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The increasing prevalence of steatotic liver disease (SLD) in potential living donors is concerning, as it limits donor's availability amid rising demand. OPTIFAST very low-calorie diet (VLCD), a meal replacement product, effectively reduces weight and hepatic steatosis before transplantation. However, data on the outcomes of recipients of VLCD-treated donors are lacking. We conducted a single-center, retrospective study on 199 living donor liver transplant recipients at Toronto General Hospital, Canada, between January 2015 and January 2020. We compared the 1-year posttransplant outcomes between recipients who received organs from donors treated with VLCD (N = 34) for either weight loss or steatosis reduction, with those who did not require treatment (N = 165). Our analysis revealed no statistically significant differences in the rates of postoperative complications (23% vs 32.4%, p = 0.3) or intensive care unit stays (70.9% vs 70.6%, p = 1) between recipients of non-VLCD and VLCD grafts. Following adjusted multivariate logistic regression, receipt of VLCD grafts was not associated with increased hospital length of stay. In addition, one-year mortality did not differ between the two groups (4.2% non-VLCD recipients vs 2.9% VLCD recipients, p = 0.6). OPTIFAST VLCD treatment for liver donors demonstrates positive and safe outcomes in recipients, expanding the pool of potential living donors for increased organ availability. [ABSTRACT FROM AUTHOR]

Background. In spite of the scientific evidence supporting health advantages of mushrooms, some of them are seriously poisonous. The clinical picture of mushroom intoxication ranges from minor gastrointestinal symptoms to organ failure, such as liver failure and death. Method. We provided demographics, clinicopathological characteristics, applied treatments, and outcomes of mushroom poisoning by Lepiota species in a series of 18 cases that were referred from Kermanshah and Lorestan provinces to Abu-Ali-Sina Hospital, Shiraz, Iran. Clinical and paraclinical data were collected by taking history and reviewing of medical documents. Pathologic findings were extracted through a review of hematoxylin and eosin pathologic slides. Results. The patients were between the ages of 18 and 67 years, composed of ten females and eight males. The most frequent clinical manifestations were nausea and vomiting followed by abdominal pain. Four cases presented decreased consciousness on admission. One of them passed away. Three other cases underwent liver transplantation, two of them died after transplantation, and one fully recovered without any major issues. All instances had elevated ALT levels, which ranged from 44 to 9,140 IU/L (mean: 3259 ± 2476), with most of them also having concurrent AST elevations (mean: 1,361 ± 1,532). Only few patients had modest elevations in alkaline phosphatase. Total and direct bilirubin elevations up to 47.6 and 24 mg/dL, respectively, were found in most cases. Decreased total protein and albumin concentrations and increased BUN and creatinine levels were observed in some patients. In addition, some instances revealed increased LDH, increased WBC, decreased hemoglobin, and decreased platelet count. Most patients had increased prothrombin time; hematuria and positive stool occult blood were observed in few patients. Histopathologic examination of three explanted livers revealed massive necrosis with moderate to severe macrovesicular steatosis, significant ductular reaction, and parenchymal inflammation. Other patients followed a recovery process with a considerable drop in liver enzymes, especially ALT, during hospitalization utilizing conservative treatment. They had no liver problems or relevant issues after a two-year follow-up. Conclusion. In our study, highly elevated liver enzymes with a significantly high ALT/AST ratio were observed in cases of mushroom poisoning by Lepiota species, leading to fulminant liver failure and death in some cases. These laboratory findings were correlated with liver necrosis and macrovesicular steatosis in explanted livers. [ABSTRACT FROM AUTHOR]

The Model for End-Stage Liver Disease (MELD) scoring system is used to prioritize liver transplantations and assess disease severity. This includes the international normalized ratio (INR), creatinine, and total bilirubin. Since there are several ways to measure creatinine, MELD scores can produce inconsistent results. The objectives of this study were to define a valid cut-off for bilirubin interference in creatinine measurement and to assess the effects of various icteric levels on creatinine measurement and liver transplant allocation. A total of 400 serum samples were categorized into four groups based on their icteric indices and total bilirubin levels, including non-, mild, moderate, and severe icteric samples. Both chemical Jaffe and enzymatic techniques were used to determine the creatinine levels in all four groups, and the findings were compared. In parallel, serum samples from 83 liver transplant candidate patients were divided into three groups depending on their bilirubin levels and then similarly evaluated and interpreted. The MELD scores were then computed for each group and compared. In icteric samples, the enzymatic method produced higher results for the creatinine concentrations than the Jaffe method did, and the mean creatinine difference rose from 0.08 in nonicteric group to 1.95 in groups with severe icterus. In addition, the enzymatic approach yielded higher findings for creatinine and subsequently for MELD scores in patients who were liver transplant candidates. When the bilirubin concentration was above the 4 mg/dL threshold, there were differences between the approaches for both the creatinine and the MELD score (p values: 0.0001 and 0.027, respectively). The chemical Jaffe is a readily available and considerably cost-effective method for measuring creatinine. However, it is influenced by a variety of known and unknown interfering substances, and it should be applied cautiously when working with icteric samples. Alternate techniques such as the enzymatic method should be considered when the bilirubin level exceeds 4 mg/dL. Though this cut-off is instrument and kit-dependent, each laboratory is advised to have its cut-off for bilirubin interference. [ABSTRACT FROM AUTHOR]

