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


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.
Spahr
Laurent
L
Division of Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland. Laurent.Spahr@hcuge.ch
Negro
Francesco
F
Leandro
Gioacchino
G
Marinescu
Oana
O
Goodman
Keith J
KJ
Rubbia-Brandt
Laura
L
Jordan
Martha
M
Hadengue
Antonine
A
D000328:Adult; D000368:Aged; D000632:Aminopyrine / Q000378:metabolism; D001706:Biopsy; D001944:Breath Tests; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D013997:Time Factors
D000632:Aminopyrine; D008715:Methionine; D010100:Oxygen