Abbas Rana

Liver transplantation for nonalcoholic steatohepatitis: the new epidemic.

Objective:To analyze incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH). Summary of Background Data:With the epidemic of obesity and metabolic syndrome in nearly 33% of the US population, NASH is projected to become the leading indication for LT in the next several years. Data on predictors of outcome and utilization of health care resources after LT in NASH is limited. Methods:We conducted an analysis from our prospective database of 144 adult NASH patients who underwent LT between December 1993 and August 2011. Outcomes and resource utilization were compared with other common indications for LT. Independent predictors of graft and patient survival were identified. Results:The average Model for End-Stage Liver Disease score was 33. The frequency of NASH as the primary indication for LT increased from 3% in 2002 to 19% in 2011 to become the second most common indication for LT at our center behind hepatitis C. NASH patients had significantly longer operative times (402 vs 322 minutes; P < 0.001), operative blood loss (18 vs 14 packed red blood cell units; P = 0.001), and posttransplant length of stay (35 vs 29 days; P = 0.032), but 1-, 3-, and 5-year graft (81%, 71%, 63%) and patient (84%, 75%, 70%) survival were comparable with other diagnoses. Age greater than 55 years, pretransplant intubation, dialysis, hospitalization, presence of hepatocellular carcinoma on explant, donor age greater than 55 years, and cold ischemia time greater than 550 minutes were significant independent predictors of survival for all patients, whereas body mass index greater than 35 was a predictor in NASH patients only. Conclusions:We report the largest single institution experience of LT for NASH. Over a 10-year period, the frequency of LT for NASH has increased 5-fold. Although outcomes are comparable with LT for other indications, health care resources are stressed significantly by this new and increasing group of transplant candidates.

The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center.

Objective:To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure. Background:The implementation of the model for end-stage liver disease (MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity. Methods:Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system. Independent predictors of survival were identified. Results:Overall, 1-, 5-, 10-, and 20-year patient and graft survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively. Recipient survival was best in children with biliary atresia and worst in adults with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs 186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P < 0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-, 5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P < 0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001) compared with pre-MELD recipients. Of 17 recipient and donor variables, era of transplantation, etiology of liver disease, recipient and donor age, prior transplantation, MELD score, hospitalization at time of OLT, and cold and warm ischemia time were independent predictors of survival. Conclusions:We present the worlds largest reported single-institution experience with OLT. Despite increasing acuity in post-MELD era recipients, patient and graft survival continues to improve, justifying the “sickest first” allocation approach.

Liver transplantation in highest acuity recipients: identifying factors to avoid futility.

Objective:To identify medical predictors of futility in recipients with laboratory Model of End-Stage Liver Disease (MELD) scores of 40 or more at the time of orthotopic liver transplantation (OLT). Background:Although the survival benefit for transplant patients with the highest MELD scores is indisputable, the medical and economic effort to bring these highest acuity recipients through OLT presents a major challenge for every transplant center. Methods:This study was undertaken to analyze outcomes in patients with MELD scores of 40 or more undergoing OLT during the period February 2002 to December 2010. The analysis was focused on futile outcome (3-month or in-hospital mortality) and long-term posttransplant outcome. Independent predictors of futility and failure-free survival were identified and a futility risk model was created. Results:During the study period, 1522 adult cadaveric OLTs were performed, and 169 patients (13%) had a MELD score of 40 or more. The overall 1, 3, 5, and 8-year patient survivals were 72%, 64%, 60%, and 56%. Futile outcome occurred in 37 patients (22%). MELD score, pretransplant septic shock, cardiac risk, and comorbidities were independent predictors of futile outcome. Using all 4 factors, the futility risk model had a good discriminatory ability (c-statistic 0.75). Recipient age per year, life-threatening postoperative complications, hepatitis C, and metabolic syndrome were independent predictors for long-term survival in nonfutile patients (Harrels c-statistic 0.72). Conclusions:Short- and long-term outcomes of recipients with MELD scores of 40 or more are primarily determined by disease-specific factors. Cardiac risk, pretransplant septic shock, and comorbidities are the most important predictors and can be used for risk stratification in these highest acuity recipients.

