Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multi-Center, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). SUMMARY BACKGROUND DATA: End-ischemic NMP is often used to aid logistics, yet its' impact on outcomes after LT remains unclear, as does its' true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at two centers (1/1/2019-6/30/2023) were included. Retransplants, splits and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra®) was implemented 10/2022 for extended-criteria DBDs, all DCDs and logistics. NMP-cases were matched 1:2 with cold storage controls (SCS) using the Balance-of-Risk (DBD-grafts) and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index (CCI) values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day CCI (27.6 vs. 41.9, P=0.028). NMP also reduced the need for early relaparotomy and renal-replacement-therapy, with subsequently less-frequent major complications (Clavien-Dindo >IVa). This effect was more pronounced in DCD-transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pre-transplant costs in context of shorter waiting-list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD-grafts, and overall complications and post-LT renal-replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day-healthcare costs-per-transplantation were comparable.

The Impact of Normothermic Machine Perfusion and Acuity Circles on Waitlist Time, Mortality and Cost in Liver Transplantation: A Multi-Center Experience.

BACKGROUND: Ex-situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. METHODS: Adult patients listed for liver transplant (LT) at two academic centers 1/1/2015-9/1/2023 were included (n=2773) to allow all patients >6-months follow-up from listing. Routine NMP was implemented on 10/14/2022. Waitlist outcomes were compared from pre-NMP pre-acuity-circles (n=1,460), pre-NMP with acuity circles (n=842) and with NMP (n=381). RESULTS: Median waitlist time was 79days (IQR 20-232 d) at baseline, 49days (7-182) with acuity circles, and 14days (5-56) with NMP (p<0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles, and 194-per-100-person-years with NMP (p<0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460), to 13.3% (n=112/843), to 6.3% (n=24/381) p<0.001) with NMP. Incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP (p<0.001). Median MELD at LT was lowest with NMP, but MELD at listing was highest in this era (p<0.0001). Median DRI of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP (p<0.001). Six-month post-LT survival was not different between eras (p=0.322). The total cost of healthcare while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p<0.001); cost-per-day did not differ between eras (p=0.152). CONCLUSION: Implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced healthcare costs.

Intensive locoregional therapy before Liver Transplantation for colorectal cancer liver metastasis: A novel pre-transplant protocol.

BACKGROUND: We describe a novel pre-liver-transplant (LT) approach in colorectal liver metastasis (CRLM) allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. METHODS: Patients undergoing LT for CRLM at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by PET scan and CEA. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. RESULTS: Nine patients received liver transplant out of 27 who were evaluated (33.3%). Median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease and four had treatment-induced cirrhosis. Pre-transplant management included chemotherapy (n=9) +/- Bevacizumab (n=6) and/or Anti-EGFR (n=6). Median pre-LT cycles of chemotherapy=16 (Range 10-40). Liver-directed therapy included Yttrium-90 (n=5), ablation (n=4), resection (n=4), and HAI-pump (n=3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n=6/8) and 60% (n=3/5). Recurrence occurred in the lungs (n=1), liver graft (n=1), and lungs+paraaortic nodes (n=1). Patients with pre-LT detectable disease had reduced RFS (p=0.04). All patients with recurrence had histologically-viable tumor in the liver explant. Patients treated in our protocol (n=16) demonstrated improved survival versus those who were not candidates (n=11) regardless of transplant status (p=0.01). CONCLUSION: A protocol defined by aggressive pre-transplant liver-directed treatment and transplant for patients with undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.

Combined Liver Transplant and Cardiac Surgery: Long-Term Outcomes and Predictors of Success.

