Takotsubo cardiomyopathy following liver transplantation: A multicenter cohort study.

Takotsubo cardiomyopathy (TCM) is an acute, stress-mediated, reversible cardiomyopathy that occurs in the absence of hemodynamically significant coronary artery disease. We aimed to investigate the characteristics and outcomes of patients who developed TCM following liver transplantation (LT) in a multicenter study. Adult patients from 6 centers across the United States who developed TCM according to Mayo Clinic criteria following LT between 2008 and 2023 were included. Demographics, perioperative and long-term outcomes, and treatment modalities were assessed. Fifty-five patients were included. The center incidence of TCM ranged from 0.1% to 0.5%. The majority were female (54.5%) and Caucasian (87.2%), and the median age at transplant was 59 years. The primary etiologies for LT were alcohol-associated cirrhosis (49.1%) and metabolic dysfunction-associated steatotic liver disease cirrhosis (21.8%). The median time from LT to TCM diagnosis was 4 days. TCM was associated with a 60.9% reduction in left ventricular ejection fraction (LVEF) from a pretransplant median LVEF of 64.0%-25.0%. The most common treatment for TCM was diuretics (67.3%) and afterload reduction (54.5%), with only 27.3% of patients requiring vasopressor support. At a median follow-up of 31.5 months, 1-year and 3-year overall survivals (OSs) were 86.3% and 69.4%, respectively. A repeat echocardiogram performed at a median of 84 days demonstrated that 45/55 patients (81.8%) had recovered LVEF ≥50%. Patients with LVEF recovery to ≥50% had significantly improved OS compared to those without LVEF recovery >50% (106.4 vs. 12.2 mo, p = 0.001). TCM following LT is associated with a significant reduction in LVEF; however, the majority of patients recover LVEF to >50% with minimal perioperative mortality. Importantly, follow-up assessment of LVEF has significant implications as lack of recovery is associated with worse OS.

Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma.

BACKGROUND: In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. METHODS: We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. RESULTS: Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. CONCLUSIONS: Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

Long-term Outcomes Following Colectomy and Liver Transplantation for Inflammatory Bowel Disease with Primary Sclerosing Cholangitis.

OBJECTIVE: To investigate the long-term outcomes of patients with combined primary sclerosing cholangitis/inflammatory bowel disease (PSC-IBD) undergoing both liver transplantation (LT) and total abdominal colectomy (TAC). SUMMARY BACKGROUND DATA: The fraction of patients with PSC-IBD that require both LT and TAC is small, thereby limiting significant conclusions regarding long-term outcomes. METHODS: Adult and pediatric patients from nine centers from the US IBD Surgery Collaborative who underwent staged LT and TAC for PSC-IBD were included. Long-term outcomes, including survival, were assessed. RESULTS: Among 127 patients, 66 underwent TAC-before-LT, with a median time from TAC to LT of 7.9 yrs, while 61 underwent LT-before-TAC, with a median time from LT to TAC of 4.4 years. Median patient survival post TAC was significantly worse in those undergoing LT-before-TAC (16.0 yrs vs. 42.6 yrs, P=0.007), while post LT survival was not impacted by the order of TAC and LT (21.6 yrs vs. 22.0 yrs, P=0.81). Patients undergoing TAC for medically refractory disease had a higher incidence of recurrent PSC (rPSC) (P=0.02) and biliary complications (0.09) compared to those undergoing TAC for oncologic indications. Definitive TAC reconstruction with either end ileostomy or ileal-pouch anal anastomosis (IPAA) did not impact post-LT or post-TAC outcomes. CONCLUSIONS: Long term survival in PSC-IBD was contingent upon progression to LT and was not impacted by the need for TAC. PSC-IBD patients undergoing TAC for medically refractory disease had a higher incidence of rPSC and biliary complications. The use of IPAA in PSC-IBD was a viable alternative to end ileostomy.

Representation of Women Authorship in the Top 5 Transplantation Journals in the United States.

BACKGROUND: In the United States, only 13% of transplant surgeons are women. We evaluated gender distribution and trends of American authorship over the past 10 y in high-impact solid organ transplantation journals to gain insight into the current status of women authorship in transplantation. METHODS: Original articles from 2012 to 2021 from the 5 highest-impact solid organ transplantation journals were extracted from Scopus. First and last author's gender was predicted using Genderize.io. Data of first and last authors, article type and topic, location, citation, and funding metrics were analyzed. Chi-square, logistic regression, and trend tests were performed where appropriate. Statistical significance was set at <0.05. RESULTS: Women's first and last authorship increased over time among all journals. There was an increase in women first authors in the American Journal of Transplantation and in senior women authors in Liver Transplantation and Transplantation . Significant differences in gender authorship in lung, intestine, pancreas, general, and islet cell transplantation were found. Women's last authorship was associated with 1.69 higher odds of having a woman first author when adjusting for year and journal. There was an increase in the rate of women's first and last author collaborations over the years. Women last authors had 1.5 higher odds of being funded by the National Institutes of Health over the years. CONCLUSIONS: Despite an increase in women transplant surgeons and physicians, the gap in women authorship in transplantation persists. Women's last authorship was associated with higher odds of having a woman first author, pointing to the importance of mentorship for women joining the transplant academia.

