Liver Transplant Recipients Research Articles

Kaposi Sarcoma in Two Lung Transplant Recipients: A Single-Center Experience

Kaposi's Sarcoma (KS) is a malignant vascular tumor commonly seen in immunocompromised individuals, particularly patients with acquired immunodeficiency syndrome. Lung transplant patients are at a high risk of developing KS due to a strong immunosuppressive regimen that can lead to donor-derived infection or reactivation of recipient human herpes virus - 8, the causative organism for KS. In this overview, we describe two recipients of lung transplants that developed pulmonary KS with poor outcomes. We review the diagnosis, bronchoscopy findings, treatment and surveillance strategies for pulmonary KS.

Isolated primary CNS lymphoma after liver transplantation for autoimmune hepatitis: a case report

Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that occurs in immunocompromised patients. It can manifest months or years after transplantation, presenting with various neurological symptoms. A 64-year-old woman, who had received a liver transplant due to autoimmune hepatitis, presented with generalized weakness, headache, and confusion. Further investigation revealed multiple ring-enhancing lesions in the right frontal and temporoparietal regions on brain MRI. A brain biopsy confirmed the diagnosis of PT-PCNSL. This case underscores the importance of considering PT-PCNSL in the differential diagnosis of contrast-enhancing brain lesions in post-transplant patients. Timely recognition of PT-PCNSL is crucial for appropriate management and improved outcomes. To the best of our knowledge, this report describes the first instance of isolated CNS lymphoma in a liver transplant recipient, due to autoimmune hepatitis, successfully brought to complete remission with a rituximab-methotrexate regimen.

Liver and pancreas transplantation in adult donor and recipients with situs inversus totalis: a case series and review of the literature

BackgroundSitus inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis.Case presentationWe describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients.ConclusionAlthough situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs.

Risk Factors for Returning of Pediatric Liver Transplant Recipients to the Intensive Care Unit

Objective To explore the risk factors for the returning of pediatric liver transplant recipients to the intensive care unit (ICU) and provide reference for the clinical decision-making after surgery. Methods A retrospective analysis was conducted with the information of all the pediatric patients who underwent liver transplantation in Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine and were returned to the ICU from 2019 to 2021.The patients returned to the ICU during hospitalization and the reasons for the return were recorded.Each patient of ICU return was matched with three pediatric patients who did not return to the ICU during hospitalization.The basic information,the vital signs and laboratory indicators on the day of transfer from ICU,immunosuppressants and drug concentrations were compared between the two groups.Multivariate Logistic regression analysis was performed to explore the risk factors for the returning of pediatric liver transplant recipients to the ICU. Results The returning rate of pediatric liver transplant recipients to the ICU was 4.36%,and it was 16.00% within 48 h.The main reasons for the return included respiratory complications,abdominal infections,and hepatic vascular occlusion.Multivariate Logistic regression analysis showed that post-operative red blood cell transfusion (OR=4.554,95%CI=1.743-11.901,P=0.002) and high serum level of uric acid (OR=1.005,95%CI=1.001-1.009,P=0.014) were the risk factors for returning to the ICU.High diastolic blood pressure (OR=0.922,95%CI=0.885-0.960,P<0.001) and high total protein level (OR=0.937,95%CI=0.891-0.986,P=0.012) were the protective factors for returning to the ICU. Conclusion Post-operative red blood cell transfusion and high serum level of uric acid are independent risk factors for the returning of pediatric liver transplant recipients to the ICU.

Machine-learning model to predict the tacrolimus concentration and suggest optimal dose in liver transplantation recipients: a multicenter retrospective cohort study

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and − 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model’s suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients.

Mechanisms of Tolerance Induction in Liver Transplantation: Lessons Learned from Fetomaternal Tolerance, Autoimmunity and Tumor Immunity.

