Enzo Andorno

Split and whole liver transplantation outcomes: A comparative cohort study

A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323 cases, respectively. SLTs were performed in situ as 147 left lateral segments (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers (MSL), used for couples of adult recipients. After a median posttransplant follow‐up of 22 months, SLTs achieved a 3‐yr patient and graft survival not significantly different from the entire series of transplants (79.4 and 72.2% vs. 80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed significantly better outcomes than patients receiving RTL and MSL (P < 0.03 for patients and P < 0.04 for graft survival). At the multivariate analysis, donor age of >60 yr, RTL transplant, <50 annual transplants volume, urgent transplantation (United Network for Organ Sharing (UNOS) status I and IIA), ischemia time of >7 hours, and retransplantation were factors independently related to graft failure and to significantly worst patient survival. Right grafts procured from RTL and either split procured as MSL had a similar outcome of marginal whole livers. In conclusion, in 5 yr, the increased number of pediatric transplants due to split liver donation reduced to 3% the in‐list children mortality, and a decrease in the adult patient dropout rate from 27.2 to 16.2% was observed. Such results justify a more widespread adoption of SLT protocols, organizational difficulties not being a limit for the application of such technique. Liver Transpl 12:402–410, 2006.

A new splitting technique for liver grafts

The in-situ split-liver (ISSL) technique allows the division of the liver of a cadaver donor in two parts that can be transplanted in two different patients. The two grafts obtained are different in size, the left one being generally suitable for transplantation only in small children. We describe here the successful use of an alternative technique, generating two grafts more similar in size, both of which are transplantable into adults or large children. The donor was a brain-dead 33-year-old man 164 cm tall and weighing 60 kg. The multiple organ harvesting was done with standard technique apart from division of the liver. After a cholecistectomy the right and left portal and hepatic arterial branches were identified. The left hepatic duct was sectioned. The right lobe was then mobilised and freed from the inferior vena cava (IVC); the right vein was encircled at its confluence with the IVC. Parenchyma transection was then done along a plane directed from the right border of the gallbladder fossa, to the division of the portal vein and to the right margin of the median hepatic vein, leaving the right lobe connected only with its vascular attachments (figure). After flushing of the organs the heart was retrieved, then came the right lobe of the liver, including the five to eight segments, the right branches of the hepatic artery and of the portal vein, the common bile duct, and the right hepatic vein with a patch of IVC. The left lobe of the liver, including the segments one to four was then removed, with the coeliac axis and the hepatic artery, the portal trunk, the left hepatic duct, and the median and left hepatic veins in continuity with the IVC. Finally, the kidneys were removed. During the 4 h operation, seven units of packed red blood cells were transfused. The right and left grafts weighed 685 g and 480 g, respectively, and were transplanted in a 53-year-old man, 178 cm tall and weighing 79 kg, with alcoholic cirrhosis, and in a 13-year-old girl 155 cm tall and weighed 48 kg, with autoimmune cirrhosis and hepatitis C virus infection. Both the grafts had immediate good function and the patients had rapid recovery. They were discharged on the 15th and 24th postoperative day, respectively, and are alive and well with normal liver function at 5 months. This alternative technique of ISSL provided two grafts of similar size, showing excellent function in two recipients of adult size. The blood loss during the split was similar to that reported from harvesting a right-lobe graft from a living donor, with a similar technique. With increasing experience this figure can be reduced. ISSL has proved a safe and effective way to increase the number of liver transplants with the available donor pool, dividing the liver mass between the large right lobe and the small left lateral segment. The minimum amount of liver tissue needed to achieve sufficient immediate function in a given patient is not well known, but should probably not be lower then 25–50% of his predicted liver volume. The left lateral segment seldon exceeds 300 g in weight, being therefore inadequate for most adults and large children. The net benefit from standard ISSL is therefore only for small children, representing a limited percentage of candidates for liver transplantation. The extension of ISSL to increase the number of adult transplants can be a further step in optimising the use of cadaver donors. Our technique increases the flexibility of the procedure and can virtually double the pool of liver grafts for adult recipients.

Incidence of Bleeding Following Invasive Procedures in Patients With Thrombocytopenia and Advanced Liver Disease

