Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.

How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27-24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study.

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients.

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

The recipient with portal thrombosis and/or previous surgery.

INTRODUCTION: Portal vein thrombosis (PVT) has been considered to be an absolute contraindication to liver transplantation (OLT) and previous upper abdominal surgery was considered to render it a high-risk procedure. Currently, these are only conditions considered risk factors increasing recipient morbidity and mortality. The objective of this study was to compare OLT perioperative morbidity, mortality, blood product consumption, and length of hospital stay among patients with or without PVT or with or without previous surgery. MATERIALS AND METHODS: Among 366 OLTs performed between July 1999 and November 2007, 33 liver transplant recipients displayed previous PVT while 34 had undergone previous surgery. The two groups of marginal recipients were compared with a cohort of 33 patients without PVT or previous surgery. RESULTS: The groups were homogeneous in terms of epidemiological variables, surgical techniques, and donor-related variables. In the PVT group, all analyzed parameters were the same as the control group; surgical time, anhepatic phase duration, early surgical complication, intensive care unit and hospital length of stay, and overall mortality. The only significant difference was the incidence of portal rethrombosis (P < .035). Among the previous surgery group, we did not observe significant differences. CONCLUSIONS: PVT and previous surgery should no longer be considered contraindications for OLT.

The role of basiliximab induction therapy in adult-to-adult living-related transplantation and deceased donor liver transplantation: a comparative retrospective analysis of a single-center series.

AIM: The aim of this study was to report our single-center experience with the use of basiliximab, in combination with a steroid and tacrolimus-based regimen in adult to adult living-related liver transplantation (ALRLT) and in deceased donor liver transplantation (DDLT). MATERIALS AND METHODS: Seventy-seven consecutive ALRLT recipients (group 1) and 244 DDLT recipients (group 2) were analyzed. All patients received 2 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and a dose regimen of steroids. Follow-up ranged from 4-1972 days after transplantation in group 1 and from 1-2741 days in group. RESULTS: In group 1, 89.32% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.51% within 3 months. Actuarial patient survival rate at 3 years was 84.49%. In group 2, 86.07% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.04% within 3 months. Actuarial patient survival rate at 3 years was 87.69%. We observed 14 cases of hepatitis C virus (HCV) recurrence in group 1 (prevalence of 26.92%) and 80 cases in group 2 (prevalence of 54.05%). CONCLUSION: Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of acute cellular rejection (ACR) and increasing ACR-free survival after ALRLT and DDLT. No difference in patient and graft survival was found between group 1 and 2, nor was there any difference in the incidence of ACR between the 2 groups. However, less risk of HCV recurrence was present in the LRLT group.

Liver transplantation using donors older than 80 years: a single-center experience.

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.

Acute cellular rejection monitoring after intestinal transplant: utility of serologic markers and zoom videoendoscopy as support of conventional biopsy and clinical findings.

Acute cellular rejection (ACR) episodes in intestinal transplant recipients are diagnosed by histologic and clinical findings. We have applied zoom video endoscopy and the use of serologic markers granzyme B (GrB) and perforin (PrF) to monitor rejection together with conventional tools. Seven hundred eighty-two blood samples (obtained at the time of the biopsy) collected from 34 recipients for GrB/PrF upregulation were positive among 64.9% of ACRs during a 3-year follow-up. Considering only the first year results posttransplantation, it reached 73.1% of rejection events. Zoom videoendoscopy was used by our group in 29 recipients of isolated intestine (n = 24) or multivisceral transplantations (n = 5) to enable observation of villi and crypt areas. From more than 270 procedures, 84% of the zoom findings agreed with the histologic results, namely, a specificity of 95%. In fact, during ongoing ACR, villi were altered in 80% of cases. Both procedures were helpful to support conventional histologic findings and clinical symptoms of ACR in intestinal transplant recipients.

Postoperative hepatic artery aneurysms development and remodeling in Ehlers-Danlos syndrome type IV. Case report.