The power of partnership: Exploring collaboration dynamics in U.S. transplant research.

INTRODUCTION: Collaboration is one of the hallmarks of academic research. This study analyzes collaboration patterns in U.S. transplant research, examining publication trends, productive institutions, co-authorship networks, and citation patterns in high-impact transplant journals. METHODS: 4,265 articles published between 2012 and 2021 were analyzed using scientometric tools, logistic regression, VantagePoint software, and Gephi software for network visualization. RESULTS: 16,003 authors from 1,011 institutions and 59 countries were identified, with Harvard, Johns Hopkins, and University of Pennsylvania contributing the most papers. Odds of international collaboration significantly increased over time (OR 1.03; p â€‹= â€‹0.040), while odds of citation in single-institution collaborations decreased (OR 0.99; p â€‹= â€‹0.016). Five major scientific communities and central institutions (Harvard University and University of Pittsburgh) connecting them were identified, revealing interconnected research clusters. CONCLUSIONS: Collaboration enhances knowledge exchange and research productivity, with an increasing trend of institutional and international collaboration in U.S. transplant research. Understanding this community is essential for promoting research impact and forming strategic partnerships.

Regional and National Trends of Adult Living Donor Liver Transplantation in the United States Over the Last Two Decades.

Background and Aims: Liver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) performed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associated with recipient survival. Methods: We retrospectively analyzed LDLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and regional trends in LDLT, recipient outcomes, and predictors of survival were analyzed. Results: Of the 223,571 candidates listed for an LT, 57.5% received an organ, of which only 4.2% were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers (n=919), while region 1 had the highest proportion (11.1%). Overall, post-LT mortality was 21.4% among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92%, 87%, and 70%, respectively. Interval analysis (2004-2019) showed that patients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95% confidence interval=0.75-0.88). Conclusions: Following a substantial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented.

Conversion to resection post radioembolization in patients with HCC: recommendations from a multidisciplinary working group.

BACKGROUND: Transarterial radioembolization (TARE) with yttrium-90 (90Y) glass microspheres is an efficacious option for converting appropriately selected patients with borderline-resectable hepatocellular carcinoma (HCC) to surgical candidacy. METHODS: In 2018 and 2019, a diverse multidisciplinary group of surgical and interventional experts with experience using 90Y for downstaging and bridging to liver transplant convened to review peer-reviewed literature and personal experience in the use of 90Y to convert borderline resectable liver cancer patients to surgical candidacy. The working group included surgical oncologists specializing in liver cancer, liver transplant surgeons with experience in complex hepatobiliary surgery, and interventional radiologists with experience using 90Y. RESULTS: This document presents expert recommendations based upon the group's experience and consensus. CONCLUSIONS: By combining related evidence from the literature with expert experiences with TARE in surgical candidates, these recommendations aim to demonstrate the safety, efficacy, and feasibility of TARE in converting borderline-resectable patients to surgical options. The document also addresses the concerns about potential complications associated with TARE during the surgical intervention.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Massive Leiomyomatous Uterine Proliferation Following Kidney Transplantation: A Case Report and Literature Review.

Uterine fibroids are the most common benign uterine tumors affecting > 50% of premenopausal women. The incidence, burden and symptoms from uterine fibroids are higher in women of African descent compared to Caucasians. Despite increasing number of African American females being evaluated for and undergoing kidney transplantation (KT), perioperative management guidelines for uterine fibroids currently do not exist. We present a case of a 40 y/o African American female with known symptomatic uterine fibroids preoperatively and medically managed, who underwent a successful KT and 4 years later progressively developed massive leiomyomatous uterine proliferation, causing a complete lateral displacement of the transplanted kidney with severe hydronephrosis, transplant ureteral obstruction and secondary urinary tract infections with bacteremia. This obstruction required a percutaneous nephrostomy tube placement followed by an interval transabdominal hysterectomy, which was complicated by transplant ureteral transection requiring ureteral reimplantation, resulting in prolonged hospitalization, follow-up and outpatient antibiotic regimen. There is a need for management guidelines for uterine fibroids incidentally encountered during the KT evaluation process to avoid similar preventable post-KT complications in patient populations most commonly affected. Literature review and perioperative management/surveillance strategies are provided.

