Assessing Liver Viability: Insights From Mitochondrial Bioenergetics in Ischemia-Reperfusion Injury.

Orthotopic liver transplantation remains the definitive treatment for patients with end-stage liver disease. Unfortunately, the increasing demand for donor livers and the limited supply of viable organs have both led to a critical need for innovative strategies to expand the pool of transplantable organs. The mitochondrion, central to hepatic cellular function, plays a pivotal role in hepatic ischemic injury, with impaired mitochondrial function and oxidative stress leading to cell death. Mitochondrial protection strategies have shown promise in mitigating IRI and resuscitating marginal organs for transplant. Machine perfusion (MP) has been proven a valuable tool for reviving marginal organs with very promising results. Evaluation of liver viability during perfusion traditionally relies on parameters including lactate clearance, bile production, and transaminase levels. Nevertheless, the quest for more comprehensive and universally applicable viability markers persists. Normothermic regional perfusion has gained robust attention, offering extended recovery time for organs from donation after cardiac death donors. This approach has shown remarkable success in improving organ quality and reducing ischemic injury using the body's physiological conditions. The current challenge lies in the absence of a reliable assessment tool for predicting graft viability and post-transplant outcomes. To address this, exploring insights from mitochondrial function in the context of ischemia-reperfusion injury could offer a promising path toward better patient outcomes and graft longevity. Indeed, hypoxia-induced mitochondrial injury may serve as a surrogate marker of organ viability following oxygenated resuscitation techniques in the future.

Risk of Hepatic Artery Complications After Liver Transplantation in Patients Who Received Pretransplant Transarterial Chemoembolization Therapy: A Single-Center Experience.

BACKGROUND: Pretransplant transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hepatic artery thrombosis (HAT) after liver transplantation (LT). Innovative surgical LT and interventional vascular radiology TACE techniques may mitigate the risk of HAT. We sought to investigate the incidence of HAT after LT in patients who received pre-transplant TACE at our center. METHODS: We performed a single-center retrospective review of all LT patients, >18 years of age, from October 1, 2012, to May 31, 2018. Outcomes were compared between patients who received pre-LT TACE and those who did not. Median follow-up was 26 months. RESULTS: Among the 162 LT recipients, 110 (67%) patients did not receive pre-LT TACE (Group I), while 52 (32%) received pre-LT TACE (Group II). The <30-day incidence rates of post-LT HAT were as follows: Group I = 1.8% and Group II = 1.9% (P = .9). Most hepatic arterial complications occurred >30 days after LT. Based on competing risks regression analysis, TACE was not associated with an increased risk of HAT. Patient or graft survivals were comparable between the 2 groups (P = .1 and .2, respectively). CONCLUSIONS: Our study shows a similar incidence of hepatic artery complications post-LT in patients who received TACE before LT compared with those who did not. In addition, we suggest that the surgical technique of early vascular control of the common hepatic artery during LT, in combination with a super-selective vascular intervention radiology approach, has clinical utility in reducing the risk of HAT in patients requiring pre-transplant TACE.

The transplant ureter causing small bowel obstruction following intraperitoneal kidney transplantation: a case report.

Internal bowel herniation under the ureter of an intraperitoneally transplanted kidney is a rare complication yet carries a high burden of morbidity and potential mortality if not recognized and managed appropriately. We describe a case where early intervention salvaged the bowel without ureteral injury. We also describe a technique to close the space beneath the ureter to prevent further episodes of internal herniation.

Liver Transplantation for Fulminant Hepatic Failure Precipitated by Pheochromocytoma Crisis in the Setting of Using Garcinia cambogia Weight Loss Supplement: A Case Report.

We report the first case of liver transplantation for fulminant hepatic failure precipitated by hepatocellular injury due to the synergistic effect of pheochromocytoma crisis and simultaneous use of Garcinia cambogia. Complex diagnosis and treatment decisions are discussed, as well as possible pathophysiology that led to liver failure.

Evolution of a Transplant Surgery Advanced Practice Provider Practice Model in the Care of High-Acuity Liver Transplant Recipients: A Single-Center Experience.

