Orthotopic Liver Transplantation Patients Research Articles

Single-institutional analysis of radiotherapy and orthotopic liver transplant for patients with unresectable cholangiocarcinoma.

466 Background: There is increasing interest in effective strategies for locoregional therapy for cholangiocarcinoma, particularly given the evolving role of orthotopic liver transplant (OLT) for select patients. This single-institution retrospective study compares the clinical efficacy and toxicity of stereotactic body radiotherapy (SBRT), conventional fractionation chemoradiation (CRT), or SBRT as a bridge to OLT in patients with unresectable early stage and locally advanced cholangiocarcinoma. Methods: We reviewed a total of 31 patients from 2010 to 2023 with intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and perihilar cholangiocarcinoma who were treated with SBRT (n=22) or CRT (n=9). SBRT was delivered in 1-5 fractions, median dose of 40 Gy, and dose ranging from 16 Gy to 60 Gy. CRT was delivered in 13-28 fractions, median dose of 50.2 Gy, and dose ranging from 45 Gy to 52.5 Gy. Kaplan-Meier was used to analyze overall survival (OS), progression-free survival (PFS), and local control (LC). Acute and late G3+ toxicity was scored using CTCAE, version 5.0. Results: We identified 13 patients with ICC, 5 with ECC, and 13 with perihilar disease where SBRT or CRT was part of upfront definitive treatment. With a median follow-up time of 11 months, there was no statistical difference between SBRT vs. CRT for OS (median 21 vs. 22 months; p=0.36), PFS (median 14.2 vs. 11 months; p=0.09), and 1-year LC (73.2% vs. 66.7%; p=0.10). However, SBRT appeared to have lower proportions of acute grade 3+ (9.1% vs. 33.3%) and chronic grade 3+ toxicities (22.7% vs. 33.3%). Four patients with early stage perihilar or ICC underwent SBRT as successful bridge to transplant, with no evidence of disease progression at 5.4 months. An additional 2 out of 8 patients were removed from protocol due to disease progression and 2 others remain on protocol, awaiting OLT. Conclusions: In our series of unresectable cholangiocarcinoma, we found no difference in OS, PFS, and LC for patients treated with SBRT vs. CRT, although the former appeared to have lower toxicity and a trend towards improved PFS. Further research is needed to compare SBRT and CRT as definitive treatment or bridge to OLT for patients with unresectable cholangiocarcinoma.

Single center experience using stereotactic body radiation therapy (SBRT) on orthotopic liver transplant protocol for unresectable cholangiocarcinoma

PurposeTo evaluate tolerability, pathologic response, and disease outcomes utilizing pre-operative stereotactic body radiation therapy (SBRT) followed by consolidation chemotherapy (CHT) prior to orthotopic liver transplant (OLT) in unresectable cholangiocarcinoma (CCA). MethodsThis was a retrospective chart review of patients treated on OLT protocol at a single tertiary center from 2012 to 2019. Patients received pre-operative SBRT (40–50 Gy in 5 fractions) followed by CHT until progression or OLT. Progression-free survival (PFS) and overall survival (OS) were compared via log-rank test and Cox proportional hazards regression. Results26 patients (84.6% hilar, 15.4% intrahepatic) were identified for analysis. Eight patients (30.8%) patients developed acute toxicity after SBRT, mostly grade 1 nausea. Nine (34.6%) patients underwent OLT of which 4 (44.4%) achieved a pathologic complete response (pCR). Five (55.6%) OLT patients, including 2 pCR, developed recurrence at a median time of 49.9 weeks after OLT. 3-year OS for the OLT and dropout cohort was 75% and 9%, respectively (p < 0.0001). OS in hilar tumors only was statistically different for those that achieved a pCR (p = 0.014). ConclusionsPre-operative SBRT is a well-tolerated and effective radiation technique as part of OLT protocol for unresectable CCA and conferred in a pCR rate of 44% within our cohort.

Intensive Care Unit-Acquired Weakness after Liver Transplantation: Analysis of Seven Cases and a Literature Review.

Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW.