Patients affected by Ehlers-Danlos syndrome (EDS) type IV are at risk for aneurysm formation and rupture. This case report shows the extreme vascular fragility of these patients. We studied a 31-year-old man that developed hepatic artery aneurysms 3 weeks after splenectomy. Computed tomography angiography showed the extreme vascular remodeling of the aneurysms. We conclude that remote site complications should be kept in mind by all surgeons in vascular EDS patients even after general surgery operations.

Adult to adult living-related liver transplant: report on an initial experience in Italy.

INTRODUCTION: Living-related liver transplantation has become the treatment of choice for many liver diseases. We present our initial analysis of 53 cases of adult to adult living-related liver transplantation performed in a single institute in Italy. MATERIALS AND METHODS: From January 2002 to September 2006, we performed 53 adult to adult living-related liver transplantations. The donors (age 18-53) all had genetic or emotional relationships; they were all ABO identical or compatible. Recipients (ages 18-68) suffered from cirrhosis secondary to viral etiology (18), hepatocellular carcinoma with viral cirrhosis (24), cystic fibrosis (2), primary biliary cirrhosis (2), hepatocellular carcinoma with non-viral cirrhosis (2), alcoholic cirrhosis (1), ornithine transcarbamylase deficiency (OTC), (1) criptogenic cryptogenic cirrhosis, (1) primary sclerosing cholangitis, (1) biliary atresia and metastatic carcinoid (1). Donor liver resection resulted in 51 right hepatectomies and two left hepatectomies. Graft body weight ratio was always above 0.8%; graft implantation was performed with the piggy back technique and, in 43 cases, with the use of veno-venous bypass. RESULTS: There was neither donor mortality nor need of blood transfusion. Actuarial recipient survival rate at 3 years was 82.66% and graft survival rate was 75.34%. Six patients underwent retransplantation: in four cases due to hepatic artery thrombosis, and in two, due to graft dysfunction. Three patients had one episode each of acute cellular rejection. CONCLUSION: Adult to adult living-related liver transplantation represents a resource to be used in confronting organ shortage, and is a valuable option for decreasing mortality and drop out from the waiting list.

In situ split liver transplantation for adult and pediatric recipients: an answer to organ shortage.

BACKGROUND: We report our initial experience with in situ split liver transplantation (SLT) for adult and pediatric patients. PATIENTS AND METHODS: From June 2003 to August 2005, 177 liver transplantations in 165 patients, 133 adults (81%) and 32 children (19%), were performed at our institution. Over this period, 45 liver transplantations (25%) were performed with an in situ split liver technique in 44 patients: 17 (39%) were adults and 27 (61%) children. All of the adult split liver recipients were transplanted with an extended right graft (ERG; segments I + IV-VIII), while pediatric recipients received in 23 cases a left lateral segment (LLS; segments II-III) and in 4 cases an ERG from a pediatric donor. The 45 split liver grafts (21 ERGs and 24 LLSs) were generated from 35 donors. In 10 cases we used both grafts generated with an in situ split procedure to transplant our patients, while in 25 cases the procurement procedure was performed in collaboration with other transplant centers. RESULTS: After a median follow-up of 9 months (range, 1-27 months), the overall patient survival rate was 88% for adult patients and 82% for pediatric patients. Graft survivals were 88% and 79%, respectively. Two adult patients (12%) died from sepsis in the early postoperative period. Five children (18%) died after their transplantations. Only one pediatric recipient (2%) of primary SLT underwent retransplantation. Vascular complications were absent in adult recipients, whereas 4 arterial (14%) and 4 venous (14%) complications developed in the pediatric population. The incidence of biliary complications was 23% in adult and 18% in pediatric recipients. CONCLUSIONS: The use of in situ SLT for adult and pediatric populations allowed us to expand the cadaveric donor pool, significantly eliminating pediatric waiting list mortality without penalizing the adult population.

Corticosteroid-free immunosuppression in pediatric liver transplantation: safety and efficacy after a short-term follow-up.

