Orthotopic Liver Transplantation Research Articles

Impact of the Acute and Chronic Liver Failure–Sequential Evaluation of Organ Failure Scoring System on the Prognosis of Liver Transplant

The use of the Model of End-Stage Liver Disease (MELD) to predict morbidity and mortality after orthotopic liver transplant (OLT) is controversial. Acute and chronic liver failure-sequential evaluation of organ failure (CLIF-SOFA) is a new score that assess the patient's global status and that have been developed exclusively for patients with end-stage liver disease. The objective is to evaluate whether the CLIF-SOFA system predicts postoperative morbidity and mortality in the short and medium term. A cohort of 123 patients who underwent OLT in a tertiary care hospital between January 2016 and December 2017 was retrospectively analyzed. The patients were divided into 2 groups: group 1 with a CLIF-SOFA score <7 and group 2 with a score CLIF-SOFA ≥7. Patients with a CLIF-SOFA ≥7 present, with statistical significance, had higher mortality at 1 and 3 years; longer duration of admission to the critical care unit; longer hospital stay; need for prolonged mechanical ventilation; surgical reintervention; higher rate of transfusion of blood products; pulmonary, neurologic, hemodynamic, surgical, infectious, kidney, metabolic, thrombotic, vascular, and graft complications; and need for kidney replacement therapy. However, no statistically significant differences were found in mortality in the first month, the need for hospital readmission, retransplant, digestive, endocrine, nutritional, hematologic, or biliary complications, and the presence of ascites. The role of CLIF-SOFA as a prognostic factor for mortality after OLT must be taken into account. Our results should be taken with caution, and more studies are necessary.

Role of Early Extubation in Decreasing Morbidity and Mortality in Liver Transplantation

BackgroundEarly extubation is a fundamental element integrated into enhanced recovery protocols in orthotopic liver transplantation (OLT). The aim is to evaluate whether early extubation influences short- and medium-term postoperative morbidity and mortality. MethodsA cohort of 209 patients who underwent OLT in a tertiary hospital in a period from January 2016 to December 2018 were retrospectively analyzed. Patients were divided into 2 groups: group 1: early extubation in the intensive care unit and group 2: delayed extubation. Mortality is compared between both groups in the first month and first and third year. Postoperative morbidity was also compared. ResultsPatients in group 1 (n = 165, 79.9%) presented, with statistical significance, lower mortality at 1 month, 1 year, and 3 years; shorter duration of admission to the critical care unit and of hospital stay; lower incidence of surgical reoperation and retransplant; lower rate of transfusion of blood products; fewer pulmonary, digestive, neurologic, cardiologic, hemodynamic, kidney, surgical, infectious, metabolic, thrombotic, vascular, and graft complications; less need for kidney replacement therapy; less refractory ascites; and greater infectious risk. However, no statistically significant differences were found in the need for hospital readmission; in biliary, endocrine, nutritional, hematologic, thrombotic, and hematologic complications; or in graft rejection.In group 1, 6.6% of patients required reintubation. In group 2, 97% of patients could be extubated during the first week; 7.8% required noninvasive mechanical ventilation type bilevel positive airway pressure and 8.1% high flow. Only 2.8% of patients required tracheotomy. ConclusionsThe role of early extubation seems key to improve outcomes in OLT because it reduces the incidence of multiple complications and mortality, with low reintubation rates. It is a feasible and safe procedure.

Liver Function Preservation and Outcome after SBRT with Functional Treatment Planning in Patients with HCC and Advanced Hepatic Cirrhosis: From Nuclear Medicine to MRI-Based Functional Treatment Planning Platform

<h3>Purpose/Objective(s)</h3> To evaluate treatment outcomes of ablative SBRT with SPECT/CT and MRI-guided functional treatment planning for localized HCC in patients with Child-Pugh B (CP-B) cirrhosis. <h3>Materials/Methods</h3> Liver SPECT with ^99mTc-sulfur colloid was co-registered to 3D-CT for identification and avoidance of functional hepatic parenchyma during SBRT in patients with advanced cirrhosis. Likewise, MRI scanner of the Unity® MR-Linac with super-paramagnetic iron oxide nanoparticle (SPION) agent Feraheme® as an alternative contrast was used for treatment planning with visualization of tumor and functional liver parenchyma during SBRT. Functional liver volumes (FLV) obtained from CT-SPECT or SPION-MRI were compared to anatomical liver volumes, as were dosimetric parameters when radiation dose constraints were adapted exclusively to FLV. Hepatic function, toxicity, and radiographic response were documented every 3-4 months following SBRT. <h3>Results</h3> With a median follow-up of 25 months, 44 patients (59 lesions treated) with CP-B cirrhosis received ablative SBRT to a median dose of 48 Gy (3–5 fractions). An automated contouring algorithm was generated for delineation and guided avoidance of best functional hepatic parenchyma on SPION-MRI. Prolonged SPION-contrast retention within hepatic parenchyma allowed per fraction treatment plan adaptation with SPION-enhanced MR imaging of tumor throughout the treatment course. FLV loss (509 cc or 41.3%, p<0.001) was observed in all patients, while the functional and anatomical liver volumes matched well in a control group of non-cirrhotic/non-HCC patients. Mean dose to residual FLV was maintained well below the liver threshold tolerance to radiation in all patients. Thirty-six transplant eligible patients received SBRT as a bridging treatment and 26 patients (60% of the cohort) were listed for liver transplant after completion of SBRT. Twenty-two patients successfully completed orthotopic liver transplant (OLT) with a median time to transplant of 6.1 months. Eight of 10 patients with intrahepatic progression received additional SBRT during follow-up and four of them completed transplant. With 95% in-field local control rate, overall, 2-year survival was 63% (90% after the OLT) with no incidence of RILD or CP class migration observed at 6+ months post SBRT. <h3>Conclusion</h3> SBRT with functional treatment planning on SPEC/CT allows identification and guided avoidance of residual functionally active hepatic parenchyma in patients with advanced hepatic cirrhosis. SPION-enhanced MRI provides consistent visibility of liver tumors and functional hepatic parenchyma on the day of treatment planning and throughout the online MR-guided SBRT. We report high local control and low toxicity leading to satisfactory pre- and post-liver transplant outcomes. Prospective clinical trial investigating MRI-SPION adaptive planning on the 1.5T Elekta Unity® MR-Linac is ongoing in our institution.

