Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

The Association Between Solid Organ Transplant and Recurrence of Acute Diverticulitis: A National Assessment.

OBJECTIVE: Compare rates and severity of recurrent acute diverticulitis in patients with and without solid organ transplant. SUMMARY BACKGROUND DATA: Immunocompromised solid organ transplant recipients have been considered higher risk for both recurrence and severity of acute diverticulitis. Current guidelines recommend an individualized approach for colectomy in these patients, but these are based on single-center data. METHODS: We identified patients with acute diverticulitis using the Merative MarketScan commercial claims data from 2014-2020. Patients were classified by history of solid organ transplant. The primary outcome was recurrence of acute diverticulitis with an associated antibiotic prescription ≥60 days from the initial episode. Secondary outcomes included hospitalization, colectomy, and ostomy in patients with recurrence. Analyses used inverse probability weighting to adjust for imbalances in covariates. RESULTS: Of 170,697 patients with evidence of acute diverticulitis, 442 (0.2%) had a history of solid organ transplantation. In the weighted cohort, among people who had not been censored at one year (n=515), 112 (22%; 95% CI 20%-25%) experienced a recurrence within the first year. Solid organ transplantation was not significantly associated with a risk of recurrence (HR 1.19; 95% CI 0.94-1.50). There was also no statistically significant difference in the hospitalization rate for recurrent diverticulitis. Restricting the analysis to hospitalized recurrences, there was no statistically significant difference observed in either length of stay or discharge status. CONCLUSIONS: In this national analysis of commercially-insured patients with acute diverticulitis we found no statistically significant differences in recurrence between those with and without a history of solid organ transplant. We do not support an aggressive colectomy strategy based on concern for increased recurrence rate and severity in a solid organ transplant population.

Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy.

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.

Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

BACKGROUND AND AIMS: The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation. APPROACH AND RESULTS: Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support. Livers maintained normal global appearance, uniform perfusion, and preservation of histologic and subcellular architecture. Oxygen consumption increased by 75% ( p = 0.16). Lactate clearance increased from -0.4 ± 15.5% to 31.4 ± 19.0% ( p = 0.02). Blinded histopathologic assessment demonstrated improved injury scores at 24 hours compared with 12 hours. Vascular integrity and vasoconstrictive function were preserved. Bile volume and cholangiocellular viability markers improved for all livers. Biliary structural integrity was maintained. CONCLUSIONS: Xenogeneic cross-circulation provided multisystem physiological regulation of ex vivo human livers that enabled functional rehabilitation, histopathologic recovery, and improvement of viability markers. We envision xenogeneic cross-circulation as a complementary technique to other organ-preservation technologies in the recovery of marginal donor livers or as a research tool in the development of advanced bioengineering and pharmacologic strategies for organ recovery and rehabilitation.

Recurrent Portal Vein Thrombosis In Liver Transplantation With Renoportal Anastomosis Caused by Spontaneous Reno-Caval Shunts: A Case Report.

BACKGROUND: Orthotopic liver transplantation (OLT) in patients with cirrhosis complicated by portal hypertension, portosystemic shunts, and chronic portal vein thrombosis (PVT) has long been challenging. Spontaneous spleno-renal shunts (SRS) allow new surgical techniques to restore portal vein patency and hepatopetal flow. Renoportal anastomosis (RPA) has emerged as an accepted method for transplanting these patients, with good long-term patient and graft survival. Orthotopic liver transplantation with RPA is known to be complicated by recurrent PVT, with few details discussed in the literature. CASE REPORT: We present a case of a 56-year-old woman with decompensated cirrhosis who underwent deceased donor whole graft OLT using RPA with iliac vein conduit. The postoperative course was complicated by occlusive thrombosis in the portal vein and iliac vein conduit. Venography revealed enlarged left gonadal and lumbar vein varices acting as reno-caval shunts with hepatofugal flow. Embolization of the varices re-established durable venous patency that was confirmed on post-transplant day 68 with no other hemodynamic complications. DISCUSSION: This showcases an interesting mechanism by which recurrent PVT may occur in patients undergoing OLT with RPA. Because durable portal vein patency can be achieved with Interventional Radiology embolization of reno-caval varices, assessing these communications is an important preoperative consideration for planned OLT with RPA.