BACKGROUND: We report our results with the use of corticosteroid-free immunosuppression after pediatric liver transplantation, evaluating the efficiency and safety of this protocol in the early posttransplantation period. PATIENTS AND METHODS: From July 2003 to October 2005, 34 liver transplantations were performed in 32 pediatric patients (19 boys, 13 girls) at our institution. Recipient median age was 5 years (range, 0.2-14 years), and median body weight was 10 kg (range, 4-49 kg). Twenty-seven patients received a graft from in situ split liver transplantation, 5 a whole graft. Twenty-nine children (90%) received an immunosuppressive therapy based on methylprednisolone IV bolus at reperfusion (10 mg/kg) plus tacrolimus given at an initial dose of 0.08 mg/kg/d and then adjusted to obtain whole blood trough levels of 10 to 15 ng/mL during the first 3 months and 5 to 10 ng/mL after the 3rd month; basiliximab was given on postoperative days 0 and 4. Biopsy-proven acute rejection episodes were treated by methylprednisone IV boluses. RESULTS: After a median follow-up of 9 months (range, 1-27 months), the overall patient survival rate was 84% and graft survival rate was 79%. Three children (9%) died after their transplantations. Three (9%) experienced episodes of biopsy-proven acute rejection, always treated with IV steroid boluses. Mean RAI score was 4. One patient experienced PTLD that resolved with temporary reduction of immunosuppression. Cytomegalovirus infection rate was 14%. Sepsis occurred in 2 cases (6%). CONCLUSIONS: Initial results with a steroid-free immunosuppressive protocol are encouraging, with low rates of acute rejection and infectious complications as in steroid-based protocols.

New model of liver regeneration induced through use of vascular endothelial growth factor.

INTRODUCTION: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen. The objective of this study was to verify the proregenerative effects of VEGF in an experimental model of acute liver failure. MATERIALS AND METHODS: Sixty four rats that underwent intraperitoneal injection of carbon tetrachloride (CCl(4)) were randomly divided into two groups: group B animals received intravenous injection of VEGF(164) 1 hour following CCl(4) poisoning. Group A hosts were untreated. To obtain daily liver function tests (LFTs) and histological samples, on each day up to 8 days we sacrificed four rats in each group. RESULTS: The laboratory examinations showed notable alteration of LFTs in group A, while group B revealed only slight changes. The histological examination showed greater liver damage in group A compared with group B. CONCLUSION: Our results suggest that administration of exogenous VEGF protects the liver from CCl(4)-induced acute hepatic failure. Further studies are underway to assess whether exogenous VEGF is effective in other liver injuries.

A safe immunosuppressive protocol in adult-to-adult living related liver transplantation.

BACKGROUND: In this series of 32 adult-to-adult living related liver transplantations, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen. Basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for cadaveric liver transplant recipients. PATIENTS AND METHODS: Thirty-two adult-to-adult living related liver transplantations were performed in the last 3 years. All patients received two 20 mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and steroids (starting with 20 mg IV switched to PO as soon as the patient was able to eat and weaned within 1-2 months). The average follow-up was 395 days after transplantation. RESULTS: Of the patients, 93.75% remained rejection-free during follow-up with an actuarial rejection-free probability of 92.59% within 3 months. Two patients (6%) had one episode of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.85% and 81.25%. One patient (3%) experienced one episode of sepsis. There was no evidence of cytomegalovirus infections or side effects related to the basiliximab. We found zero de novo malignancy but we observed two patients with metastatic spread of their primary malignancy during the follow-up. CONCLUSION: Basiliximab in association with tacrolimus and steroids is effective as prophylaxis of ACR among adult living related liver transplant recipients.

Improvements in hepatic parenchymal transection for living related liver donor.