Postoperative Blood Pressure Deficit and Acute Kidney Injury After Liver Transplant

Acute kidney injury is a common cause of morbidity in liver transplant recipients. In critically ill patients who received an orthotopic liver transplant, we examined whether those with acute kidney injury had a greater deficit between pretransplant and posttransplant hemodynamic pressure-related parameters compared with those without acute kidney injury in the early postoperative period. We included patients who underwent an orthotopic liver transplant during the study period. We obtained premorbid and intensive care unit time-weighted average values for hemodynamic pressure-related parameters (systolic, diastolic, and mean arterial pressure; central venous pressure; mean perfusion pressure; and diastolic perfusion pressure) and calculated deficits in those values. We defined acute kidney injury progression as an increase of ≥1 Kidney Disease: Improving Global Outcomes stage. We included 150 eligible transplantrecipients, with 88 (59%) having acute kidney injury progression. Acute kidney injury was associated with worse clinical outcomes. All achieved pressure-related values were similar between transplant recipients with or without acute kidney injury progression. However, those with acute kidney injury versus those without progression had greater diastolic perfusion pressure deficit at 12 hours (-8.33% vs 1.93%; P = .037) and 24 hours (-7.38% vs 5.11%; P = .002) and increased central venous pressure at 24 hours (46.13% vs 15%; P = .043) and 48 hours (40% vs 20.87%; P = .039). Patients with acute kidney injury progression had a greater diastolic perfusion pressure deficit and increased central venous pressure compared with patients without progression. Such deficits might be modifiable risk factors for the prevention of acute kidney injury progression.

Enhanced recovery after surgery is feasible and safe in liver transplantation: a cohort study.

The principles of enhanced recovery after surgery (ERAS) are being applied to still more advanced procedures. Liver transplantation offers a unique opportunity for a multimodal approach including donor care as well. Our objective was to determine if ERAS was applicable and safe in orthotopic liver transplantation (OLT). A national single centre retrospective study showing the implementation of ERAS from 2013 to 2019 with the proceeding 2 years serving as baseline. The primary endpoints were mortality, length of stay (LOS) in the ward and intensive care unit stay. Secondary endpoints were complications estimated by Dindo-Clavien classification, comprehensive complication index (CCI®) and re-admissions. A total of 334 patients were included. LOS was significantly reduced from a median of 22.5 days at introduction to 14 days at 2019. Cold ischaemia time was reduced from a mean of 10.7 to 6.0h and the use of blood products (erythrocytes, plasma and thrombocytes) from a median of 28 to 6 units. Complications were reduced in severity. Mortality and readmission rates were not affected. ERAS principles are safe and recommended in patients undergoing OLT resulting in reduced severity of complications and LOS without affecting re-admissions or mortality.

Impact of Point-of-Care Assays for Hemostasis Monitoring According to Type of Donor in a Cohort of Liver Transplant Recipients

• Donation after circulatory death liver transplant offers excellent outcomes. • Perioperative hemostasis monitoring protocols with a viscoelastic point-of-care testing assay reduce blood loss and transfusion volume. • Use of machine perfusion is likely to further expand donation after circulatory death liver transplant. The aim is to compare 2 groups of liver transplant recipients, according to type of donor, within the framework of a hemostasis monitoring program using a point-of-care testing assay in terms of reduction in transfusion of blood products. This retrospective analytical observational study included 527 liver transplant recipients from 2014 to 2021. Of these, 460 were recipients of livers from donation after brain death (DBD) and 67 were orthotopic liver transplant recipients with donation after cardiac death (DCD). Statistical analysis of differences between the 2 groups included a series of intraoperative variables of blood product consumption: erythrocyte concentrate (red blood cells), fresh frozen plasma, platelets, and fibrinogen concentrates guided by algorithm with a viscoelastic technique using the ClotPro analyzer. The transfusion management was decided according to pre-established guidelines and cutoff values. The mean follow-up period was 40.3 months. Transfused red blood cells and fibrinogen units were significantly higher in the DBD group. The percentage of retransplant was significantly higher in the DCD group, and vascular complications were significantly more frequent in the DCD group ( P < .05). Cox univariate analysis showed that the DCD group had a risk ratio of death significantly higher than 1. Intraoperative monitoring of hemostasis with a point-of-care testing assay reduced blood product requirements. Type of donor had prognostic utility in our cohort. We hypothesize that other variables such as extraction technique, methods used to preserve the allograft, and later complications have a significantly greater impact than perioperative hemostasis management on retransplant rates and death.

