USE OF HEPATIC LIDOCAINE METABOLISM TO MONITOR PATIENTS WITH CHRONIC LIVER DISEASE

Shiffman ML; Luketic VA; Sanyal AJ; Thompson EB; Hepatology Section, Medical College of Virginia, Virginia; Commonwealth University, Richmond 23298, USA. Ther Drug Monit, 1996 Aug, 18:4, 372-7

Lidocaine is converted to its primary metabolic product monoethylglycinexylodide (MEGX) via cytochrome P-4503A4 within the liver. A steady-state concentration of MEGX appears in serum within 15 min following the intravenous administration of lidocaine. The present article reviews some of the data suggesting that this MEGX value can be utilized to assess hepatic function. MEGX production declines stepwise with the severity of chronic hepatitis. In patients with cirrhosis, MEGX declines further with worsening Child class. Nearly all persons with MEGX of < 20 ng/ml had cirrhosis confirmed upon histologic evaluation. Severe life-threatening complications of cirrhosis were observed only in patients with MEGX production below 20 ng/ml. One-year survival for patients with an MEGX value of < 10 ng/ml was only 50%. In contrast, 1-year survival for patients with MEGX of > 10 ng/ml was approximately 80%. These data suggest that MEGX could be utilized as an accurate test of hepatic function and to predict morbidity and mortality related to complications of chronic liver disease. However, this test does have several limitations. There is wide interpatient variability between MEGX and hepatic histology, which severely impairs the ability of this test to accurately predict hepatic histology. In addition, MEGX is affected by gender and several medications. However, since MEGX does decline stepwise with advancing histology in any given patient, the available data suggest that serial monitoring of MEGX could be utilized to track hepatic metabolic capacity in patients with chronic hepatitis and cirrhosis.

HEPATIC LIDOCAINE METABOLISM AND LIVER HISTOLOGY IN PATIENTS WITH CHRONIC HEPATITIS AND CIRRHOSIS

Shiffman ML; Luketic VA; Sanyal AJ; Duckworth PF; Purdum PP 3^rd; Contos MJ; Mills AS; Edinboro LE; Poklis A; Hepatology Section, Medical College of Virginia, Richmond 23298. Hepatology, 1994 Apr, 19:4, 933-40

Recent advances in the medical and surgical treatment of chronic hepatitis and cirrhosis have made it increasingly important to develop noninvasive tests of liver function. Our study has evaluated the hepatic conversion of lidocaine to its primary metabolite monoethylglycinexylodide and compared this with liver histological findings in 225 patients with chronic hepatitis (161 with hepatitis C, 23 with hepatitis B, 21 with autoimmune hepatitis and 20 with cryptogenic hepatitis). One hundred seven (47.7%) patients had cirrhosis at the time of evaluation. A decline in monoethylglycinexylodide production was observed with worsening liver histological conditions from a mean of 81.5 +/- 7.0 ng/ml in patients with chronic persistent hepatitis to 61.2 +/- 5.5 ng/ml for chronic active hepatitis and 20.9 +/- 1.5 ng/ml in patients with cirrhosis (p < 0.05). A further stepwise decline in monoethylglycine xylodide production was observed with worsening Child class: from 25.5 +/- 2.2 ng/ml for class A patients to 8.9 +/- 1.4 ng/ml for patients with Child class C disease (p < 0.05). All patients with monoethylglycinexylodide production less than 20 ng/ml had cirrhosis confirmed on histological examination. In contrast, no relationship was observed between liver histological status and serum transaminases (AST or ALT), bilirubin, albumin and prothrombin time. Thirty-five patients underwent repeat histological evaluation and monoethylglycinexylodide testing after receiving at least 6 mo treatment for chronic hepatitis (interferon for hepatitis B and C and corticosteroids for autoimmune hepatitis). The change in monoethylglycinexylodide production observed in these patients was a linear function of the change in Knodell histological index (r = 0.73, p < 0.005).

EVALUATION OF THE LIVER FUNCTION OF CIRRHOTIC PATIENTS BASED ON THE FORMATION OF MONOETHYLGLYCINE XYLIDIDE (MEGX) FROM LIDOCAINE

Schinella M; Guglielmi A; Veraldi GF; Boni M; Frameglia M; Caputo M; Laboratorio di Chimica Clinica ed Ematologia, Università degli Studi di Verona, Ospedale Civile Maggiore, Italy. Eur J Clin Chem Clin Biochem, 1993 Sep, 31:9, 553-7

Determination of the functional hepatic reserve is still controversial. Many tests have been proposed, but the assay based on formation of the lidocaine metabolite, monoethylglycine xylidide, seems to offer a promising approach to this problem. In this study we evaluated the effectiveness of the monoethylglycine xylidide test in the clinical evaluation of 31 cirrhotic patients submitted to three different therapeutic options (sclerotherapy, transjugular intrahepatic protosystemic shunt and surgical procedures) and in 1 patient submitted to right hepatectomy for giant hepatic angioma. We found a statistically significant difference between Child A and C patients and between Child B and C patients. The test did not differentiate Child A from Child B patients. We found no correlation between the Child-Pugh score, serum bilirubin, albumin and prothrombin time. There were no differences among the three groups of patients that could be statistically related to their therapy. The monoethylglycine xylidide test seems to be an attractive alternative to previous methods for the evaluation of the functional hepatic reserve, but further studies are necessary to assess the prognostic value of the test in cirrhotics, to separate the independent contribution of portosystemic shunting and hepatocyte dysfunction to monoethylglycine xylidide formation, and to evaluate the test as a prognostic index in cirrhotic patients submitted to general surgery.

AGE AND PLATELET COUNT: A SIMPLE INDEX FOR PREDICTING THE PRESENCE OF HISTOLOGICAL LESIONS IN PATIENTS WITH ANTIBODIES TO HEPATITIS C VIRUS. METAVIR AND CLINIVIR COOPERATIVE STUDY GROUPS.

Poynard T; Bedossa P; Service d'Hépatogastroentérologie, Groupe Hospitalier Pitié-Salpétriére, CNRS URA 1484, Paris, France. J Viral Hepat, 1997 May, 4:3, 199-208

The aim of this study was to identify clinical and biological factors associated with histological lesions in patients with chronic hepatitis C and to construct a simple diagnostic index. A database consisting of 500 patients with untreated biopsy-proven chronic non-A non-B hepatitis was used. Liver biopsies were reviewed, blind, by a panel of pathologists. Patients were classified according to the presence of necroinflammatory lesions (histological activity) and fibrosis. The diagnostic value of nine clinical and 10 biological factors was assessed using logistic regression analysis, sensitivity, specificity and predictive values, and a score was constructed combining the most significant factors identified. The validation used an independent population of 120 patients. Serum platelet concentration and age were the two main factors significantly and independently correlated with the presence of fibrosis and/or histological activity. A simple score referred to as AP, combining age and platelet count, varied from 0-10. For the presence of significant histological disease (moderate to severe necroinflammatory lesions and/or septal fibrosis to cirrhosis), an AP score of 6 or more had a specificity of 0.93 and a sensitivity of 0.52%. In the validation population, the area under the curve was 0.690 +/- 0.085, not significantly different from that of the first population, 0.763 +/- 0.043. Hence, a simple score combining age and platelet count enabled the accurate prediction of the presence of activity and fibrosis in patients infected with the hepatitis C virus. When this score reached 6, liver biopsy could be avoided owing to its high predictive value. However, the negative predictive value was not high enough to prevent a liver biopsy in patients with a lower score.

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