CALFAN syndrome is an extremely rare disease consisting of recurrent pediatric acute liver failure (PALF), neurodegenerative diseases, and skeletal abnormalities associated with SCYL1 gene mutation. To date, three of 18 patients reported underwent liver transplantation in infancy and early childhood (7–23 months). Here, we report a case of CALFAN syndrome with infantile onset, recurrent jaundice/PALF requiring liver transplantation in early adulthood. At the most recent follow-up, 3 years after transplantation, the patient is doing well. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with recurrent retinochoroiditis. However, immunocompromised patients can cause disseminated disease due to the reactivation of the latent tissue cysts or due to a primary infection. Here, we present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The diagnosis was confirmed by PCR of anterior chamber fluid and brain biopsy, and no other sites of disseminated disease were detected on PET-CT. The patient has been treated with sulfamethoxazole-trimethoprim 800/160 mg with virtually complete resolution of the neurological and ocular symptoms. Iatrogenic blockade of the CD40 pathway may elicit a particular susceptibility for CNS reactivation of T. gondii. [ABSTRACT FROM AUTHOR]

Background. Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that results from defective mechanisms of bile secretion. We aim to describe different types of PFIC and their clinical features, treatment modalities, and outcomes in Saudi Arabia. Patients and Methods. This is a retrospective study of all patients diagnosed with PFIC at King Faisal Specialist Hospital and Research Center in Riyadh from January 1, 2002, to December 31, 2021. All relevant information was collected from patient charts and transferred into the REDcap® database for statistical analysis. Results. A total of 79 patients were identified with PFIC, and PFIC type 3 was the most common (59.5%), followed by PFIC type 2 (34.2%), PFIC type 1 (5.1%), and PFIC type 4 (1.3%). Males and females were affected in 54.4% and 45.6%, respectively. Mutations in ATP8B1, ABCB11, and ABCB4 genes were observed in PFIC type 1, PFIC type 2, and PFIC type 3, and loss of function in a variant of TJP2 was detected in PFIC type 4, respectively. A total of 51 (64.6%) patients underwent liver transplantation: three patients (3/4) with PFIC type 1 (75%), twenty patients (20/27) with PFIC type 2 (74.1%), twenty-seven patients (27/47) with PFIC type 3 (57.4%), and one patient with PFIC type 4 (100%). The mean duration of disease before transplantation was 53.9 ± 67 months with a median of 30 months. Following liver transplantation, symptomatic control was achieved in 47 patients (92.2%). Recurrence after transplantation occurred in 4 patients (7.8%) within an average of 22.5 months and a median of 17 months. Conclusion. PFIC is considered a rare disorder in Saudi Arabia; however, early recognition of the disease is important for appropriate management and early referral for liver transplantation evaluation. The overall rate of liver transplantation in our cohort was 64.6% with an excellent five-year survival rate. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survival after tumor resection. Aim. This study evaluated the relation between MVI and HCC within various anatomical Couinaud's segments of the liver. Method. A multicenter retrospective review of HCC records was conducted from 2012 to 2017. HCC cases were identified using ICD-9 and 10 codes 155, C22.0, and C22.8. HCC patients who underwent liver transplants were included in this study. Liver segment of the location of HCC was obtained from radiographic records, and MVI information was obtained from pathology reports. Segmental distributions of HCC in MVI versus non-MVI groups were compared using Wilcoxon rank sum tests. p value was set at <0.05. Results. We analyzed 120 HCC patients who underwent liver transplantation. The mean age of our cohort was 57 years, and the most common etiology of liver disease was hepatitis C at 58.3%. The median HCC size was 3.1 cm, and MVI was present in 23.3% of the explanted specimens. MVI was 2 to 3 times significantly higher in patients with HCC affecting segments 2 and 3 and segments 4b and 5 (p = 0.01). Moreover, median survival was significantly lower in patients with MVI versus those without MVI (50 vs. 137 months, p < 0.05). Conclusion. MVI was significantly higher in HCC tumors located in liver segments 2 and 3 and 4b and 5, and survival was lower in patients with MVI compared with those without. [ABSTRACT FROM AUTHOR]