Immune characterization of a xenogeneic human lung cross-circulation support system.

Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed for the growing population with end-stage lung disease. Cross-circulation (XC) of whole blood between swine and explanted human lungs has previously been reported to enable the extracorporeal recovery of donor lungs that declined for transplantation due to acute, reversible injuries. However, immunologic interactions of this xenogeneic platform have not been characterized, thus limiting potential translational applications. Using flow cytometry and immunohistochemistry, we demonstrate that porcine immune cell and immunoglobulin infiltration occurs in this xenogeneic XC system, in the context of calcineurin-based immunosuppression and complement depletion. Despite this, xenogeneic XC supported the viability, tissue integrity, and physiologic improvement of human donor lungs over 24 hours of xeno-support. These findings provide targets for future immunomodulatory strategies to minimize immunologic interactions on this organ support biotechnology.

Pulmonary artery banding in sheep: a novel large animal model for congestive hepatopathy.

Congestive hepatopathy is becoming increasingly recognized among Fontan-palliated patients. Elevated central venous pressure is thought to drive the pathologic progression, characterized by sinusoidal dilatation, congestion, and fibrosis. A clinically relevant large animal model for congestive hepatopathy would provide a valuable platform for researching novel biomarkers, treatment, and prevention. Here, we report on a titratable, sheep pulmonary artery banding model for this disease application. Pulmonary artery banding was achieved by progressively inflating the implanted pulmonary artery cuff. Right ventricular catheter was implanted to draw venous blood samples and measure pressure. The pulmonary artery cuff pressure served as a surrogate for the intensity of pulmonary artery banding and was measured weekly. After about 9 wk, animals were euthanized, and the liver was harvested for histopathological assessment. Nine animal subjects received pulmonary artery banding for 64 ± 8 days. Four of the nine subjects exhibited moderate to severe liver injury, and three of those four exhibited bridging fibrosis. Increasing pulmonary artery cuff pressure significantly correlated with declining mixed venous oxygen saturation (P = 3.29 × 10-5), and higher congestive hepatic fibrosis score (P = 0.0238), suggesting that pulmonary artery banding strategy can be titrated to achieve right-sided congestion and liver fibrosis. Blood analyses demonstrated an increase in plasma bile acids, aspartate aminotransferase, and γ-glutamyltransferase among subjects with moderate to severe injury, further corroborating liver tissue findings. Our large animal pulmonary artery banding model recapitulates congestive hepatopathy and provides a basis to bridge the current gaps in scientific and clinical understanding about the disease.NEW & NOTEWORTHY We present here a large animal platform for congestive hepatopathy, a disease growing in clinical prevalence due to the increasing number of Fontan-palliated patients. Further data are needed to develop a better clinical management strategy for this poorly characterized patient population. Previous reports of animal models to study this disease have mostly been in small animals with limited fidelity. We show that congestive hepatopathy can be replicated in a chronic, progressive pulmonary artery banding model in sheep. We also show that the banding strategy can be controlled to titrate the level of liver injury. To date, we do not know of any other large animal model that can achieve this level of control over disease phenotype and clinical relevance.

Comparison of Invasive Pancreatic Ductal Adenocarcinoma versus Intraductal Papillary Mucinous Neoplasm: A National Cancer Database Analysis.

