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Impaired hepatic mitochondrial oxidation using the 13C-methionine breath test in patients with macrovesicular steatosis and patients with cirrhosis.

AbstractBACKGROUND:
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.
AuthorsLaurent Spahr, Francesco Negro, Gioacchino Leandro, Oana Marinescu, Keith J Goodman, Laura Rubbia-Brandt, Martha Jordan, Antonine Hadengue
JournalMedical 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
PMID12552242 (Publication Type: Journal Article)
Chemical References
  • Aminopyrine
  • Methionine
  • Oxygen
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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