Diagnostic value of anti-hepatitis C virus (HCV) core immunoglobulin M in recurrence of HCV infection after orthotopic liver transplantation.

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation.

MR cholangiography of late biliary complications after liver transplantation.

OBJECTIVE: The aim of our study was to assess the role of MR cholangiography in the diagnosis of late biliary complications after liver transplantation. SUBJECTS AND METHODS: Twenty-three liver transplantation patients (18 men and five women; mean age, 46 years) underwent MR cholangiography using a nonbreath-hold, fat-suppressed three-dimensional turbo spin-echo sequence (TR/TE, 3000/700; echo train length, 128) optimized on a 0.5-T magnet. Inclusion criteria were liver function tests with abnormal results and hyperbilirubinemia with a clinical pattern not specific for biliary obstruction. All patients were referred by clinicians for contrast-enhanced cholangiography. Diagnostic confirmation was obtained with percutaneous transhepatic cholangiography (n = 4), endoscopic retrograde cholangiography (n = 8), T-tube cholangiography (n = 1), or clinical follow-up (n = 10). RESULTS: In 11 patients, no abnormalities of the biliary tract were revealed by MR cholangiography. In 11 patients, twelve strictures were diagnosed (nine anastomotic, two nonanastomotic-intrahepatic, and one nonanastomotic-extrahepatic, with association between anastomotic and nonanastomotic strictures in two cases). In one other patient, kinking of the common bile duct at the level of the anastomosis was observed. In all cases, MR cholangiography correctly showed the site of the stricture and the dilatation of bile ducts above, with excellent correlation with contrast-enhanced cholangiographic findings. Strictures were correctly graded in eight of 10 patients and were overestimated in two. Other findings included a 1-cm stone detected proximal to the obstructed common bile duct in one patient and multiple intrahepatic stones in another patient. CONCLUSION: MR cholangiography can show biliary obstruction and provide important information for planning therapeutic procedures.

Recurrence of hepatitis C virus infection after orthotopic liver transplantation: role of genotypes.

In this study, we evaluated the correlation between alanine aminotrasferase levels and hepatitis C virus genotypes in liver transplant patients. We studied 18 patients who had undergone orthotopic liver transplantation because of end-stage cirrhosis (n = 9) or hepatocellular carcinoma (n = 9) hepatitis C virus related. Serum HCV-RNA testing was performed monthly on all the 18 series of serum samples from the first week after liver transplant until the end of the follow up, this period ranging from 1 to 39 months. After liver transplantation, serum HCV-RNA was detected in 14 patients (78%). Of the 8 patients infected with subtype 1b. 1 remained asymptomatic, 2 developed acute liver failure and 5 developed chronic hepatitis. In patients infected with types 1a (Choo et al., 1989), 2a (Choo et al., 1989), with a mixed infection 1b/3 (Kuo et al., 1989) or with an undetermined genotype, significant laboratory abnormalities were not observed. Recurrence of hepatitis C virus infection after liver transplantation is common, and recurrent hepatitis occurs in 50% of cases. Genotype 1b appears to be associated with a higher rate of recurrent hepatitis, compared to other genotypes.

Anaesthesia for liver transplantation in cystic fibrosis patients.

INTRODUCTION: Cystic fibrosis (CF) is a disease caused by an inherited genetic defect. While pulmonary and pancreatic abnormalities predominate the clinical spectrum, other organ involvement is common, including liver. The severity of liver disease does not appear to be related to the severity of exocrine pancreatic or lung function. We discuss anaesthesia in four CF patients undergoing liver transplantation. METHODS: We studied haemodynamic and oxygenation modifications during anaesthesia in four patients affected by CF with end-stage liver disease and mild to moderate pulmonary abnormalities. The patients received pancreatic enzyme prior to transplantation and two had insulin-dependent diabetes mellitus. All patients were treated with broad-spectrum antibiotic therapy. After a waiting time ranging one week to three months, all patients were successfully transplanted. General anaesthesia was induced with fentanyl, thiopental and pancuronium, and maintained with isoflurane supplemented by fentanyl in O2:air. Haemodynamic and oxygenation evaluations were made during the main phases of the transplant. After the intubation and at the end of the procedure all patients received a broncho-alveolar toilet through fiberoptic bronchoscopy. RESULTS: During anaesthesia for liver transplantation, PaO2 increased proportionally to the decreasing of Qs/Qt. In postoperative follow-up, Fev1 and FVC improved from preoperative time in all patients. In conclusion, even if cystic fibrosis is a multisystem disease, liver transplantation can be offered to CF patients with endstage liver disease and mild to moderate pulmonary function abnormalities. The four patients are still alive, enjoying good health. The improved respiratory function and quality of life of these children is remarkable.

