Prognosis of human liver transplantation.

The results of publications on liver transplantation were diverse since several years, without model prognosis. The impossibility was due to the international system of measurement. We resorted to vector functions for calculating the ratios of biological values. We studied 2 samples with the same total number (35 patients) in the same conditions. We proposed 2 vector functions of transplants: (alpha)v1 weight/age donor and recipient in proportion to obtain a medium coefficient; (gamma)v2 ratio of biliary volume/700 mL (minimum secretion); beta was the coefficient of ratio ALT/AST (transaminases). After evaluation of 560 observations and mathematical control about 3000 numbers, we compared the samples with 10 parameters without significant difference between variances, means, other values; with consented errors alpha= beta = 0.05; gamma < 10(-7); means of relative errors = +/- 0.03 negligible. The results were verified by diverse tests (standard deviation of differences, chi2-test, relative risk, odds ratio, comparisons of distributions, parent population, equations of normality, partial correlations, partial regression coefficients, multiple regression, coefficient beta. Final results : quantitative prognosis by grading ; right responders to immunosuppressive treatment without complications, RR1 fast response (scores 3.5 ; 4) ; RR2 slow response (scores 2 ; 2.5 ; 3). Partial responders: very slow response (score 2; 2.5; 3) with transitory complications. Those patients were in recovery (81.5c/o). Wrong responders (score 2), 4 deaths (5.55c/o) by ARS; score 2.5, 1 death (1.5 5c/o) by ARS. We subtracted beta from these scores to differentiate them. Non-responders (score 1.5), 2 deaths (35c/o) by ARS.

Immunohistochemical hepatocytes nuclear test for the evaluation of responses to treatment of the chronic hepatitis C by interferon alpha.

The results of the microscopic examinations on 23 paired liver biopsies of patients affected by the chronic hepatitis C, were realized successively before and after treatment by interferon alpha during six months. They showed a particular interest in the use of the antibody Anticore. The other antibody Anti C100-3-clone Tordji 32, was partially associated with the Anticore to improve its total number of positive responses by interchanging the loss of 3 wrong positive numbers (-) of the same patients from the Anticore, against earnings of 3 wrong negative numbers (+) for the same patients from the Anti C100-3-clone 32. This operation led to 70% of sensitivity. The results were submitted to mathematical verification and allowed to look for the maximum of the predictive probabilities. As for the other antibody Anti C100-3-Tordji-clone 22, it only used as a witness for some positive values. Moreover, this work brought a practical implementation to solve the problem concerning the indeterminate responses. Elsewhere, it appeared plausible for the Anticore to advance beyond its value, if the improvement of its conditions of realization were requiring. That hope was reasonable since it was yielded from the results of the predictive equations of the likelihood ratios by the logistic regression method which built two mathematical models to comparison for confirmation.

Evaluation of glycogen loss in human liver transplants. Histochemical zonation of glycogen loss in cold ischemia and reperfusion.

To find a prognosis model of human liver transplant, we evaluate 62 surgical biopsies for the loss of glycogen and its variations in relation to cold ischemia, reperfusion, lobular zonation and donor's ages. We applied univariate, multivariate and discriminant analysis and logistic regression. There was a clear lobular zonation of glycogen during cold ischemia and at reperfusion. During cold ischemia, the mean loss was 48% in periportal zones and 74% in pericentrilobular zones. At reperfusion, it was in the range of 60% in periportal zones and 95% in pericentrilobular zones. It was observed in 64% of the grafts for an ischemia time less than 10 hr and in 82% of the grafts for an ischemia time of 10 hr or more. It was increased by 90% at reperfusion with pericentral predominance. Donors' age was an aggravating factor of glycogen loss beyond 28 years of age. In conclusion, in periportal zones, mean global glycogen depletion was about 54% during cold ischemia and reperfusion. It decreased by 90% at reperfusion with pericentral predominance. Logistic regression has allowed modelization of cold ischemia and reperfusion.

Circadian variations in the responsiveness of human gallbladder to sulfated mineral water.

It is well known that the intake of sulfate-containing natural mineral waters leads to contraction of the gallbladder, probably induced by the release of cholecystokinin (CCK). As early as 1959, there were some hints in the literature of circadian variations in gallbladder response; to find out whether this applies with sulfate as a stimulus, a pretest for basic information about gallbladder reaction to sulfate-containing mineral water was carried out on 19 healthy volunteers. On this basis, 15 healthy subjects of both sexes were then studied. After 6h of fasting, 500 mL of a sulfate-containing mineral water (2,800 mg SO4(2-)/L) were ingested within 5 min. The size of the gallbladder was registered ultrasonographically before and 15, 30, 60, and 120 min after drinking. The experiments were carried out seven times at different hours of the day for each volunteer. After the intake of the mineral water, the mean gallbladder size decreased significantly, followed by an increase after 60 min (P < .001). Significant circadian spontaneous variation in gallbladder size was detected (acrophase around 09:00; amplitude was 30.0% of daily average, P < .001). The contraction induced by the sulfate-containing water was most marked in the early morning hours and minimal around mid-day; the amplitude of this variation accounting for 29.0% of the daily average (P < .01). In contrast, the postdrinking relaxation was maximal around 18:00 and minimal around 9:00 (amplitude 38.5%. P < .001). These results show that the basal size of the gallbladder and its reaction to stimuli show a marked circadian variation: Whereas contractibility is maximal in the morning, dilatation is stronger in the afternoon.

Analysis by confocal laser scanning microscopy imaging of undilated bile canaliculi F-actin staining in the hepatocytes of human extrahepatic cholestatic liver.

Many studies have demonstrated the role of bile canalicular microfilaments in bile secretion and bile flow. It is now admitted that modification of bile canalicular network of microfilaments play a role in dysfunction of bile secretion observed in many cases of cholestasis. This work intends to study F-actin, a major component of microfilaments, in human hepatocytes in extrahepatic cholestasis. Normal and extrahepatic cholestatic liver were studied. F-actin was stained with fluorescent phallotoxin and quantified by using confocal laser scanning microscopy and an image analysis method. Mean specific fluorescence (MSF) of bile canaliculi was measured. Since dilated and bile plugged canaliculi were rarely observed in cholestatic liver sections, only undilated bile canaliculi were analysed. Bile canalicular MSF was significantly increased (p < 0.05) in cholestatic hepatocytes (1.3 to 1.7 fold higher than in controls). These data demonstrate a pericanalicular thickening of F-actin microfilaments in human extrahepatic cholestatis, similar to that described in literature in many cases of human intrahepatic and extrahepatic cholestasis cases as well as in experimentally induced cholestasis. However, further studies are needed to understand this increase in F-actin pericanalicular microfilaments in human extrahepatic cholestasis.

Immunohistochemical detection of hepatitis C virus related C100-3 and core antigens in formalin-fixed liver tissue.

HCV C100-3 non-structural and core proteins have been detected by immunohistochemical methods on paraffin-embedded tissue sections using monoclonal antibodies in 22 cases of chronic hepatitis C. C100-3 protein was detected in cytoplasm and nuclei of hepatocytes whereas core protein was only detected in nuclei. The specificity of the nuclear localization of HCV antigens was discussed in relation to cross-reactivity of the anti core antibody with host-derived GOR antigen.