Patterns of Recurrence and Progression for Unresectable Cholangiocarcinoma on Orthotopic Liver Transplant Protocol

<h3>Purpose/Objective(s)</h3> Neoadjuvant radiotherapy and chemotherapy (CHT) followed by orthotopic liver transplant (OLT) offers the highest chance of disease-free survival for patients with unresectable cholangiocarcinoma (CCA). The purpose of this study was to evaluate patterns of disease recurrence and progression in patients treated on OLT protocol. <h3>Materials/Methods</h3> Through retrospective chart review, we identified patients treated on institutional OLT protocol for unresectable intrahepatic or hilar CCA at a single academic institution from 2012-2019. Patients received SBRT to a total dose of 40 Gy in 5 fractions, delivered over 7-12 days followed by adjuvant CHT (gemcitabine/cisplatin, fluorouracil [5FU] or a capecitabine based regimen). Per protocol, restaging scans were obtained every 3 months until progression or OLT. <h3>Results</h3> Of 26 patients treated on protocol, nine underwent OLT (34.6%), of which six were male (66.7%), median age 51 (36-66), eight hilar tumors (88.9%), one intrahepatic (11.1%), and median size 2.85 cm (2.2-4.3). All patients were treated to 40 Gy in five fractions with a median PTV of 66.6 cc (30.4-202) and median time of 20.4 weeks (8.7-89.1) on adjuvant CHT. Median time from completion of SBRT to OLT was 61.4 weeks (26.6-97.6). Following OLT, four of nine (44.4%) achieved a pathologic complete response (ypT0) in the explanted liver, of which two patients developed recurrence (one at the porta hepatis, one in the lung). Five of nine OLT patients (55.6%) developed recurrent disease (three local, one local and distant, one distant) with median time to recurrence of 49.9 weeks (35.9-127.7) and median time to death of 124.0 weeks (39.3-200.9). Four patients remain in remission with median follow-up of 166.1 weeks (2.4-370.7). 17/26 patients did not proceed to OLT due to disease progression in 13 (10 local, 3 distant), with a median time to progression after SBRT of 37.0 weeks (3.7-81.4), death following recurrent cholangitis in three, and liver failure in one. Median OS for patients who underwent OLT versus those who did not was 172.2 (135.3-285.0) and 78.4 (26.1-219.6) weeks, respectively. <h3>Conclusion</h3> In this small group of patients with unresectable CCA treated with SBRT, CHT, and OLT, there were encouraging rates of pathologic complete response; however, a subset of patients will still develop disease recurrence. All patients who did not make it to OLT developed progression, illustrating a continued unmet need to improve therapeutic options for CCA.

Outcomes for Salvage Abdominal Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma after Liver Transplantation

<h3>Purpose/Objective(s)</h3> While orthotopic liver transplantation (OLT) is considered curative for most hepatocellular carcinoma (HCC) patients, recurrence can occur in 10-20% of these patients. Data has shown stereotactic body radiation therapy (SBRT) to be safe and effective as treatment for primary HCC, however few studies have investigated the safety and efficacy of SBRT as treatment for HCC after OLT. The aim of this study is to evaluate the safety and efficacy of intra-abdominal salvage SBRT for HCC in patients who previously underwent OLT. <h3>Materials/Methods</h3> A retrospective chart review of a single, large institution was conducted to identify patients who received intra-abdominal SBRT as treatment for recurrent HCC after OLT from 1/1/2013 to 12/1/2021. Clinical safety was measured by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0 for grading adverse events, Child-Turcott-Pugh (CTP) score, and Albumin-Bilirubin (ALBI) grade for HCC. Dosimetric analysis was performed. Efficacy was measured by local control (LC) and objective response using modified Response Evaluation Criteria in Solid Tumors (mRECIST). The Kaplan-Meier method was used to evaluate overall survival (OS) and progression free survival (PFS). <h3>Results</h3> 18 lesions, treated among 15 patients were identified that received intra-abdominal SBRT for HCC recurrence after OLT. Nine patients were male, median age was 62 (interquartile range 52 to 80). The American Joint Committee on Cancer stage at diagnosis was most often T1N0M0 (n=8, 53%) or T2N0M0 (n=5, 33%). The most common etiology for HCC diagnosis was hepatitis C virus (n=9, 56%). Median CTP and ALBI scores at baseline were 5 (range 5 to 11) and -3.02 (range -3.36 to -1.35), respectively. Median change in CTP score from baseline to CTP at 3, 6, and 12 months was 0.00, 1.00, and 1.00. Median change in ALBI score from baseline to at 3, 6, and 12 months was 0.14, 0.40, and 0.42. The median treatment dose was 4750 cGy (interquartile range 500 cGy), all patients received 5 fractions. There was no grade 3 or above CTCAE toxicities. During 6 (33%) SBRT treatments, patient experienced grade 1 or 2 CTCAE toxicity with nausea, emesis, or fatigue. Local control was achieved in 94% of lesions (n=17). Local treatment response was: 11 (61.2%) complete response, 5 (27.8%) partial response, 1 (5.5%) stable disease, and 1 (5.5%) progressive disease. After median follow up of 19.2 months, 8 patients (53%) were deceased and 7 (47%) had no evidence of disease progression. OS was 100% at 6 months and 60.8% at 12 months. PFS was 92.9% at 6 months and 60.9% at 12 months. No dosimetric factor was found to predict for increased toxicity. <h3>Conclusion</h3> For patients with HCC after OLT, SBRT appears to be a safe and effective treatment modality, as no patients experienced significant toxicities and the majority had complete treatment response.

