A. Rossetto

Cardiovascular risk factors and immunosuppressive regimen after liver transplantation.

Cardiovascular and metabolic diseases represent important long-term complications after liver transplantation (LT), impairing long-term and disease-free survivals. A few mechanisms underlie the development of those complications, but the role of immunosuppressive drugs is major. Although several patients develop temporary metabolic diseases, which normalize after a short postoperative period and do not need long-term drug therapy, the incidences of de novo long-lasting arterial hypertension, hyperlipidemia, and diabetes mellitus are high during the first year after LT. The aim of this retrospective study was to evaluate new-onset arterial hypertension, hyperlipidemia, or diabetes among 100 LT patients at a single institution. We used chi-square statistical analysis to compare incidences during tacrolimus versus cyclosporine therapy. Hypertension did not seem to be more strongly related to tacrolimus than to cyclosporine, nor did diabetes, whereas there was a difference for the development of hyperlipidemia.

Long-Term Outcomes of Orthotopic Liver Transplantation in Human Immunodeficiency Virus–Infected Patients and Comparison With Human Immunodeficiency Virus–Negative Cases

Human immunodeficiency virus (HIV) positivity is no longer a contraindication for orthotopic liver transplantation (OLT) due to the efficacy of antiretroviral therapy. The aim of this study was to compare OLT among HIV-positive and HIV-negative cohorts; the results were also stratified for hepatitis C virus (HCV) coinfection. Between 2004 and 2009, all HIV-infected patients undergoing OLT from heart-beating deceased donors (n=27) were compared with an HIV-negative cohort (n = 27). The pure HCV infection rate was similar between HIV-positive and HIV-negative subjects (63% each). HIV-positive recipients were younger (P=.013). The CD4 count for HIV-positive subjects was 376 ± 156 at transplantation. The mean model for end-stage liver disease (MELD) score at transplantation was 15 ± 7 in both groups (P=.92). No differences were observed for donor age (P=.72) or time on the waiting list (P=.56). The median follow-up was 26 (range, 1-64) and 27 months (range, 1-48) for HIV and non-HIV recipients, respectively (P=.85). The estimated 1-, 3-, and 5-year patient and graft survival rates were 88%, 83%, and 83% versus 100%, 73%, and 73% (P=.95), and 92%, 87%, and 87% versus 95%, 88%, and 88% (P=.59) for HIV and non-HIV cases, respectively. HIV/HCV-coinfected patients were younger, namely 47 (range, 40-53) versus 52 years (range, 37-68; P=.003), and displayed lower MELD scores at transplantation compared with HCV-mono-infected patients 10 (range, 7-19) versus 17 (range, 8-30) (P=.008). For HIV/HCV-coinfected and HCV-mono-infected cases the estimated 1-, 3-, and 5-year patients and graft survival rates were respectively 93%, 76%, and 76% versus 100%, 70%, and 60% (P=.99) and 93%, 84%, and 84% versus 100%, 70%, and 60% (P=.64), respectively. No difference was observed in the histological severity of HCV recurrence. In conclusion, under specific, well-determined conditions, OLT can be a safe, efficacious procedure in HIV patients.

Safety of Conversion From Twice-Daily Tacrolimus (Prograf) to Once-Daily Prolonged-Release Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Nonadherence to immunosuppressive regimens among solid organ transplantation to range has been estimated from 15% to 55%. This problem has been identified as a leading cause of preventable graft loss. Tacrolimus once daily Advagraf has been developed to provide a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily tacrolimus (Prograf) to Advagraf in 36 stable liver transplant recipients. The tacrolimus whole blood trough level at T0 was 6.7 +/- 2.9 ng/mL with a daily dose of 3.7 +/- 1.8 mg. The mean tacrolimus blood trough levels at T1 (7 days) and T2 (14 days) were 5.8 +/- 2.5 and 5.8 +/- 1.8 ng/mL with mean daily doses of 3.9 +/- 1.9 and 4.1 +/- 1.8 mg, respectively. There was no significant difference between T0, T1, and T2, either for tacrolimus blood trough levels or for tacrolimus daily dosages. Liver and renal function tests remained stable; no episodes of acute rejection were encountered after the conversion. A switching policy using a dose ratio of 1:1 from twice-daily tacrolimus to once-daily prolonged-release tacrolimus was safely applied to stable liver transplant recipients.

Steatosis of the graft is a risk factor for posttransplantation biliary complications.

BACKGROUNDnDespite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles heel of liver transplantation. The aim of this study was to retrospectively analyze the incidence of biliary complications and identify predisposing risk factors.nnnMETHODSnFrom January 2004 to December 2007, 117 consecutive deceased donor liver transplantations were retrospectively analyzed for the development of biliary complications by review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74).nnnRESULTSnThe overall biliary complication rate was 36.8%; leakage 6% and stricture 30.8%. Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (P = .037) and macrovacuolar steatosis of the graft >25% (P = .004). A stepwise logistic regression model demonstrated that >25% macrosteatosis of the graft was the only independent risk factor predicting biliary complications after liver transplantation (odds ratio [OR] = 5.21; CI 95% [1.79-15.15]; P = .002). No differences were noted in patient or graft survival between the 2 groups.nnnCONCLUSIONnTransplantation of a liver with >25% steatosis was a risk factor for the development of a biliary complication.