SIRT1 regulates hepatocyte programmed cell death via GSDME - IL18 axis in human and mouse liver transplantation

Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates the inflamed liver’s canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain. Here, we undertook translational studies in human and mouse orthotopic liver transplantation (OLT) to interrogate the significance of hepatocyte-specific SIRT1 in cold-stored donor livers and liver grafts after reperfusion. In the clinical arm of sixty human OLT patients, hepatic SIRT1 levels in cold-preserved donor livers correlated with the anti-apoptotic Bcl-2 expression. After reperfusion, improved OLT function was accompanied by hepatic SIRT1 levels negatively associated with cleaved caspase-3 expression. In the experimental arm, we compared FLOX-control with hepatocyte-specific SIRT1-KO livers after orthotopic transplantation into WT mouse recipients, parallel with primary murine hepatocyte cultures subjected to cold activation with/without knockdown of SIRT1, GSDME, and IL18Rβ. Indeed, hepatocyte SIRT1 deficiency upregulated apoptosis and GSDME-mediated programmed cell death, deteriorating hepatocellular function and shortening OLT survival. Augmented GSDME processing, accompanied by increased secretion of IL18 by stressed hepatocytes, was prominent in SIRT1-deficient, cold-stored livers. Hepatocyte SIRT1 expression regulated anti-apoptotic Bcl-2/XIAP proteins, suppressed cold stress-triggered apoptosis, and mitigated GSDME licensing to release IL18. Notably, consistent with the ability of IL18 to depress hepatocyte SIRT1 and Bcl-2/XIAP in vitro, IL18 neutralization in vivo prevented hepatocellular damage and restored the anti-apoptotic phenotype in otherwise injury-prone SIRT1-deficient OLTs. In conclusion, this translational study identifies a novel hepatocyte SIRT1-IL18 molecular circuit as a therapeutic target in the mechanism underpinning hepatocyte death pathways in human and mouse liver transplantation.

Anaesthesia management for liver transplantation: A narrative review.

Orthotopic liver transplantation is the definitive standard treatment for end-stage liver disease. Orthotopic liver transplantation anaesthesia management is a complex procedure that requires a multidisciplinary team approach. Understanding the complex pathophysiology of end-stage liver disease and its complications in the affected systems is essential for proper anaesthesia management in orthotopic liver transplantation. Orthotopic liver transplantation is a dynamic process, and preoperative optimisation is essential in these patients. Therefore, anaesthesiologists should focus on rapidly fluctuating physiology, haemodynamics, metabolic, and coagulation status in the anaesthesia management of these patients. Perioperative care and anaesthesia for orthotopic liver transplantation can be divided into preoperative evaluation, anaesthesia induction and management, dissection, anhepatic, neo-hepatic, and postoperative care, with essential anaesthetic considerations at each point. Considering the clinical situation, haemodynamic changes, misapplications, knowledge, attitude, and multimodal and multidisciplinary approach are vital in anaesthesia and the perioperative period. In our review, in line with the literature, we aimed to present the perioperative and anaesthesia management in orthotopic liver transplantation patients.

Predictors of intraoperative massive transfusion in orthotopic liver transplantation.

Although transfusion management has improved during the last decade, orthotopic liver transplantation (OLT) has been associated with considerable blood transfusion requirements which poses some challenges in securing blood bank inventories. Defining the predictors of massive blood transfusion before surgery will allow the blood bank to better manage patients' needs without delays. We evaluated the predictors of intraoperative massive transfusion in OLT. Data were collected on patients who underwent OLT between 2007 and 2017. Repeat OLTs were excluded. Analyzed variables included recipients' demographic and pretransplant laboratory variables, donors' data, and intraoperative variables. Massive transfusion was defined as intraoperative transfusion of ≥10 units of packed red blood cells (RBCs). Statistical analysis was performed using SPSS version 17.0. The study included 970 OLT patients. The median age of patients was 57 (range: 16-74) years; 609 (62.7%) were male. RBCs, thawed plasma, and platelets were transfused intraoperatively to 782 (80.6%) patients, 831 (85.7%) patients, and 422 (43.5%) patients, respectively. Massive transfusion was documented in 119 (12.3%) patients. In multivariate analysis, previous right abdominal surgery, the recipient's hemoglobin, Model for End Stage Liver Disease (MELD) score, cold ischemia time, warm ischemia time, and operation time were predictive of massive transfusion. There was a direct significant correlation between the number of RBC units transfused and plasma (Pearson correlation coefficient r = .794) and platelets (r = .65). Previous abdominal surgery, the recipient's hemoglobin, MELD score, cold ischemia time, warm ischemia time, and operation time were predictive of intraoperative massive transfusion in OLT.