Since the first published report of experimental kidney transplantation in dogs in 1902, there were many experimental and clinical trials of organ transplantation, with many sacrifices. After the establishment of the surgical technique and the discovery of immunosuppressive drugs, transplantation became the definitive treatment strategy for patients with terminal organ failure. However, this is not a common therapy method due to the difficulty of solving the fundamental issues behind organ transplantation, including the shortage of donor graft, potential risks of transplant surgery and economic capability. The pre- and post-transplant management of recipients is another critical issue that may affect transplant outcome. Most liver transplant recipients experience post-transplant complications, including infection, acute/chronic rejection, metabolic syndrome and the recurrence of hepatocellular carcinoma. Therefore, the early prediction and diagnosis of these complications may improve overall and disease-free survival. Furthermore, how to induce operational tolerance is the key to achieving the ultimate goal of transplantation. In this review, we focus on liver transplantation, which is known to achieve operational tolerance in some circumstances, and the mechanical similarities and differences between liver transplant immunology and fetomaternal tolerance, autoimmunity or tumor immunity are discussed.

Outpatient parenteral antibiotic therapy in non-cystic fibrosis lung transplant recipients: characteristics, efficacy and safety.

Bacterial isolation is associated with worse outcomes after lung transplantation (LTx), and successful bacterial eradication is shown to improve long-term survival and pulmonary function. Outpatient Parenteral Antibiotic Therapy (OPAT) may be an effective therapeutic modality for bacterial eradication post-LTx. A single-center, retrospective analysis of OPAT characteristics, efficacy, safety, and costs in non-cystic fibrosis LTx recipients. A total of 156 OPAT courses (from June 2019 to December 2022) were evaluated in 108 distinct LTx recipients. OPAT mainly consisted of dual antibiotic therapy (69%) for pulmonary bacterial isolation (97%), mostly Pseudomonas aeruginosa (66%). Successful eradication at 3 months post-OPAT was achieved in 71%. Eradication rate was significantly higher in patients treated after the first post-operative year (79%), compared to patients within the first year (61%) (p = 0.017). Eradication rate was similar for multidrug resistance (eradication rate 61%) versus no multidrug resistance (74%) (p = 0.116). Spirometry remained stable at 90 days post-OPAT. A statistically significant, but clinically negligible, increase in serum creatinine at 90 days post-OPAT was observed (1.33mg/dL vs. 1.39mg/dL, p < 0.001), yet unrelated to the antibiotic regimen used. OPAT-related hospital admissions occurred in 13% and line-related adverse events in 6%. Median number of hospitalization days saved per OPAT-course was 10 days (range 2-92), accounting for a total of 1841 avoided admission days and an estimated net cost reduction of 47% per treatment course. OPAT is an effective and safe therapeutic modality for bacterial eradication post-LTx, associated with a significant reduction in hospitalization days and treatment costs.

Risk Factors and Outcomes Associated With the Development of Persistent Acute Kidney Injury in Non-Renal Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Persistent acute kidney injury (pAKI), compared with acute kidney injury (AKI) that resolves in <72h, is associated with worse prognosis in critically ill patients. Definitions and prognosis of pAKI are not well characterized in solid organ transplant patients. Our aims were to investigate (a) definitions and incidence of pAKI; (b) association with clinical outcomes; and (c) risk factors for pAKI among heart, lung, and liver transplant recipients. We systematically reviewed the literature including PubMed, Embase, Web of Science, and Cochrane from inception to 8/1/2023 for human prospective and retrospective studies reporting on the development of pAKI in heart, lung, or liver transplant recipients. We assessed heterogeneity using Cochran's Q and I2. We identified 25 studies including 6330 patients. AKI (8%-71.6%) and pAKI (2.7%-55.1%) varied widely. Definitions of pAKI included 48-72h (six studies), 7days (three studies), 14days (four studies), or more (12 studies). Risk factors included age, body mass index (BMI), diabetes, preoperative chronic kidney disease (CKD), intraoperative vasopressor use, and intraoperative circulatory support. pAKI was associated with new onset of CKD (odds ratio [OR] 1.41-11.2), graft dysfunction (OR 1.81-8.51), and long-term mortality (OR 3.01-13.96), although significant heterogeneity limited certainty of CKD and graft dysfunction outcome analyses. pAKI is common and is associated with worse mortality among liver and lung transplant recipients. Standardization of the nomenclature of AKI will be important in future studies (PROSPERO CRD42022371952).