BACKGROUND: The role of advanced practice providers (APPs) in an academic transplant surgical acute care setting remains to be defined. We sought to evaluate the impact of a transplant surgeon-APP (TSAPP) practice model on patient access and outcomes in the care of critically ill patients with end-stage liver disease (ESLD) in an academic transplant center. METHODS: A retrospective analysis evaluated the effect of practice model evolution over an 11-year period on hospital access of patients with ESLD to an academic liver transplantation center and survival outcomes. We compared 3 practice models: era 1 (transplant surgeon-general surgery resident; January 2009 to Sept 2012): vs era 2 ( transition transplant surgeon-general surgery resident to TSAPP; October 2012 to December 2016): vs era 3 (TSAPP; January 2017 to December 2020). RESULTS: Patient access to hospitalization and inpatient service census increased significantly over time with TSAPP model (P < .01). At the time of liver transplant, the median Model for End-Stage Liver Disease scores for era 1 (25), era 2 (33), and era 3 (34), P < .01, and patient requirement for intensive care unit for era 1 (7.1%), era 2 (44.8%), and era 3 (56.4%), P < .01, have increased. The overall 1-year patient survival rates remained comparable across all eras: era 1 (93.88%), era 2 (93.11%), and era 3 (94.06%), P = .77 CONCLUSIONS: The APPs play an integral role in clinical transplantation practice. The integration of APPs into the transplant surgical workforce increased access of high-acuity patients with ESLD to the transplantation center. In addition, it provided excellent patient and graft survival outcomes after liver transplant.

Effect of an Integrated Transplantation Mental Health Program on Alcohol Relapse After Liver Transplantation for Severe Alcoholic Hepatitis: A Single-Center Prospective Study.

BACKGROUND: Liver transplantation (LT) for severe alcohol-associated hepatitis (AH) remains controversial due to perceived increased recidivism risk after LT because of a lack of protracted abstinence before LT. Data on risk stratification for alcohol relapse after LT are limited. We sought to evaluate the utility of having a mental health program embedded in a transplantation center in risk assessment for alcohol relapse-free patient survival after LT. METHODS: We conducted a prospective analysis of all patients with a diagnosis of severe AH hospitalized at a single transplant center from April 2015 to April 2020. After a comprehensive mental health risk stratification, patients were either waitlisted for LT or declined for waitlisting. The primary endpoint was alcohol relapse-free patient survival rate for those who received LT. The secondary endpoint compared survival rates between patients who received LT and those who did not. The median follow-up was 10 months. RESULTS: Among the 83 patients included in the study, 54 patients were waitlisted for LT (65%, group 1) and 29 were declined (35%, group 2). Patient characteristics and median Model for End-Stage Liver Disease score on presentation were comparable for both cohorts (36 in group 1, 38 in group 2; P = .8). Group 1 had significantly better Stanford Integrated Psychosocial Assessment for Transplantation total scores (median 40 vs 57; P < .01), presence of social support (100% of patients in group 1 vs 76% in group 2; P < .01), and less prevalence of active tobacco smokers (30% in group 1 vs 66% in group 2; P < .01). For those who were not waitlisted, 72.5% experienced rapid deterioration of hepatic function. Among the 54 patients waitlisted, 29 patients received LT (54%), whereas 19 died while on the waiting list (35%). One- and 3-year patient survival after LT were 92.5% and 92.5%, respectively. The overall and sustained alcohol relapse rates after LT were 10.3% and 3.5%, respectively. CONCLUSION: Severe AH is a complex medical and mental health disease and requires an intense risk assessment for recidivism after LT. Our study shows that an integrated transplantation mental health program provides an accurate risk stratification for alcohol relapse after LT, a successful intervention to mitigate recidivism risk, and optimal short-term alcohol relapse-free patient survival. Future studies should focus on enhancing the guidelines for broader application.

Assessment of Patient Knowledge of the Role of Advanced Practice Providers in Transplantation Surgical Care: A Single-Center Prospective Study.

BACKGROUND: Advanced practice providers (APPs) are integral to the contemporary transplant surgeon-APP practice model. Patient understanding of APPs' role is vital for optimal patient care and experience. Data on patient knowledge of APPs' roles remain scarce. We sought to assess patient awareness of APPs in their transplantation surgical team. METHODS: We conducted a prospective study on 100 consecutive transplant candidates and recipients ≥18 years, hospitalized in the transplant surgeon-APP Transplantation Intensive Care Unit (primary service) from September 16, 2019 through June 10, 2021. All patients received a 5-question survey (Table 1). Group 1 (first 50 patients) did not receive any printed introductory materials (Figs 1 and 2) before completing the questionnaire, whereas group 2 (last 50 patients) completed the survey after receiving the materials. RESULTS: Although > 90% of patients were knowledgeable about physician assistants (PAs) and nurse practitioners (NPs), the term "advanced practice providers" was unfamiliar to patients in both groups (Table 1). The level of patient recognition and comfort with APPs in the transplant surgeon-APP care team were comparable for both groups. CONCLUSIONS: Our study showed that transplant candidates and recipients were knowledgeable and highly comfortable that PAs and NPs are members of their transplantation surgical team. However, the term advanced practice providers was unfamiliar to the patients. Our study suggested that patient education on provider terms used in current health care delivery is essential and may enhance the patient experience.