BACKGROUND: Current evidence on overall survival (OS) between invasive pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) is limited to single-center reports. We aimed to compare the characteristics, management, and OS of invasive PDAC vs. IPMN using a national United States (US) database. METHODS: Invasive PDAC or IPMN adult (≥18 years) patients were identified in the National Cancer Database (2004-2016). OS was assessed with the Kaplan-Meier method and the stratified log-rank test. RESULTS: We included 101,190 patients (100,834 PDAC, 356 IPMN). A higher proportion of PDAC vs. IPMN patients had clinical N1 (36.8% vs. 15.7%, p < 0.001) and M1 disease (41.2% vs. 5.9%, p < 0.001). A lower proportion of PDAC patients underwent surgery (25.5% vs. 80.3%, p < 0.001), but a higher proportion received chemotherapy (65.4% vs. 46.1%, p < 0.001) or radiation (25.3% vs. 20.5%, p = 0.04). A higher proportion of surgical patients with PDAC vs. IPMN underwent margin-positive resection (23.0% vs. 14.0%, p = 0.001). The median OS for PDAC vs. IPMN was 8.3 vs. 33.4 months. In the stratified analysis for N0M0 disease, the median OS for PDAC vs. IPMN was 12.8 vs. 43.3 months, for N1M0, it was 11.5 vs. 17.0 months, while for M1, it was 4.0 vs. 7.0 months. In both diagnoses, surgery yielded improved OS, while stratified analysis in the surgical cohort demonstrated similar findings. CONCLUSIONS: Invasive PDAC is more aggressive than invasive IPMN, yet in the case of metastasis, OS is equally poor. Excellent long-term OS is achievable with surgical resection in highly selected cases, and efforts should focus on facilitating surgical treatment.

Update on combined heart and liver transplantation: evolving patient selection, improving outcomes, and outstanding questions.

PURPOSE OF REVIEW: Combined heart and liver transplantation (CHLT) is an uncommon but increasingly performed procedure with rising need as the population who has undergone Fontan palliation for single ventricle physiology grows. This article reviews the current literature to summarize what is known about patient selection and outcomes and highlights the questions that remain. RECENT FINDINGS: Congenital heart disease (CHD) with Fontan-associated liver disease (FALD) has surpassed noncongenital heart disease as the most common indication for CHLT. In patients with failing Fontan physiology, accurate assessment of recoverability of liver injury remains challenging and requires multifaceted evaluation to determine who would benefit from isolated versus dual organ transplantation. Patient survival has improved over time without significant differences between those with and without a diagnosis of CHD. En bloc surgical technique and best use of intraoperative mechanical circulatory support are topics of interest as the field continues to evolve. SUMMARY: A more refined understanding of appropriate patient selection and indication-specific outcomes will develop as we gain more experience with this complex operation and perform prospective, randomized studies.

Successful liver transplantation in patients with active SARS-CoV-2 infection.

The Coronavirus Disease 2019 (COVID-19) pandemic has substantially impacted solid organ transplantation, including temporary inactivation of waitlist candidates with COVID-19 infection. We report two cases of liver transplantation (LT) in individuals with asymptomatic COVID-19 infection. The first patient is a 68-year-old female with decompensated cirrhosis complicated by worsening frailty and sarcopenia. The second patient is a 22-year-old female with acute liver failure likely secondary to drug/toxin exposure. Both patients were treated with COVID-19-directed therapies and neither patient developed symptomatic disease. These cases demonstrate that LT can be safely performed in select patients with asymptomatic COVID-19 infection at the time of transplant.

Pediatric Liver Transplant Survival in Alagille Syndrome Is Comparable to Biliary Atresia-A Linked Database Analysis.

OBJECTIVES: This study aims to report liver transplantation (LT) outcomes and cardiac disease manifestations in children with Alagille Syndrome (ALGS) in a contemporary cohort. METHODS: This project used a novel linkage between the Scientific Registry of Transplant Recipients and Pediatric Health Information System databases. All children ≤21 years undergoing a first LT were identified (2002-2018). The presence of ALGS was identified using Scientific Registry of Transplant Recipients diagnosis coding. Subjects with ALGS were age-matched 1:2 to LT recipients with biliary atresia (BA). The Kaplan-Meier method and log-rank test were used to compare patient and graft survival between groups. RESULTS: A total of 156 LT recipients with ALGS were identified and matched to a control group of 312 LT recipients with BA. Children with ALGS were more likely to have an associated diagnosis of congenital heart disease (80.7% vs 16.4%; P = 0.001) compared with children with BA with 40 (25.6%) children with AGS requiring cardiac intervention (catheter or surgical) either before or after LT. Those patients with ALGS had a higher creatinine, laboratory MELD, and PELD scores before LT. No difference was observed regarding patient or graft survival between children with ALGS and children with BA ( P = 0.08 and P = 0.27, respectively). CONCLUSIONS: Despite increased rate of congenital heart defects and cardiac interventions, higher creatinine, and higher laboratory MELD/PELD scores at time of transplant, this study demonstrates that there is no difference in either patient or graft survival between patients with ALGS and BA.