Deep Vein Thrombosis and Pulmonary Embolism in Liver Transplant Patients: Risks and Prevention.

UNLABELLED: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are surgical complications estimated to occur in 5% to 10% of patients. There are limited data regarding DVT/PE in the early postoperative period in liver transplant patients. The aim of this study is to determine risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis. METHODS: We reviewed the records of 999 patients who underwent initial liver transplant between January 2000 and June 2012 at Henry Ford Hospital. In 2011, a standardized prophylactic regimen using subcutaneous (SQ) heparin was initiated. All patients that developed either upper/lower extremity DVT or PE within the first 30 days of transplant formed the cohort of this study. RESULTS: On multivariate analysis, only peripherally inserted central catheter (PICC) placement and SQ heparin were associated with DVT/PE. In patients receiving heparin, 3 (1.0%) had DVT/PE versus 25 (3.5%) who did not receive heparin (P = 0.03). Sixteen (6.9%) patients that had a PICC developed DVT/PE compared with 12 (1.6%) patients without a PICC (P < 0.001). In the heparin group, DVT/PE with PICC was reduced to 3 (3.0%) versus 13 (9.9%) in those with a PICC and did not receive heparin (P = 0.03). Mean time from transplant to DVT/PE diagnosis was 12.3 days. Length of hospitalization was significantly longer in patients who developed DVT/PE (18.5 vs 10.0 days, P < 0.001). CONCLUSIONS: In this study, we demonstrated that PICC placement significantly increases the likelihood of DVT/PE in liver transplant recipients. Prophylactic SQ heparin effectively reduced DVT/PE events in this patient population.

Intrahepatic Cholangiocarcinoma in the Liver Explant After Liver Transplantation: Histological Differentiation and Prognosis.

BACKGROUND: The aim of this study was to evaluate the outcome of patients with intrahepatic cholangiocarcinoma (ICCA) incidentally found in the explanted liver after liver transplantation. MATERIAL AND METHODS: We retrospectively reviewed 1188 recipients undergoing liver transplantation from August 2003 to August 2014; 13 patients were found to have ICCA (1.1%). Recurrence-free survival (RFS) rate was compared between ICCA patients and the matched cohort of 39 patients with hepatocellular carcinoma (HCC). We also investigate the relevance of clinical and pathological parameters in recurrence of ICCA. RESULTS: ICCA patients showed significantly higher recurrence rate with lower 1-year and 3-year RFS rates than HCC patients (recurrence rate, 12.8% vs. 54.8%; 1-year and 3-year RFS rates, 94% and 84% vs. 67% and 42%). Of the 13 ICCA patients, 4 were diagnosed with a well-differentiated ICCA and 9 with a moderately-differentiated ICCA. There was no recurrence among those with a well-differentiated ICCA, whereas 78% recurred in the moderately-differentiated group. The median RFS time for the moderately-differentiated group was 13.0 months, yielding RFS rates of 56% at 1 year and 22% at 3 years. CONCLUSIONS: Liver transplantation in patients with a well-differentiated ICCA yielded excellent outcomes as compared to patients with a moderately-differentiated ICCA. This may allow consideration of transplantation in the setting of a well-differentiated ICCA, and obviate the need for adjuvant systemic treatment. Conversely, a moderately-differentiated ICCA carries a poor prognosis with a prohibitively high recurrence rate and poor survival. Liver transplantation should remain a contraindication in this group.

Peritransplant lymphopenia is a novel prognostic factor in recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Absolute lymphocyte count (ALC) is considered a surrogate marker for the level of immunosuppression and nutritional status of patients and a prognostic factor for survival and recurrence in several cancers. The aim of this study was to investigate the prognostic value of peritransplant ALC for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: HCC patients who underwent LT between 2000 and 2010 were evaluated. Exclusion criteria were combined HCC and cholangiocarcinoma. Peritransplant ALCs (before LT and 2 weeks and 1 month after LT) were analyzed along with tumor, operative, and donor characteristics to identify risk factors for the recurrence of HCC. RESULTS: HCC developed in 27 of the 173 LT patients investigated for risk factors (15.6%). The median time to recurrence was 1.14 years. Low ALCs before and after LT were associated with a higher recurrence rate in a continuous manner (before LT: hazard ratio=1.12, P=0.003; 2 weeks after LT: hazard ratio=1.14, P=0.008; 1 month after LT: hazard ratio=1.06, P=0.055) (increased risk per 100/µL down). On multivariate Cox regression analysis, peritransplant persistent lymphopenia (<1000/µL before LT and <500/µL at 2 weeks and 1 month after LT) was an independent risk factor for cancer recurrence (hazard ratio=7.05, P<0.001), along with tumor characteristics. CONCLUSION: Peritransplant lymphopenia is a powerful prognostic factor for the recurrence of HCC after LT, which suggests that maintaining ALCs in LT patients might improve cancer outcome.

Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT. METHODS: This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used. RESULTS: A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively. CONCLUSIONS: Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies.

Mini-incision right hepatic lobectomy with or without laparoscopic assistance for living donor hepatectomy.

Minimally invasive procedures are considered to be safe and effective approaches to the management of surgical liver disease. However, this indication remains controversial for living donor hepatectomy. Between 2000 and 2011, living donor right hepatectomy (LDRH) was performed 58 times. Standard right hepatectomy was performed in 30 patients via a subcostal incision with a midline extension. Minimally invasive procedures began to be used for LDRH in 2008. A hybrid technique (hand-assisted laparoscopic liver mobilization and minilaparotomy for parenchymal dissection) was developed and used in 19 patients. In 2010, an upper midline incision (10 cm) without laparoscopic assistance for LDRH was innovated, and this technique was used in 9 patients. The perioperative factors were compared, and the indications for minimally invasive LDRH were investigated. The operative blood loss was significantly less for the patients undergoing a minimally invasive procedure versus the patients undergoing the standard procedure (212 versus 316 mL, P = 0.001), and the operative times were comparable. The length of the hospital stay was significantly shorter for the minimally invasive technique group (5.9 versus 7.8 days, P < 0.001). The complication rates were 23% and 25% for the standard technique and minimally invasive technique groups, respectively (P = 0.88). Patients undergoing minilaparotomy LDRH had a body mass index (24.0 kg/m(2)) similar to that of the hybrid technique patients (25.8 kg/m(2), P = 0.36), but the graft size was smaller (780 versus 948 mL, P = 0.22). In conclusion, minimally invasive LDRH can be performed without safety being impaired. LDRH with a 10-cm upper midline incision and without laparoscopic assistance may be appropriate for donors with a smaller body mass. Laparoscopic assistance can be added as needed for larger donors. This type of LDRH with a 10-cm incision is innovative and is recommended for experienced centers.

Transjugular intrahepatic portosystemic shunt following liver transplantation: can outcomes be predicted?

Transjugular intrahepatic portosystemic shunt (TIPS) has been fairly effective in managing portal hypertension in the setting of cirrhosis. The aim is to study the safety and efficacy of TIPS in liver transplant (LT) recipients. Fifteen patients underwent TIPS insertion following LT. Indications were refractory ascites (12), hepatic hydrothorax (2), and bleeding esophageal varices (1). Seven patients (46.6%) had complete (C) resolution of ascites, while eight (53.4%) had partial or no (PN) resolution. Portal pressure and portal-right atrial pressure gradients post-TIPS were comparable. Ammonia levels were significantly higher in the PN group. Encephalopathy occurred in two patients (PN group). Four patients required re-transplantation and seven patients expired. The five-yr survival probability was 60.0% for the C group and 66.7% for the PN group. Currently, six patients are alive without clinical evidence of ascites. Two patients are alive but require re-transplantation. TIPS is a safe and effective method to control refractory ascites after LT. Portal pressure changes did not seem to correlate with resolution of ascites. Earlier allograft dysfunction is more likely with PN resolution of ascites after TIPS, and thus early re-transplantation should be considered. Re-transplantation in the context of organ dysfunction and graft failure should be a priority when considering TIPS.

No difference in clinical transplant outcomes for local and imported liver allografts.

In the United States, liver allograft allocation is strictly regulated. Local centers have the first option to accept a donor liver; this is followed by regional allocation for those donor livers not used locally and then by national allocation for those donor livers not accepted regionally. This study reviews the outcomes of all liver allografts used over 6 years (2001-2007) and evaluates initial and long-term function stratified by the geographic source of the donor liver allograft. The records for 845 consecutive deceased donor liver transplants at a single center were reviewed. The geographic origin of the allograft was recorded along with donor and graft characteristics to determine the probable reason for graft refusal. Within our local organ procurement organization, there is 1 liver transplant center, and within the region, there are 8 active centers. Early graft failure included any graft loss within 7 days of transplant, and initial function was measured with liver enzymes 30 days post-transplant. Graft survival and patient survival were evaluated with Kaplan-Meier and Cox survival modeling. Median follow-up was 43 months. The geographic distribution of organs included local organs (562, 66%), regionally imported organs (126, 15%), and nationally imported organs (157, 19%). There were no differences between the 3 groups in initial graft function, intraoperative death, or early graft loss. Survival curves for the 3 study groups demonstrated no difference in survival up to 5 years post-transplant. In conclusion, liver allografts rejected for use by a large number of transplant centers can still be successfully used without early graft function or long-term survival being affected.