Predictive Value of Fatty Liver Index for Long-Term Cardiovascular Events in Patients Receiving Liver Transplantation: The COLT Study.

Cardiovascular disease (CVD) is the leading cause of early mortality in orthotopic liver transplantation (OLT) patients. The fatty liver index (FLI) is strongly associated with carotid and coronary atherosclerosis, as well as cardiovascular mortality, surpassing traditional risk factors. Given the lack of data on FLI as a predictor of cardiovascular events in OLT recipients, we conducted a retrospective study to examine this topic. We performed a multicenter retrospective analysis of adult OLT recipients who had regular follow-up visits every three to six months (or more frequently if necessary) from January 1995 to December 2020. The minimum follow-up period was two years post-intervention. Anamnestic, clinical, anthropometric and laboratory data were collected, and FLI was calculated for all patients. gov registration ID NCT05895669. A total of 110 eligible patients (median age 57 years [IQR: 50-62], 72.7% male) were followed for a median duration of 92.3 months (IQR: 45.7-172.4) post-liver transplantation. During this period, 16 patients (14.5%) experienced at least one adverse cardiovascular event (including fatal and non-fatal myocardial infarction and stroke). Receiver Operating Characteristic (ROC) analysis identified a cut-off value of 66.0725 for predicting cardiovascular events after OLT, with 86.7% sensitivity and 63.7% specificity (68% vs. 31%; p = 0.001). Kaplan-Meier analysis showed that patients with FLI > 66 had significantly reduced cardiovascular event-free survival than those with FLI ≤ 66 (log-rank: 0.0008). Furthermore, multivariable Cox regression analysis demonstrated that FLI > 66 and pre-OLT smoking were independently associated with increased cardiovascular risk. Our findings suggest that FLI > 66 and pre-OLT smoking predict cardiovascular risk in adult OLT recipients.

Peculiarities of orthotopic liver transplantation in patients with liver cirrhosis and severe hemophilia A

In the presented clinical case reports, patients with decompensated liver cirrhosis resulted from chronic viral hepatitis C, being stable responders to antiviral therapy and having severe hemophilia A, underwent orthotopic liver transplantation from a post-mortem donor. The volume of intraoperative blood loss and the course of the immediate postoperative period on the background of the replacement therapy with recombinant VIII coagulation factors did not differ from other liver transplant recipients of the City Clinical Hospital n.a. S.P. Botkin. In the late postoperative period, the level of coagulation factor VIII returned to normal in patients, which made it possible to cancel the replacement therapy.

Celiac trunk stenosis by median arcuate ligament in orthotopic liver transplantation: a potential hidden foe to the biliary tree

BackgroundCeliac trunk compression by the median arcuate ligament (MAL) increases the risk of ischemic complications following gastrointestinal surgical procedures. Previous studies suggest increased risk of hepatic artery thrombosis (HAT) in orthotopic liver transplant (OLT) recipients. The aim of this study is to investigate the impact of untreated MAL compression (MAL-C) on biliary complications in OLT. MethodsContrast-enhanced imaging was used to classify celiac trunk stenosis by MAL-C. Medical records were reviewed to extract pre-transplant, transplant and post-transplant data. Patients were divided into two groups: no MAL compression (nMAL-C) and MAL-C. The primary endpoint was biliary complications. Secondary endpoints were HAT and graft survival. Results305 OLT were performed from 2010 to 2021, of which 219 were included for analysis: 185 (84.5%) patients without and 34 (15.5%) with MAL-C. The incidence of HAT was 5.9% in both groups. Biliary complications were more common in the MAL-C group (35.3% vs. 17.8%, p = 0.035). Graft survival was decreased in patients with MAL-C (p = 0.035). ConclusionsMAL-C of the celiac trunk was associated with increased risk of biliary complications and inferior graft survival in OLT patients. These findings highlight the importance of preoperative screening and treatment of MAL in this population.

Relationship Between Perioperative Factors and Splenic Artery Steal Syndrome After Orthotopic Liver Transplant: A Retrospective Clinical Study.

