Reassessment of monoethylglycinexylidide as preoperative liver function test in a rat model of liver cirrhosis and man.
It is known that lidocaine is rapidly metabolized by the hepatic cytochrome P-450 system to form monoethylglycinexylidide (MEGX), its primary metabolite. We analyzed serum MEGX levels experimentally and clinically by fluorescent polarization immunoassay to reassess preoperative liver microsome functions.


METHODS
Liver cirrhosis was produced in rats by intra-abdominal injection of thioacetamide. MEGX, indocyanine green test (ICG), and liver biochemical variables were measured periodically. Then, survival rates were assessed after the rats received a 70% hepatectomy.


METHODS
MEGX levels were measured in various human patients with chronic hepatitis or liver cirrhosis who underwent hepatectomy. Serum MEGX levels significantly dropped and ICG levels significantly rose with macroscopic and histologic progression of liver cirrhosis in rats. The MEGX levels correlated closely with albumin levels and ICG. Preoperative MEGX and ICG levels of the mortal group of rats differed significantly from those of the survival group with 70% hepatectomy. Furthermore, 100% of the rats with MEGX levels above 40 ng/ml and ICG levels below 1.0%. In the clinical study, MEGX levels were significantly lower in patients with chronic hepatitis or liver cirrhosis than in healthy volunteers and correlated significantly with liver function tests such as albumin, Fischer's ratio, prothrombin time, hepaplastin and ICG. A significant difference was found in MEGX levels between patients receiving lobectomy and those receiving subsegmentectomy or partial hepatectomy. All patients tolerated their operations. Our data indicate that the MEGX test combined with ICG test and Child-Pugh classification is a better predictor of residual liver reserve capacity, and the analysis of hepatic MEGX formation might prove useful for rapid and reliable assessment liver function and choice of surgical treatment.
Kaneko
H
H
Second Department of Surgery, Toho University School of Medicine, Tokyo, Japan. hironori@med.toho-u.ac.jp
Otsuka
Y
Y
Katagiri
M
M
Maeda
T
T
Tsuchiya
M
M
Tamura
A
A
Ishii
T
T
Takagi
S
S
Shiba
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D004195:Disease Models, Animal; D006498:Hepatectomy; D006505:Hepatitis / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D007202:Indicators and Reagents / Q000032:analysis; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D008106:Liver Cirrhosis, Experimental / Q000097:blood* / Q000473:pathology / Q000601:surgery; D008111:Liver Function Tests; D008297:Male; D009930:Organic Chemicals; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D012709:Serum Albumin / Q000032:analysis; D013853:Thioacetamide / Q000633:toxicity
D007202:Indicators and Reagents; D009930:Organic Chemicals; D012709:Serum Albumin; D013853:Thioacetamide; C013014:hepaplastin; D008012:Lidocaine; C001173:monoethylglycinexylidide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007208:Indocyanine Green; D001663:Bilirubin