OBJECTIVE: We aim to report our institutional outcomes of single-staged combined liver transplantation (LT) and cardiac surgery (CS). SUMMARY BACKGROUND DATA: Concurrent LT and CS is a potential treatment for combined cardiac dysfunction and end-stage liver disease, yet only 54 cases have been previously reported in the literature. Thus, the outcomes of this approach are relatively unknown, and this approach has been previously regarded as extremely risky. METHODS: Thirty-one patients at our institution underwent combined cardiac surgery and liver transplant. Patients with at least one-year follow-up were included. The Leave-One-Out Cross-Validation (LOOCV) machine-learning approach was used to generate a model for mortality. RESULTS: Median follow-up was 8.2 years (IQR 4.6-13.6 y). One- and five-year survival was 74.2% (N=23) and 55% (N=17), respectively. Negative predictive factors of survival included recipient age>60 years (P=0.036), NASH-cirrhosis (P=0.031), Coronary Artery Bypass-Graft (CABG)-based CS (P=0.046) and pre-operative renal dysfunction (P=0.024). The final model demonstrated that renal dysfunction had a relative weighted impact of 3.2 versus CABG (1.7), age ≥60y (1.7) or NASH (1.3). Elevated LT+CS risk score was associated with an increased five-year mortality after surgery (AUC=0.731, P=<0.001). Conversely, the widely accepted STS-PROM calculator was unable to successfully stratify patients according to 1- (P>0.99) or 5-year (P=0.695) survival rates. CONCLUSIONS: This is the largest series describing combined LT+CS, with joint surgical management appearing feasible in highly selected patients. CABG and pre-operative renal dysfunction are important negative predictors of mortality. The four-variable LT+CS score may help predict patients at high risk for post-operative mortality.

Successful orthotopic liver transplantation in a patient with a positive SARS-CoV2 test and acute liver failure secondary to acetaminophen overdose.

SARS-CoV2, first described in December 2019, was declared a pandemic by the World Health Organization in March 2020. Various surgical and medical societies promptly published guidelines, based on expert opinion, on managing patients with COVID-19, with a consensus to postpone elective surgeries and procedures. We describe the case of an orthotopic liver transplantation (OLT) in a young female who presented with acute liver failure secondary to acetaminophen toxicity to manage abdominal pain and in the setting of a positive SARS-CoV2 test. Despite a positive test, she had no respiratory symptoms at time of presentation. The positive test was thought to be residual viral load. The patient had a very favorable outcome, likely related to multiple factors including her young age, lack of respiratory COVID-19 manifestations and plasma exchange peri-operatively. We recommend a full work-up for OLT in COVID-19 patients with uncomplicated disease according to standard of care, with careful interpretation of COVID-19 testing in patients presenting with conditions requiring urgent or emergent surgery as well as repeat testing even a few days after initial testing, as this could alter management.

Coronavirus disease 2019 in an orthotopic liver transplant recipient living with human immunodeficiency virus.

Coronavirus disease 2019 (COVID-19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with flu-like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID-19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well-controlled HIV who successfully recovered from a mild, flu-like illness attributed to SARS-CoV-2.

Post liver transplant short term and survival outcomes in patients living with obesity.

The objectives of our study were to examine and compare patient and graft survival over a 5-year period across BMI groups, and examine immediate and short-term complications post-LT. This was a retrospective study that examined all liver transplants that occurred at our institution between January 2015-October 2022. Patients were divided into 4 BMI groups (n = 888): normal-overweight (BMI 18.5- 29.9 kg/m2), class I obesity (BMI 30-34.9 kg/m2), class II obesity (BMI 35-39.9 kg/m2), and class III obesity (BMI ≥40 kg/m2) patients. Kaplan Meier curves with the log rank test were created to assess survival outcomes and multivariate Cox regression analysis was performed. Patient and graft survival did not differ statistically between each BMI group. However, patient survival was significantly lower in patients with BMI ≥40 compared to patients with BMI <40. In multivariate analysis, BMI ≥40, admission to the ICU, and age were independent predictors of increased risk of mortality. Infection, arrhythmia, cardiac arrest, and myocardial infarction were more frequent immediate complications in the class III obesity group. Efforts to closely monitor patients with BMI ≥40 post LT to maximize survival are needed. Further studies are needed to improve post LT survival among patients with BMI ≥40.