INTRODUCTION: To eliminate mortality and morbidity risk in living related liver donors, we developed a new surgical technique to resect hepatic parenchyma using an ultrasonic surgical aspirator in association with a monopolar floating ball cautery. METHODS: We performed 17 right hepatectomies and 2 left hepatectomies using this technique. We performed a retrospective analysis of perioperative mortality, length of hospitalization (LOS), blood transfused during surgery (IBT), intraoperative blood lost (IBL), biliary complications (BC), and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) peak in the first postoperative week. This group of patients (Group A) was compared, using the analysis of variance (ANOVA) test (P < .05) with 2 different groups of 19 patients: Group B with liver neoplasms that had the same technique as Group A, and Group C wherein a crushing clamp technique was used. RESULTS: All of the analyzed variables showed significative statistical differences, especially between Group A and Group C (IBL, P < .000; IBT, P < .006; LOS, P < .028; BC, P < .000; AST peak, P < .041; and ALT peak, P < .023). DISCUSSION: The association of these 2 techniques seems to reduce the LOS, and the need for intraoperative blood transfusions. Moreover, the surgical complications (biliary leaks) and the postoperative parenchymal cytonecrosis seem to be less using this technique.

Basiliximab in a triple-drug regimen with tacrolimus and steroids in liver transplantation.

BACKGROUND: Basiliximab, a chimeric monoclonal antibody (mAb) directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for kidney transplant recipients, more frequently in combination with a cyclosporine-based regimen. In this study, we assessed the efficacy and safety of basiliximab in combination with tacrolimus and steroids following liver transplantation. METHODS: One hundred fifty-two liver transplant recipients (141 cadaveric donors and 11 living donors [LRLT]) in the last 4 years were treated with 2 20-mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and steroids (500 mg intravenous [IV] bolus at the reperfusion followed by 20 mg orally daily and weaning off in 1 or 2 months). Follow-up ranged from 104 to 1630 days after transplantation (mean, 665 days; SD +/- 442.65; median, 509 days). RESULTS: Eighty-five percent of patients remained rejection-free during follow-up with an actuarial rejection-free probability of 78% within 3 months. Nineteen patients had 22 episodes of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.7% and 75.8%, respectively. Twenty-seven patients (20.6%) experienced 1 episode of sepsis, requiring temporary reduction of immunosuppressive therapy. There was no evidence of CMV infections or side effects related to basiliximab. We observed 2 de novo malignancies, 1 recurrence from an ileal carcinoid tumor and 1 pulmonary recurrence of hepatocellular carcinoma (HCC) in 1 recipient of LRLT. CONCLUSIONS: Basiliximab in association with tacrolimus and steroids is effective prophylaxis of ACR in liver transplant recipients and does not increase the incidence of infections or adverse effects.

Acceptance of marginal liver donors increases the volume of liver transplant: early results of a single-center experience.

To expand the donor pool, clinicians are continually modifying criteria to accept organs, particularly those in the so-called expanded or marginal donor pool. The concept and definition of a marginal donors continues to evolve. The impact of their use is the result of a combination of donor and recipient factors. Most clinicians accept steatosis above 30%, donor age over 60 years, prolonged ischemia time, prolonged intensive care unit stay, hypernatremia, previous cardiac arrest, prolonged episodes of hypotension, large use of inotrope drugs, and elevated liver function tests as criteria for designation of a marginal organ. In June 2003, we started to use marginal donors each year tripling the number of transplants per year at our center.

Transjugular intrahepatic portosystemic shunt in adult liver recipient with delayed graft function.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has become an effective treatment for the complications of portal hypertension. We assessed the feasibility and outcome of TIPS in liver transplant recipients who developed delayed graft function (DGF) with portal hypertension. METHODS: From June 2003 to June 2004, 80 cadaveric orthotopic liver transplantation (OLTx) have been performed at our institution. Five patients (6.25%) developed DGF with hyperbilirubinemia and ascites with severe portal hypertension and were treated with TIPS placement (in the 6-month time period from the transplantation). RESULTS: There were no complications related to the procedure. No episodes of encephalopathy were seen. Four patients had better control of the ascites. In one case, we observed complete recovery of the transplanted liver with normalization of the liver function test. Three patients underwent retransplantation (within 7 days from the TIPS), whereas 1 is still on the list 6 months after TIPS placement with recurrent episodes of ascites. CONCLUSIONS: In our preliminary series, TIPS reduced dramatically the portosystemic gradient and improved clinical conditions. The results were negatively affected by the fact that the transplanted liver did not recover its function.