¹³C‐methacetin breath test as liver function test in patients with chronic hepatitis C virus infection

Abstract

SUMMARY Background:The 13 C-methacetin breath test enables the quantitative evaluation of the cytochrome P450-dependent liver function. Aim: To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. Methods: Sixty-one healthy controls and 81 patients with chronic hepatitis C underwent a 13 C-methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index-Knodell score.Results: Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 ± 9.2& vs. 24.1 ± 5.7&; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 ± 4.8% and in healthy controls 13.8 ± 2.8% (P < 0.002).However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 ± 7.9& vs. 22.6 ± 7.2&; P ¼ 0.61) or cumulative recovery (13.6 ± 3.7% vs. 13.2 ± 3.8%; P ¼ 0.45) from patients with more advanced fibrosis (histology activity index IVC).Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13 Cmethacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 ± 4.9&; P < 0.005 and cumulative recovery after 30 min: 5.6 ± 3.2%; P < 0.003). The 13 C-methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. Conclusion:The non-invasive 13 C-methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C. can be quantified by isotope ratio mass spectrometry or nondispersive isotope-selective infrared spectroscopy. 4-6Like the 13 C-aminopyrine breath test and the monoethylglycinexylidide (MEGX) test, the 13 C-MBT is a microsomal liver function test.To determine the degree of fibrosis in patients with chronic liver disease, liver biopsy is still considered as the gold standard. Non-invasive serum tests to classify patients as having mild or advanced liver fibrosis allow correct determination in approximately 40-70% of the cases only. [7][8][9][10][11] Most liver function tests, including the 13 C breath tests, together with the clinical judge-

Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high‐risk for hepatocellular carcinoma

“…However, these noninvasive tests are cumbersome, expensive, and do not fulfill the criteria of an ideal test for hepatic fibrosis. [17][18][19][26][27][28] Liver biopsy and most noninvasive tests are not feasible for communitybased screening; and another simple, inexpensive, accurate, and easily applicable parameter is necessary. The platelet count is a simple test, and its results are determined easily by routine laboratory procedure.…”

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

“…Moreover, the female participants were always examined in the same phase of the menstrual cycle. 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.…”

“…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.…”

Update on diagnostic value of breath test in gastrointestinal and liver diseases

“…The magnitude of appearance of 13C in breath analysis is correlated with the process of de methylation. This test has been reported to be a reliable marker for the differentiation between early cirrhotic (Child A) and noncirrhotic patients but its performance for the detection of liver fibrosis remains questionable [59] .…”