Thromboelastography characteristics in critically ill patients with liver disease.

OBJECTIVE: The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT). BACKGROUND: TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice. STUDY: This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019. RESULTS: The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA. CONCLUSION: Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience.

BACKGROUND: Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre. METHODS: A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan-Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. RESULTS: Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9-147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% ( n =504) and 86.6% ( n =493). Five-year RFS and OS were 78.9% ( n =449) and 79.1% ( n =450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9-0.95). Tumour size greater than 3 cm ( P =0.012), increasing tumour number on imaging ( P =0.001) and explant pathology ( P <0.001) was associated with recurrence. Transplant within Milan ( P <0.001) or UCSF criteria ( P <0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence ( P <0.001) and reduced OS ( P =0.008). Chemoembolization was predictive of recurrence in the overall population ( P =0.043) and in those outside-Milan criteria ( P =0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS ( P <0.001) in the total cohort and predict both, RFS ( P =0.007) and OS ( P =0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts ( n =15/58, 25.6%, P =0.009). Donor age was associated with a higher HCC recurrence ( P =0.006). Both total ischaemia time (TIT) greater than 6hours ( P =0.016) and increasing TIT correlated with higher HCC recurrence ( P =0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence ( P =0.039) and reduced survival ( P =0.033). CONCLUSION: This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.

Emerging and Clinically Accepted Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.

Expanding Selection Criteria in Deceased Donor Liver Transplantation for Hepatocellular Carcinoma: Long-term Follow-up of a National Registry and 2 Transplant Centers.

BACKGROUND: This study compares selection criteria for liver transplant (LT) for hepatocellular carcinoma (HCC) for inclusivity and predictive ability to identify the most permissive criteria that maintain patient outcomes. METHODS: The Scientific Registry of Transplant Recipients (SRTR) database was queried for deceased donor LT's for HCC (2003-2020) with 3-y follow-up; these data were compared with a 2-center experience. Milan, University of California, San Francisco (UCSF), 5-5-500, Up-to-seven (U7), HALT-HCC, and Metroticket 2.0 scores were calculated. RESULTS: Nationally, 26 409 patients were included, and 547 at the 2 institutions. Median SRTR-follow-up was 6.8 y (interquartile range 3.9-10.1). Three criteria allowed the expansion of candidacy versus Milan: UCSF (7.7%, n = 1898), Metroticket 2.0 (4.2%, n = 1037), and U7 (3.5%, n = 828). The absolute difference in 3-y overall survival (OS) between scores was 1.5%. HALT-HCC (area under the curve [AUC] = 0.559, 0.551-0.567) best predicted 3-y OS although AUC was notably similar between criteria (0.506 < AUC < 0.527, Mila n = 0.513, UCSF = 0.506, 5-5-500 = 0.522, U7 = 0.511, HALT-HCC = 0.559, and Metroticket 2.0 = 0.520), as was Harrall's c-statistic (0.507 < c-statistic < 0.532). All scores predicted survival to P < 0.001 on competing risk analysis. Median follow-up in our enterprise was 9.8 y (interquartile range 7.1-13.3). U7 (13.0%, n = 58), UCSF (11.1%, n = 50), HALT-HCC (6.4%, n = 29), and Metroticket 2.0 (6.3%, n = 28) allowed candidate expansion. HALT-HCC (AUC = 0.768, 0.713-0.823) and Metroticket 2.0 (AUC = 0.739, 0.677-0.801) were the most predictive of recurrence. All scores predicted recurrence and survival to P < 0.001 using competing risk analysis. CONCLUSIONS: Less restrictive criteria such as Metroticket 2.0, UCSF, or U7 allow broader application of transplants for HCC without sacrificing outcomes. Thus, the criteria for Model for End-stage Liver Disease-exception points for HCC should be expanded to allow more patients to receive life-saving transplantation.

