The monoethylglycinexylidide test for grading of liver cirrhosis.

BACKGROUND: Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration. AIM: To determine the optimal sampling time for MEGX determination. METHODS: A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score). RESULTS: Only the MEGX fractional formation rate (kf) and formation delay (tau) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 +/- 0.03 vs. 0.32 +/- 0.10 min-1 (mean +/- s.d.); tau = 7.7 +/- 2.0 vs. 3.9 +/- 2.9 min-1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method. CONCLUSION: The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.

Splenic Doppler impedance indices: influence of different portal hemodynamic conditions.

The spleen plays a pivotal role in the pathogenesis and maintenance of portal hypertension. Few data exist about splenic hemodynamics evaluated by duplex sonography in this condition. Twenty-six normal subjects, 207 patients with portal hypertension of various causes, and in different splenoportal hemodynamic conditions, and 31 patients with liver transplantation were evaluated. In each patient the splenic resistive index (RI = peak systolic--end diastolic velocity/peak systolic velocity) and pulsatility index (PI = peak systolic--end diastolic velocity/mean velocity) were measured. In 17 cirrhotic patients, splenic indices were compared with portal hemodynamics as invasively evaluated by hepatic vein catheterization. In the various groups, RI and PI were respectively: normal subjects, 0.51 +/- 0.05 and 0.72 +/- 0.11; cirrhotic patients with hepatopetal portal blood flow (n = 167), 0.64 +/- 0.08 and 1.03 +/- 0.24; cirrhotic patients with hepatofugal portal flow (n = 3), 0.74 +/- 0.08 and 1.27 +/- 0.08; cirrhotic patients with portal vein thrombosis (n = 9), 0.74 +/- 0.08 and 1.36 +/- 0.34; patients with noncirrhotic obstruction of the portal system (n = 7), 0.69 +/- 0.11 and 1.16 +/- 0.28; cirrhotic patients with surgical decompression of splenic vein system (n = 21), 0.54 +/- 0.07 and 0.76 +/- 0.15; patients with liver transplantation (n = 31), 0.50 +/- 0.08 and 0.70 +/- 0.15. Both RI and PI were significantly higher in cirrhotic patients with hepatopetal portal flow compared with controls (P < .0001), and even higher in cirrhotic patients with portal vein thrombosis (P < .004 and P < .001 in comparison with RI and PI values of cirrhotic patients). In patients with noncirrhotic portal vein thrombosis, splenic impedance indices were higher than those in controls (RI and PI P < .0001). Cirrhotic patients who underwent surgery for the therapy of portal hypertension showed splenic impedance indices significantly decreased compared with other cirrhotic patients (RI and PI P < .0001). In patients who underwent liver transplantation, splenic impedance indices were the same as those in controls. In 23 of the 52 patients surgically treated (surgical shunt or liver transplantation), impedance indices were evaluated both before and after surgical treatment. All these patients showed a decrease in splenic impedance indices (RI and PI, P < .0001) after surgical treatment. RI and PI values were higher in patients with large esophageal varices as compared with patients without or with small varices (P < .02 and P < .01). RI and PI values were not related to age, mean arterial pressure, sex, Child-Turcotte-Pugh score, presence of ascites, or cause. A significant correlation was found between splenic impedance indices and portal resistance as evaluated by hepatic vein catheterization (r = .80, P < .001 for RI values; r = .87, P < .001 for PI values). In conclusion, this study shows that splenic impedance indices are increased in cirrhotic patients, and seems to demonstrate that in patients with cirrhosis these indices reflect portal vein blood flow resistance.

The effect of drugs on bile flow and composition. An overview.

Many drugs are eliminated via the hepatobiliary route, after biotransformation in the liver. Some of them may affect bile flow and/or the hepatic secretion of biliary lipids such as bile acids, cholesterol and phospholipids. Bile acids are the most potent agents which increase bile flow, especially unconjugated bile acids. Other drugs which increase bile flow include phenobarbitone (phenobarbital), theophylline, glucagon and insulin. In contrast, ethacrynic acid, amiloride, ouabain, oestrogens and chlorpromazine are among those agents which decrease bile flow. Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol. The composition of bile can also be altered by drug therapy. Thus, clofibrate increases biliary cholesterol secretion, and reduces bile acid concentrations, without altering biliary phospholipid concentrations. However, other clofibrate derivatives may produce changes of a different pattern, suggesting that the risk of developing gallstones may differ for each derivative. Nicotinic acid and d-thyroxine also increase biliary cholesterol saturation, while CDCA and UDCA reduce biliary cholesterol concentration. The potential consequences of drug-induced changes in bile flow and composition extend to the liver, the gallbladder and the intestine. If adverse effects are to be avoided, further study in this often overlooked area is required.