Outcomes after Stereotactic Body Radiation for Hepatocellular Carcinoma in Patients with Childs Pugh A vs. Childs Pugh B/C Cirrhosis

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) has been shown to be a safe and effective local treatment for hepatocellular carcinoma (HCC). However, limited data exist in patients with CP B and C cirrhosis. The purpose of our study was to compare local control (LC), overall survival (OS), and toxicity outcomes for patients with CP A versus CP B and C cirrhosis. We hypothesized that CP B and C patients would have poorer overall survival, increased toxicity, and similar local control. <h3>Materials/Methods</h3> Patients with HCC who were treated with SBRT were prospectively enrolled into our institutional database from 2012-2021. Patients were separated into cohorts based on their liver function to generate a CP A and CP B/C cohort. LC and OS were evaluated using the Kaplan-Meier method. Local control was evaluated using both radiographic and pathologic data when available. <h3>Results</h3> 78 patients with a total of 94 tumors were included in our analysis with a median follow up of 23.6 months. Median tumor size was 3.6 cm. Median dose delivered was 47.5 Gy in a median of 5 fractions. There were 50 (64%) CP A and 28 (36%) CP B/C patients. The cohorts were comparable in terms of tumor size and baseline AFP. The mean EQD2 was significantly greater in the CP A cohort 85.47 Gy compared to the CP B/C cohort 57.14 Gy (<i>p</i> < .01) Furthermore, a greater proportion of CP B/C patients (64% 18/28) were listed for orthotopic liver transplant compared to CP A patients (30% 15/50) (<i>p</i> =0.004). The estimated 1-year LC rate were similar between the two cohorts with 92.5% LC in the CP A group and 90.9% LC in the CP B/C group (<i>p</i> =0.554). OS was not statistically different between cohorts with an estimated 1-year OS of 85.4% in the CP A group and 60% in the CP B/C group (<i>p</i> =0.225). Radiographic complete response (rCR) was comparable for CP A and CP B/C cohorts at 74% (42/57) and 63% (17/27) respectively. Of the tumors that were pathologically analyzed (CP A n=19; CP B/C n=13), the CP A and CP B/C cohorts had similar pathologic complete response rates of 63% and 62% respectively. 24 (41%) CP A patients and 14 (40%) CP B/C patients developed elsewhere liver tumor recurrence. 9 (15%) CP A patients and 3 (9%) CP B/C patients developed distant metastatic disease. Toxicity rates were low with only 3 patients (6%) in the CP A cohort and 6 patients (21%) in the CP B/C cohort that had grade 3+ adverse events. CP progression occurred in 16% of the CP A group and 29% of the CP B/C group. <h3>Conclusion</h3> Despite receiving lower radiation doses, CP B/C patients had similar LC and pCR rates when compared to CP A patients. OS was not statistically different between the cohorts but analysis was limited due to small numbers and higher number of liver transplant patients in the CP B/C group could also be confounding this result. Although the toxicity rate was reasonable, grade 3+ adverse events and CP progression were higher in CP B/C patients compared to CP A patients.

The effects of bicarbonated versus acetated Ringer's solutions on acid-base status and kidney injury following orthotopic liver transplantation: Protocol for a single-centre, randomised controlled trial (The BETTER trial).

The ideal crystalloid fluid of choice for fluid therapy during liver transplantation is unknown. Conventional balanced crystalloids are buffered with organic anions, which requires liver metabolism to prevent matabolic acidosis and protect renal function. Therefore they can not function properly during liver transplantation. On the contrary, the bicarbonated Ringer's solution (BRS) can maintain acid-base status regardless of liver function. In this study, we aimed to test the hypothesis that, in patients undergoing orthotopic liver transplantation, compared with acetated Ringer's solutions (ARS), perioperative fluid therapy with BRS could better maintain the acid-base status. This is a prospective, single-centre, randomised controlled trial. 72 eligible patients will be randomised to receive either BRS or ARS perioperatively. The primary endpoint is the difference in standard base excess (SBE) before and after operation. Secondary endpoints include the incidence of acute kidney injury (AKI) within 48 h post operation and free and alive days to day 14 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy (RRT). Metabolic acidosis is common perioperatively, potentially leading to decreased renal blood flow and reduced glomerular filtration rate. The use of balanced solutions can prevent hyperchloremic metabolic acidosis, thereby avoiding AKI in some patients. However, during liver transplantation, when well-functioning liver metabolism is lacking, the organic anions in conventional balanced solutions may remain strong anions and thus fail to maintain the acid-base status, but no solid clinical evidence exists now. This study will, for the first time, provide evidence on the relative effects of BRS vs. ARS on acid-base status and renal injury in patients undergoing liver transplantation. The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100046889) on 29 May 2021.

