Update on the Use of Metabolic Probes to Quantify Liver Function: Caffeine versus Lidocaine

Abstract

The search continues for a safe, accurate and reliable method to quantify liver function similar in principle to renal creatinine clearance or pulmonary function spirometry tests. When evaluating patients in the more advanced stages of chronic liver disease, one’s clinical judgement regarding the degree of liver dysfunction usually suffices, but in patients with early or only intermediate disease, an estimate based on routine blood tests and/or clinical severity scores is often unreliable. A more quantitative approach under investigation at present has been to monitor specific pharmacokinetic parameters of ‘probe’ drugs metabolized primarily by hepatic cytochrome P-450. These parameters include the plasma or salivary clearance rate of the parent compound and/or the formation rate of its metabolites. Following a review of basic hepatic pharmacology relevant to this topic, we shall explore the advantages and disadvantages of two ‘metabolic probes’ that have shown the most promise to date, caffeine and lidocaine.

Serum Metabolite/Caffeine Ratios as a Test for Liver Function

“…33 The main application of the MEGX test is in the field of liver transplantation: to determine the appropriate timing for transplantation and predict postoperative outcome, to assess the viability of the donor liver, and to monitor patients with posttransplantation complications. 2,33 Diagnostic sensitivity/specificity of this test for patients with serious hepatic disorder (cirrhosis and chronic hepatitis) was 84.5%/88.5%. 35 Similar values-a sensitivity of 75% and a specificity of 84%-were calculated by Fabris and colleagues 36 for patients with cirrhosis.…”

“…During the study and for 1 day before, all participants were asked to avoid methylxanthine-containing beverages as well as foods containing substances that can affect caffeine biotransformation, such as brussel sprouts, broccoli, white cabbage, and charcoal-broiled meat. At the time of the study, most patients were being treated with one or more of the following drugs (the number of patients is in parentheses): spironolactone (10), furosemide (8), ranitidine (6), hyoscine butylobromide (6), etamsylate (6), propranolol (5), nootropil (5), metoclopramide (5), enarenal (4), metronidazole (4), diazepam (5), exacyl (4), ornithine (3), ampicillin (2), and aspartic acid (2). Patients taking medications affecting hepatic drug metabolism, such as theophylline, cimetidine, and phenytoin, were not enrolled in the study.…”

“…Indocyanine green clearance, which is useful in measuring hepatic perfusion (not metabolic capacity), has not been widely adopted in clinical practice. 2 The serum level of monoethylglycinexylidide (MEGX), formed from lidocaine, was proposed by Oellerich and colleagues 34 as a liver function test that has found widespread application due to its simplicity and rapid turnaround time. 33 The main application of the MEGX test is in the field of liver transplantation: to determine the appropriate timing for transplantation and predict postoperative outcome, to assess the viability of the donor liver, and to monitor patients with posttransplantation complications.…”

“…These include the measurement of galactose elimination, rate of lidocaine biotransformation, breath tests employing labeled aminopyrine and antipyrine, and indocyanine green clearance. 2,4 In general, these tests do not enjoy widespread use in clinical practice since they offer no diagnostic benefit, are com-plex to perform, or use potentially harmful substances. 5 Caffeine has been suggested as an almost ideal test substance for the metabolic function of liver because of its relative lack of toxicity, rapid absorption, complete biotransformation by the hepatic cytochrome P450-dependent monooxygenases, and widespread consumption.…”

“…Some authors have considered this complex approach to be useful for patients with advanced liver damage but of limited value for individuals with mild or intermediate dysfunction. [1][2][3] Thus, a number of tests for the evaluation of hepatic metabolic capacity have been proposed. These include the measurement of galactose elimination, rate of lidocaine biotransformation, breath tests employing labeled aminopyrine and antipyrine, and indocyanine green clearance.…”