Unresectable Squamous Cell Carcinoma of Donor Origin Treated With Immunosuppression Withdrawal and Liver Retransplantation

Posttransplantation allograft malignancy of donor origin is a rare complication after liver transplantation. In the case described, subjective fevers and nonspecific abdominal complaints nearly 6 months following cadaveric liver transplantation in a young woman prompted an evaluation which was remarkable for a large central liver mass. A poorly differentiated squamous cell carcinoma was diagnosed, but was unresectable at exploration. The tumor was confined to the liver. Histocompatibility testing using polymerase chain reaction (PCR) amplification techniques identified both donor and recipient HLA alleles. The patient was treated with chemoembolization, systemic chemotherapy and cessation of immunosuppression. Repeat biopsy 2 months later showed the tumor to be completely necrotic. With decompensated liver disease, she was relisted and retransplanted. More than 2 years later she remains disease-free with complete pathological remission. This is the only reported case of squamous cell carcinoma of donor origin arising in a transplanted liver.     

Tailoring the Type of Donor Hepatectomy for Adult Living Donor Liver Transplantation

Donor hepatectomies for adult living donor liver transplantations were performed in 200 consecutive donors to harvest a left liver (LL) graft (n = 5), a LL plus caudate lobe (LL + CL) graft (n = 63), a right liver (RL) graft (n = 86), a RL and middle hepatic vein (RL + MHV) graft (n = 28) or a right lateral sector (RLS) graft (n = 18). The graft type was selected so that at least 40% of the recipient's standard liver volume was harvested. No donor deaths occurred, and no significant differences in the morbidity rates among either donors or recipients were observed when the outcomes were stratified according to the graft type. Donors who donated RL exhibited higher values of serum total bilirubin and prothrombin time than those who donated non-RL (LL, LL + CL, RLS) grafts. The time taken for hilar dissection and parenchymal transection increased in the following order: RLS graft, LL graft and RL graft harvesting. In conclusion, non-RL grafting was more time consuming, but the hepatic functional loss in the donors was smaller. Our graft selection criteria were useful for reducing the use of RL grafts with acceptable morbidity in both donors and recipients.     

Adult Right-Lobe Living Liver Donors: Quality of Life, Attitudes and Predictors of Donor Outcomes

To refine selection criteria for adult living liver donors and improve donor quality of care, risk factors for poor postdonation health-related quality of life (HRQOL) must be identified. This cross-sectional study examined donors who underwent a right hepatectomy at the University of Toronto between 2000 and 2007 (n = 143), and investigated predictors of (1) physical and mental health postdonation, as well as (2) willingness to participate in the donor process again. Participants completed a standardized HRQOL measure (SF-36) and measures of the pre- and postdonation process. Donor scores on the SF-36 physical and mental health indices were equivalent to, or greater than, population norms. Greater predonation concerns, a psychiatric diagnosis and a graduate degree were associated with lower mental health postdonation whereas older donors reported better mental health. The majority of donors (80%) stated they would donate again but those who perceived that their recipient engaged in risky health behaviors were more hesitant. Prospective donors with risk factors for lower postdonation satisfaction and mental health may require more extensive predonation counseling and postdonation psychosocial follow-up. Risk factors identified in this study should be prospectively evaluated in future research.     

Adult Living Donor Liver Transplantation

Adult living donor liver transplantation (LDLT) begun in response to deceased donor organ shortage and waiting list mortality, grew rapidly after its first general application in the United States in 1998. There are significant risks to the living donor, including the risk of death and substantial morbidity, and two highly publicized donor deaths have led to decreased LDLT since 2001. Significant improvements in outcomes have been seen over recent years that have not been reported in single center studies; however, LDLT still comprises less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors now comprise the majority. The ethics, optimal utility and application of LDLT remain to be defined. In addition, studies to date have focused on post-transplant outcomes and not included the potential impact of LDLT on waiting time mortality. Future analyses should include appropriate control or comparison groups that capture the effect of LDLT on overall mortality from the time of listing. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers.     

Outcomes of Donor Evaluations for Adult-to-Adult Right Hepatic Lobe Living Donor Liver Transplantation

The purpose of this study is to determine the role of liver biopsy and outcome of patients undergoing donor evaluation for adult-to-adult right hepatic lobe living donor liver transplantation (LDLT). Records of patients presenting for a comprehensive donor evaluation between 1997 and February 2005 were reviewed. Liver biopsy was performed only in patients with risk factors for abnormal histology. Two hundred and sixty patients underwent a comprehensive donor evaluation and 116 of 260 (45%) were suitable for donation, 14 of 260 (5.4%) did not complete evaluation and 130 of 260 (50%) were rejected. Four patients underwent unsuccessful hepatectomy surgery due to discovery of intraoperative abnormalities. Between 1997 and 2001, the acceptance rate of donor candidates (63%) was higher than 2002-2005 (36%), p < 0.0001. Sixty-six of the 150 eligible patients (44%) fulfilled criteria for liver biopsy and 28 of 66 (42%) had an abnormal finding. Less than half of the patients undergoing donor evaluation were suitable donors and the donor acceptance rate has declined over time. A large proportion of the patients undergoing liver biopsy have abnormal findings. Our evaluation process failed to identify 4 of 103 who had aborted donor surgeries.     

