The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study

Jepsen, Peter; Vilstrup, Hendrik; Ott, Peter; Keiding, Susanne; Andersen, Per Kragh; Tygstrup, Niels

doi:10.1186/1471-230x-9-50

Cited by 29 publications

(27 citation statements)

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“…This novel finding expands upon our previous finding that the GEC is a predictor of the mortality of cirrhosis patients [3]: It is now clear that loss of hepatic metabolic capacity causes hepatic encephalopathy and then death [1]. Our previous study suggested that a GEC above 1.75 mmol/min was associated with a relatively favorable prognosis, whereas mortality increased linearly with GEC when GEC fell below this limit [3]. We speculate that the same limit applies to the risk of hepatic encephalopathy, but our current study did not have sufficient statistical power to clarify this.…”

Section: Discussionsupporting

confidence: 82%

The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

et al. 2012

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BackgroundThe cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence. Therefore prognoses based on the presence or absence of these clinical complications are inherently inaccurate, and other determinants of the clinical course should be identified. Here we present our study of patho-etiological factors that may be causally involved in the development of specific complications to alcoholic cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing hepatic metabolic capacity, continued alcohol consumption, and circulatory dysfunction.MethodsWe followed a Danish community-based cohort of 466 patients with alcoholic cirrhosis. Stratified Cox regression was used to examine the effects of GEC (a measure of hepatic metabolic capacity), alcohol consumption, and plasma sodium concentration (a measure of circulatory dysfunction) on the hazard rates of first-time hepatic encephalopathy, first-time ascites, first-time variceal bleeding, and mortality. We adjusted for confounding by comorbidity, gender, and age. Data on risk factors and confounders were updated during follow-up.ResultsA low GEC increased the risk of first-time hepatic encephalopathy (hazard ratio [HR] 1.21 per 0.1 mmol/min GEC loss, 95% CI 1.11-1.31), but was unassociated with other adverse events. Alcohol consumption increased the risk of first-time ascites (HR 3.18, 95% CI 1.19-8.47), first-time variceal bleeding (HR 2.78, 95% CI 1.59-4.87), and mortality (HR 2.45, 95% CI 1.63-3.66), but not the risk of first-time hepatic encephalopathy. Hyponatremia increased the risk of all adverse events.ConclusionsReduced hepatic metabolic capacity, alcohol consumption, and hyponatremia were causally involved in the development of specific complications to alcoholic cirrhosis.

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Section: Discussionsupporting

confidence: 82%

The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

et al. 2012

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“…The hepatic removal of galactose follows Michaelis–Menten kinetics in vivo (27,40). The hepatic galactose elimination rate at near-saturating concentration, that is, the galactose elimination capacity, is used as a measure of metabolic liver function (41), with documented prognostic information for patients with liver diseases (42). However, the galactose elimination capacity does not provide any information on possible intrahepatic regional variations that are also clinically relevant and can be explored by PET…”

Section: Hepatic Metabolism Studied By Petmentioning

confidence: 99%

Bringing Physiology into PET of the Liver

Keiding¹

2012

J Nucl Med

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Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time–activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time–activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time–activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time–activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic 18F-FDG PET/CT recording. Later, steady-state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, 18F-FDG and 11C-palmitate.

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“…When corrected for the amount of galactose excreted in urine, an approximate estimate of the hepatic V max for galactose is achieved from the blood disappearance curve using blood concentrations ensuring near-saturation of the enzymatic system [1–4]. The GEC accurately assessed survival prognosis of patients with acute liver failure [5], chronic liver disease [6,7], and patients undergoing liver resection [8]. More interestingly, it has been shown that quantitative liver function tests such as the GEC are far more predictive of the remaining liver function following partial hepatectomy than measurements of liver volumes [9–11].…”

Section: Introductionmentioning

confidence: 99%

Determination of hepatic galactose elimination capacity using 2-[¹⁸F]fluoro-2-deoxy-d-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

Sørensen

2010

Scandinavian Journal of Gastroenterology

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Objective A PET method is developed for non-invasive measurement of regional metabolic liver function using the galactose analog 2-[18F]fluoro-2-deoxy-D-galactose, FDGal. The aim of the present study was to determine the reproducibility of the method in pigs before translating it to human studies. Material and methods Five anesthetized pigs were studied twice within an interval of three days. A dynamic PET recording was performed with an injection of 100 MBq FDGal. Non-radioactive galactose was administered throughout the PET recordings to achieve near-saturated elimination kinetics. Arterial blood samples were collected for determination of blood concentrations of FDGal and galactose (cgal). Net metabolic clearance of FDGal, KFDGal, was calculated from linear representation of data. The approximate maximal hepatic removal rate, Vmax, of galactose (mmol/l tissue/min) was calculated as KFDGal cgal. The estimates from Day 1 and Day 2 were compared and the coefficient of variation, COV, of the estimates calculated. Functional heterogeneity in normal pig liver was evaluated as COV of the tissue concentration of radioactivity during quasi steady-state metabolism. Results There was no significant difference between Vmax from Day 1 and Day 2 (p = 0.38), and the reproducibility was good with a COV of 14% for the whole liver. In normal pig liver tissue, mean COV after an injection of FDGal was on average 15.6% with no day-to-day variation (p = 0.7). Conclusions The novel FDGal PET method for determination of hepatic metabolic function has a good reproducibility and is promising for future human studies of regional liver function.

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The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study

Cited by 29 publications

References 27 publications

The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

Bringing Physiology into PET of the Liver

Determination of hepatic galactose elimination capacity using 2-[¹⁸F]fluoro-2-deoxy-d-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

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The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study

Cited by 29 publications

References 27 publications

The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

Bringing Physiology into PET of the Liver

Determination of hepatic galactose elimination capacity using 2-[18F]fluoro-2-deoxy-d-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

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Determination of hepatic galactose elimination capacity using 2-[¹⁸F]fluoro-2-deoxy-d-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model