De Novo Autoimmune Hepatitis after COVID-19 Infection in an Unvaccinated Patient.

Liver test abnormalities have been described during severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection causing coronavirus disease 2019. Most of them consist of elevation of the aminotransferases that resolve once the infection subsides. There are several reports of autoimmune hepatitis developing after vaccination against COVID-19 and one case of autoimmune hepatitis following COVID-19 infection. We present a patient that was not vaccinated against COVID-19 and developed resistant de novo autoimmune hepatitis following COVID-19 infection requiring aggressive immunosuppression.

Human Leukocyte Antigen Class I Antibodies and Response to Platelet Transfusion in Patients Undergoing Liver Transplantation.

BACKGROUND: Patients undergoing liver transplantation (LT) frequently receive platelet transfusion (PLT) to minimize their risk of hemorrhage. Alloimmunization to platelets may lead to refractoriness to PLT. Data on the implications of platelet alloimmunization in patients undergoing LT remain limited. We examined the effect of human leukocyte antigen class I (HLA-I) antibodies on PLT refractoriness and short-term outcomes after LT. METHODS: Peritransplant clinical and PLT factors were reviewed for all adult liver or simultaneous liver-kidney transplantations from 2012 to 2017. Sensitized patients (SE) with pretransplant HLA-I calculated panel-reactive antibody ≥20% were compared with unsensitized patients (US) with calculated panel-reactive antibody <20%. The mean follow-up was 21.4 mo. RESULTS: Alloimmunization was observed in 39% of the study cohort. SE (n = 28) received 272 PLTs, and US (n = 44) received 246 PLTs. History of pregnancy was higher among SE than US (P < 0.01); otherwise, both groups had similar clinical characteristics. SE had higher rates of PLT refractoriness (66% versus 47%; P < 0.01) than US. The mean platelet corrected count increment was lower among SE compared with US up to 100 min after PLT (P < 0.05). Alloimmunization and simultaneous liver-kidney transplantation independently predicted refractoriness on multivariate logistic regression (P < 0.05). Early allograft rejection and patient survival rates were comparable for both groups. CONCLUSIONS: LT patients experienced high rates of HLA-I alloimmunization and PLT refractoriness. SE had higher rates of refractoriness and lower mean corrected count increment after transfusion compared with US. Our study suggests that further research to evaluate the utility of HLA-matched PLTs in HLA-I alloimmunized LT patients is warranted.

Staged Biliary Reconstruction After Orthotopic Liver Transplantation: A Practical Surgical Strategy for High-Acuity Adult Recipients.

Biliary complications (BC) following orthotopic liver transplantation (OLT) is strongly associated with inferior patient outcomes and increased healthcare cost. BC in high-acuity patients can be lethal. While the utility of staged biliary reconstruction after liver transplantation (SBRALT) has been reported in adult and pediatric OLT, biliary outcome data are scarce. We sought to evaluate the clinical utility and outcomes of SBRALT in high-acuity transplant recipients. METHODS: We conducted an analysis from our prospective database of 149 adult OLT between January 1, 2012, and September 30, 2017. Mean follow-up was 26 months. Variables were compared for Group I: one-stage OLT with biliary reconstruction (N = 58) versus Group II: SBRALT (N = 91). RESULTS: Compared with Group I, patients in Group II had higher acuity of illness: median model for end-stage liver disease scores (19 vs 35 P = 0.002), requirement for pretransplant intensive care unit (29.3% vs 54.9%, P = 0.022), pretransplant renal replacement therapy (15.5% vs 48.4%), estimated blood loss (2000 vs 4750 mL, P < 0.001), and intraoperative packed red blood cells transfusion (4 vs 10 units, P < 0.001). For Group II, biliary reconstruction was performed between 1 and 6 days after OLT. Hepaticojejunostomy was performed in 8.6% (Group I) and 26.4% (Group II), P = 0.010. For Groups I and II, BC rates (8.6% vs 7.7%, P = 0.955) and 1-year graft failure-free survival rates (89.7% vs 88.2%, P = 0.845) were comparable. CONCLUSIONS: Graft failure-free survival and biliary outcomes of SBRALT in high-acuity recipients are excellent and comparable to one-stage OLT for low-risk patients. SBRALT is a practical surgical strategy in complex OLT.