Incidence of Gastrointestinal Bleeding After Transesophageal Echocardiography Use in Orthotopic Liver Transplantation.

The risk of upper gastrointestinal bleeding (UGIB) after transesophageal echocardiography (TEE) in patients with high grade esophageal varices (EV) that are undergoing Orthotopic Liver transplantation (OLT) is poorly understood. This was a retrospective single-centre cohort study in all patients that underwent OLT at Queen Elizabeth Hospital Birmingham between September 2016 and September 2018. The primary outcome was to determine the incidence of UGIB in patients that have undergone OLT with EV that received TEE. 401 patients were included in the study, of which 320 (80%) received TEE. The incidence of post-operative UGIB in patients that received TEE was 1.6% (5/320) in the entire cohort: 2.7% (4/149) in patients with no evidence of EV and 0.6% (1/171) in patients with EV. UGIB occurred in 1 patient with grade 2 EV and did not occur in patients with grade 1 or 3 EV. The incidence of UGIB in patients that received TEE was not statistically different to patients that did not: 1.6% (5/320) vs. 3.7% (3/81) p = 0.218. In conclusion, in patients that underwent OLT, intra-operative TEE use was associated with low rates of UGIB, even in cohorts with high grade EV. This suggests that TEE is a relatively safe method of haemodynamic monitoring in patients undergoing OLT.

From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation.

Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)-derived liver cells are being utilized to study liver disease and to identify and test potential therapeutics. Moreover, bioengineered livers containing pig hepatocytes and endothelial cells have been shown to function and survive after transplantation into pig models of liver failure, providing preclinical evidence toward future clinical applications. Finally, bioengineered livers containing human iPSC-derived liver cells have been shown to function and survive after transplantation in rodents but require considerable optimization and testing prior to clinical use. In conclusion, bioengineered livers have emerged as a suitable tool for modeling liver diseases and as a promising alternative graft for clinical transplantation. The integration of novel technologies and techniques for the assembly and analysis of bioengineered livers will undoubtedly expand future applications in basic research and clinical transplantation.

RESULTS OF THERMAL VISION EXAMINATION BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION IN INBRED RATS

This article describes the using of thermal imaging examination in orthotopic liver transplantation in inbred rats. For the experiment, 40 inbred rats of the Vistar line were selected: 20 females, weighing 400–550 g, 20 males, weighing 600–750 g, about a year old. For comparison, we identified the control group, which underwent only an incision of the skin and muscles of the abdominal wall, and then closed the surgical wound, experimental group No. 1, in which the left lateral lobe of the liver was excluded from the bloodstream to create a model of graft ischemia, and experimental group No. 2 who underwent orthotopic transplantation. All manipulations were performed under anesthesia, in compliance with the rules of asepsis and antisepsis. Thermal imaging examination was carried out with a medical thermal imager model ULIRvision Ti120 before the operation, then on the first, third, fifth, seventh day after. When comparing the thermograms of rats from the experimental group No. 2 and the control group, differences were observed on the 3rd day after the operation, then the temperature in the graft area in the experimental group No. 2 was higher than the temperature of the same skin area in the control group. This may be due to a slight ischemia of the graft during its disconnection from the blood flow, as well as to surgical intervention. After conducting research, we came to the conclusion that on the 3rd day in the transplant area there is a local increase in temperature, which is associated with ischemia of the organ due to temporary blockage of blood vessels, which occurs from the moment of explantation of the liver until its subsequent connection to the bloodstream. Rats in which this process affects 33% of the liver die on the first day from developing fulminant sepsis.

Experience of liver transplantation in the regional clinical hospital

The purpose of the study is to summarize the first experience of liver transplants. Material and methods. Liver transplantation was performed at the Regional Clinical Hospital. 5 liver transplants from a posthumous donor were performed. Based on the available data, the analysis was carried out according to the following criteria: gender, age, MELD- Na index, cause of liver cirrhosis, method of liver transplantation, duration of surgery, postoperative complications, average bed-day, outcome. Results. In total, 5 liver transplants were performed from a posthumous donor. Among the patients there was 1 man and 4 women. The age of men is 41 years, women are 55.4 ± 9.2 years on average. The MELD- Na index is from 15 to 28, on average 17.8 ± 5.1. When transplanting a cadaveric liver, the method of classical orthotopic liver transplantation was used in 4 cases, in one the piggyback technique was used. The duration of surgical intervention in minutes averaged 394 ± 17.4. Postoperative complications on the Clavien-Dindo scale ranged from I to IIIb. The average bed-day of the patient’s stay in the hospital is 20.2 ± 8.9, including 6.2 ± 1.7 days in the intensive care unit. In all 5 cases, the outcome of liver transplantation is satisfactory. Conclusion. The first results of liver transplantation on the basis of the Regional Clinical Hospital showed that performing such a level of operations is possible in a multidisciplinary medical institution.

