13C‐methacetin breath test for monitoring hepatic function in cirrhotic patients before and after liver transplantation

Sirs, We read with interest the paper published by Petrolati et al. in a recent issue of Alimentary Pharmacology and Therapeutics.1 We agree with the authors that 13C breath testing may be useful for monitoring hepatic function in patients waiting for orthotopic liver transplantation and during follow-up after this procedure, as described in a recent paper.2 In particular, we have shown that 13C-aminopyrine and 13C-methionine breath tests are useful in the early phases after orthotopic liver transplantation to predict primary non-function of the transplanted liver.2 However, we prefer to use the 13C-aminopyrine breath test for the investigation of liver function in end-stage cirrhotic patients, which, in our opinion, is more reliable than the 13C-methionine breath test. Methacetin is a drug with a high hepatic extraction ratio (more than 0.8) and, for this reason, is dependent on the blood flow to the liver.3, 4 Patients with advanced hepatic cirrhosis generally have a low hepatic blood flow because of portal hypertension and porto-systemic shunts; in addition to impaired liver metabolic function, a low value of 13C measured in breath after 13C-methacetin ingestion may therefore reflect the presence of shunts. In contrast, aminopyrine has a low hepatic extraction ratio (less than 0.3) and, for this reason, should be less influenced by blood flow to the liver.4 Moreover, it has recently been reported that the 13C-methionine breath test is influenced by both age and blood oxygenation.5, 6 Ciccocioppo et al. showed that the 13C-methionine breath test was influenced by age in healthy subjects and inversely related to the intra-hepatic resistance index, assessed by Doppler pulsed wave analysis.5 Zipprich et al. demonstrated that oxygen supplementation increased the liver oxidation capability in cirrhotic patients in different Child classes.6 Finally, as far as the toxicity is concerned, both methacetin and aminopyrine seem to be safe. Indeed, although agranulocytosis has been described with the chronic pharmacological administration of aminopyrine, no case has been reported in the literature with the low, single dose used for breath testing analysis.