BACKGROUND & AIMS Patients with advanced liver disease often undergo invasive procedures, so the combination of thrombocytopenia, coagulopathy, and bleeding should be carefully assessed. We evaluated the prevalence of thrombocytopenia in a series of patients with liver cirrhosis who were being evaluated for orthotopic liver transplantation (OLT) and determined the number of invasive procedures and procedure-related incidences of bleeding in patients with thrombocytopenia. METHODS We studied 121 consecutive patients who were being evaluated for OLT. Thrombocytopenia was defined as a platelet count <150,000/μL and severe thrombocytopenia as a platelet count <75,000/μL. The presence of significant coagulopathy was defined as an international normalized ratio >1.5. Invasive procedures and incidences of procedure-related bleeding were recorded for each patient. RESULTS The prevalence of thrombocytopenia and severe thrombocytopenia were 84% and 51%, respectively. Among the 102 thrombocytopenic patients, 50 (49%) underwent an invasive procedure (32 with severe thrombocytopenia; 64%). Bleeding occurred in 10 of the patients who underwent an invasive procedure (20%). Among the 50 patients who underwent invasive procedure, 32 had severe thrombocytopenia and 18 had moderate thrombocytopenia. Bleeding occurred in 10 of the 32 patients (31%) with severe thrombocytopenia and in none of those with moderate thrombocytopenia. There was no difference in prevalence of significant coagulopathy between patients with severe thrombocytopenia who underwent invasive procedure and bled (3/10; 30%) and those who did not bleed (10/22; 45%). CONCLUSIONS Thrombocytopenia has a high prevalence among patients with advanced liver disease. Bleeding related to invasive procedures occurs most frequently in patients with severe thrombocytopenia, whereas significant coagulopathy does not seem to be associated with bleeding.

Oxidative damage in human liver transplantation

The aim of this study was to evaluate oxygen-dependent hepatic reperfusion injury in humans following orthotopic liver transplantation. To this end, a number of blood indices of impaired tissue redox balance were monitored in 19 adult patients for 3 weeks after liver transplantation. Both red cell malonaldehyde and plasma lipid peroxides increased significantly soon after organ reperfusion. This finding was consistently accompanied by decreased plasma vitamin E and red cell total glutathione. A peak of oxidative stress, as measured by the parameters monitored, was evident within 24 h after reperfusion, together with a maximum expression of cytolysis, as measured by plasma alanine aminotransferase. The occurrence of redox imbalance after hepatic reperfusion was shown to be linearly related to irreversible cell damage. As regards the low plasma levels of the two antioxidants after reperfusion, only that of vitamin E appeared statistically related to oxidative stress. With the background of an increasing body of proof, mainly from animal models, the involvement of toxic oxygen metabolites in hepatic cytolysis following orthotopic liver transplantation appears likely. The statistical correlation among the markers of redox imbalance monitored indicates their combined use in further investigation.

Sister Joseph's nodule in a liver transplant recipient: Case report and mini-review of literature

BackgroundUmbilical metastasis is one of the main characteristic signs of extensive neoplastic disease and is universally referred to as Sister Mary Josephs nodule.Case presentationA 59-years-old Caucasian female underwent liver transplant for end stage liver disease due to hepatitis C with whole graft from cadaveric donor in 2003. After transplantation the patient developed multiple subcutaneous nodules in the umbilical region and bilateral inguinal lymphadenopathy. The excision biopsy of the umbilical mass showed the features of a poorly differentiated papillary serous cystadenocarcinoma. Computed tomographic scan and transvaginal ultrasonography were unable to demonstrate any primary lesion. Chemotherapy was start and the dosage of the immunosuppressive drugs was reduced. To date the patient is doing well and liver function is normal.ConclusionsThe umbilical metastasis can arise from many sites. In some cases, primary tumor may be not identified; nonetheless chemotherapy must be administrated based on patients history, anatomical and histological findings.

Sirolimus therapy in liver transplant patients: an initial experience at a single center.

Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Since February 2005, we introduced SRL in liver transplant patients in group a, in whom the primary disease was hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic or autoimmune liver cirrhosis, and group b, HCC-negative patients who developed posttransplantation cancers de novo. Of 18 patients in group a, 11 received SRL ab initio (subgroup a1), starting for 10 patients at 66.1+/-29.2 days after surgical healing and after 10 days in 1 case; the remaining 7 patients (subgroup a2) received SRL at 31.2+/-24.2 months. Three patients in group b, included 1 with Kaposis sarcoma, 1 with bladder cancer, and 1 with thyroid cancer. In this group, SRL was introduced at 80.8+/-40.4 months. In all patients but one, who received a single 5 mg loading dose, SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CNI drugs, present as primary therapy, were gradually tapered to low levels and eventually stopped. The following observations were drawn from this initial experience: (1) 4/21 (19.0%) patients had to discontinue SRL because of early and late side effects: thrombocytopenia (n=2) and headache with leukopenia and leg edema associated with knee joint arthralgia (n=2); (2) 14 patients (11 in group a and 3 in group b) are still on SRL monotherapy; (3) 1 HCC recurrence and 1 de novo pancreatic adenocarcinoma were observed at 14 and 16 months, respectively (at the time of transplantation, both patients were beyond the MIlan HCC criteria), and (4) 1 patient, from subgroup a1, died after 99 days due to pneumonitis and possible relation to SRL lung toxicity. In conclusion, SRL appeared to be an effective immunosuppressant that could be used as monotherapy in liver transplant patients. Any conclusion on SRL anticancer effects can only come from randomized large studies after long follow-up.

