Pancreas transplantation from hepatitis C viremic donors to uninfected recipients.

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Hepatic Artery Microvascular Anastomosis in Liver Transplantation: A Systematic Review of the Literature.

BACKGROUND: The operating microscope is used in many centers for microvascular hepatic arterial reconstruction in living as well as deceased donor liver transplantation in adult and pediatric recipients. To date, a systematic review of the literature examining this topic is lacking. METHODS: This systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three different electronic databases (PubMed, Embase OVID, and Cochrane CENTRAL) were queried. RESULTS: A total of 34 studies were included. The rate of hepatic artery thrombosis (HAT) in noncomparative studies (28) ranged from 0% to 10%, with 8 studies reporting patient deaths resulting from HAT. Within comparative studies, the rate of HAT in patients who underwent arterial reconstruction using the operating microscope ranged from 0% to 5.3%, whereas the rate of HAT in patients who underwent arterial reconstruction using loupe magnification ranged from 0% up to 28.6%, and 2 studies reported patient deaths resulting from HAT. Two comparative studies did not find statistically significant differences between the 2 groups. CONCLUSIONS: Our comprehensive systematic review of the literature seems to suggest that overall, rates of HAT may be lower when the operating microscope is used for hepatic arterial reconstruction in liver transplantation. However, matched comparisons are lacking and surgical teams need to be mindful of the learning curve associated with the use of the operating microscope as compared with loupe magnification, as well as the logistical and time constraints associated with setup of the operating microscope.

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS: The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS: Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody.

OBJECTIVES: The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA: IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS: Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

Surgical approach, cost, and complications of appendectomy in kidney transplant recipients.

Kidney transplant recipients (KTRs) have greater morbidity and length of stay (LOS) following certain surgical procedures than non-KTR. Given that appendectomy is one of the most common surgical procedures, we investigated differences in outcomes between 1336 KTR and 2 640 247 non-KTR postappendectomy at transplant and nontransplant centers in the United States from 2000 to 2011, using NIS data and adjusting for patient-level and hospital-level factors. Postoperative complications were identified using ICD-9 codes. Among KTR, there were no post-appendectomy in-hospital deaths, compared to a 0.2% in non-KTR (P = .5). Overall complications were similar among KTR and non-KTR (17.0% vs 11.6%; aOR:0.77 1.121.61 ). LOS and costs were greater for KTR compared to non-KTR (LOS ratio 1.19 1.311.45 ; cost ratio 1.11 1.171.26 ). Only 44.8% of KTR had laparoscopic approach compared to 54.5% of non-KTR, but had similar complication rates (10.6 vs 8.7%, P = .5). When treated at transplant centers, KTR had similar complications (aOR 0.44 0.791.43 ), but longer LOS (ratio 1.21 1.371.55 ) and greater hospital-associated costs (ratio 1.19 1.291.41 ) than non-KTR. Conversely, at nontransplant centers, KTR and non-KTR had similar complications (aOR 0.75 1.232.0 ), LOS (ratio 0.84 0.961.09 ), and cost (ratio 0.93 1.011.10 ). Contrary to other procedures, KTR did not constitute a high-risk group for patients undergoing appendectomy.

Three-year Results of a Pilot Program in Early Liver Transplantation for Severe Alcoholic Hepatitis.

OBJECTIVE: To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012. BACKGROUND: Six months of alcohol abstinence is typically required before liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability. METHODS: Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groups: severe alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with ≥6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking. RESULTS: Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for Groups 1 and 2, respectively (P = 0.27). Alcohol relapse was similar in Group 1 versus Group 2: 23.5% versus 29.2% (P > 0.99). Harmful drinking was higher in Group 1 versus Group 2, despite lack of statistical significance: 23.5% versus 11.5% (P = 0.42). CONCLUSIONS: In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary.

Frailty, Length of Stay, and Mortality in Kidney Transplant Recipients: A National Registry and Prospective Cohort Study.

OBJECTIVE: To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. BACKGROUND: Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. METHODS: We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). RESULTS: Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). CONCLUSIONS: Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.

Nontraditional sites for vascular anastomoses to enable kidney transplantation in patients with major systemic venous thromboses.

