Non-Invasive Assessment of Human Hepatic Mitochondrial Function through the<sup>13</sup>C-Methionine Breath Test

Armuzzi, Alessandro; Marcoccia, Stefania; Zocco, Maria Assunta; Lorenzo, Antonino De; Grieco, Antonio; Tondi, Paolo; Pola, Paolo; Gasbarrini, Giovanni; Gasbarrini, Antonio

doi:10.1080/003655200750023633

Cited by 43 publications

(40 citation statements)

References 14 publications

(18 reference statements)

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“…Therefore, it could be a clinically useful liver function test as has been postulated. 26,27 That a MET breath test does not solely reflect mitochondrial function but is influenced by many other processes is evident from the present data. However, this does not distract from its potential clinical utility.…”

Section: Discussionsupporting

confidence: 65%

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[² H₃ -methyl-1-¹³ C]methionine

2002

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Disturbances of the methionine cycle may result in liver injury. Patients with alcoholinduced liver disease often exhibit hypermethioninemia and a delayed clearance (CL) of methionine, but the extent to which transsulfuration and remethylation pathways of the cyclic methionine metabolism are affected is unknown. Methionine turnover was determined in 7 healthy volunteers and 6 patients with alcohol-induced cirrhosis after oral administration of 2 mg/kg [ 2 H 3 -methyl-1-13 C]methionine, which permitted us to follow transsulfuration by its decarboxylation to 13 CO 2 and remethylation by replacement of the labeled methyl group by an unlabeled one. Basal plasma concentrations of endogenous methionine (50 ؎ 5 vs. 25 ؎ 2 mol/L, mean ؎ SEM, P < .001) were significantly higher in patients with cirrhosis and its CL was significantly decreased (774 ؎ 103 vs. 2,050 ؎ 141 mL/min, P < .001). Methionine turnover amounted to 42 ؎ 4 vs. 27 ؎ 3 mol/kg/h (P < .05) in controls and patients with cirrhosis, respectively. The fraction of administered methionine undergoing remethylation was lower in patients with cirrhosis (7.6 ؎ 1.5 vs. 14.1 ؎ 1.1%, P < .005). However, because of the larger pool of circulating methionine, the total flux of methionine through the remethylation pathway was similar in both groups. A significantly lower fraction of the administered dose appeared in the form of 13 CO 2 in breath in patients with cirrhosis (2.2 ؎ 0.4 vs. 11.0 ؎ 0.8%, P < .001). In conclusion, the data indicate that the liver with cirrhosis compensates for a decreased activity of remethylating enzymes by operating at higher concentrations of methionine. In contrast, transsulfuration is impaired in patients with alcohol-induced cirrhosis such that an assessment of transsulfuration by a simple breath test may provide a clinically useful estimate of hepatic function.

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Section: Discussionsupporting

confidence: 65%

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[² H₃ -methyl-1-¹³ C]methionine

2002

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“…Therefore, many procedures have been reported to evaluate hepatic reserve capacity. [18][19][20][21][22][23][24] The results of the L-[1-13 C] PBT in our two patients suggest its usefulness for following-up LC patients. In addition, it has the advantages of noninvasiveness, limited burden on patients, simplicity, and absence of radiation exposure.…”

Section: Discussionmentioning

confidence: 74%

Patients with severe liver cirrhosis followed up by L-[1- 13 C] phenylalanine breath test

Ishii

Suzuki

Kohno

et al. 2003

Journal of Gastroenterology

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Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-(13)C] phenylalanine breath test (PBT). We performed this test several times during the clinical course in two patients with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B, non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment. Because the patient wanted to receive nonsurgical treatment for HCC, intraarterial administration of zinostatin stimalamer was performed. The patient was hospitalized four times before her death from liver failure on December 20, 2000. During her clinical course, PBT was performed four times. Values for both the rate of hepatic phenylalanine oxidation (%(13)C dose h(-1)) and %(13)C cumulative excretion gradually decreased during her clinical course. Patient 2 was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was hospitalized seven times between December 1998 and his death on May 24, 2001. During his clinical course, PBT was performed four times. Values for both %(13)C dose h(-1) and %(13)C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.

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“…The use of different 13 C-labelled substrates to obtain information regarding different metabolic hepatic pathways is based on the assumption that the 13 C-tracers used should be representative for specific hepatic functions. [ 13 C]methacetin and [methyl-13 C]methionine were found to be appropriate and reliable liver test substrates for the evaluation of the microsomal and mitochondrial functions, respectively, when used in human beings [27][28][29][30][31]. The [ 13 C]methacetin breath test is mainly used for the discrimination of cirrhotic and non-cirrhotic patients.…”

Section: Discussionmentioning

confidence: 99%

Effect of alcohol consumption on the liver detoxication capacity as measured by [¹³C]methacetin- and [methyl-¹³C]methionine-breath tests

Wutzke

Forberger

Wigger

2008

Isotopes in Environmental and Health Studies

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The aim of this study was to investigate the hepatic microsomal and mitochondrial functions by using the 13CO2-breath test in healthy subjects either before or after the consumption of red wine. Fourteen adults received [13C]methacetin and [methyl-13C]methionine together with a standardised dinner. Expired air samples were taken over 6 h. After a wash-out period, the subjects consumed 0.4 ml ethanol/kg/day together with dinner over a 10-day period. Thereafter, 13C-tracer administration was repeated under identical conditions. The 13CO2-enrichments were measured by isotope ratio mass spectrometry. The mean cumulative percentage 13C-dose recovery (CPDR) after administration of [13C]methacetin and [methyl-13C]methionine either without or with red wine consumption amounted to 38.2+/-6.3 vs. 36.3+/-6.7% (p=0.363) and 9.5+/-3.3 vs. 8.8+/-2.5% (p=0.47), respectively. Moderate alcohol consumption does not induce significant short-term changes of the microsomal and the mitochondrial functions of the human liver in healthy subjects.

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Non-Invasive Assessment of Human Hepatic Mitochondrial Function through the¹³C-Methionine Breath Test

Cited by 43 publications

References 14 publications

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[² H₃ -methyl-1-¹³ C]methionine

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[² H₃ -methyl-1-¹³ C]methionine

Patients with severe liver cirrhosis followed up by L-[1- 13 C] phenylalanine breath test

Effect of alcohol consumption on the liver detoxication capacity as measured by [¹³C]methacetin- and [methyl-¹³C]methionine-breath tests

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Non-Invasive Assessment of Human Hepatic Mitochondrial Function through the13C-Methionine Breath Test

Cited by 43 publications

References 14 publications

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[2 H3 -methyl-1-13 C]methionine

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[2 H3 -methyl-1-13 C]methionine

Patients with severe liver cirrhosis followed up by L-[1- 13 C] phenylalanine breath test

Effect of alcohol consumption on the liver detoxication capacity as measured by [13C]methacetin- and [methyl-13C]methionine-breath tests

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Product

Resources

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Non-Invasive Assessment of Human Hepatic Mitochondrial Function through the¹³C-Methionine Breath Test

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[² H₃ -methyl-1-¹³ C]methionine

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[² H₃ -methyl-1-¹³ C]methionine

Effect of alcohol consumption on the liver detoxication capacity as measured by [¹³C]methacetin- and [methyl-¹³C]methionine-breath tests