Outcome analysis of continuous intraoperative renal replacement therapy in the highest acuity liver transplant recipients: A single-center experience.

BACKGROUND: Orthotopic liver transplantation is the definitive treatment modality for patients with end-stage liver disease. Pre-orthotopic liver transplantation renal dysfunction has a significant negative influence on outcomes post-orthotopic liver transplantation. Intraoperative renal replacement therapy is an adjunctive therapy to address the metabolic challenges during orthotopic liver transplantation in patients with a high acuity of illness. The impact of intraoperative renal replacement therapy on post-orthotopic liver transplantation outcomes, however, is unclear. METHODS: From October of 2012 to April of 2016, 96 adult patients underwent orthotopic liver transplantation for end-stage liver disease. Three groups were identified: (1) Group I: patients with pre-orthotopic liver transplantation renal dysfunction who underwent intraoperative renal replacement therapy, (2) Group II: patients with pre-orthotopic liver transplantation renal dysfunction who did not receive intraoperative renal replacement therapy, and (3) Group III: patients with orthotopic liver transplantation without evidence of pretransplant renal dysfunction. RESULTS: At 17.7 months follow-up, there was no difference in survival among the study groups. Physiologic model for end-stage liver disease at the time of orthotopic liver transplantation was significantly higher in both groups with renal dysfunction (I = 43, II = 39) than in Group III (18). Post-orthotopic liver transplantation, 12-month patient survival in Group II was 100%. While the model for end-stage liver disease score at orthotopic liver transplantation was significantly different between Group I and Group III, the 12-month, post-orthotopic liver transplantation patient survival was comparable at 78% vs 88%, respectively. CONCLUSION: Intraoperative renal replacement therapy is a safe adjunctive therapy during liver transplantation of critically ill patients with renal dysfunction. Identifying patients who require intraoperative renal replacement therapy would improve intraoperative and post-liver transplant survival and may facilitate recovery of native kidney function after transplant.

Hydroxocobalamin for Vasoplegic Syndrome in Liver Transplantation: Restoration of Blood Pressure Without Vasospasm.

Systemic vasoplegia is common in patients undergoing liver transplantation. In this report, we present a case in which treatment with conventional vasopressors caused peripheral arterial spasm, rendering arterial blood pressure monitoring impossible. Administration of methylene blue resolved the vasospasm; however, concern for toxic dose requirements limited its use. Hydroxocobalamin administration resolved the vasospasm and increased blood pressure without the potential adverse effects seen with methylene blue. This case represents the first report of hydroxocobalamin use in liver transplantation and may represent a new option for the treatment of vasoplegia and the potential vasospasm that may result from traditional vasopressors.

Pathologic sequelae of allosensitization in liver transplantation.

The long-term impact of allosensitization between ABO compatible donor/recipient pairs in liver transplantation is unclear. Accumulating clinical evidence suggests that donor-specific antibody formation may lead to antibody-mediated rejection and is causally linked to pathologic injury, graft loss, and death. Although this immune-mediated graft dysfunction is increasingly being associated with poor outcomes, the specific pathologic sequelae are not defined. Herein, we examine the relationship between allosensitization, antibody-mediated rejection, and subsequent graft pathology.

Tumors with intrahepatic bile duct differentiation in cirrhosis: implications on outcomes after liver transplantation.

BACKGROUND: The role of liver transplantation (LT) in the management of cirrhotic patients with tumors exhibiting intrahepatic bile duct differentiation remains controversial. The objective of this study was to characterize the spectrum of these tumors and analyze post-LT outcomes. METHODS: Retrospective pathology database search of explant histology analysis of liver transplants between April 1993 and November 2013. RESULTS: Thirty-two patients were analyzed, 75% were men with a mean age of 60 years. Seven patients had nodules demonstrating intrahepatic cholangiocarcinoma (I-CCA), nine had I-CCA nodules occurring concomitantly with hepatocellular carcinoma (HCC), and 16 had mixed HCC-CCA nodules. The median number of tumors was 1 and size was 2.5 cm. Overall patient survival post-LT at 1 and 5 years was 71% and 57%, respectively. Patients within Milan criteria, especially with I-CCA features, showed a 5-year tumor recurrence rate (10%) and 5-year survival rate (78%) comparable with other patients having HCC within Milan criteria. CONCLUSION: This series showed that patients with CCA within Milan criteria may be able to achieve acceptable long-term post-LT survival.