Proposing a Sex-Adjusted Sodium-Adjusted MELD Score for Liver Transplant Allocation.

Importance: Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex. Objective: To use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment. Design, Setting, and Participants: A retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant waiting list data from the liver simulated allocation modeling system. Patients who regularly used VUMC with measurements for any MELDNa component laboratory were included in the analyses. Analysis took place from November 2019 to March 2021. Exposures: Electronic health record-reported sex. Main Outcomes and Measure: Creatinine, bilirubin, international normalized ratio, and sodium levels. Results: The VUMC sample was composed of 623 931 individuals (359 976 [57.7%] female) with a median (IQR) age of 44 (23-61) years. All component MELDNa laboratory values and calculated MELDNa scores yielded significant sex differences within VUMC (mean [SD] creatinine: male, 0.99 [0.39] mg/dL; female, 0.79 [0.30] mg/dL; P < .001; bilirubin: male, 0.76 [0.83] mg/dL; female, 0.58 [0.64] mg/dL; P < .001; international normalized ratio of prothrombin rate: male, 1.24 [0.42]; female, 1.20 [0.40]; P < .001; sodium: male, 139.00 [2.36] mEq/L; female, 139.03 [2.28] mEq/L; P < .001), resulting in MELDNa scoring that disadvantaged female individuals. This pattern persisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD]: male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD]: male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death. Conclusions and Relevance: These results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.

Extracorporeal membrane oxygenation in patients with hepatopulmonary syndrome undergoing liver transplantation: A systematic review of the literature.

BACKGROUND: Isolated cases of extracorporeal membrane oxygenation (ECMO) in patients with hepatopulmonary syndrome (HPS) undergoing liver transplantation (LT) have been reported with increasing frequency. We aimed to systemically review and synthesize the available literature on ECMO use in this population. METHODS: A systematic literature review of the PubMed, Web of Science, Cochrane Library, and Embase databases (end-of-search date: November 14, 2021) was conducted in accordance with the PRISMA statement. Eligible studies presented clinical parameters and outcomes of adult or pediatric patients with HPS receiving ECMO support at the time of, or following, LT. RESULTS: Sixteen studies from 4 continents reporting on 17 patients who were initiated on ECMO prior to (n = 2), during (n = 1) or after LT (n = 14) were included. Nine of the 16 studies were published between 2019 and 2021. The median pre-LT PaO2 was 38.0 mmHg (IQR 35.0-52.0). The median time from LT to ECMO initiation was 7 days (IQR, 3-12). Six patients (50%, n = 6 of 12) were extubated post-LT, before deterioration, development of refractory hypoxemia, and initiation of ECMO. Most patients were cannulated with a venovenous configuration (75%, n = 12 of 16). Most patients cannulated with a venoarterial or veno-arterial-venous strategy (75%, n = 3 of 4) had concurrent hemodynamic instability. The median total time on ECMO was 13 days (IQR 10-29). Using linear regression, for patients cannulated postoperatively, each day between LT and ECMO initiation was associated with a 3.5-day increase in total ECMO duration (95%CI: 2.23-4.73, p < 0.001, R2 = 73.7%). The median postoperative intensive care unit length of stay was 40 days (IQR, 37-61) and hospital length of stay was 59.5 days (IQR 42-77). 82.4% of patients (14 of 17) survived to discharge. CONCLUSIONS: ECMO is feasible in patients with HPS undergoing LT and appears to be associated with better outcomes compared to other causes of cardiopulmonary failure in LT patients. As the volume of experience grows, ECMO may become a central part of perioperative support in LT patients with severe HPS.

Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review.

Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases (end-of-search date: 31 July 2020). Our outcomes were overall survival (OS) and disease-free survival (DFS). We evaluated the effect of clinically relevant variables on outcomes using the Kaplan-Meier method and log-rank test. Sixty-seven studies reporting on 245 children undergoing LT for HCC were included. DFS data were available for 150 patients and the 1-, 3-, and 5-year DFS rates were 92.3%, 89.1%, and 84.5%, respectively. Sixty of the two hundred and thirty-eight patients (25.2%) died over a mean follow up of 46.8 ± 47.4 months. OS data were available for 222 patients and the 1-, 3-, and 5-year OS rates were 87.9%, 78.8%, and 74.3%, respectively. Although no difference was observed between children transplanted within vs. beyond Milan criteria (p = 0.15), superior OS was observed in children transplanted within vs. beyond UCSF criteria (p = 0.02). LT can yield favorable outcomes for pediatric HCC beyond Milan but not beyond UCSF criteria. Further research is required to determine appropriate LT selection criteria for pediatric HCC.

A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer.

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.

A Single-Center Study of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Recurrence in Recipients of Liver Transplant for Treatment of Nonalcoholic Steatohepatitis Cirrhosis.

OBJECTIVES: Nonalcoholic steatohepatitis is a growing indication for liver transplant. We examined multiple granular elements to determine risk factors for recurrence of nonalcoholic steatohepatitis or recurrence of nonalcoholic fatty liver disease. MATERIALS AND METHODS: This is a retrospective, single-center study of patients who underwent liver transplant for nonalcoholic steatohepatitis. Demographic differences were assessed with the Wilcoxon and Pearson tests for continuous and discrete variables, respectively. We used a linear mixed effects model to estimate mean changes in body mass index and laboratory measurements. Time to graft loss was analyzed with the Cox proportional hazards model. RESULTS: From 1998 to 2017, there were 275 patients at our center who underwent liver transplant as treatment for nonalcoholic steatohepatitis cirrhosis. Of these patients, 31 (11%) were diagnosed with recurrent nonalcoholic steatohepatitis and 60 (22%) had recurrent nonalcoholic fatty liver disease. Patients with or without recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease were similar with regard to Model for End-Stage Liver Disease score, body mass index, sex, ethnicity, comorbidity, and donor characteristics, including donor macrosteatosis. Exposures to several medication classes were examined, but there was no association with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease. Changes in aspartate aminotransferase and alanine aminotransferase levels over time were correlated with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease versus levels observed in the groups with no recurrent disease. There was no difference in graft survival for the groups with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease. CONCLUSIONS: Recurrence of nonalcoholic fatty liver disease and recurrence of nonalcoholic steatohepatitis were not associated with increased mortality after liver transplant. There were notable steady increases in body mass index after transplant for all patients who received liver transplant as treatment for nonalcoholic steatohepatitis.

Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature.

BACKGROUND: Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. METHODS: All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. RESULTS: A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. CONCLUSIONS: LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Liver transplant after donation from controlled circulatory death versus brain death: A UNOS database analysis and publication bias adjusted meta-analysis.

BACKGROUND: Donation after circulatory death (DCD) is an increasingly utilized alternative to donation after brain death (DBD) to expand the liver donor pool. We compared the outcomes of liver transplant (LT) after DCD versus DBD. METHODS: A PRISMA-compliant systematic literature review was performed using the PubMed, Cochrane Library, and Embase databases (end-of-search-date: July 2, 2020). US outcomes were analyzed using the UNOS database (February, 2002-September, 2020). Pooled hazard ratios (HR) for patient and graft survival were obtained through random effect meta-analyses and adjusted for publication bias. RESULTS: Thirteen studies reporting on 1426 DCD and 5385 DBD LT recipients were included. 5620 DCD and 87561 DBD LT recipients were analyzed from the UNOS database. Meta-analysis showed increased risk of patient mortality for DCD (HR = 1.36; 95%CI, 1.09-1.70; P = .01; I2  = 53.6%). When adjusted for publication bias, meta-analysis showed no difference in patient survival between DCD and DBD (HR = 1.15; 95%CI, .91-1.45; P = .25; I2  = 61.5%). Meta-analysis showed increased risk of graft loss for DCD (HR = 1.50; 95%CI, 1.20-1.88; P < .001; I2  = 67.8%). When adjusted for publication bias, meta-analysis showed a reduction in effect size (HR = 1.36; 95%CI, 1.06-1.74; P = .02; I2  = 73.5%). CONCLUSION: When adjusted for publication bias, no difference was identified between DCD and DBD regarding patient survival, while DCD was associated with an increased risk of graft loss.