Elderly Versus Young Liver Transplant Recipients: Patient and Graft Survival

The indications for organ transplantation continue to broaden with advances in perioperative care and immunosuppression. The elderly have especially benefited from this progress; advanced age is no longer considered a contraindication to transplantation at most centers. Although numerous studies support the use of renal allografts in older patients, only a few centers have addressed this issue as it pertains to liver transplantation. Published studies have revealed that operative course, length of hospitalization, and incidence of perioperative complications among patients older than 60 years of age are comparable with their younger adult counterparts. In our study we analyzed the clinical experiences of two centers with primary cadaveric orthotopic liver transplantations comparing patients older than 63 with patients younger than 40 years of age, suggesting no difference in unadjusted survival with age stratification. Now age cannot be considered to be a contraindication to liver transplantation.

Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation.

Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n=19) versus CPAr (group 2; n=21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P=.83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 ± 8 vs 37 ± 7 minutes; P<.001), while SPAr had a longer arterial ischemia 103 ± 42 vs 66 ± 8 minutes (P=.0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P=.29). At a median follow-up of 13 ± 6 versus 14 ± 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P=.78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P=.01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.

Protection of the intrahepatic biliary tree by contemporaneous portal and arterial reperfusion: results of a prospective randomized pilot study

Sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (LT), contemporaneous portal and arterial revascularization (CPAr) was used to reduce arterial ischemia to the bile ducts. Aim of this pilot study is to prospectively compare SPAr (group 1 #38) versus CPAr (group 2 #42) in 80 consecutive LTs. Biliary anastomosis was always duct to duct [T-tube in 21xa0% of cases (pxa0=xa00.83) in both groups]. CPAr had longer warm ischemia 61xa0±xa010 versus 39xa0±xa013xa0min, pxa0<xa00.0001, while SPAr had longer arterial ischemia 96xa0±xa039xa0min (pxa0=xa00.0001). No PNF while DGF was encountered in 10 versus 5xa0% (pxa0=xa00.32). One-year graft and patient’s survival were respectively 87 versus 93xa0% and 83 versus 88xa0% in groups 1 and 2 (pxa0=xa00.31 and pxa0=xa00.39). At a median follow-up of 19xa0±xa08 versus 17xa0±xa08xa0months (pxa0=xa00.24), biliary complications were 28xa0%, being 39xa0% in group 1 and 19xa0% in group 2 (pxa0=xa00.04). Anastomotic stenoses were present in 11 versus 12xa0% (pxa0=xa00.84), biliary leakage in 5 versus 5xa0% (pxa0=xa00.72) and intrahepatic non-anastomotic biliary strictures in 23 versus 0xa0% (pxa0=xa00.0008) in groups 1 and 2. CPAr is safe and feasible and reduces the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.

Contemporaneous Portal-Arterial Reperfusion during LiverTransplantation: Preliminary Results

We prospectively compared sequential portal-arterial revascularization (SPAr, group 1 no. 19) versus contemporaneous portal-hepatic artery revascularization (CPAr, group 2 no. 21) in 40 consecutive liver transplantation (LT). There were no differences in the demographics characteristics, MELD score, indication to LT, and donors parameters between the two groups. CPAr had longer warm ischemia 66 ± 8 versus 37 ± 7 min (P < .001), while SPAr had longer arterial ischemia 103 ± 42u2009min (P = .0004). One-year patients and graft survival were, respectively, 89% and 95% versus 94% and 100% (P = .29). At median followup of 13 ± 6 versus 14 ± 7 months biliary complications were anastomotic stenosis in 15% versus 19% (P = .78), and intrahepatic nonanastomotic biliary strictures in 26% versus none (P = .01), respectively, in SPAr and CPAr. CPAr reduces the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia.

De Novo Solid Tumors After Kidney Transplantation: Is It Time for a Patient-Tailored Risk Assessment? Experience From a Single Center

BACKGROUNDnProgress in immunosuppressive therapy and perioperative techniques has improved the survivals of both grafts and patients. The patient, however, is exposed to the risks of aging and side effects of immunosuppression. De novo tumors are the 2nd cause of death in the organ transplant population. The aim of this study was to evaluate whether the current accepted guidelines for the pre-transplantation study and the post-transplantation follow-up have been effective, in our kidney transplant population, regarding early detection and treatment, improving prognosis, and reducing mortality of some curable neoplastic diseases.nnnMETHODSnWe considered de novo tumors in kidney transplant patients from 1995 to 2010 (nxa0= 636) excluding hematologic and nonmelanoma skin tumors from our study.nnnRESULTSnThere were 64 de novo tumors in 59 patients out of 636 kidney transplant patients; 29.68% were urogenital cancer, 26.56% gastrointestinal cancer, 12.5% melanoma, 6.25% lung cancer, 6.25% biliopancreatic cancer, 4.68% visceral Kaposi sarcoma, 4.68% breast cancer, 4.68% thyroid cancer, 1 pleural mesothelioma, 1 meningioma, 1 merkeloma. Twenty patients died because of cancer. Ten patients had a late de novo tumor diagnosis, when the stage of tumor was advanced and not suitable for curative treatment.nnnCONCLUSIONSnBecause of the increased neoplastic risk, we consider it mandatory to carry out a meticulous screening and to implement pre-transplantation study concerning this increased neoplastic risk population to detect a subgroup of patients presenting the highest risk to improve their outcome.

Kidney Transplanted Population and Risk for De Novo Tumors. Is itPossible to Improve the Outcome? Definition of a Personal Risk Score

Also solid tumors have increased incidence in transplant population than in general population; many studies have shown that the transplanted organ is related to different rate of risk for different kind of solid tumors [1,4]. In a previous study about de novo solid tumors (excluding skin non melanoma cancer) of our group we found that urogenital cancer and gastrointestinal cancer were the most occurring solid cancer in the kidney transplant population at the center of Udine [5].