Donor Safety in Live-Related Liver Transplantation

Living donor liver transplantation (LDLT), since its advent in late 1980’s and early 1990’s, has rapidly increased especially in countries like Japan, Korea and India where cadaveric programmes are not as well established as in the western world. The main advantage of LDLT is the availability of an organ in the elective setting in the course of a progressive liver disease. This is most applicable in patients with Cirrhosis and Hepatocellular carcinoma. LDLT, from the donor’s perspective does carry a risk of not only morbidity but mortality. To date the surgical mortality risk is estimated at 0.1% for left lateral donation and 0.5% for right liver donation. Donor mortality has been reported from various centres in India. There are reports of complications like Hepatic artery thrombosis, portal vein thrombosis and especially biliary leaks and strictures occurring at a significantly increased frequency after living as compared to deceased donor liver transplantation. The key to reduce donor morbidity and mortality is meticulous donor selection and thorough donor work up. In the present study we will analyse the factors that contributed to donor mortality and morbidity and prepare a detailed work up plan, intraoperative and post-operative strategy to reduce donor morbidity and mortality.     

Liver and Vascularized Posterior Rectus Sheath Fascia Composite Tissue Allotransplantation

Abdominal wall closure in pediatric solid organ recipients may be confounded by donor size discrepancy and structural insults from previous surgery. Here we describe the novel use of vascularized donor abdominal wall posterior rectus sheath fascia, as a composite tissue allotransplant (CTA), to achieve abdominal wall closure in a liver and double kidney pediatric recipient who could not be closed primarily due to donor/recipient size mismatch. The posterior rectus sheath fascia was procured in continuity with the liver and falciform ligament. Blood supply was achieved using the single hepatic artery anastomosis as part of the standard liver transplantation procedure. Specimens of posterior rectus sheath fascia taken on postoperative days 3 and 30 showed no signs of acute rejection. The patient succumbed to an overwhelming fungal infection on day 51, with no signs of intraabdominal involvement. The patient received no additional immunosuppression in conjunction with the posterior rectus sheath fascia allotransplant.     

Discontinuation of Living Donor Liver Transplantation for PSC Due to Histological Abnormalities in Intraoperative Donor Liver Biopsy

Liver transplantation is the only curative treatment known to date for end-stage liver disease occurring as a result of primary sclerosing cholangitis (PSC). Here, we report a case in which living donor liver transplantation (LDLT) for PSC was cancelled because of histological abnormalities in intraoperative biopsy of the donor liver. The donor was the mother of the recipient, and her preoperative evaluation revealed no abnormalities. In the donor operation, the donor liver biopsy revealed expansion of the portal zone with lymphocytic infiltration and dense concentric fibrosis developed around a bile duct. These histological findings were identical to those of early-stage PSC; therefore, the LDLT was called off. The experience in this case suggests that preoperative liver biopsy may be useful to exclude first-degree relative donors with potential PSC prior to LDLT for PSC.     

The Survival Benefit of Deceased Donor Liver Transplantation as a Function of Candidate Disease Severity and Donor Quality

The survival benefit of liver transplantation depends on candidate disease severity, as measured by MELD score. However, donor liver quality may also affect survival benefit. Using US data from the SRTR on 28 165 adult liver transplant candidates wait-listed between 2001 and 2005, we estimated survival benefit according to cross-classifications of candidate MELD score and deceased donor risk index (DRI) using sequential stratification. Covariate-adjusted hazard ratios (HR) were calculated for each liver transplant recipient at a given MELD with an organ of a given DRI, comparing posttransplant mortality to continued wait-listing with possible later transplantation using a lower-DRI organ. High-DRI organs were more often transplanted into lower-MELD recipients and vice versa. Compared to waiting for a lower-DRI organ, the lowest-MELD category recipients (MELD 6–8) who received high-DRI organs experienced significantly higher mortality (HR = 3.70; p < 0.0005). All recipients with MELD ≥20 had a significant survival benefit from transplantation, regardless of DRI. Transplantation of high-DRI organs is effective for high but not low-MELD candidates. Pairing of high-DRI livers with lower-MELD candidates fails to maximize survival benefit and may deny lifesaving organs to high-MELD candidates who are at high risk of death without transplantation.     

Adult Living Liver Donors have Excellent Long‐Term Medical Outcomes: The University of Toronto Liver Transplant Experience

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end‐stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow‐up of 12 months (range 12–96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 ± 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long‐term follow‐up may contribute to favorable donor outcomes.     

Liver Graft Regeneration in Right Lobe Adult Living Donor Liver Transplantation

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 ± 12.6% (range, 58–151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.     