Detection of Coronary Artery Disease With Coronary Computed Tomography Angiography and Stress Testing in Candidates for Liver Transplant

Cardiac complications are the leading cause of morbidity and mortality in liver transplant (LT) recipients. Prior guidelines recommended stress testing to exclude coronary artery disease (CAD), though recent guidelines recommend coronary computed tomography angiography (CCTA). We aimed to assess the prevalence and predictors of CAD on CCTA and compare CCTA with stress testing in consecutive adult LT candidates undergoing CAD non-invasive assessment between 2020 to 2023. Patients who underwent a stress test between 01/2020 and 12/2020 formed the stress cohort, and patients who underwent CCTA between 01/2021 and 09/2023 formed the CCTA cohort. There were 141 in the stress test cohort and 269 patients in the CCTA cohort. Stress tests were non-diagnostic or inconclusive in 18 (12.8%) whereas CCTA was non-diagnostic in 6 (2.2%) patients. In patients evaluated with CCTA, mean coronary artery calcium (CAC) score was 332 ± 716 AU, with moderate or greater (>50%) stenosis in 33 (12.3%) patients. New CAD was diagnosed in 158 (58.7%) using CCTA and in 5 (3.5%) patients using stress tests. Clinically actionable CAD (CAC >100) on CCTA was present in 96 (35.7%) patients. The number of CAD risk factors were associated with the presence of CAD on CCTA. In conclusion, there was a high burden of CAD, mainly non-obstructive, in a large cohort of LT candidates undergoing CAD testing over a 4-year period. The current recommended risk-based evaluation of LT candidates using CCTA as a first line test was feasible and effective. Diagnosis of clinically actionable CAD on CCTA provides a vast opportunity for optimizing cardiac care in LT candidates and recipients.

Disparities in Liver Transplant Outcomes: Race/Ethnicity and Individual- and Neighborhood-Level Socioeconomic Status.

Race/ethnicity and individual-level socioeconomic status (SES) may contribute to health disparities in liver transplant (LT) outcomes. The socioeconomic conditions of a neighborhood may either mitigate or exacerbate these health disparities. This retrospective study investigated the relationship between race/ethnicity, individual- and neighborhood-level SES, and LT outcomes, and whether neighborhood-level SES modified the relationship between individual factors and LT outcomes. Adult individuals who underwent LT between 2010 and 2019 (n = 55,688) were identified from the United Network for Organ Sharing database. Primary exposures were race/ethnicity, education, primary insurance type, and the Social Deprivation Index (SDI) scores. Education and primary insurance type were used as proxies for individual-level SES, while SDI scores were used as a proxy for neighborhood-level SES. The primary outcome was time to occurrence of graft failure or mortality. Cox proportional hazard models were used to examine the associations between the exposures and outcomes. LT recipients who were Black (hazard ratio [HR]: 1.27, p < .0001), completed high school or less (HR: 1.06, p = .002), and had public insurance (HR: 1.14, p < .0001) had a higher rate of graft failure or mortality than those who were White, completed more than high school, and had private insurance, respectively. The SDI scores were not significantly associated with LT outcomes when adjusting for individual factors (HR: 1.02, p = .45) and did not modify the associations between individual factors and LT outcomes. Findings of this study suggest that disparities based on individual factors were not modified by neighborhood-level SES. Tailored interventions targeting the unique needs associated with race/ethnicity and individual-level SES are needed to optimize LT outcomes.

Association of Frailty With Clinical and Financial Outcomes Following Liver Transplantation.

