Critical appraisal of ¹³C breath tests for microsomal liver function: aminopyrine revisited

Abstract

As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the 13 C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the 13 C 2 -aminopyrine and the 13 C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the 13 C 2 -aminopyrine breath test in clinical practice.

Microsomal Liver Function in Patients with Phenylketonuria Assessed by 13C-Methacetin Breath Test

“…Along with the 13C-aminopyrine breath test, it is the most extensively studied of the liver breath tests. Although the 13C-MBT test is strongly dependent on hepatic blood flow (7,9), we decided to use 13C methacetin instead of another substrate due to its high safety index (20) Furthermore, there are no available data describing alterations of hepatic blood flow in PKU patients. As there are many conditions affecting the cytochrome P450 function (7), the present study was designed to eliminate potential bias -the control group was matched for age and sex, all the participants were instructed not to smoke cigarettes and avoid 13C-naturally rich products, and the test was performed after an overnight fast.…”

“…On the basis of the obtained results, the absence of any abnormalities of liver function was affirmed. Although the parameters used in the aforementioned study are basic and commonly used, they do not indicate any metabolic dysfunction of the liver (9,18). Furthermore, Ramati et al observed that low blood concentrations of vitamin B6 (the source for ALT co-factor, Pyridoxal-5-Phosphate) results in lower ALT activity amongst patients of internal medicine departments (23).…”

“…Methacetin undergoes O-dealkylation by cytochrome P450 1A2 (CYP1A2) to acetaminophen and 13CO2 (8). 13CO2 output in exhaled air reflects the activity of cytochrome P450 enzymes and thereby microsomal function of the liver (9). The available data of previous studies show that 13C-MBT was used for the assessment of liver status in such conditions as hepatitis B and C (10), non-alcoholic steatohepatitis (11), fibrosis (12,13) and cirrhosis (13,14).…”

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

“…For many probe drugs, the initial metabolic reaction, often a dealkylation step, is catalyzed by CYP450 enzymes and, therefore, the amount of 13 CO 2 in breath should reflect enzyme activity. For a full overview of published breath tests, available probe drugs and their clinical utility, we refer to several recent reviews on this topic [117][118][119][120][121]. Here, we highlight a number of selected studies in which the potential of breath tests for CYP450 phenotyping has been evaluated by comparison with other indices of enzyme activity ( Table 1).…”

Use of the methacetin breath test to classify the risk of cirrhotic complications and mortality in patients evaluated/listed for liver transplantation

“…The amplitude and rate of appearance of the labeled metabolite represent liver enzymatic activity; hence, a decline may represent hepatic injury or decreased access of substrate to hepatocytes because of portosystemic shunting. Candidate methods include the indocyanine green clearance test [9], cholate shunt test [10], aminopyrine breath test [11], and methacetin breath test (MBT) [12].…”