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.

Intra-Operative Contrast Cholangiography in Living Donor Liver Transplantation: The ISMETT Experience.

BACKGROUND: We evaluated the clinical impact of donor biliary anatomy discrepancies (DBAD) achieved by comparing pre-operative evaluation obtained with magnetic resonance (MR)/magnetic resonance cholangiopancreatography (MRCP) imaging, with intra-operative cholangiography (IOC) on the living related liver donor (LDLT) and recipient. METHODS: This single-center, retrospective study included 97 consecutive adult-to-adult (A2A) LDLT performed in our hospital in the last 12 years. Donor sex and age, living donors with biliary and/or vascular anomalies, recipient age, sex, primary etiology, re-transplantation, Model of End-Stage Liver Disease score, co-morbidities, arterial and biliary recipient complications assessed on the basis of clinical follow-up were collected and analyzed for significance through the use of a multivariate linear regression model. RESULTS: Biliary complications in the donor (DBC) were detected in 8 (8.2%) cases. Biliary complications in the recipients (RBC) were detected in 38 (39%) cases. DBADs were found in 32 (33%) cases and resulted strictly related to RBC (P = .05). CONCLUSIONS: After adjusting for co-variables, results of the linear regression analysis confirmed that DBAD is an independent predictor of RBC, but it is not significantly associated with vascular complications or patient survival. We showed that RBCs after LDLT were influenced by DBAD.

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.

Combined microwave thermal ablation and liver resection for single step treatment of otherwise unresectable colorectal liver metastases; a monoistitutional experiences.

OBJECTIVE: Over half of colorectal cancer patients will develop liver metastases. BACKGROUND: Thermal ablation with or without associated liver resection for colorectal hepatic metastasis has been suggested as an alternative method to improve survival if radical surgical resection is not achievable. A retrospective case series of patients treated with microwave ablation(MWA) associated with hepatic resection in one step procedure, was reviewed to analyze the clinical outcome. MATERIALS AND METHODS: In a group of 40 patients surgically cured for liver tumors in our Department, 5 patients with technically unresectable disease underwent combined treatment LR-MWA. RESULTS: Four patients were treated with multiple segmentectomies and MWA and one patient received a left lobectomy (S2-S3) and MWA. Only 1 patient (20%) developed post surgical complication which was a liver abscess (grade II of Dindo classification). CONCLUSIONS: Hepatic resection combined with MWA expanded indications for operative treatment of multiple bilobar liver metastasis. This procedure promise to have good long-term outcomes.

Evolution of surgical technique in conventional open hepatectomy for living liver donation over a 12-year period in a single center.

We report details of the experience from the largest Italian program with hepatic living donation, focusing particularly on the use of intraoperative ultrasound in liver transplantation and living donation. During a 12-year period we changed our surgical technique in the conventional open procedures thanks to the experience gained into the laparoscopic setting. Intraoperative ultrasound has been implemented during these delicate procedures for ensuring a fast and safer detection of the accessory veins and final severing of the vascular stumps during liver transection.

Recipient-donor age matching in liver transplantation: a single-center experience.

OBJECTIVE: The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching. METHODS: We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009. RESULTS: Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02-15.47; P = .046). CONCLUSIONS: The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients.

Two brothers with renal and hepatic polycystic disease treated with combined liver and kidney transplantation: a case report.

We report two brothers with renal and hepatic polycystic disease who developed end-stage renal failure, requiring hemodialysis, and organomegaly syndrome related to the gigantic size of the liver and both kidneys. Although there was no liver failure, combined liver and kidney transplantation was performed owing to worsening of the clinical condition. In both cases, successful transplantation was accomplished with intra-abdominal engraftment of the liver and kidneys through the same abdominal incision.

Marrow-derived mesenchymal stem cells restore biochemical markers of acute liver injury in experimental model.

Bone marrow-derived mesenchymal stem cells were investigated as prompters of liver regeneration in an experimental model of acute hepatic injury. A model was created in Wistar rats through intraperitoneal injection of carbon tetrachloride (CCl4). Bone marrow-derived mesenchymal stem cells collected from the long bones of 10 Wistar rats were intravenously infused 24 hours after induction of acute liver failure in 16 rats, group A. In group B, the control group, 16 rats received a peritoneal injection of CCl4, and an intravenous infusion of normal saline solution. All rats were sacrificed at 2, 3, 4, and 7 days post-CCl4 injection to examined biochemical markers and pathological appearances. The platelet counts were higher in group A versus group B on post-CCl4 infusion days 2 (P = .02) and 3 (P = .001), as were the transaminase trends in glutamic oxaloacetic (P = .002), and glutamic-pyruvic transaminases (P < .0001). Pathological examination showed a greater grade of hepatocellular necrosis with neutrophilic infiltration in group B (P = .02). In conclusion, infusion of bone marrow-derived mesenchymal stem cell resulted in a less aggressive picture of hepatic damage.

The Charlson comorbidity index as a predictor of outcomes in liver transplantation: single-center experience.

Several comorbidity indices, such as the Child-Turcotte-Pugh (CTP) score and the Model for End-Stage Liver Disease (MELD) score, have been used to optimize available organ resources and adjust priorities in diagnosis and allocation of grafts for patients who are candidates for liver transplantation. There have also been various attempts to create instruments to accurately predict outcomes after liver transplantation, but none has proved to be truly applicable, with the exception of the Charlson comorbidity index (CCI). We retrospectively reviewed data of 221 liver recipients, including living-related liver transplantation and multiple organ transplantation performed between January 2006 and September 2009. Survival analysis revealed a significant association of the CCI with decreased posttransplantation patient survival (P = .003). Furthermore, Kaplan-Meier plots and log-rank test showed a significant association between graft survival and the score (P = .039). Our data suggest that the CCI is a simple tool for the evaluation of comorbidity and that increased preoperative patient comorbidity increases the risk of graft loss and patient death after liver transplantation. The CCI should be considered an important tool for improving patient care because of its potential applications for patient management.

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.

Unusual presentation of left hepatic vein in deceased donor: case report.

An anomaly of the left hepatic vein was discovered in a deceased donor for whole liver transplantation. This vein was attached by a thin bridge of tissue to the suprahepatic inferior vena cava cuff, which received the right and middle hepatic vein in a common trunk. The left hepatic vein and the common trunk drained together into the right atrium. The thin bridge of tissue connecting the 2 independent vessels was severed, and ex situ reduction of the left lateral segments was using a harmonic scalpel. Although a graft with reduced size is not ideal, ex situ reduction should be considered a valuable option when viability of the left lateral segments is uncertain in the donor or at the back table.

Technical aspects of living-related liver donation: single-center experience.

Living-related donor liver transplantation is the newest and both technically and ethically most challenging evolution in liver transplantation and has contributed to reduction in donor shortage. We briefly report the technical aspects of surgical procedures performed to achieve a partial graft from a live donor. Eighty-four adult and two pediatric recipients underwent living-related donor liver transplantation at our center. There were no donor deaths, and all patients returned to their normal activities after the perioperative period. This single-center experience may contribute to refinement of the surgical technique required to improve the outcome of these complex operations.

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.