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept.

INTRODUCTION: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. METHODS: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. RESULTS: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1-124). The median time from pre-operative testing to surgery was 3 months (IQR: 1-4; range: 0-5), and from surgery to post-operative testing, it was 9 months (IQR: 2-22; range: 0.4-112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6-40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/-). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA-/- (n = 1, 10%), and ctDNA-/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. CONCLUSIONS: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

Neoplastic Progression of Barrett's Esophagus Among Organ Transplant Recipients: a Retrospective Cohort Study.

BACKGROUND: Several small studies reported high risk of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) patients who undergo solid organ transplantation (SOT) and implied that this may be due to immunosuppressant use. However, the major shortcoming of these studies was the lack of a control population. Therefore, we aimed to determine the rates of neoplastic progression in BE patients who underwent SOT and compare to that in controls and identify the predictors of progression. METHODS: This was a retrospective cohort study of BE patients seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. Demographics, endoscopic and histological findings, history of SOT and fundoplication, immunosuppressant use, and follow-up were abstracted. RESULTS: The study population consisted of 3466 patients with BE, of which 115 had SOT (lung 35, liver 34, kidney 32, heart 14, and pancreas 2) and 704 patients on chronic immunosuppressants but no history of SOT. During a median follow-up of 5.1 years, there was no difference in the annual risk of progression between the three groups (SOT=0.61%, no SOT but on immunosuppressants= 0.82%, and no SOT/no immunosuppressants= 0.94%, p=0.72). On multivariate analysis, immunosuppressant use (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.04-1.82, p=0.025) but not SOT (OR 0.39, 95%CI 0.15-1.01, p=0.053) was associated with neoplastic progression in BE patients. CONCLUSION: Immunosuppression is a risk factor for progression of BE to HGD/EAC. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered.

Therapies for non-alcoholic fatty liver disease: A 2022 update.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and lifestyle interventions to treat this disease by addressing the underlying metabolic syndrome are often limited. Many pharmacological interventions are being studied to slow or even reverse NAFLD progression. This review for hepatologists aims to provide an updated understanding of the pathogenesis of NAFLD, current recommended therapies, and the most promising treatment options that are currently under development.

Hepatic Epstein-Barr Virus-Associated Smooth Muscle Tumor in a Heart and Liver Transplant Recipient.

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMT) have been described in immunosuppressed states, including in post-transplant patients. Here, we discuss a heart-liver transplant recipient who was found to have multifocal hepatic EBV-SMT. His immunosuppression was initially transitioned from tacrolimus to sirolimus because of the proposed benefits of the mechanistic target of rapamycin inhibitors on EBV-SMT. Unfortunately, he suffered acute rejection of his liver allograft while on sirolimus therapy, which ultimately led to consideration of retransplantation.

Positive autoantibodies in living liver donors.

BACKGROUND: There is a nationwide shortage of organs available for liver transplantation. Living donors help meet this growing demand. Not uncommonly, donors will have positive autoantibodies. However, it is unclear whether donor positive autoantibodies are correlated with worse outcomes following living liver donor transplantations. AIM: To analyze the significance of positive autoantibodies in donors on post-transplant outcomes in recipients. METHODS: We performed a retrospective review of living liver donors who had undergone liver transplantation between January 1, 2012 and August 31, 2021. Demographic characteristics and pre-transplant data including antinuclear antibodies (ANA) and anti-smooth muscle antibody titers were collected in donors. Outcomes of interest were post-transplantation complications including mortality, biliary strictures, biliary leaks, infection, and rejection. Pediatric recipients and donors without measured pre-transplant autoantibody serologies were excluded from this study. RESULTS: 172 living donor liver transplantations were performed during the study period, of which 115 patients met inclusion criteria. 37 (32%) living donors were autoantibody-positive with a median ANA titer of 1:160 (range 1:80 to 1:1280) and median anti-SMA titer of 1:40 (range 1:20 to 1:160). There were no significant differences in baseline demographics between the autoantibody positive and negative donors. Post-transplantation rates of death (P value = 1), infections (P value = 0.66), and overall rates of complications (P value = 0.52) were similar between the autoantibody positive and negative groups. Higher incidences of anastomotic strictures and rejection were observed in the autoantibody positive group; however, these differences were not statistically significant (P value = 0.07 and P value = 0.30 respectively). CONCLUSION: Isolated pre-transplant autoantibody positivity is not correlated to worse post-transplant outcomes in living liver donor transplants.