After orthotopic liver transplant, ischemia of biliary tract and graft loss may occur due to impaired hepatic arterial blood flow. This situation with hypersplenism and impaired hepatic arterial blood flowis defined as splenic artery steal syndrome.The aim of this study was to investigate the relationship between perioperative factors and splenic artery steal syndrome in orthotopic liver transplant patients. Forty-five patients who underwent orthotopic liver transplant between 2014 and 2022 were included in the study. The data for the patients were obtained from the hospital database, including the intraoperative anesthesiology and postoperative intensive care records. Eleven patients were diagnosed with splenic artery steal syndrome. Patients with splenic artery steal syndrome had higher need for intraoperative vasopressor agents (P = .016) and exhibited lower intraoperative urine output (P = .031). In the postoperative intensive care follow-up, patients with splenic artery steal syndrome had higher levels of C-reactive protein during the first 48 hours (P = .030). Intraoperative administration of vasopressor drugs, low urine output, and early postoperative high C-reactive protein levels were associated with the development of splenic artery steal syndrome in patients undergoing orthotopic liver transplant. Future studies should focus on investigation of biomarkers associated systemic hypoperfusion that may contribute to the development of splenic artery steal syndrome.

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians.

Despite recent advances in the transplant field, infectious complications after orthotopic liver transplantation (OLT) are major causes of morbidity and mortality. Bacterial intra-abdominal infections (IAIs) are predominant during the first month post-transplantation and affect patient and graft survival. Recently, the emergence of multidrug resistant bacteria has generated great concern in OLT patients. We performed this narrative review of the literature in order to propose a "ready-to-use" flowchart for reasoned empirical antibiotic therapy in the case of suspected post-OLT IAIs. The review was ultimately organized into four sections: "Epidemiology and predisposing factors for IAI"; "Surgical-site infections and perioperative prophylaxis"; "MDRO colonization and infections"; and "Reasoned-empirical antibiotic therapy in early intra-abdominal infections post OLT and source control". Multidisciplinary teamwork is warranted to individualize strategies for the prevention and treatment of IAIs in OLT recipients, taking into account each patient's risk factors, the surgical characteristics, and the local bacterial epidemiology.

Abstract P3012: Routine Monitoring For Intracardiac Thrombosis And Pulmonary Embolism With Intraoperative Transesophageal Echocardiography In Orthotopic Liver Transplantation

Background: Intracardiac thrombosis (ICT) and pulmonary embolism (PE) are significant intraoperative complications during orthotopic liver transplantation (OLT). Despite the high mortality associated with these events, current monitoring practices are inadequate at detecting these complications during OLT. Transesophageal echocardiography (TEE) allows continuous monitoring of myocardial function and detection of ICT/PE. In this study, we aim to report the incidence of ICT/PE during OLT at our center and to advocate for the use of intraoperative TEE as a standard monitoring tool. We also propose a medical management algorithm stratified by the severity of RV dysfunction and pulmonary artery pressure (PAP) in cases of ICT with/without PE. Methods: We conducted a single-center retrospective chart review of OLT patients with intraoperative TEE monitoring from March 13, 2019 - March 13, 2023. Intraoperative data of interest included hemodynamics, RV dysfunction, PAP, presence of ICT and/or PE as identified on TEE and associated medical management. RV dysfunction was graded as mild, moderate, or severe reduction in cardiac contractility. Secondary outcome was mortality during index hospitalization. Results: We identified 99 patients at our center who had intraoperative TEE monitoring during OLT. Prevalence of ICT in this population was 9.09% (n=9), of which 44.4% (n=4) developed hemodynamically significant PE. ICT patients who remained hemodynamically stable were observed without intervention (33%, n=3). Heparin was administered to prevent thrombus enlargement in patients with an increase in PAP but no significant RV dysfunction detected on TEE (22%, n=2). Those showing signs of hemodynamically significant PE with moderate or severe RV failure were given tissue plasminogen activator (tPA) for thrombolysis (44%, n=4). Perioperative mortality among all ICT patients was 44.4% (n=4) due to hemorrhagic shock secondary to coagulopathy and heart failure. Conclusion: The results of this study show the utility of routine TEE use in intraoperative monitoring for identifying ICT and PE in OLT patients, given the high mortality associated with these complications. TEE also allows for a stepwise approach to medical management based on RV function and PAP.

