L-[1- ¹³ C] phenylalanine breath test for monitoring hepatic function after living donor liver transplant surgery

Abstract

Although metabolic response after partial hepatectomy has been well studied in animal models, there are few studies examining restoration of metabolic capacity after right hepatectomy in humans. The L-[1-(13)C]-phenylalanine breath test (PBT) is a simple non-invasive diagnostic tool which allows measurement of liver functional reserve. We investigated the PBT for monitoring hepatic function in living liver donors by measuring the metabolism of L-[1-(13)C]-phenylalanine ((13)C-Phe). We used (13)C-Phe administered orally and iv to adult living liver donor patients and measured exhaled (13)CO(2) to determine the extent of metabolic impairment and time course of its return. Patients given oral (13)C-Phe had approximately 70-90% reduction in (13)CO(2) production compared with baseline 2-3 days after surgery. Patients given iv (13)C-Phe had only 40-50% reduction in (13)CO(2) production and recovered their baseline (13)C-Phe metabolism much sooner than their oral (13)C-Phe metabolic capacity (P < 0.05). In some cases oral (13)C-Phe did not recover to baseline for as long as 56 days after surgery. Patients recovering (13)C-Phe metabolism had significantly higher (13)CO(2) recovery 60 min after ingestion by day 4 (0.97 versus 3.06, P = 0.033) and day 7 (1.50 versus 5.02, P = 0.031). We conclude that orally administered amino acids may not be well absorbed and/or metabolized in some subjects for weeks after partial hepatectomy whereas intravenously delivered substrates are much better oxidized by the regenerating liver. These findings may be due to impaired gut motility due to trauma to the gastrointestinal tract or portal venous flow that reduces delivery of oral agents after liver surgery. In early recovery phase for living liver donor patients, the iv PBT would be a better predictor of functional hepatic reserve.

Early diagnosis of primary nonfunction and indication for reoperation after liver transplantation

“…Pauwels et al28 showed the higher effectiveness of intravenous tests versus oral breath tests with 14 C‐aminopyrine already in 1982. More recent studies of Freeman17 and Tugtekin et al29 pointed out that the oral substrate administration in breath tests precludes a valid analysis of hepatic enzyme kinetics during postoperative periods. The intravenous administration during the LiMAx test, combined with online real‐time analysis, enables the in vivo assessment of the metabolic liver function capacity.…”

Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: pharmacokinetic models for assessing liver function

“…Post-operative recovery from organ transplant is generally monitored with organ biopsy and/or assessment of specific biomarkers in blood. The recovery of liver function, in particular, can also be assessed by dynamic tests such as the plasma clearance of indocyanine green [1], sulfobromophthaleinand galactose [2] or the monitoring in breath of metabolites of labeled compounds [3,4]. However, all these procedures are invasive for requiring intravenous administration of xenobiotics.…”

Further characterization of a 13 C-dextromethorphan breath test for CYP2D6 phenotyping in breast cancer patients on tamoxifen therapy

“…In our previous study [8], we observed a non-linearity between gene activity score and DOB 50 in CYP2D6 IMs and EMs, with flattening of the curve in EMs, suggesting that CYP2D6 enzyme Correlation between DOB 50 with AUC 0-120min (left) is better than with AUC 0-240min (right), but it should be stated that patients numbers are low. Abbreviations: AUC, Area under the Curve; DOB, Delta-over = Baseline; DM-BT, 13 C-dextromethorphan breath test. activity was saturable in IMs and limited by 13 C-DM dose in EMs.…”

“…DOB (‰, average (point) and SD (lines)) versus time curves for 6 different patients undergoing CYP2D6 phenotype test by DM-BT on 3 separate days.Abbreviations: DOB, Delta-over=Baseline; DM-BT,13 C-dextromethorphan breath test; SD, standard deviation.…”

“…Enrichment of13 CO 2 in expired air as a consequence of13 C-DM is expressed as the increase in the 13 CO 2 / 12 CO 2 ratio relative to predose baseline sample and is termed delta-over baseline (DOB), reflecting CYP2D6 activity: DOB= 1000x[( 13 CO 2 / 12 CO 2 ) Postdose -[( 13 CO 2 / 12 CO 2 ) Baseline]/R PDB where DOB is expressed in units of Δ per mil (‰), and R PDB =0.012373 is 13 C/ 12 C in PDB (international standard Pee Dee Belemnite). Production of the drug substance meets Good Manufacturing Practice (GMP) guidelines.…”