Epstein-Barr virus-associated smooth muscle tumors in immunocompromised patients: Six case reports.

BACKGROUND: Epstein-Barr virus associated smooth muscle tumor (EBV-SMT) is a rare oncological entity. However, there is an increasing incidence of EBV-SMTs, as the frequency of organ transplantation and immunosuppression grows. EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder (PTLD). There is no clear consensus on the treatment of EBV-SMTs. However, surgical resection, chemotherapy, radiation therapy, and immunosuppression reduction have been explored with varying degrees of success. CASE SUMMARY: Our case series includes six cases of EBV-SMTs across different age groups, with different treatment modalities, adding to the limited existing literature on this rare tumor. The median latency time between immunosuppression and disease diagnosis is four years. EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency. CONCLUSION: It is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.

Weight loss interventions in living donor liver transplantation as a tool in expanding the donor pool: A systematic review and meta-analysis.

BACKGROUND: With increasing rates of liver transplantation and a stagnant donor pool, the annual wait list removals have remained high. Living donor liver transplantation (LDLT) is an established modality in expanding the donor pool and is the primary method of liver donation in large parts of the world. Marginal living donors, including those with hepatic steatosis, have been used to expand the donor pool. However, due to negative effects of steatosis on graft and recipient outcomes, current practice excludes overweight or obese donors with more than 10% macro vesicular steatosis. This has limited a potentially important source to help expand the donor pool. Weight loss is known to improve or resolve steatosis and rapid weight loss with short-term interventions have been used to convert marginal donors to low-risk donors in a small series of studies. There is, however, a lack of a consensus driven standardized approach to such interventions. AIM: To assess the available data on using weight loss interventions in potential living liver donors with steatotic livers and investigated the feasibility, efficacy, and safety of using such donors on the donor, graft and recipient outcomes. The principal objective was to assess if using such treated donor livers, could help expand the donor pool. METHODS: We performed a comprehensive literature review and meta-analysis on studies examining the role of short-term weight loss interventions in potential living liver donors with hepatic steatosis with the aim of increasing liver donation rates and improving donor, graft, and recipient outcomes. RESULTS: A total of 6 studies with 102 potential donors were included. Most subjects were males (71). All studies showed a significant reduction in body mass index post-intervention with a mean difference of -2.08 (-3.06, 1.10, I 2 = 78%). A significant reduction or resolution of hepatic steatosis was seen in 93 of the 102 (91.2%). Comparison of pre- and post-intervention liver biopsies showed a significant reduction in steatosis with a mean difference of -21.22 (-27.02, -15.43, I 2 = 56%). The liver donation rates post-intervention was 88.5 (74.5, 95.3, I 2 = 42%). All donors who did not undergo LDLT had either recipient reasons or had fibrosis/steatohepatitis on post intervention biopsies. Post-operative biliary complications in the intervention group were not significantly different compared to controls with an odds ratio of 0.96 [(0.14, 6.69), I 2 = 0]. The overall post-operative donor, graft, and recipient outcomes in treated donors were not significantly different compared to donors with no steatosis. CONCLUSION: Use of appropriate short term weight loss interventions in living liver donors is an effective tool in turning marginal donors to low-risk donors and therefore in expanding the donor pool. It is feasible and safe, with comparable donor, graft, and recipient outcomes, to non-obese donors. Larger future prospective studies are needed.