The Combined Organ Effect : Protection Against Rejection?

Objectives:To further our understanding of the potential protective effects of one organ allograft for another in combined organ transplants by comparing rejection-free survival and the 1-year rejection rate of each type of combined organ transplant. Summary Background Data:Liver allografts have been thought to be immunoprotective of other donor-specific allografts. Recent observations have extended this property to other organs. Methods:Analysis of data from the United Network of Organ Sharing included recipients 18 years or older (except those receiving intestinal transplants) transplanted between January 1, 1994, and October 6, 2005, and excluded those with a previous transplant (n = 45,306), live-donor transplant (n = 80,850), or insufficient follow-up (n = 4304). Patients were followed from transplant until death (n = 41,524), retransplantation (n = 4649), or last follow-up (n = 87,243). Results:A total of 133,416 patients were analyzed. Rejection rates for allografts co-transplanted with donor-specific primary liver, kidney, and heart allografts are significantly lower than rejection rates for allografts transplanted alone. Allografts accompanying primary intestinal or pancreatic allografts did not have reduced rejection rates. A decreased rate of rejection was seen in interval kidney-heart transplants when allografts shared partial antigenic identity. Decreased rates of rejection were also seen in transplants of 2 donor-specific organs of the same type. Conclusions:In combined simultaneous transplants, heart, liver, and kidney allografts are themselves protected and protect the other organ from rejection. Analysis of interval heart-kidney allografts suggests the need for partial antigenic identity between organs for the immunoprotection to take effect. This was not demonstrated in interval liver-kidney transplants. Increased antigen load of identical antigens, as seen in double-lung and double-kidney transplants, also offers immunologic protection against rejection.

The Altruistic Unbalanced Paired Kidney Exchange: Proof of Concept and Survey of Potential Donor and Recipient Attitudes

Background. Altruistic unbalanced paired kidney exchanges (AUPKE) use compatible live donor/recipient pairs to facilitate transplants for individuals with incompatible live donors. We report a three donor/recipient pair complex AUPKE. Little is known of the circumstances under which individuals are likely to trade away a compatible live donor or the overall impact that AUPKE could have on the organ supply. Methods. (1) A retrospective analysis of live donor renal transplants was performed using United Network for Organ Sharing data and our own center experience to determine the potential impact of AUPKE. (2) At initial evaluation, potential donors and recipients were administered a survey regarding attitudes toward AUPKE using a 5-point Likert Scale. Results. (1) One thousand three hundred ninety-six (22.8%) ABO compatible but nonidentical live donor transplants were performed in the United States in 2005. Ninety-one percent of donors were blood group O. (2) Recipient survey respondents were more likely than donors (P=0.002) to favor participation in AUPKE with no advantage to themselves. A number of circumstances increased the propensity to view AUPKE favorably (P<0.05). Conclusions. (1) AUPKE can have a profound impact on the kidney supply. (2) By using ABO compatible but nonidentical donors, AUPKE can be performed at individual centers without requiring large sharing networks. (3) O recipients with incompatible donors are likely to be the primary beneficiary of AUPKE. (4) Attitudes are not static and can be influenced in favor of participation if there is a perceived benefit to the recipient. (5) Both donors and recipients are more willing to participate if their intended recipient or donor is enthusiastic about participating. (6) AUPKE reflects a paradigm shift for live donation, converting a private resource (the donor) to a shared one.

Blood transfusion requirement during liver transplantation is an important risk factor for mortality.