Frailty, a measure of physiological aging and reserve, has been validated as a prognostic indicator of mortality in patients with cirrhosis. However, large-scale analyses of the independent association of frailty with clinical and financial outcomes following liver transplantation (LT) are lacking. Adults (≥18 years) undergoing LT were identified in the 2016-2020 National Readmissions Database. Frailty was defined using the binary Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable linear and logistic regression models were developed to evaluate the independent association of frailty with in-hospital mortality, perioperative complications, and costs. Of an estimated 34 442 patients undergoing LT, 8265 (24%) were frail. After adjustment, frailty was associated with greater odds of mortality (adjusted odds ratio [AOR] 1.80; 95% Confidence Interval [CI]: 1.49-1.18), postoperative length of stay (β+11 days; 95% CI:+10,+12), and hospitalization costs (+$86 880; 95% CI:+75 660,+98 100), as well as a two-fold increase in relative risk of nonhome discharge (AOR 2.17, 95% CI: 1.90-2.49). Frailty is associated with an increased risk of in-hospital mortality, complications, and resource utilization among LT recipients. As the proportion of frail LT patients continues to rise, our findings underscore the need for novel risk-stratification and individualized care protocols for such vulnerable patients.

Clinical outcomes of lung transplant recipients with pre-transplant Mycobacterium avium complex infection.

Lung transplant recipients (LTRs) are at risk for Mycobacterium avium complex (MAC) infections, in part due to the presence of structural lung disease pre-transplant and relatively higher levels of immunosuppression post-transplant. There is a lack of data regarding outcomes of LTR with MAC infections pre-transplant. This is a single-center retrospective analysis of patients who received lung transplants (LTs) from 2013 to 2020 with 1) evidence of MAC on culture or polymerase chain reaction before or at the time of transplant or 2) granulomas on explant pathology and positive acid-fast bacillus stains with no other mycobacteria identified. Patients were deemed to have MAC pulmonary disease (MAC-PD) if they met the American Thoracic Society/Infectious Disease Society of America criteria. Fourteen patients (14/882, 2%) met inclusion criteria. Seven patients (7/14, 50%) had pre-transplant MAC-PD, four of whom had cavitary disease. None of the 14 patients had smear-positive cultures at the time of transplant. Two patients in our cohort received treatment for MAC before transplant. Thirteen patients were bilateral LTR (13/14, 93%). One single LTR was the sole patient to receive MAC treatment post-transplant. No patients developed MAC-PD after transplant. The bilateral LTR in our cohort did not develop MAC-PD despite not receiving MAC treatment post-transplant. It is possible source control was achieved with native lung explantation. Our observations suggest patients may not uniformly require pre- or post-transplant MAC treatment if they are smear-negative and undergo bilateral LT.

Informatics-driven solutions for optimal care delivery in liver transplantation.

Clinical informatics, which combines health information technology and clinical expertise, aims to improve health care delivery and outcomes. For candidates and recipients of liver transplants, the complexities of their management are vast. Care often involves significant volumes of data from various sources and multiple health care settings and health care systems. Informatics represents an opportunity to support the care of these patients through this process; however, it has been underutilized to date. Preliminary examples of informatics use exist for this patient population, such as clinical decision support to link patients to hepatology providers, utilization of digital health technologies to track responses to medical therapy, and artificial intelligence to characterize organ donor compatibility. Further deployment of these tools can optimize care delivery for patients with cirrhosis and across the transplant cascade. In this review, we explore the utility of various techniques of clinical informatics mainly within the transplant care cascade, barriers to implementation, and highlight opportunities for future investigation and optimized use. Although barriers to widespread adoption remain such as interoperability, data access and availability, and structured implementation strategies, the integration of informatics and clinical decision support/artificial intelligence-based tools into routine care for liver transplantation represents an opportunity for marked enhancement in how we deliver care to these patients.

Waitlist outcomes of pediatric recipients of liver transplant relisted as adults.

Waitlist outcomes of pediatric recipients of liver transplant relisted as adults.

Population pharmacokinetics study of tacrolimus in liver transplant recipients: a comparison between patients with or without liver cancer before surgery.