T Cell CEACAM1–TIM-3 Crosstalk Alleviates Liver Transplant Injury in Mice and Humans

Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) acts through homophilic and heterophilic interactions with T cell immunoglobulin domain and mucin domain-containing protein 3 (TIM-3), which regulates innate immune activation in orthotopic liver transplantation (OLT). We investigated whether cluster of differentiation (CD) 4+ T cell-dependent CC1-TIM-3 crosstalk may affect OLT outcomes in mice and humans. Wild-type (WT) and CC1-deficient (CC1 knock-out [KO]) mouse livers were transplanted into WT, CC1KO, or T-cell TIM-3 transgenic (TIM-3Tg)/CC1KO double-mutant recipients. CD4+ T cells were adoptively transferred into T/B cell-deficient recombination activating gene 2 protein (Rag2) KO recipients, followed by OLT. The perioperative liver-associated CC1 increase was analyzed in 50 OLT patients. OLT injury in WT livers deteriorated in CC1KO compared with CC1-proficient (WT) recipients. The frequency of TIM-3+CD4+ T cells was higher in WT than CC1KO hosts. Reconstitution of Rag2KO mice with CC1KO-T cells increased nuclear factor (NF)-κB phosphorylation and OLT damage compared with recipients repopulated with WT T cells. T-cell TIM-3 enhancement in CC1KO recipients (WT→ TIM3Tg/CC1KO) suppressed NF-κB phosphorylation in Kupffer cells and mitigated OLT injury. However, TIM-3-mediated protection was lost by pharmacologic TIM-3 blockade or an absence of CC1 in the donor liver (CC1KO→ TIM-3Tg/CC1KO). The perioperative CC1 increase in human OLT reduced hepatocellular injury, early allograft dysfunction, and the cumulative rejection rate. This translational study identifies T cell-specific CC1 signaling as a therapeutic means to alleviate OLT injury by promoting T cell-intrinsic TIM-3, which in turn interacts with liver-associated CC1 to suppress NF-κB in Kupffer cells. By suppressing peritransplant liver damage, promoting T-cell homeostasis, and improving OLT outcomes, recipient CC1 signaling serves as a novel cytoprotective sentinel.

Prediction, prevention, and treatment of post reperfusion syndrome in adult orthotopic liver transplant patients.

This review explores proposed predictors, preventative measures, and treatment options for post-reperfusion syndrome (PRS) in liver transplantation and provides updated data for clinicians. The review aims to understand the status and progress made regarding PRS during orthotopic liver transplantation. Moreover, the predictors of PRS will be analyzed to highlight risk factors. Mediators of PRS and the modes of action of the currently available preventative and management agents that target particular PRS factors will be investigated. Data is drawn from secondary sources from databases of peer-reviewed journals. The bibliographies of select sources were also used to obtain additional data studies using the 'snowball' method. The initial data search provided 1394 studies analyzed using PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. After applying the eligibility criteria, 18 studies were fit for inclusion. The study identified that in addition to the severity of underlying medical conditions, other significant PRS predictors included patient age, sex, duration of cold ischemia, and the surgical technique. While the use of epinephrine and norepinephrine is well-established, further preventative measures commonly involve specifically targeting known mediators of the syndrome, such as antioxidants, vasodilators, free radical scavengers, and anticoagulants. Current management strategies involve supportive therapy. Machine Perfusion may ultimately decrease the risk of PRS. PRS still holds unknowns, including the underlying pathophysiology, controllable factors, and ideal management practices. There is a need for further study, particularly prospective trials since liver transplantation is the gold standard for treating end-stage liver disease and the incidence of PRS remains high.

Simultaneous Live Donor Liver Transplantation, Aortic Valve Replacement, and Atrial Septal Defect Repair in a Patient With End Stage Liver Disease: A Case Report

Valvular heart disease creates an important barrier for orthotopic liver transplantation in patients with end-stage liver disease and increases mortality. Selection of the appropriate surgical scheme and adequate postoperative management can be lifesaving in these cases. This study presents a 32-year-old man diagnosed with hepatitis C-associated cirrhosis and severe aortic regurgitation due to subacute bacterial endocarditis. Initially, simultaneous aortic valve replacement (AVR) and live donor liver transplantation (LDLT) was planned. However, intraoperative transesophageal echocardiography revealed an additional atrial septal defect (ASD) and AVR, ASD repair, and LDLT surgery were performed. During the 2-year follow-up period, there were no early or late complications. To the best of our knowledge, this is the first patient to have simultaneous AVR, ASD repair, and LDLT surgery. Additionally, the present case is also unique in being the first person in the Republic of Azerbaijan to undergo concomitant cardiac surgery and LDLT.