BACKGROUND Blood loss during liver transplantation is not incorporated into the dominant models for post-transplant survival. Our objective was to investigate blood transfusion requirement as a risk factor for mortality after liver transplantation, and to further analyze risk factors for intraoperative blood transfusion requirement and hepatectomy time. STUDY DESIGN We conducted a retrospective analysis of 233 consecutive liver transplant recipients over a span of 3 years by a single experienced surgeon. Mean follow-up was 2.5 years. Independent risk factors for patient survival after liver transplantation were identified using Cox proportion hazard regression. Independent risk factors for intraoperative blood transfusion requirement and hepatectomy time were identified using logistic regression. RESULTS Two factors were identified as significant predictors in multivariate analysis for survival after liver transplantation: hepatocellular carcinoma (hazard ratio [HR] 1.9, 95% CI 1.1 to 3.2) and intraoperative blood transfusion requirement per unit (HR 1.01, 95% CI 1.0 to 1.02). Threshold analysis revealed that intraoperative blood transfusion volume ≥28 units or 85(th) percentile (HR 2.5, 95% CI 1.3 to 4.7) was a significant risk factor for patient survival. Four covariates were identified as significant risk factors for intraoperative blood requirement: warm ischemia time (odds ratio [OR] 1.12, 95% CI 1.06 to 1.18), bilirubin (OR 1.04, 95% CI 1.02 to 1.08), previous surgery (OR 1.7, 95% CI 1.02 to 2.9), and hepatectomy time (OR 1.01, 95% CI 1.00 to 1.02). The only risk factor for prolonged hepatectomy time was previous major abdominal surgery (OR 4.0, 95% CI 1.7 to 9.5). CONCLUSIONS Intraoperative blood transfusion requirement is an important risk factor for mortality after liver transplantation. The strongest risk factors for intraoperative blood transfusion requirement are warm ischemia time and bilirubin levels. Intraoperative blood loss and its risk factors should be incorporated into models to predict survival after liver transplantation.

Assessment of hepatic steatosis by transplant surgeon and expert pathologist: A prospective, double‐blind evaluation of 201 donor livers

An accurate clinical assessment of hepatic steatosis before transplantation is critical for successful outcomes after liver transplantation, especially if a pathologist is not available at the time of procurement. This prospective study investigated the surgeons accuracy in predicting hepatic steatosis and organ quality in 201 adult donor livers. A steatosis assessment by a blinded expert pathologist served as the reference gold standard. The surgeons steatosis estimate correlated more strongly with large‐droplet macrovesicular steatosis [ld‐MaS; nonparametric Spearman correlation coefficient (rS) = 0.504] versus small‐droplet macrovesicular steatosis (sd‐MaS; rS = 0.398). True microvesicular steatosis was present in only 2 donors (1%). Liver texture criteria (yellowness, absence of scratch marks, and round edges) were mainly associated with ld‐MaS (variance = 0.619) and were less associated with sd‐MaS (variance = 0.264). The prediction of ≥30% ld‐MaS versus <30% ld‐MaS was excellent when liver texture criteria were used (accuracy = 86.2%), but it was less accurate when the surgeons direct estimation of the steatosis percentage was used (accuracy = 75.5%). The surgeons quality grading correlated with the degree of ld‐MaS and the surgeons steatosis estimate as well as the incidence of poor initial function and primary nonfunction. In conclusion, the precise estimation of steatosis remains challenging even in experienced hands. Liver texture characteristics are more helpful in identifying macrosteatotic organs than the surgeons actual perception of steatosis. These findings are especially important when histological assessment is not available at the donors hospital. Liver Transpl 19:437–449, 2013.

Islet grafting and imaging in a bioengineered intramuscular space

Background. Because the hepatic portal system may not be the optimal site for islet transplantation, several extrahepatic sites have been studied. Here, we examine an intramuscular transplantation site, bioengineered to better support islet neovascularization, engraftment, and survival, and we demonstrate that at this novel site, grafted beta cell mass may be quantitated in a real-time noninvasive manner by positron emission tomography (PET) imaging. Methods. Streptozotocin-induced rats were pretreated intramuscularly with a biocompatible angiogenic scaffold received syngeneic islet transplants 2 weeks later. The recipients were monitored serially by blood glucose and glucose tolerance measurements and by PET imaging of the transplant site with [11C] dihydrotetrabenazine. Parallel histopathologic evaluation of the grafts was performed using insulin staining and evaluation of microvasularity. Results. Reversal of hyperglycemia by islet transplantation was most successful in recipients pretreated with bioscaffolds containing angiogenic factors when compared with those who received no bioscaffolds or bioscaffolds not treated with angiogenic factors. PET imaging with [11C] dihydrotetrabenazine, insulin staining, and microvascular density patterns were consistent with islet survival, increased levels of angiogenesis, and with reversal of hyperglycemia. Conclusions. Induction of increased neovascularization at an intramuscular site significantly improves islet transplant engraftment and survival compared with controls. The use of a nonhepatic transplant site may avoid intrahepatic complications and permit the use of PET imaging to measure and follow transplanted beta cell mass in real time. These findings have important implications for effective islet implantation outside of the liver and offer promising possibilities for improving islet survival, monitoring, and even prevention of islet loss.

