Michelle Gigou

Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation.

BACKGROUND/AIMS Several genotypes of hepatitis C virus (HCV) have been identified by phylogenetic analysis, but their clinical relevance remains elusive. Liver transplantation for HCV-related cirrhosis offers a unique opportunity for prospective studies of this issue. METHODS Sixty anti-HCV-positive liver recipients with precise virological and histological assessments were included. HCV genotype was determined with both type-specific capsid primers and a line probe genotyping assay. RESULTS HCV genotype 1b was the predominant type before transplantation (40 of 60 patients); after liver transplantation, acute and chronic active hepatitis developed more frequently in these patients than in patients infected by other genotypes (31 of 40 and 24 of 40 vs. 8 of 20 and 4 of 20 patients). Actuarial rates of acute hepatitis and chronic active hepatitis were 77% and 59%, respectively, 3 years after transplantation in patients infected by type 1b and 40% (P = 0.008) and 22% (P = 0.004) in those infected by other types. There was no statistical relation between the level of HCV viremia and HCV genotypes both before and after transplantation. In contrast, after transplantation, serum HCV RNA values were significantly increased in patients who developed hepatitis after transplantation. CONCLUSIONS This study provides direct evidence that HCV 1b is associated with more aggressive recurrent liver disease than other genotypes.

Neurological improvement during bioartificial liver sessions in patients with acute liver failure awaiting transplantation.

BACKGROUND Brain edema is the main cause of death in acute liver failure patients awaiting transplantation. We assessed the HepatAssist 2000, a liver-assist system containing porcine hepatocytes, as a bridge to transplantation in patients with acute liver failure. METHODS Thirteen patients suffering from acute liver failure with criteria for transplantation entered an open baseline-controlled study, with liver-assist treatment sessions at 24-hr intervals until transplantation. Neurological status was regularly evaluated using the Glasgow Coma Scale. RESULTS Three patients were not treated: one had an immediate transplantation and two improved spontaneously. Ten patients received one to three courses of HepatAssist. A significant neurological improvement (mean Glasgow Coma Scale before and after treatment: 6.5+/-3.7 and 9.6+/-4.4, respectively, P<0.02) was observed, which was related to the volume of plasma processed per square meter of body surface. A significant decrease was observed in mean levels of bilirubin (P=0.0005) and transaminases but not in the other indicators of liver function. Six patients had transient episodes of hemodynamic instability, and five had bleeding complications. Two patients died after transplantation. Eight patients survived with a mean follow-up of 24.3 (18-32) months. CONCLUSION The HepatAssist 2000 is well tolerated, improves cerebral function, and may be used as a bridge to transplantation for patients with liver failure.

SPECIFIC ABSORPTION OF LYMPHOCYTOTOXIC ALLOANTIBODIES BY THE LIVER IN INBRED RATS

It has been suggested that liver allografts are less sensitive to lymphocytotoxic antibodies than other organ allografts. In this experimental study in sensitized inbred rat recipients, we have used extracorporeal liver hemoperfusion to study interactions between the liver and lymphocytotoxic antibodies. Donor-specific liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. Immunofluorescence examination of the hemoperfused liver revealed deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. In control rats in which a third-party liver, a donor-specific splenic or renal hemoperfusion was performed, heart allograft survival was less prolonged. The decrease in antibody levels was not significant and the deposit of C3 and IgG was much less evident. Similarly, previous blockade of the Kupffer cells of the donor-specific hemoperfused liver by dextran sulfate suppressed the effect of liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies onto nonparenchymal liver cells.