’ experience

Abstract

Section snippets

Patients and methods

Results

Discussion

Liver Transpl

Gastroenterology

Liver Transpl

J Hepatol

Lancet

Hepatology

J Hepatol

Hepatology

Hepatology

Potential use of pharmacological markers to quantitatively assess liver function during liver transplantation surgery

Anaesth Intensive Care

Determination of the hepatic elimination capacity (Lm) of galactose by single injection

Scand J Clin Lab Invest Suppl

Functioning liver mass in uncomplicated and fulminant acute hepatitis

Scand J Gastroenterol

Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity

Eur Surg Res

Prognostic indicators of survival in patients with cirrhosis and esophageal varices, without previous bleeding

Am J Gastroenterol

Accurate prediction of death by serial determination of galactose elimination capacity in primary biliary cirrhosisa comparison with the Mayo model

Hepatology

Original article
Galactose elimination capacity as a prognostic marker in patients with severe acetaminophen-induced hepatotoxicity: 10 years’ experience