Elena Torri

Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients.

Background. Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. Tauroursodeoxycholic acid (TUDCA), a natural amidated hydrophilic bile salt, protects from cholestasis and hepatocellular damage in a variety of experimental models, as well as from ischemia-reperfusion injury. We investigated in the human liver transplantation setting the effect of the addition of TUDCA at time of liver harvesting and cold storage on the intra- and postoperative enzyme release and liver histopathology at the end of cold storage, at reperfusion, and 7 days after transplantation. Methods. Eighteen patients undergoing elective liver transplantation were studied, including 6 serving as controls. In six patients, TUDCA was added to the University of Wisconsin solution used during harvesting and cold storage, to reach final concentrations of 2 mM. In three of these patients, TUDCA (3 g) was infused in the portal vein of the donor before organ explantation; in the other three cases, TUDCA was given through both routes. Results. The use of TUDCA did not cause adverse events. The release of aspartate aminotransferase in the inferior vena cava blood during liver flushing was significantly lower (P =0.05) in TUDCA-treated than in control grafts, as were cytolytic enzyme levels in peripheral blood during the first postoperative week (P <0.02). At electron microscopy, an overt endothelial damage (cytoplasmic vacuolization, cell leakage, and destruction with exposure of hepatocytes to the sinusoidal lumen) was invariably found in control grafts, both at reperfusion and at day 7 after transplant. These features were significantly ameliorated by TUDCA (P <0.001). Several ultrastructural cytoplasmic abnormalities of hepatocytes were seen. Among these, damage to mitochondria matrix and crystae was significantly reduced in TUDCA-treated versus control grafts (P <0.01). Mild to severe damage of bile canaliculi was a constant feature in control biopsies, with dilatation of canalicular lumen and loss of microvilli. Both these abnormalities were markedly ameliorated (P <0.001 by TUDCA). The best preservation was observed when TUDCA was given through both routes. Conclusions. The use of TUDCA during harvesting and cold storage of human liver is associated with significant protection from ischemia-reperfusion injury. The clinical significance of this findings must be studied.

Gigantomastia and breast lumps in a kidney transplant recipient

KIDNEY transplantation (Tx) is the treatment of choice for chronic renal failure. A successful graft permits recovery of renal function and a good quality of life, both being seriously compromised by the disease and the haemodialytic therapy. From the first hours after the operation, patients must receive several drugs to prevent rejection and infections, many immunosuppressive regimens are adopted worldwide. The most commonly used is the triple therapy with cyclosporine A (CyA), prednisolone (P), and azathioprine (A). The former two drugs are demonstrated to interfere with the neuroendocrine system, being able to alter the function of different organs and to modify hormone blood levels. Kidney graft recipients are prone to develop high arterial blood pressure (ABP); and despite advances in patient management, the prevalence of posttransplant hypertension (HT) is about 50%. As HT is known to deteriorate renal function, ABP should be kept in the normal range values. Calcium antagonists (CA) are preferred to regulate ABP. Unfortunately, they also somehow interfere with the neuroendocrine system. In this paper, we describe the case of a woman who, a few years after undergoing a cadaver kidney transplant, developed gigantomastia in association with two lumps.

Effect of steroids amount on hepatitis C recurrence following orthtopic liver transplantation.

ONE of the leading causes for orthotopic liver transplantation (OLTx) is hepatitis C. The presence of viremia post-transplant is reported in 95% of patients; one year after OLTx and 30% to 70% of recipients develop histopathologic recurrence of HCV. The intensity of immunosuppression correlates with viral replication. The number of acute rejection episodes correlated with recurrence of HCV (HCV-R). Feray et al reported a positive correlation of the amount of serum HCV-RNA and the occurrence of hepatitis in the transplanted liver, suggesting that intense HCV replication causes severe histological damage. In agreement there is a recent publication which shows how high serum HCV-RNA levels are associated with severe graft damage. The aim of this study is to correlate histologic recurrence of hepatitis C with the administration of steroids in a group of patients who underwent OLTx for the HCV induced cirrhosis.

Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis

Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation. We investigated the efficacy of a reinforced triple course of HBV vaccination in 17 patients transplanted for HBsAg-positive cirrhosis 2 to 7 years earlier. The first cycle consisted of 3 double intramuscular doses (40 microg) of recombinant vaccine at month 0, 1, and 2, respectively. This was followed, in nonresponders, by a second cycle of 6 intradermal 10 microg doses every 15 days. All nonresponders then received a third cycle identical to the first one. Vaccination started 4.5 months after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. All patients were seronegative for HBsAg and HBV-DNA (by PCR) and positive for anti-HBe, and 7 were positive for anti-HDV. After the first cycle one patient (#5, 53 years old, male) developed an anti-HBs titer of 154 IU/L, another (#12) reached a titer of 20 IU/L and the remainder had titers <10 IU/L. At month 7, patient #5 reached a titer of 687 IU/L. After the second cycle only one additional patient (#9) had a slight response (an anti-HBs titer of 37 IU/L). After the third cycle patient #9 rose to an anti-HBs titer of 280 IU/L, patient #12 dropped to 10 IU/L, and no other patient responded. In conclusion, a highly reinforced HBV vaccination program is effective only in a few patients who had liver transplants for HBV-related cirrhosis.