Effect of Sodium Bicarbonate Ringer's Solution on Intraoperative Blood Gas Analysis and Postoperative Recovery Time in Liver Transplantation: A Single-Center Retrospective Study.

BACKGROUND Sodium bicarbonate Ringer's solution (BRS) is the latest generation of balanced crystal solutions. BRS does not increase the liver burden, but its impact in liver transplantation is unclear. The aim of this study was to investigate the effect of BRS as a fluid therapy on intraoperative blood gas analysis and postoperative recovery time in orthotopic liver transplantation (LT) patients. MATERIAL AND METHODS The study included 101 patients who received classical in situ liver transplantation at the Second Affiliated Hospital of Guangxi Medical University from November 2019 to January 2022. The patients were divided into 2 groups according to the intraoperative fluid infusion: the BRS group and the sodium lactate Ringer's solution group (LRS group). Intraoperative blood gas analysis, including pH, base excess (BE), bicarbonate, and lactic acid levels of radial artery blood, were collected after induction (T0), 30 min before opening (T1), 30 min after no liver period (T2), 30 min after opening (T3), and at the end of the operation (T4). Postoperative ICU catheter time, ICU stay time, and total hospitalization days were also recorded and compared between the 2 groups. RESULTS Lactic acid levels were decreased significantly at T3 in the BRS group (P<0.05). ICU catheter time, ICU hospitalization days, and total hospitalization days were significantly shorter in the BRS group (P<0.05). CONCLUSIONS BRS can decrease the lactic acid level at 30 min after opening, reducing the postoperative recovery time. BRS is more effective than LRS in liver transplantation.

Implications of Pleural Fluid Composition in Persistent Pleural Effusion following Orthotopic Liver Transplant

Persistent pleural effusions (PPEf) represent a known complication of orthotopic liver transplant (OLT). However, their clinical relevance is not well described. We evaluated the clinical, biochemical, and cellular characteristics of post-OLT PPEf and assessed their relationship with longitudinal outcomes. We performed a retrospective cohort study of OLT recipients between 2006 and 2015. Included patients had post-OLT PPEf, defined by effusion persisting >30 days after OLT and available pleural fluid analysis. PPEf were classified as transudates or exudates (ExudLight) by Light's criteria. Exudates were subclassified as those with elevated lactate dehydrogenase (ExudLDH) or elevated protein (ExudProt). Cellular composition was classified as neutrophil- or lymphocyte-predominant. Of 1602 OLT patients, 124 (7.7%) had PPEf, of which 90.2% were ExudLight. Compared to all OLT recipients, PPEf patients had lower two-year survival (HR 1.63; p = 0.002). Among PPEf patients, one-year mortality was associated with pleural fluid RBC count (p = 0.03). While ExudLight and ExudProt showed no association with outcomes, ExudLDH were associated with increased ventilator dependence (p = 0.03) and postoperative length of stay (p = 0.03). Neutrophil-predominant effusions were associated with increased postoperative ventilator dependence (p = 0.03), vasopressor dependence (p = 0.02), and surgical pleural intervention (p = 0.02). In summary, post-OLT PPEf were associated with increased mortality. Ninety percent of these effusions were exudates by Light's criteria. Defining exudates using LDH only and incorporating cellular analysis, including neutrophils and RBCs, was useful in predicting morbidity.

Early intrahepatic recurrence of HBV infection in liver transplant recipients despite antiviral prophylaxis