D-MELD, a Simple Predictor of Post Liver Transplant Mortality for Optimization of Donor/Recipient Matching

Numerous donor and recipient risk factors interact to influence the probability of survival after liver transplantation. We developed a statistic, D-MELD, the product of donor age and preoperative MELD, calculated from laboratory values. Using the UNOS STAR national transplant data base, we analyzed survival for first liver transplant recipients with chronic liver failure from deceased after brain death donors. Preoperative D-MELD score effectively stratified posttransplant survival. Using a cutoff D-MELD score of 1600, we defined a subgroup of donor–recipient matches with significantly poorer short- and long-term outcomes as measured by survival and length of stay (LOS). Avoidance of D-MELD scores above 1600 improved results for subgroups of high-risk patients with donor age ≥60 and those with preoperative MELD ≥30. D-MELD ≥1600 accurately predicted worse outcome in recipients with and without hepatitis C. There is significant regional variation in average D-MELD scores at transplant, however, regions with larger numbers of high D-MELD matches do not have higher survival rates. D-MELD is a simple, highly predictive tool for estimating outcomes after liver transplantation. This statistic could assist surgeons and their patients in making organ acceptance decisions. Applying D-MELD to liver allocation could eliminate many donor/recipient matches likely to have inferior outcome.     

Extended Survival by Urgent Liver Retransplantation after Using a First Graft with Metastasis from Initially Unrecognized Donor Sarcoma

A 58-year-old man underwent orthotopic liver transplantation for polycystic liver disease. Shortly after the procedure, it was discovered that the donor harbored a sarcoma of the aortic arch that had metastasized to the spleen, and bilateral renal cell carcinomas. The two sole organ recipients, our liver recipient and a lung recipient at another institution, were both listed for urgent retransplantation, which they received from the same second donor. The liver explant contained metastatic sarcoma. Twenty-four months survival following lung retransplantation has been previously reported. We report the 76-month disease-free survival in the liver recipient.     

ABO‐Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.     

Liver Transplantation from an Identical Twin without Immunosuppression, with Early Recurrence of Hepatitis C

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon alpha and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.     

Dendritic Cell Subset Ratio in Peripheral Blood Correlates with Successful Withdrawal of Immunosuppression in Liver Transplant Patients

Human dendritic cell (DC) subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage- cells that are further characterized as CD11c+ CD123-/lo (IL-3Ralpha-/lo) (pDC1) or as CD11c- CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 - similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression.     

Initial Experience of Dual Maintenance Immunosuppression With Steroid Withdrawal in Vascular Composite Tissue Allotransplantation

Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2–12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow‐up of 43.6 months (median = 40 months, range 34–64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid‐resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections. Although further experience and a cautious approach are warranted, dual‐steroid free maintenance immunosuppression appears feasible in a series of five VCA recipients.     

Impact of Donor Age on the Growth of Young Recipient Rats After Liver Transplantation

Purpose We studied the age-related changes in graft livers, and their impact on post-transplantation liver function and the growth of young recipient rats. Methods Rats aged 11–68 weeks old were studied as controls to assess liver histology, liver function, and body weight. We performed orthotopic liver transplantation using Kamada's cuff technique without arterial reconstruction. Young rats aged 11 weeks were randomized to receive livers from either 11-week-old donors (YD group) or 52-week-old donors (OD group). Recipient rats were killed 0, 8, or 16 weeks after surgery and we assessed the same variables as in the controls. Results We confirmed an age-related increase in the average size of hepatocytes and their nuclei. These age-related changes persisted and progressed in the graft liver after transplantation. There were no significant differences in the levels of serum transaminases or total bilirubin between the YD and OD groups, but the serum albumin level was significantly lower in the OD group. The YD group grew normally, whereas the OD group recipients lagged significantly in gaining body weight. Conclusion We found that 52-week-old grafts transplanted into 11-week-old recipients resulted in deficient growth and a decline in serum albumin, suggesting that grafted old livers fail to produce enough protein to meet the demands of growth adequately.     

Graft Selection Algorithm Based on Congestion Volume for Adult Living Donor Liver Transplantation

A major concern in adult‐to‐adult living donor liver transplantation is the selection of graft type; that is, is it is better to use the right lobe with or without the middle hepatic vein (MHV)? This choice has a considerable impact on donor safety, vascular reconstruction and graft function in the recipient. To facilitate making an appropriate choice, on the basis of a preliminary study (n = 17), we herein propose a graft selection algorithm using three parameters: graft‐to‐recipient body weight ratio (GRWR), percentage remnant liver volume (%RLV) and estimated congestion ratio (ECR). The algorithm was evaluated with 50 consecutive cases with respect to postoperative liver function of donors and recipients and survival of recipients. Postoperative recovery was comparable between the two groups (p = NS). The overall cumulative 18‐month survival rate was 86.7% for the ‘with MHV graft group’, and 76.1% for the gwithout MHV graft grouph (p = NS). For 41 cases (82%), graft types were chosen according to the algorithm, whereas the remaining 9 cases (18%) needed detailed discussion of donor, recipient and operative factors. In conclusion, we constructed a graft selection algorithm based on congestion volume, which will contribute to objective graft‐type selection in adult‐to‐adult LDLT .