Kidneys derived from mice transgenic for human complement blockers are protected in an in vivo model of hyperacute rejection.

PURPOSE: The major obstacle to successful discordant kidney xenotransplantation is hyperacute rejection (HAR). Complement plays a key role in the induction of HRA, defined by endothelial cell activation, loss of vascular integrity, hemorrhage and thrombosis. The activation of complement is tightly controlled by a number of species-specific regulatory proteins which inhibit, at different points, the cascade of events leading to the formation of the membrane attack complex (MAC). We have tested the hypothesis that kidneys derived from transgenic mice expressing two human complement inhibitors, Decay Accelerating Factor (hDAF) and Membrane Cofactor Protein (MCP), could be protected from human complement-mediated damage. MATERIALS AND METHODS: Control and transgenic mice were perfused with human plasma by cannulation of the right jugular vein, at a perfusion rate of 10 microL./min. for two hours. Complement C3 deposition was detected on kidney sections by immunohistochemistry using specific FITC antibody. Complement-induced tissue damage was evaluated by histopathological examination. RESULTS: Heavy deposition of complement C3 was observed on kidneys derived from perfused control mice. This was associated with a characteristic HAR pathology of severe interstitial hemorrhage, inflammatory reaction, loss of glomerula and tubuli structure. Kidneys derived from mice transgenic for hDAF or hMCP were partially protected from both complement C3 deposition and tissue damage. The expression of both hDAF and hMCP in double transgenic mice significantly increases the protection from human complement-mediated damage. CONCLUSION: A novel model of in vivo perfusion with human plasma has been adopted to recreate the initial event of HAR. Our data show that this murine model could be very valuable to determine the effect of transgenic human molecules in protecting vascularized organs from human complement attack.

Kidney transplantation from living unrelated donors.

Our center activated our living-related donor (LRD) kidney transplantation program in 1967 and the living-unrelated donor (LURD) kidney transplantation program in 1968. We performed 62 kidney transplants (of which 6 were LURD) under conventional immunosuppression therapy of the period. During the cyclosporine era, our group performed the first living-donor kidney transplant in 1982 and the first LURD transplant in Europe in 1983. Since then 184 LURD transplants (1/3 of all living kidney transplants) took place in our center under cyclosporine therapy. LURD remains a controversial procedure as a consequence of problems related both to the donor's risk, which can be reduced by careful medical evaluation and selection, and to the recipient's outcome, including the importance of HLA compatibility, as well as concerns about the danger of commercialism. According to international evidence, as well as our own experience, LURD kidney transplantation is a safe and effective approach to increase the donor pool. Living donor mortality is extremely low, while long-term graft survival is the same as that observed after LRD transplantation and is superior to that for cadaver donor transplantation. We do not recommend DST because the long-term survival benefits do not justify the risks of sensitization and infections. At least for primary transplants, there is not an increased risk of transplantation from a husband to his wife with previous pregnancies. The pretransplant screening of taboo HLA mismatches could be useful to increase long-term graft survival. It is our opinion that LURD transplantation should be considered at least as good a clinical option as cadaver donor transplantation for patients with end-stage renal failure. A selective advantage of this procedure is that dialysis could be avoided before transplantation, with significant socio-economic benefits and improved recipient quality of life.