Background & AimsProphylaxis with nucleos(t)ide analogues (NUCs) and hepatitis B immunoglobulin (HBIG) has decreased the rate of HBV recurrence after orthotopic liver transplantation (OLT), but the duration of this prophylaxis remains debated. Our aim was to investigate the recurrence of both intrahepatic and serum HBV markers after OLT in patients receiving long-term NUC and HBIG prophylaxis. MethodsA total of 31 HBV-positive patients benefiting from OLT were prospectively enrolled in five French centres between 2012 and 2015. Tissue samples from the native liver, liver reperfusion biopsy, and 12-month post-OLT (M12) biopsy were collected. Intrahepatic HBV markers were quantified using Droplet Digital PCR. Serum hepatitis B core-related antigen (HBcrAg) and HBsAg were quantified using the Lumipulse platform. ResultsAmong the 31 patients, 26 were HBeAg negative and 28 had undetectable serum HBV DNA at OLT. All patients received HBIG and NUC after OLT, and serum HBV DNA was undetectable at M12. Of the 27 available native livers, 26 had detectable total HBV DNA (median, 0.045 copies/cell), 21 were positive for cccDNA (0.001 copies/cell), and 19 were positive for 3.5-kb HBV RNA (0.0004 copies/cell). Among the 14 sequential reperfusion and M12 biopsies, seven were positive for HBV markers on the reperfusion sampling, and six of them were also positive at M12. Of the 27 patients with available serum samples at M12, eight were positive for HBcrAg and five were positive for HBsAg by ultrasensitive quantification, although they were negative by conventional techniques. Overall, among the 17 patients having a matched biopsy and serum sample at M12, only one had undetectable HBV markers in both the liver and serum. ConclusionsOur results demonstrate a very early detection of viral genome in the graft and intrahepatic viral recurrence despite NUC and HBIG prophylaxis. Clinical Trials RegistrationThis study is registered at ClinicalTrials.gov (NCT02602847). Impact and ImplicationsIn this work, we show that, despite the recommended prophylaxis based on NUC and HBIG, HBV can infect the new liver very rapidly after transplantation. Twelve months after transplantation, the majority of patients had at least one HBV marker detected in either serum or the liver. Therefore, our results demonstrate early intrahepatic viral recurrence despite NUC and HBIG therapy and underline the importance of an optimal patient compliance to the antiviral prophylaxis to prevent viral rebound.

Survival in People Living with HIV with or without Recurrence of Hepatocellular Carcinoma after Invasive Therapy

To address the overall survival (OS) and recurrence (RE) in people living with HIV (PLWH) treated with invasive therapy (IT) for hepatocellular carcinoma (HCC). This is a retrospective cohort study on 41 PLWH with HCC receiving IT, defined as liver resection (LR), orthotopic liver transplantation (OLT), radiofrequency thermo-ablation (RFTA) trans arterial chemo, or radioembolization (CRE). OS and RE were investigated by Kaplan-Meier curves. The Cox proportional hazard regression model was used for multivariate analyses. Recurrence occurred in 46.3% PLWH; in 36.7% of participants at 2 years and in 52% at 5 years from HCC diagnosis; it was less frequent in males, p = 0.036. Overall, 2- and 5-year survival after HCC diagnosis was 72% and 48%, respectively. Two-and five-year survival was 100% and 90.9%, respectively, in PLWH receiving OLT, compared to other IT (60.9% and 30.6%, respectively) log-rank p = 0.0006. Two- and five-year survival in participants with no-RE was 70.5% and 54.6%, respectively, and 73.7% and 42.1% among RE, respectively, log-rank p = 0.7772. By multivariate analysis, AFP at values < 28.8 ng/mL, at HCC diagnosis, was the only factor predicting survival. Fifty percent of PLWH survived five years after HCC diagnosis; 90.9% among OLT patients. Recurrence after IT was observed in 46% of HCC/PLWH. AFP cut-off levels of 28.8 ng/mL were the only independent variable associated with survival.

Utility of transesophageal echocardiography during orthotopic liver transplantation: A narrative review.

Orthotopic liver transplantation (OLT) is the standard of care for patients suffering from end stage liver disease (ESLD). This is a high-risk procedure with the potential for hemorrhage, large shifts in preload and afterload, and release of vasoactive mediators that can have profound effects on hemodynamic equilibrium. In addition, patients with ESLD can have preexisting coronary artery disease, cirrhotic cardiomyopathy, porto-pulomary hypertension and imbalanced coagulation. As cardiovascular involvement is invariable and patient are at an appreciable risk of intraoperative cardiac arrest, Trans esophageal echocardiography (TEE) is increasingly becoming a routinely utilized monitor during OLT in patients without contraindications to its use. A comprehensive TEE assessment performed by trained operators provides a wealth of information on baseline cardiac function, while a focused study specific for the ESLD patients can help in prompt diagnosis and treatment of critical events. Future studies utilizing TEE will eventually optimize examination safety, quality, permit patient risk stratification, provide intraoperative guidance, and allow for evaluation of graft vasculature.