Abstract | BACKGROUND: In cirrhosis, hepatic mitochondriae exhibit morphological and functional abnormalities. In human steatosis, ultrastructural changes are reported in the absence of ethanol. Routine evaluation of mitochondrial function is difficult. We used a breath test to explore hepatic mitochondrial oxidation in vivo. MATERIAL/METHODS: The 13C-methionine breath test was performed in healthy subjects (n=15), patients with cirrhosis (n=25), and patients with biopsy-proven severe (> 40% involved hepatocytes), non-alcoholic macrovesicular steatosis (n=18). After oral administration of 13C-methionine (200 mg), hepatic mitochondrial decarboxylation was measured by breath [13C]-C02 enrichment, expressed as dose/h and delta over base (DOB), for 1 hour, by isotope ratio infrared spectroscopy. Results were normalized against BMI. RESULTS: At 60 minutes, patients with steatosis had reduced exhalation of 13C02 as compared to healthy subjects (dose/h: -47%, 18.8+/-12 vs 36+/-6.1; DOB: -52%, 40.4+/-32 vs 85+/-20, p<0.05). Cirrhotics had even lower values as compared to patients with steatosis (dose/h: -60%, 7.5+/-3.4 vs 18.8+/-12, p<0.05). In cirrhosis, dose/h correlated (r=0.68) to aminopyrine breath test values, a microsomal function test, and was inversely correlated (r=-0.48) to the Child-Pugh score. CONCLUSIONS: Hepatic mitochondrial oxidation as reflected by the 13C-methionine breath test is impaired both in patients with pure non alcohol-related severe macrovesicular steatosis and in patients with cirrhosis of mixed etiologies. This non- invasive test can be used to monitor hepatic mitochondrial function in vivo.
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Authors | Laurent Spahr, Francesco Negro, Gioacchino Leandro, Oana Marinescu, Keith J Goodman, Laura Rubbia-Brandt, Martha Jordan, Antonine Hadengue |
Journal | Medical science monitor : international medical journal of experimental and clinical research
(Med Sci Monit)
Vol. 9
Issue 1
Pg. CR6-11
(Jan 2003)
ISSN: 1234-1010 [Print] United States |
PMID | 12552242
(Publication Type: Journal Article)
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Chemical References |
- Aminopyrine
- Methionine
- Oxygen
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Topics |
- Adult
- Aged
- Aminopyrine
(metabolism)
- Biopsy
- Breath Tests
- Case-Control Studies
- Female
- Fibrosis
(metabolism)
- Hepatocytes
(metabolism)
- Humans
- Liver Cirrhosis
(metabolism)
- Liver Cirrhosis, Alcoholic
(metabolism)
- Liver Diseases
(metabolism)
- Male
- Methionine
(metabolism)
- Middle Aged
- Mitochondria, Liver
(metabolism)
- Obesity
(metabolism)
- Oxygen
(metabolism)
- Time Factors
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