Balanced Blood Product Transfusion during Adult Liver Transplantation

Background: Orthotopic liver transplant (LT) is often associated with massive blood loss and significant transfusion requirements. Recent recommendations for resuscitation strategy in massive bleeding include the transfusion of balanced blood products, fresh frozen plasma (FFP), platelets, packed red blood cells (PRBC), and restricted use of crystalloids. Objectives: To evaluate whether the intraoperative transfusion ratio of fresh frozen plasma to packed red blood cell units (FFP: PRBC ≤1:1 versus &gt;1:1) plays a positive role in reducing PRBC transfusion in LT. Methods: This is a retrospective study of 84 liver transplant recipients who received at least one PRBC unit during the surgery. The patients were grouped into those who received intraoperative FFP: PRBC ratio ≤1:1 (low ratio) versus the ratio&gt;1:1 (high ratio). Selected perioperative variables were compared between the two groups. Results: Patients in the low-ratio versus high-ratio group had lower intraoperative requirements for PRBC (P&lt;0.001). Importantly, in the high-ratio group, the mean postoperative PRBC transfused units were 1.76 times that of the low-ratio group (incidence rate ratio [IRR], 1.76; 95% CI=1.07-2.90). There was a significant difference between the two groups in preoperative body mass index (P=0.047), hemoglobin (P=0.005), and surgical time (P=0.071); moreover, all the variables were higher in the high-ratio group. After adjusting the variables, postoperative PRBC consumption in the low-ratio group was 43% less than that in the high-ratio group (P=0.007). Conclusion: The intraoperative low-ratio transfusion was associated with a reduced need for total PRBC transfusion in LT.

The Effects of sodium bicarbonate Ringer's solution on acute kidney injury and the clinical outcomes after liver transplantation: A randomized controlled trial.

Background: Acute kidney injury is the most common complication after liver transplantation. Sodium bicarbonate Ringer’s solution is a new type of crystalloid solution that has been recently used in the clinical setting. Whether sodium bicarbonate Ringer’s solution reduces the occurrence of postoperative AKI and improves the clinical outcomes of liver transplantation patients is not clear. Objective: To compare the effects of sodium bicarbonate Ringer’s solution versus normal saline on acute kidney injury and clinical outcomes following classic orthotopic liver transplantation. Methods: Sixty-four participants were randomly assigned to the sodium bicarbonate Ringers (BRS) group or the normal saline (NS) group. The primary outcomes were the incidence and severity of acute kidney injury after liver transplantation. The secondary outcomes included the rate of renal replacement therapy, length of mechanical ventilation, stay in the ICU, stay in the hospital after surgery and 30-day mortality. Other outcomes included the concentration of sodium, chloride, bicarbonate, anion gap, lactate concentration and changes in chloride preoperatively and postoperatively. Result: Sixty-two patients completed the trial and were analyzed, with 31 patients in each group. There was a significantly lower rate of postoperative acute kidney injury in the BRS group (14/31, 45.2%) than in the NS group (24/31, 77.4%), with a relative risk of 0.58 (95% CI, 0.38–0.90; p = 0.009). The severity of AKI in the BRS group was lower than that in the NS group (Z = -2.932, p = 0.003). There was no significant difference observed in the secondary outcomes. For other outcomes, the concentration of preoperative sodium was lower than postoperative sodium in the NS group (137.2 vs. 140.4, p = 0.009). The concentration of preoperative chloride was lower than that of postoperative chloride in the NS group (102.9 vs. 106.2, p < 0.001). The change in the concentration of chloride in the BRS group was lower than that in the NS group (1.6 vs. 4.7, p = 0.006). Conclusion: Sodium bicarbonate Ringer’s solution reduced the incidence and severity of acute kidney injury after classic orthotopic liver transplantation.

S2908 Liver Transplant for Management of Neurological Wilson Disease in a Patient With Preserved Liver Function

Introduction: The role of orthotopic liver transplant (OLT) solely for the management of neurological Wilson disease (WD) is unclear. We present a patient with WD who underwent OLT for neurological deterioration with compensated cirrhosis. Case Description/Methods: A 19-year-old male presented with three-month history of dysarthria, akinesia, and fine tremors. His past medical history was remarkable for unexplained splenomegaly and thrombocytopenia. He denied history and risk factors for liver disease. Physical exam showed slurred speech, bilateral hand tremors, spasticity of the lower extremities, and absence of Kayser-Fleischer ring. Labs were unremarkable, except for platelets of 79 k/uL. MRI brain showed bilateral, symmetric hyper-intensity in the basal ganglia, lateral thalami and midbrain on T2-weighted images. (Figure) CT liver revealed cirrhosis, portal hypertension, and mild splenomegaly. Copper metabolism study confirmed low serum copper (8 µmol/L) and high 24-hr urine copper (234 µg/d) consistent with diagnosis of WD. He was promptly started on Zinc and Trientine 250 mg daily. After one month, the patient was re-admitted for worsening dysphagia, dysarthria and rigidity, eventually becoming bedridden with inability to talk and eat requiring G-tube placed). Liver biopsy showed cirrhosis with little inflammatory activity and abundant copper on Rhodanine stain ( >600 mcg/g). The patient underwent OLT after being granted a Metabolic MELD exception of 40 due to medically unresponsive neurological impairment, with preserved liver function (calculated MELD 8). Post-OLT, he had gradual neurological improvement, except persistent dystonia and spasticity. Serum ceruloplasmin levels normalized but repeat MRI showed persistent signal alterations at the basal ganglia and brainstem. At 16 month follow-up, his neurological recovery remained largely stagnant with minimal improvement in extrapyramidal symptoms. Discussion: OLT for management of neurological WD remains highly debatable. Most data on neurological recovery after LT are based on patients with mixed liver and neurological involvement with success rate of 62%. In our patient, he failed to display complete neurological recovery 1.5 years after OLT despite initial improvement. The rapid neurologic deterioration that led to OLT occurred after initiation of chelation therapy which may indicate paradoxical worsening. Additional research is needed to determine the timing of OLT and role of medical optimization prior to OLT in patients with neurological WD.Figure 1.: (A) MRI Brain with contrast showing (T2/FLAIR) hyperintensity and mild edema symmetrically in the caudate heads, putamina, ventral lateral thalami, and midbrain. Findings are suspicious for Wilson Disease. (B) Cirrhotic nodules accompanying mild chronic inflammation (Hematoxylin and eosin, 100X). (C) The liver cells of this cirrhotic nodule are extensively filled with copper (Rhodanine stain, 100X) (D) The liver cells show bright red granules of copper in the cytoplasm (Rhodanine stain, 200X).