Fully Robotic-Assisted Technique for Total Pancreatectomy with an Autologous Islet Transplant in Chronic Pancreatitis Patients: Results of a First Series

Received November 7, 2013; Revised December 3, 2 December 9, 2013. From the Section of Minimally Invasive and Robotic Su Samame), Institute for Cellular Transplantation (Rilo), a Transplantation and Hepatopancreaticobiliary Surgery (P Gruessner), Department of Surgery, University of Arizona, Correspondence address: Carlos A Galvani, MD, Section Invasive and Robotic Surgery, Department of Surgery, Arizona, College of Medicine, 1501 N Campbell Ave, PO Tucson, AZ 85724-5066. email: cgalvani@surgery.arizona.e

A Single-institution Retrospective Cases Series of Childhood Undifferentiated Embryonal Liver Sarcoma (UELS): Success of Combined Therapy and the Use of Orthotopic Liver Transplant

Background/Introduction: Undifferentiated embryonal liver sarcoma (UELS) makes up 9% to 15% of all malignant liver tumors in children. UELS is characteristically diagnosed between the ages of 6 and 10 years and presents with abdominal pain, vomiting, and an abdominal mass. There is currently no standardized treatment for UELS except attempt at complete surgical resection. There have been only about 150 cases of UELS reported in the literature all with historically poor overall survival of <37.5% at 5 years. This report is one of the largest single-institution reports of UELS consisting of 5 patients over 2 decades. The purpose of this study is to characterize presentation and to report treatment success in UELS in children, adolescents, and young adults and the use of liver transplantation and, lastly, to suggest a use of positron emission tomography/computed tomography (PET/CT) in monitoring of this disease process. Methods: We conducted an Institutional Review Board–approved retrospective chart review. Data were collected from UELS patients younger than 21 years seen at the University of California Los Angeles over the past 20 years (January 2001 to September 2011). Descriptive analysis was conducted including multiple parameters of patient demographics, tumor characteristics, treatment modalities, and morbidity and mortality. Results: Five patients with UELS were identified. Patients initially presented with fever, abdominal pain, or nausea. Ages ranged from 10 to 19 years old (median age 13 y old), and there was a 4:1 male-to-female predominance. Tumor size ranged from 6 to 22 cm in largest diameter. One patient presented with metastatic disease to the lungs and heart and 1 patient recurred 2 years from diagnosis with bilateral paraspinal masses. Treatment included local control surgery with neoadjuvant and adjuvant chemotherapy with an anthracycline/alkylating agent combination. One patient with recurrent and refractory disease achieved local control with an orthotopic liver transplantation (OLT). Metastatic disease was controlled with surgery and radiation therapy. 18-Fluorodeoxyglucose PET/CT was a useful imaging tool for judging response to therapy with complete loss of metabolic activity in tumor after neoadjuvant chemotherapy in 2 representative cases. Although follow-up is short for some patients, overall survival in these 5 patients was 100% with follow-up ranging from 21 to 68 months. Disease-free survival ranged from 8 to 46 months with no patients with residual disease. Conclusions: UELS is an aggressive high-grade primary liver sarcoma with high metastatic potential. This report represents one of the largest single-institution studies of UELS. Using multimodality therapy, patients have achieved 100% overall survival even in the setting of extensive disease, metastases, and recurrence. In cases of unresectable primary tumor or recurrent and refractory disease isolated to the liver, OLT is a potential therapeutic option. We report success with adjuvant chemotherapy and complete surgical resection with OLT as an alternative in unresectable or refractory cases. We also suggest a possible utility of PET/CT in monitoring treatment response in this disease.