Feasibility and limits of split liver transplantation from pediatric donors: an italian multicenter experience.

Objective:To report the results of a multicenter experience of split liver transplantation (SLT) with pediatric donors. Summary Background Data:There are no reports in the literature regarding pediatric liver splitting; further; the use of donors weighing <40 kg for SLT is currently not recommended. Methods:From 1997 to 2004, 43 conventional split liver procedures from donors aged <15 years were performed. Nineteen donors weighing ≤40 kg and 24 weighing >40 kg were used. Dimensional matching was based on donor-to-recipient weight ratio (DRWR) for left lateral segment (LLS) and on estimated graft-to-recipient weight ratio (eGRWR) for extended right grafts (ERG). In 3 cases, no recipient was found for an ERG. The celiac trunk was retained with the LLS in all but 1 case. Forty LLSs were transplanted into 39 children, while 39 ERGs were transplanted into 11 children and 28 adults. Results:Two-year patient and graft survival rates were not significantly different between recipients of donors ≤40 kg and >40 kg, between pediatric and adult recipients, and between recipients of LLSs and ERGs. Vascular complication rates were 12% in the ≤40 kg donor group and 6% in the >40 kg donor group (P = not significant). There were no differences in the incidence of other complications. Donor ICU stay >3 days and the use of an interposition arterial graft were associated with an increased risk of graft loss and arterial complications, respectively. Conclusions:Splitting of pediatric liver grafts is an effective strategy to increase organ availability, but a cautious evaluation of the use of donors ≤40 kg is necessary. Prolonged donor ICU stay is associated with poorer outcomes. The maintenance of the celiac trunk with LLS does not seem detrimental for right-sided grafts, whereas the use of interposition grafts for arterial reconstruction should be avoided.

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.

Full‐Right‐Full‐Left Split Liver Transplantation: The Retrospective Analysis of an Early Multicenter Experience Including Graft Sharing

Full‐right‐full‐left split liver transplantation divides a donor liver into two grafts to be transplanted in adult‐size patients. Major technical and organizational difficulties have limited its application to few single center series. We retrospectively analyzed the long‐term results of the first multicenter series of this procedure with graft sharing. Between November 1998 and January 2005, 43 transplants were performed by five centers from 23 full‐right‐full‐left in situ split liver procedures; 65% of the grafts were shared. A total of 31 (72%) patients had complications above grade II; 3 (6.9%) were retransplanted. Hospital mortality was 23% with sepsis as the main cause. Six patients died in the long term, two of them for a road accident. A total of 27 patients are alive after a median follow‐up of 3200 days (2035–4256). Actuarial survival at 1 and 10 years were 72.1%, 62.6% and 65.1%, 57.9%, respectively for patients and grafts. These figures are similar to those reported for adult living donor liver transplantation by the European Registry over a similar period. Multicenter collaboration in sharing of these grafts is feasible and can help facing the organizational limits, thus increasing diffusion of full‐right‐full‐left split liver transplantation.

MELD score versus conventional UNOS status in predicting short-term mortality after liver transplantation*

The Model for End‐stage Liver Disease (MELD) provides a score able to predict short‐term mortality in patients awaiting liver transplantation (LT). In the early 2002, United Network for Organ Sharing (UNOS) has proposed to replace the conventional statuses 3, 2B, and 2A with a modified MELD score. However, the accuracy of the MELD model to predict post‐transplantation outcome is fairly elusive. In the present study we investigated the predictive value of the MELD score for short‐term patient and graft mortality in comparison with conventional UNOS status. Sixty‐nine patients listed at UNOS status 3 (n = 5), 2B (n = 55) or 2A (n = 9) who underwent LT were enrolled according to strict criteria. No donor‐related parameters affected 3‐month patient survival. Through univariate Cox regression, pretransplantation international normalized ratio (P = 0.049) and activated partial thromboplastin time (P = 0.032) were significantly associated with 3‐month patient survival, although not in the subsequent multivariate analysis. The overall MELD score was 17 ± 6.63 (median: 16, range: 4–34), increasing from UNOS Status 3 to 2A (r2 = 0.171, P = 0.0001). No significant difference occurred in the median MELD score between patients who underwent a second LT and those who did not (P =0.458). The inter‐rate agreement between UNOS status and MELD score after categorization for clinical urgency showed a fair agreement (κ = 0.244). The 3‐month patient and graft mortality was 15.94% and 20.29% respectively. The concordance statistic did not find significance between UNOS status and MELD score for 3‐month patient (P = 0.283) or graft mortality (P = 0.957), although the MELD score revealed a major sensitivity for short‐term patient mortality (0.637; 95%CI: 0.513–0.75). These findings suggest the need to implement MELD model accuracy for both inter‐rate agreement with UNOS Status and patient outcome.