S2870 Successful Use of EUS-Guided Choledochoduodenostomy With LAMS in a Post-Liver Transplant Patient With Recurrent Choledocholithiasis and Cholangitis

Introduction: Biliary complications, like anastomotic stricture and cholangitis, are seen in 10-15% of orthotopic liver transplants (OLT). OLTs often require multiple endoscopic retrograde cholangiopancreatoscopy (ERCP) for recurrent disease. Endoscopic ultrasound guided choledochoduodenostomy (EUS-CD) has been effective in treatment of malignant distal biliary obstruction after failed ERCP; however, there are limited reports regarding EUS-CD in OLTs. We present a case of successful EUS-CD with lumen apposing metal stents (LAMS) in an OLT with recurrent cholangitis secondary to benign anastomotic stricture refractory to management with ERCP. Case Description/Methods: A 61-year old female with 3 OLTs (1996 and twice in 2008) for autoimmune hepatitis presented with recurrent cholangitis secondary to anastomotic biliary stricture in the setting of duct mismatch with a dilated common hepatic bile duct to 3 cm. She had recurrent choledocholithiasis measuring 3 cm despite prior mechanical and electrohydraulic lithotripsy with cholangioscopy confirmed clearance. As a result, she had undergone a total of 26 prior ERCP treatments (2012-2021). She underwent an EUS-CD with LAMS for definitive treatment. 2-weeks later, an upper endoscope was traversed through the LAMS to perform lithotripsy of remaining choledocholithiasis. At this time, the patient remains free of cholangitis for the past 8 months. (Figure) Discussion: Biliary complications, like anastomotic stricture and recurrent cholangitis, are a common occurrence in OLTs. With use of various ERCP techniques, obstructions can be removed or ameliorated. Timely treatment of cholangitis is imperative as the mortality rate is high (10-30%). With each cholangitis episode and subsequent ERCP, the cumulative procedural risk and mortality increases. EUS-CD has been demonstrated to be effective in treatment for malignant distal biliary obstruction after failed ERCP. Our patient had previously undergone 26 ERCPs and additionally was on Warfarin for pulmonary embolism putting her at very high risk for complications with additional future endoscopic procedures. This represents a case of successful use of EUS-CD with LAMS in a patient post-OLT with a significant distal common bile duct stricture which had been refractory to traditional management via ERCP. Long term studies are indicated to see if this can provide durable benefit.Figure 1.: 1A. MRI imaging demonstrating a large 3 cm choledocholithiasis within the dilated CBD, which formed as a result of bile stasis. 1B. CT coronal view demonstrating successful deployment of LAMS to complete EUS-CD. 1C. Fluoroscopic view of the standard upper scope traversing through the LAMS for definitive lithotripsy and dredging of remaining choledocholithiasis. 1D. Endoscopic view of the final LAMS placement with double pigtail plastic stents.

S1286 Impact of Cardiovascular Disease on Liver Transplant Candidacy During Transplant Evaluation in a North American Center With High Obesity Prevalence