Successful renal transplantation requires low-pressure venous drainage to permit adequate outflow from the allograft. We report here a series of three patients in whom the inferior vena cava as well as bilateral iliac veins were thrombosed, making it necessary to explore less traditional vessels for venous drainage of the renal allograft. We utilized the splanchnic vasculature in two cases and the native left renal vein in another. The resulting atypical intra-abdominal locations of these allografts also presented difficulties for arterial anastomoses and for urinary drainage. Arterial conduits were utilized in two cases to facilitate anastomosis to the common iliac artery or the aorta, and in the third case, the splenic artery was used for arterial inflow. A traditional ureterocystostomy was technically feasible for only one patient. In another, ureteroureterostomy to the native ureter was performed, and in the third case, the creation of an ileal conduit was necessary. All three patients had antibodies to human leukocyte antigens and two required desensitization. All three kidneys had immediate graft function and continued to function at 1 year post-transplant. With a combination of planning, creativity, and persistence, patients with IVC thrombosis can enjoy the benefits of renal transplantation.

Outcomes and risk stratification for late antibody-mediated rejection in recipients of ABO-incompatible kidney transplants: a retrospective study.

The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR; 26% of patients had at least one AMR episode; 49% of AMR episodes occurred within 30-days after transplant and were considered early AMR. Patients with an early AMR episode had a 5.5-fold greater incidence of developing late AMR [IRR = 5.5, (95% CI: 1.5-19.3), P = 0.01]. ABOi/HLAi recipients trended toward increased late AMR risk [IRR = 1.9, (95% CI: 0.5-6.6), P = 0.3]. High-risk recipients (those with an early AMR or those who were ABOi/HLAi) had a sixfold increased incidence of late AMR [IRR = 6.3, (95% CI: 1.6-24.6), P = 0.008] versus low-risk recipients. The overall incidence of late AMR was 20.8% vs. 1.5% in low-risk recipients. Changes in anti-A/B titer did not correlate with late AMR (IRR = 0.9 per log titer increase, P = 0.7). This risk-stratification scheme uses information available within 30 days of ABOi transplantation to determine risk for late AMR and can help direct longitudinal follow-up for individual patients.

Predictive Modeling of Massive Transfusion Requirements During Liver Transplantation and Its Potential to Reduce Utilization of Blood Bank Resources.

BACKGROUND: Patients undergoing liver transplantation frequently but inconsistently require massive blood transfusion. The ability to predict massive transfusion (MT) could reduce the impact on blood bank resources through customization of the blood order schedule. Current predictive models of MT for blood product utilization during liver transplantation are not generally applicable to individual institutions owing to variability in patient population, intraoperative management, and definitions of MT. Moreover, existing models may be limited by not incorporating cirrhosis stage or thromboelastography (TEG) parameters. METHODS: This retrospective cohort study included all patients who underwent deceased-donor liver transplantation at the Johns Hopkins Hospital between 2010 and 2014. We defined MT as intraoperative transfusion of > 10 units of packed red blood cells (pRBCs) and developed a multivariable predictive model of MT that incorporated cirrhosis stage and TEG parameters. The accuracy of the model was assessed with the goodness-of-fit test, receiver operating characteristic analysis, and bootstrap resampling. The distribution of correct patient classification was then determined as we varied the model threshold for classifying MT. Finally, the potential impact of these predictions on blood bank resources was examined. RESULTS: Two hundred three patients were included in the study. Sixty (29.6%) patients met the definition for MT and received a median (interquartile range) of 19.0 (14.0-27.0) pRBC units intraoperatively compared with 4.0 units (1.0-6.0) for those who did not satisfy the criterion for MT. The multivariable model for predicting MT included Model for End-stage Liver Disease score, whether simultaneous liver and kidney transplant was performed, cirrhosis stage, hemoglobin concentration, platelet concentration, and TEG R interval and angle. This model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P = .45) and good discrimination (c statistic: 0.835; 95% confidence interval, 0.781-0.888). A probability cutoff threshold of 0.25 was found to misclassify only 4 of 100 patients as unlikely to experience MT, with the majority such misclassifications within 4 units of the working definition for MT. For this threshold, a preoperative blood ordering schedule that allocated 6 units of pRBCs for those unlikely to experience MT and 15 for those who were likely to experience MT would prevent unnecessary crossmatching of 338 units/100 transplants. CONCLUSIONS: When clinical and laboratory parameters are included, a model predicting intraoperative MT in patients undergoing liver transplantation is sufficiently accurate that its predictions could guide the blood order schedule for individual patients based on institutional data, thereby reducing the impact on blood bank resources. Ongoing evaluation of model accuracy and transfusion practices is required to ensure continuing performance of the predictive model.

Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice.

BACKGROUND: Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their survival in the adult brain, with administration of the dual CSF1R/c-kit inhibitor PLX3397 leading to the near-complete elimination of all microglia brainwide. Here, we determined the dose-dependent effects of a specific CSF1R inhibitor (PLX5622) on microglia in both wild-type and the 3xTg-AD mouse model of Alzheimer's disease. METHODS: Wild-type mice were treated with PLX5622 for up to 21 days, and the effects on microglial numbers were assessed. 3xTg-AD mice were treated with PLX5622 for 6 or 12 weeks and effects on microglial numbers and pathology subsequently assessed. RESULTS: High doses of CSF1R inhibitor eliminate most microglia from the brain, but a 75% lower-dose results in sustained elimination of ~30 of microglia in both wild-type and 3xTg-AD mice. No behavioral or cognitive deficits were found in mice either depleted of microglia or treated with lower CSF1R inhibitor concentrations. Aged 3xTg-AD mice treated for 6 or 12 weeks with lower levels of PLX5622 resulted in improved learning and memory. Aß levels and plaque loads were not altered, but microglia in treated mice no longer associated with plaques, revealing a role for the CSF1R in the microglial reaction to plaques, as well as in mediating cognitive deficits. CONCLUSIONS: We find that inhibition of CSF1R alone is sufficient to eliminate microglia and that sustained microglial elimination is concentration-dependent. Inhibition of the CSF1R at lower levels in 3xTg-AD mice prevents microglial association with plaques and improves cognition.

Surgical management of early and late ureteral complications after renal transplantation: techniques and outcomes.

BACKGROUND: In this study, we present our experience with ureteral complications requiring revision surgery after renal transplantation and compare our results to a matched control population. METHODS: We performed a retrospective analysis of our database between 1997 and 2012. We divided the cases into early (<60 d) and late repairs. Kaplan-Meier and Cox proportional hazards models were used to compare graft survival between the intervention cohort and controls generated from the Scientific Registry of Transplant Recipients data set. RESULTS: Of 2671 kidney transplantations, 51 patients were identified as to having undergone 53 ureteral revision procedures; 43.4% of cases were performed within 60 d of the transplant and were all associated with urinary leaks, and 49% demonstrated ureteral stenosis. Reflux allograft pyelonephritis and ureterolithiasis were each the indication for intervention in 3.8%; 15.1% of the lesions were located at the anastomotic site, 37.7% in the distal segment, 7.5% in the middle segment, 5.7% proximal ureter, and 15.1% had a long segmental stenosis. In 18.9%, the location was not specified. Techniques used included ureterocystostomy (30.2%), ureteroureterostomy (34%), ureteropyelostomy (30.1%), pyeloileostomy (1.9%), and ureteroileostomy (3.8%). No difference in overall graft survival (HR 1.24 95% CI 0.33-4.64, p = 0.7) was detected when compared to the matched control group. CONCLUSION: Using a variety of techniques designed to re-establish effective urinary flow, we have been able to salvage a high percentage of these allografts. When performed by an experienced team, a ureteric complication does not significantly impact graft survival or function as compared to a matched control group.

Desensitization in HLA-incompatible kidney recipients and survival.

