[13C]methacetin breath test for evaluation of liver damage

Abstract

Methacetin undergoes rapid O-dealkylation by hepatic microsomal enzyme systems, and the resultant CO2 is present in the expired air. The rate of O-dealkylation of methacetin was assessed by the [13C]methacetin breath test in seven healthy volunteers and 30 patients with histologically proven chronic liver diseases. The 30-min recovery of orally administered [13C]methacetin as 13CO2 in the exhaled air was significantly reduced in patients with chronic aggressive hepatitis and in those with liver cirrhosis but not in patients with chronic persistent hepatitis or healthy controls. Patients with either advanced cirrhosis or hepatocellular carcinoma showed significantly lower values than those with well-compensated cirrhosis. The levels in two patients with late primary biliary cirrhosis were reduced. These results show that the severity of liver damage can be effectively evaluated by [13C]methacetin breath test. In addition, this test is simple, safe, and time efficient.

Evaluation of 13C-Phenylalanine and 13C-Tyrosine Breath Tests for the Measurement of Hepatocyte Functional Capacity in Patients with Liver Cirrhosis.

“…13 C-aminopyrine 18) and 13 C-methacetin 19) are microsomal substrates, which have been used in breath tests to assess the degree of hepatic dysfunction. However, these tests are measuring drug metabolism instead of degradation of natural metabolites.…”

13C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

“…While designing the study protocol we decided to adopt the currently accepted mode of administration of 13 C-methacetin, namely a fixed oral dose of 75 mg [5,6,8,13,15,20,37,38] . It should be noted, however, that formerly other body mass adjusted dosage regimens were applied, encompassing 5 mg/kg in the pioneer work by Krumbiegel et al [39] , then 2 mg/kg [7,11,12,40] , as well as 1 mg/ kg [10,41] , and finally Iikura et al [42] applied in infants 0.5 mg/kg 13 C-methacetin. Taking into account the investigative nature of our research, we generously took as many as 19 samples of breath air throughout 3 h. This approach appears to be precedential in nature, because for routine clinical use just a few measurement points are usually considered [15,42] .…”

“…A number of features support its usefulness as a functional liver probe: a fast metabolism to acetaminophen and 13 CO2 by cytochrome P450 1A2 (CYP 1A2), safety at low doses applied for a breath test, and a low cost [1][2][3][4] . Accordingly very promising results on its diagnostic usefulness were obtained in patients with chronic hepatitis C virus infection [5,6] , primary biliary cirrhosis [7,8] , non-alcoholic steatohepatitis [9] , and various stages of liver cirrhosis [10][11][12][13][14] , including those awaiting a liver transplantation [15] . A vital asset of any measurement or diagnostic method used in medical practice is an ability to provide reproducible results.…”

Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C

“…Os testes respiratórios com diferentes substratos exógenos têm sido utilizados com esse fim e têm as vantagens de serem não-invasivos, de fácil execução e baixa ou nenhuma toxicidade (1,9) . Dentre os substratos utilizados, a metacetina marcada com carbono 13 ( 13 C-metacetina), tem sido empregada nas doenças hepáticas crônicas (1,6,8,9,13) , particularmente em portadores de cirrose hepática e de hepatite crônica C (2,3,7,10,11) . Essa substância seria rapidamente absorvida no duodeno e metabolizada pelo sistema microssomal hepático, dependente do citocromo P450.…”