Giuseppe Piccolo

A prospective policy development to increase split-liver transplantation for 2 adult recipients: Results of a 12-year multicenter collaborative study

Objective:To analyze in a multicenter study the potential benefit of a new prospective policy development to increase split-liver procedures for 2 adult recipients. Background:Split-liver transplantation is an important means of overcoming organ shortages. Division of the donor liver for 1 adult and 1 pediatric recipient has reduced the mortality of children waiting for liver transplantation but the benefits or disadvantages to survival when the liver is divided for 2 adults (adult-to-adult split-liver transplant, AASLT) compared with recipients of a whole graft have not been fully investigated. Methods:We developed a computerized algorithm in selected donors for 2 adult recipients and applied it prospectively over a 12-year period among 7 collaborative centers. Patient and graft outcomes of this cohort receiving AASLT either as full right grafts or full left grafts were analyzed and retrospectively compared with a matched cohort of adults who received a conventional whole-liver transplant (WLT). Univariate and multivariate analysis was done for selected clinical variables in the AASLT group to assess the impact on the patient outcome. Results:Sixty-four patients who received the AASLT had a high postoperative complication rate (64.1% grade III and IV) and a lower 5-year survival rate than recipients of a WLT (63.3% and 83.1%) Conclusions:AASLT should be considered a surgical option for selected smaller-sized adults only in experimental clinical studies in experienced centers.

Interaction between calcineurin inhibitors and IL-28B rs12979860 C>T polymorphism and response to treatment for post-transplant recurrent hepatitis C

BACKGROUND The impact of calcineurin inhibitors on achievement of sustained virological response to antiviral therapy for post-transplant recurrent hepatitis C is controversial. This study aimed at investigating the interactions between calcineurin inhibitors and interleukin-28B (IL-28B) gene polymorphisms and sustained virological response. METHODS Retrospective study of 147 liver transplant recipients with recurrent hepatitis C, who received 48 weeks of peg-interferon-α (N=113) or standard interferon (N=34), in association with ribavirin. Cyclosporine and tacrolimus were administered in 68 and 79 patients, respectively. IL-28B rs12979860 allele frequency was assessed in both donors and recipients. RESULTS Overall, 57 patients (38.8%) obtained sustained virological response; no difference was found between cyclosporine and tacrolimus-treated patients (42.6% vs. 35.4%, p=0.371). Recipient and donor IL-28B genotypic frequencies were C/C=30.6%, C/T=51.7%, T/T=17.7% and C/C=44.9%, C/T=50.3%, T/T=4.8%, respectively. Combining donor and recipient alleles, response rates decreased from cyclosporine-treated patients carrying ≤ 1 T allele (56.1%) to tacrolimus-treated patients carrying ≤ 1 T allele (44.7%) to patients carrying ≥ 2 T alleles (25.0%, p=0.0009). CONCLUSIONS Donor and recipient rs12979860 alleles synergistically influence sustained virological response rate to antiviral treatment for recurrent hepatitis C. In patients carrying <2 T alleles cyclosporine favours a better response than tacrolimus, while no difference was found in the presence of ≥ 2 T alleles.

Genetic Polymorphisms Influencing Therapy and Susceptibility to Rejection in Organ Allograft Recipients

Solid organ transplantation during the past 30 years has developed from an experimental procedure into routine clinical practice. The current repertoire of immunosuppressive agents has made a major contribution to transplant survival; however, problems in different areas still need to be overcome.Several gene polymorphisms are supposed to influence immunosuppressive therapy and susceptibility to rejection. Therefore, a priority of transplant biologists is to estimate individual patient risk and to characterise the genetic profile of patients in need of a transplant in order to optimise the use of a scarce resource such as organs from cadaver donors, and to avoid serious drug-induced adverse effects. Polymorphisms in genes encoding tumour necrosis factor-α (TNFα), interleukin (IL)-6, IL-10, interferon-γ (IFNγ), transforming growth factor-β (TGFβ) and thiopurine S-methyltransferase (TPMT) can have significant effects on an individual’s risk of rejection, as well as their ability to tolerate immunosuppressive therapy. Genotyping of known polymorphisms in these genes may in the future contribute to our ability to individualise immunosuppressive therapy in organ transplant recipients.