BACKGROUND: More than 20,000 candidates for kidney transplantation in the United States are sensitized to HLA and may have a prolonged wait for a transplant, with a reduced transplantation rate and an increased rate of death. One solution is to perform live-donor renal transplantation after the depletion of donor-specific anti-HLA antibodies. Whether such antibody depletion results in a survival benefit as compared with waiting for an HLA-compatible kidney is unknown. METHODS: We used a protocol that included plasmapheresis and the administration of low-dose intravenous immune globulin to desensitize 211 HLA-sensitized patients who subsequently underwent renal transplantation (treatment group). We compared rates of death between the group undergoing desensitization treatment and two carefully matched control groups of patients on a waiting list for kidney transplantation who continued to undergo dialysis (dialysis-only group) or who underwent either dialysis or HLA-compatible transplantation (dialysis-or-transplantation group). RESULTS: In the treatment group, Kaplan-Meier estimates of patient survival were 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and 30.5%, respectively, for patients in the dialysis-only group and rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, for patients in the dialysis-or-transplantation group (P<0.001 for both comparisons). CONCLUSIONS: Live-donor transplantation after desensitization provided a significant survival benefit for patients with HLA sensitization, as compared with waiting for a compatible organ. By 8 years, this survival advantage more than doubled. These data provide evidence that desensitization protocols may help overcome incompatibility barriers in live-donor renal transplantation. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Charles T. Bauer Foundation.).

Liver Transplantation as a Treatment for Unresectable Hepatic Adenoma in a Patient With Abernethy Syndrome.

Abernethy syndrome is a rare congenital anomaly characterized by an intrahepatic or extrahepatic portosystemic shunt. Most patients are asymptomatic; however, due to the alteration in, or lack of, a portovenous flow, patients with Abernethy syndrome are at high risk of developing sequelae of liver failure. Once these complications develop, the only definitive treatment is transplantation. Patients with Abernethy syndrome are also at a higher risk of developing benign and malignant liver lesions, including hepatic adenomas. Here, we describe the first case of deceased donor liver transplantation as a treatment for a patient with type 1 Abernethy syndrome complicated by large, unresectable hepatic adenoma, found to have focal hepatocellular carcinoma on pathologic examination. Our male patient was found to have elevated liver enzymes at age 33, during a routine outpatient medical appointment. Despite being asymptomatic, his history of prior liver resection prompted CT imaging, which revealed two large liver lesions concerning for hepatic adenomas. When surveillance imaging showed a significant growth of the liver lesions, biopsy was pursued, which confirmed a diagnosis of hepatic adenomas. However, given the size of these lesions, resection was not a viable option for the patient. Instead, the patient underwent liver transplantation at age 41, which he tolerated well. Our case demonstrates the utility of deceased donor liver transplantation as a treatment for patients with Abernethy syndrome complicated by unresectable adenomas.

Estimates of early death, acute liver failure, and long-term mortality among live liver donors.

BACKGROUND & AIMS: We sought to estimate the risk of perioperative mortality or acute liver failure for live liver donors in the United States and avoid selection or ascertainment biases and sample size limitations. METHODS: We followed up 4111 live liver donors in the United States between April 1994 and March 2011 for a mean of 7.6 years; deaths were determined from the Social Security Death Master File. Survival data were compared with those from live kidney donors and healthy participants of the National Health and Nutrition Examination Survey (NHANES) III. RESULTS: Seven donors had early deaths (1.7 per 1000; 95% confidence interval [CI], 0.7-3.5); risk of death did not vary with age of the liver recipient (1.7 per 1000 for adults vs 1.6 per 1000 for pediatric recipients; P = .9) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 1.5 per 1000 for right lobe; P = .8). There were 11 catastrophic events (early deaths or acute liver failures; 2.9 per 1000; 95% CI, 1.5-5.1); similarly, risk did not vary with recipient age (3.1 per 1000 adult vs 1.6 per 1000 pediatric; P = .4) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 3.3 per 1000 for right lobe; P = .9). Long-term mortality of live liver donors was comparable to that of live kidney donors and NHANES participants (1.2%, 1.2%, and 1.4% at 11 years, respectively; P = .9). CONCLUSIONS: The risk of early death among live liver donors in the United States is 1.7 per 1000 donors. Mortality of live liver donors does not differ from that of healthy, matched individuals over a mean of 7.6 years.

Donor-transmitted malignancy in a liver transplant recipient: a case report and review of literature.