The main challenge for immunosuppressive therapy using tacrolimus in liver transplantation is the considerable variability in its oral bioavailability and the narrow treatment range. Many population pharmacokinetic (PopPK) models have been established to precisely estimate the PK variability of tacrolimus in liver transplant recipients. However, it remains unclear whether there is a significant difference in the PK behavior of tacrolimus between patients with or without liver cancer before surgery. Therefore, we aimed to compare the differences of PK parameters and simulate exposures of tacrolimus between populations preoperatively diagnosed with liver cancer or not by PopPK modeling. In total, 802 blood concentrations of tacrolimus from 196 patients (118 liver cancer and 78 non-liver-cancer samples) were included in this study. Demographic data and clinical parameters were integrated to perform a PopPK analysis using the nonlinear mixed-effects modeling approach. Potential covariates were evaluated by using a stepwise method. Goodness-of-fit plot and bootstrap were performed to assess the model stability and predictive performance. Simulations were introduced to optimize dosing regimens of both the liver cancer and non-liver-cancer groups according to the guidance. The PK of tacrolimus was best described by a one-compartment model with first-order absorption and linear elimination, with weight and direct bilirubin as the significant covariates. In the process of constructing the basic model, we tried to separately estimate the PK parameters in liver cancer and non-liver-cancer populations. The results showed that the PK parameters in the two populations were similar, and the individual variation in Ka in non-liver-cancer subjects was large. Hence, the final model did not distinguish between the two populations. Moreover, a minor increase of less than 10% was observed in the simulated exposure in the patients preoperatively diagnosed with liver cancer compared with that in non-liver-cancer groups. The established PopPK model was capable of optimizing tacrolimus dosing in whole populations who underwent liver transplantation. Although a minimal difference was found in tacrolimus exposure between the liver cancer and non-liver-cancer groups, more research is warranted to explore the differences between the two populations in the future, given the potential limitations of this study.

Human Liver Organoids to Predict the Outcome of Kasai Portoenterostomy

BackgroundKasai portoenterostomy (KPE) remains the primary intervention for biliary atresia (BA), but its outcomes are highly variable. Reliable prognostic biomarkers remain elusive, complicating the management and prediction of postoperative progression. MethodLiver biopsies from BA patients taken at and after KPE (post-KPE) were used to generate organoids for RNA-sequencing analysis. Control organoids were derived from non-BA livers. Differential gene expression and enrichment analyses were performed to assess post-KPE transcriptomic changes between native liver survivors (NLS) and patients who eventually became liver transplant recipients (LTR). ResultsOrganoid datasets: 70 from liver biopsies at KPE (10 patients), 112 from post-KPE livers (13 livers; 12 patients), and 47 from control livers (9 patients). At KPE, BA organoids displayed mainly hepatocyte expression, a trait notably reduced in control organoids. Similarly, post-KPE organoids from NLS revealed a significant decrease in hepatocyte expression features and an overall increase in cholangiocyte expression features. A similar hepatocyte-to-cholangiocyte expression transition was evidenced in paired liver organoids (at- and post-KPE) generated from an NLS. In contrast, post-KPE organoids from LTR maintained a high level of hepatocyte expression features. ConclusionOur study demonstrated that an elevated expression of hepatocyte features in KPE organoids may indicate aberrant cholangiocyte development in BA livers. In contrast, a post-KPE hepatocyte-to-cholangiocyte expression transition in NLS may imply effective biliary recovery. The lack of this transition in LTR organoids indicates ongoing disease progression, highlighting the potential for organoid-based transcriptomic profiling to inform KPE success and guide BA management. Level of EvidenceLevel III.

Utilizing Generalized Linear Mixed Effects Models for Prediction of Bone Mineral Decrease After Lung Transplant - A Preliminary Study.

Recipients of lung transplants are at heightened risk of developing low bone mineral density (BMD). They also have increased risk of developing osteoporosis-related fractures. This rate of BMD decline is not well characterized. The aim of this manuscript is to characterize the rate of BMD decrease after lung transplant. This is a preliminary retrospective cohort study of 200 patients who received lung transplants. Each patient had pre-transplant dual energy X-ray absorptiometry (DXA) and post-transplant DXA scans on the same DXA scanner. The BMD at each lumbar vertebra, total hip, and femoral neck were recorded. Generalized linear mixed effects models with random intercepts and random slopes were used to model the rate of change of BMD after transplant, adjusting for time since transplant, sex, and sex*time interaction. We found that men had higher baseline BMD than women at all sites (P<0.05 for all). The rate of BMD decrease was fastest at the femoral neck (P<0.05). Men lost BMD at a faster rate (-5.23 x10-5 g/cm2/day) than women at the femoral neck (-2.22 x10-5 g/cm2 /day). BMD decreases after lung transplant and occurs faster in men than women.