Introduction: There are no large studies that examined the impact of obesity and cardiovascular disease in patients undergoing evaluation for orthotopic liver transplantation (OLT). Methods: We retrospectively analyzed patients undergoing OLT evaluation between Jan 2012 and Nov 2021 in a liver transplant center in the Mid-West US. Results: 912 patients underwent OLT evaluation (59% males, mean age 57.4±10.5 years, Mean Na-MELD 18.7±8.7, 82% Caucasian and 8.6% African Americans) etiology of cirrhosis NASH (48.1%), alcohol (37.7%), and hepatitis C (18.5%). 31.8% and 41.7% were overweight and obese respectively. 261 (31.8%) underwent OLT, 554 (60.7%) were denied listing, and 51(5.6%) died during evaluation. 224 patients had coronary artery disease (CAD) and among them, 50% were denied OLT. Of all patients denied listing, 32% were denied OLT due to CAD. Comorbid medical conditions (30%), substance use (15%) and socioeconomic condition (19.3%) were other causes for denial for listing. 239 (26.2%) had metabolic syndrome (MS), of which 143 (59.8%) were denied OLT. Among patients denied, 55(10%) were morbidly obese (BMI >40). Gender, residential location(urban v/s rural), hypertension, diabetes, CAD, BNP levels, atrial fibrillation, chronic kidney disease, hyperlipidemia,MS,6-minute walk test (6MWT) did not correlate with transplant denial on univariate analysis (Table). Ethnicity (African American, p=0.03), vitamin-D deficiency (< 30 ng/ml) and BMI (p=0.038) had significant correlation. On multivariate analysis (MVA), BMI >30), (OR 0.71 [0.51-0.98], p = 0.04) and vitamin-D deficiency (OR 0.21 (0.15-0.29), p < .01) were independent predictors of denial. For predicting death during OLT evaluation, on univariate analysis, 6-minute walk test (6MWT), estimated pulmonary artery pressure (PAP) on transthoracic echocardiography, mean PAP on right heart catheterization, significant coronary obstruction on left heart catheterization were not predictors, but female gender and vitamin-D deficiency were predictors. On stratified analysis of patients denied listing due to CAD, the presence of MS (OR 2.1(1.3-3.5), p=0.003) was an independent predictor of denial, and normal BNP levels (< 100pg/ml) lowered the risk of denial (OR 0.42 (0.20-0.88), p=0.02). Conclusion: Obesity (BMI >40) and vitamin-D deficiency increased the risk of denial for transplant listing. Presence of metabolic syndrome increased the risk of denial for listing due to CAD and normal BNP levels (< 100pg/ml) significantly lowered the risk of denial from CAD. Table 1. - Univariate analysis for predictors of liver transplant denial and death in waiting list Transplant denial (p value) Death during evaluation (p value) Gender 0.09 0.04* Ethnicity 0.03* 0.21 Location (rural v/s urban) 0.15 0.5 Hypertension 0.86 0.41 Diabetes 0.81 0.98 BMI 0.04* 0.59 CAD 0.55 0.42 Chronic kidney disease 0.06 0.16 Atrial fibrillation 0.73 0.96 Hyperlipidemia 0.66 0.22 Metabolic syndrome 0.68 0.77 Vitamin-D deficiency < 0.01* < 0.01* 6 Minute Walk Test (6MWT) 0.67 0.56 BNP levels 0.19 0.65 Cardiac ejection fraction on echocardiography 0.58 Elevated estimated PAP 0.81 Elevated mean PAP 0.12 Computed tomography calcium score 0.35 Positive dobutamine stress echocardiography 0.68 Significant coronary obstruction in left heart catheterization 0.44

S2910 Transcatheter Aortic Valve Replacement Restoring Candidacy for Liver Transplant in Cirrhotic Patients

Introduction: Current guidelines for preoperative workup for an orthotopic liver transplant (OLT) recommend echocardiogram and cardiac testing that classically rule-out patients with superimposed severe aortic stenosis as transplant candidates. We evaluated the potential of transcatheter aortic valve replacement (TAVR) as a bridging therapy to restore the candidacy of cirrhotic patients with severe AS for liver transplant. Case Description/Methods: A retrospective chart review was performed on 472 patient records that underwent liver transplants at a single large tertiary care center between 2017 and mid-2021. We identified patients who had a history of severe aortic stenosis corrected by TAVR. We extracted demographic and long-term outcome data. Two patients underwent the TAVR procedure which alleviated AS and allowed for reinstatement of eligibility for OLT. Evaluation at 1-month, 3-months and 1-year post-liver transplant showed no complications in the function of or related to the prosthetic aortic valves. Patient survival at 1 year and 2 years post-transplant was 100%. Mean time of follow-up post-transplant was 27 months. Graft survival at 1 year and 2 years was 100% with no evidence of rejection. Both 1 year and 2-year follow-up labs showed that patients were normotensive and had lipid profiles within the normal range. One of the patients had baseline high HbA1c consistent with their history of type 2 diabetes that continued to show in their follow-up labs while the other had normal glucose and HbA1C throughout. Noteworthy post-transplant complications included a left lower quadrant hematoma in one patient which resolved spontaneously and alcoholic recidivism managed through transplant psychiatry care. One patient did have a left-sided facial droop and right-sided pronator drift two days following the liver transplantation. CTA showed 74% stenosis of the right ICA and MRI confirmed hypoxic ischemia. Facial droop and drift resolved upon revaluation a few hours after onset. (Table) Discussion: In the setting of these growing contraindicated problems of AS and liver cirrhosis, we wanted to contribute to the currently scarce compilation of case reports that illustrates the effect that the TAVR procedure has on relieving the pre-transplantation risks of aortic stenosis in high-risk patients. The patients do have the potential for other cardiovascular diseases long-term and should be monitored closely with modification of risk factors. Table 1. - This is a comparison of echocardiogram parameters of aortic valve morphology and function for both patients #1 and #2 before and after TAVR as well as after OLT Parameters Patient #1 Patient #2 Before TAVR After TAVR After OLT Before TAVR After TAVR After OLT Aortic valve peak gradient (mmhg) 16.9 12.2 16.6 67.7 51.4 50.0 Aortic valves mean gradient (mmhg) 8.4 5.8 9.8 38.3 24.5 25.5 Left ventricular ejection fraction (%) 61 46 55 >70 67 63 Aortic valve area, Vmax (cmÂ2) 2.22 1.53 3.12 0.92 0.98 1.18 The post-TAVR parameters occurred 2 days after the procedure for patient #1 and <6 months for patient #2 due to care referral to our offices. The post OLT echo parameters were measured two months after patient #1's transplant and 4 days after patient #2 transplant.