Organ transplantation from "increased infectious risk donors": the experience of the Nord Italia Transplant program - A retrospective study

The purpose of this study was to assess the safety and the clinical outcome associated with organ transplantation from increased infectious risk donors (IRD). We retrospectively identified all adult deceased IRD referred to the Nord Italia Transplant program coordinating center from November 2006 to November 2011. All potential donors were screened for social risk factors that may increase the risk of donor‐derived infection with human immunodeficiency (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). All recipients were followed monthly for the first 6 months post‐transplant. A total of 86 potential IRD were identified during the study period. Three hundred and seventy‐nine organs from IRD were offered to the transplant centers, but only 185 (48.8%) were used for transplantation. Organs from IRD were transplanted into 174 recipients. The complete follow‐up data were available for 152 of 174 (87.3%) recipients. During a mean follow‐up of 11.7 months (median 12; range 2.4–12), no transmission of HIV, HBV, or syphilis was documented by serology and nucleic acid testing (NAT) testing. Two patients transplanted with organs from HCV‐RNA‐positive donors, as expected, developed post‐transplant HCV infection. In conclusion, the use of organs from IRD was associated with a safe increase in the transplant procedures in our country.

Policies for Boosting Donor Enlistment in the North Italy Transplant Program Macro-area

The imbalance between patients on waiting list and organ availability is the core problem for the transplantation community and search for strategies to increase the number of donors is still the priority of all transplant organizations. North Italy Transplant program (NITp), the first italian transplant organization, was founded in 1972 and during 40-year activity 10229 donors have been used and 30573 organ transplants have been performed. In NITp, the identification of key steps to expand the donor pool and continous education programs, not only on the procurement side but also dedicated to all professionals involved in the donation-transplantation process, have allowed to reach these results.

CRYOPRESERVED HUMAN HEPATOCYTES FROM CELL BANK: IN VITRO FUNCTION AND CLINICAL APPLICATION

UNLABELLED We Aimed to analyze the in vitro function of isolated and cryopreserved human hepatocytes (CHH) from a cell bank and to define their potential clinical application in a bioartificial liver (BAL) device. METHODS Over 24 months, 103 not transplantable livers were utilized for human hepatocytes isolation and cryopreservation. Hepatocytes isolated by collagenase were analyzed for yield, viability, diazepam metabolism, and production of human albumin after isolation and cryopreservation in LN(2). RESULTS The causes for refusal for transplantation were macrosteatosis >60%, ischemic damage due to donor hypotension, and nonviral cirrhosis in 60%, 11%, and 8%, respectively. Cell yields averaged 7 million hepatocytes per gram of liver of mean viability of 80% +/- 13%. The viability of CHH after thawing averaged 50%. Thawed hepatocytes showed diazepam metabolism, and human albumin synthesis comparable to fresh cells. CHH were utilized as the biological component of a BAL for temporary support as three applications of two patients affected by fulminant hepatic failure awaiting urgent transplant. Ten to 13 billion viable CHH were loaded into each BAL. Liver function showed bilirubin and ammonia reduction at the end of each treatment. One patient was successfully bridged to emergency OLTx after one BAL; in the second case there was spontaneous recovery of liver function after two BAL. CONCLUSIONS Recovery of donor human livers unwanted for transplantation allowed isolation and cryopreservation of viable and functionally active human hepatocytes, which have been banked and successfully used for clinical applications of a BAL device.

Donor organ procurement in the North Italy Transplant program (NITp) in 1994: the beginning of a promising trend?

Abstract  Donor organ procurement is a world‐wide problem. In Italy it is particularly so and the reasons for this are investigated. An overall increase in the number of donors has been noted in 1994 and the first 8 months of 1995, and ways of continuing this encouraging trend should be pursued by improvements in education, legislation, and hospital organization.