Perioperative Use of IgM-Enriched Immunoglobulins in Liver Transplantation Recipients at High Risk for Infections: A Preliminary Study.

Background: Infections frequently occur after orthotopic liver transplantation (OLT) and are associated with increased mortality. In 2018, we introduced perioperative administration of intravenous immunoglobulin enriched in IgM as an optional therapy in recipients at a high risk of infection. This preliminary study evaluated whether this preparation reduced infections in the early post-transplantation period. Methods: Adult patients with a high risk of postoperative infections who underwent OLT between January 2014 and December 2021 in our center were included in the study. The primary outcome was the occurrence of new postoperative bacterial and fungal infections within the first 30 days after OLT. Results: Ninety recipients at a high risk of postoperative infections who underwent OLT were included, of whom 51 (57%) received IgM preparation. Patients treated and not treated with IgM were similar in terms of demographics, model of end-stage liver disease score, and risk factors for postoperative infections. The occurrence of new infections was lower (absolute risk reduction (ARR) 21.2%; p = 0.038) in patients who received IgM than in those who did not. Multivariate analysis adjusted for confounders (OR 0.348; p = 0.033) and propensity score-based matching analysis (ARR 21.2%, p = 0.067) confirmed an association between IgM preparation and lower occurrence of postoperative infections. The 90-day mortality rate was lower (ARR 13.4%, p = 0.018) in patients who received IgM preparation. Conclusions: In OLT recipients at high risk for infections, perioperative administration of an IgM-enriched preparation seems to reduce the development of new infections within the first 30 days after OLT.

Intrinsic Causes of Nonfibrotic Portal Hypertension-A Clinicopathologic Review of 56 Patients.

Aim: The differential diagnosis of intrinsic nonfibrotic conditions that may lead to portal hypertension include hepatoportal sclerosis (HPS), nodular regenerative hyperplasia (NRH), and sinusoidal obstruction syndrome (SOS). In this article, we characterize the clinical features and outcome of these lesions when they manifest as portal hypertension. Methods: Data was collected through retrospective patient medical records. Results: Patients (HPS: 28, NRH: 17, SOS: 11) were identified more frequently in recent years. All groups presented with signs and symptoms of portal hypertension. All patients had complex medical histories. An elevated serum alkaline phosphatase occurred in all groups and an elevated bilirubin with SOS. Imaging of the liver with HPS and NRH suggested cirrhosis, which was not seen with SOS. 11%, 12%, and 9% of patients in the HPS, NRH, and SOS respectively, underwent transjugular intrahepatic portosystemic shunt placement to manage the complications of portal hypertension, while 43%, 24%, and 36% of patients respectively, received a liver transplant. Conclusions: Patients with HPS, NRH, and SOS had complex medical histories, likely contributing to the development of these lesions. They are recognized more frequently now. In contrast to HPS and NRH, SOS occurred in liver transplant recipients, was associated with elevated serum bilirubin, and imaging did not suggest the presence of advanced fibrosis/cirrhosis. Liver transplantation appeared to be a viable treatment for complications related to HPS and NRH. Retransplantation for SOS yielded mixed results. HPS, SOS, and NRH should be considered when evaluating liver specimens from patients with unexplained nonfibrotic portal hypertension. Key message: Intrinsic nonfibrotic causes of portal hypertension appear to be increasing in frequency. The differential diagnosis includes NRH, HPS, and SOS. These conditions are associated with complex diseases and possibly due to treatments. Pathologists need to be aware of this differential diagnosis when presented with liver biopsies performed to assess portal hypertension.

Significantly reduced patient and graft survival for left vs right donor lungs for lung transplant recipients

Significantly reduced patient and graft survival for left vs right donor lungs for lung transplant recipients