Donor-transmitted malignancy is a rare complication of organ transplantation. This case illustrates a donor-transmitted adenocarcinoma in a patient 11 months after an orthotopic liver transplant for cryptogenic cirrhosis and hepatocellular carcinoma (HCC). Diagnosis of donor-transmitted malignancy may be challenging and can be confused with HCC recurrence. A timely diagnosis is crucial as a delay may limit treatment options. Biopsy of newly found liver lesions and the use of karyotypic and microsatellite analysis may be essential for diagnosis. Protocols should be in place to help recognize and limit the incidence of donor-transmitted malignancy.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Pregnancy outcomes of liver transplant recipients: a systematic review and meta-analysis.

Approximately 14,000 women of reproductive age are currently living in the United States after liver transplantation (LT), and another 500 undergo LT each year. Although LT improves reproductive function in women with advanced liver disease, the associated pregnancy outcomes and maternal-fetal risks have not been quantified in a broad manner. To obtain more generalizable inferences, we performed a systematic review and meta-analysis of articles that were published between 2000 and 2011 and reported pregnancy-related outcomes for LT recipients. Eight of 578 unique studies met the inclusion criteria, and these studies represented 450 pregnancies in 306 LT recipients. The post-LT live birth rate [76.9%, 95% confidence interval (CI) = 72.7%-80.7%] was higher than the live birth rate for the US general population (66.7%) but was similar to the post-kidney transplantation (KT) live birth rate (73.5%). The post-LT miscarriage rate (15.6%, 95% CI = 12.3%-19.2%) was lower than the miscarriage rate for the general population (17.1%) but was similar to the post-KT miscarriage rate (14.0%). The rates of pre-eclampsia (21.9%, 95% CI = 17.7%-26.4%), cesarean section delivery (44.6%, 95% CI = 39.2%-50.1%), and preterm delivery (39.4%, 95% CI = 33.1%-46.0%) were higher than the rates for the US general population (3.8%, 31.9%, and 12.5%, respectively) but lower than the post-KT rates (27.0%, 56.9%, and 45.6%, respectively). Both the mean gestational age and the mean birth weight were significantly greater (P < 0.001) for LT recipients versus KT recipients (36.5 versus 35.6 weeks and 2866 versus 2420 g). Although pregnancy after LT is feasible, the complication rates are relatively high and should be considered during patient counseling and clinical decision making. More case and center reports are necessary so that information on post-LT pregnancy outcomes and complications can be gathered to improve the clinical management of pregnant LT recipients. Continued reporting to active registries is highly encouraged at the center level.

Center-level factors and racial disparities in living donor kidney transplantation.

BACKGROUND: On average, African Americans attain living donor kidney transplantation (LDKT) at decreased rates compared with their non-African American counterparts. However, center-level variations in this disparity or the role of center-level factors is unknown. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 247,707 adults registered for first-time kidney transplants from 1995-2007 as reported by the Scientific Registry of Transplant Recipients. PREDICTORS: Patient-level factors (age, sex, body mass index, insurance status, education, blood type, and panel-reactive antibody level) were adjusted for in all models. The association of center-level characteristics (number of candidates, transplant volume, LDKT volume, median time to transplant, percentage of African American candidates, percentage of prelisted candidates, and percentage of LDKT) and degree of racial disparity in LDKT was quantified. OUTCOMES: Hierarchical multivariate logistic regression models were used to derive center-specific estimates of LDKT attainment in African American versus non-African American candidates. RESULTS: Racial parity was not seen at any of the 275 transplant centers in the United States. At centers with the least racial disparity, African Americans had 35% lower odds of receiving LDKT; at centers with the most disparity, African Americans had 76% lower odds. Higher percentages of African American candidates (interaction term, 0.86; P = 0.03) and prelisted candidates (interaction term, 0.80; P = 0.001) at a given center were associated with increased racial disparity at that center. Higher rates of LDKT (interaction term, 1.25; P < 0.001) were associated with less racial disparity. LIMITATIONS: Some patient-level factors are not captured, including a given patient's pool of potential donors. Geographic disparities in deceased donor availability might affect LDKT rates. Center-level policies and practices are not captured. CONCLUSIONS: Racial disparity in attainment of LDKT exists at every transplant center in the country. Centers with higher rates of LDKT attainment for all races had less disparity; these high-performing centers might provide insights into policies that might help address this disparity.