Introduction and Purpose. Given the importance of a successful transition to adult care for pediatric transplant recipients, there is a critical need to better understand modifiable factors which may affect that process. This study assessed the knowledge of adolescent liver transplant recipients about their disease and evaluated if a disease-specific educational intervention could increase their knowledge and impact clinical outcome. Methods. A four-category measure was created to assess the knowledge regarding diagnosis, surgical history, lab values, and medications in adolescent liver transplant patients. Teens were randomized to receive one-on-one, verbally administered education from a medical provider versus standard care (control). Results. Fifty-six liver transplant recipients completed the measure, with 24 completing a posttest. The median age at transplant was 6.9 years and at pre-test was 17.8 years. Thirty-eight percent did not know their original diagnosis at pretest. The average pretest total score was 43%. Teens who received the intervention had an average posttest score of 61% versus 42.4% for controls (p < 0.05). Teens who scored ≥50% at pretest had 2.0 rejection episodes per patient while those scoring < 50 % had 0.95 rejection episodes per patient (p = 0.04). Conclusions. Adolescent liver transplant recipients have low baseline knowledge about their condition. Tailored outpatient education is effective at improving knowledge, but this did not translate to improved outcomes. The role of oppositional behaviors, parental supervision, and other high-risk activities on clinical outcomes needs to be determined by further studies. These data suggest that teen liver transplant recipients require more supervision than their level of knowledge implies. [ABSTRACT FROM AUTHOR]

Introduction. Histopathological assessment of liver biopsies is the current "gold standard" for diagnosing graft dysfunction after liver transplantation (LT), as graft dysfunction can have nonspecific clinical presentations and inconsistent patterns of liver biochemical dysfunction. Most commonly, post-LT, graft dysfunction within the first year, is due to acute T-cell mediated rejection (TCMR) which is characterised histologically by the degree of portal inflammation (PI), bile duct damage (BDD), and venous endothelial inflammation (VEI). This study aimed to establish the relationship between global assessment, which is the global grading of rejection using a "gestalt" approach, and the rejection activity index (RAI) of each component of TCMR as described in revised Banff 2016 guidelines. Methods. Liver biopsies (n = 90) taken from patients who underwent LT in 2015 and 2016 at the Australian National Liver Transplant Unit were identified from the electronic medical records. All biopsy slides were microscopically graded by at least two assessors independently using the revised 2016 Banff criteria. Data were analysed using IBM SPSS v21. A Fisher–Freeman–Halton test was performed to assess the correlation between the global assessment and the RAI scores for each TCMR biopsy. Results. Within the cohort, 60 (37%, n = 164) patients underwent at least 1 biopsy within 12 months after LT. The most common biopsy outcome (total n = 90) was acute TCMR (64, 71.1%). Global assessment of TCMR slides strongly positively correlated with PI (p value <0.001), BDD (p value <0.001), VEI (p value <0.001), and total RAI (p value <0.001). Liver biochemistry of patients with TCMR significantly improved within 4 to 6 weeks post-biopsy compared to the day of the biopsy. Conclusion. In acute TCMR, global assessment and total RAI are strongly correlated and can be used interchangeably to describe the severity of TCMR. [ABSTRACT FROM AUTHOR]

Recently, magnetic resonance imaging (MRI) has been developed as a widely available and noninvasive method for detecting and evaluating hepatic iron overload. This case report presents a successful living donor liver transplantation (LDLT) in which the donor was suspected to have hepatic iron deposition by MRI evaluation. A preoperative donor liver biopsy and genetic examination were performed to exclude hereditary hemochromatosis and other chronic liver diseases. A liver biopsy showed an almost normal liver specimen with a slight deposition of iron in 2-3% of hepatocytes, and a genetic examination of hereditary hemochromatosis revealed no typical mutations in HFE, TFR2, HJV, HAMP, or SLC40A1. Despite the traumatic hemothorax complication caused by the liver biopsy, the liver transplant eligibility was confirmed. Two months after the hemothorax complication, an LDLT donor operation was performed. The donor was discharged from the hospital on postoperative day (POD) #17 with favorable liver function. The recipient's posttransplant clinical course was generally favorable except for acute cellular rejection and biliary complications, and the recipient was discharged from the hospital on POD #87 with excellent graft function. A one-year follow-up liver biopsy of the recipient demonstrated almost normal liver with iron deposition in less than 1% of the hepatocytes, and no iron deposition was identified in the liver graft by MRI examination. Liver biopsy and genetic examination are effective methods to evaluate the eligibility of liver transplant donors with suspected hepatic iron deposition. The living donor with slight hepatic iron deposition, if hereditary hemochromatosis was ruled out, can donate partial liver safely. [ABSTRACT FROM AUTHOR]

Background. Intraoperative anesthetic requirements might be altered due to the modulated metabolic function in living donor liver transplant recipients. Remimazolam may provide appropriate anesthesia in patients with cirrhosis. However, the efficacy and safety of remimazolam in liver transplant recipients have not been reported. We present the successful anesthesia management of a liver transplant recipient using remimazolam. Case Presentation. A 54-year-old woman who was diagnosed with Child-Pugh C cirrhosis of unknown etiology was scheduled for living donor liver transplantation. Remimazolam was used for anesthesia management under electroencephalogram monitoring, including bispectral index (BIS) and patient state index (PSI) values. Despite the prolonged surgical time (1,037 min) and massive blood loss (22,500 mL), BIS and PSI values were maintained within acceptable ranges intraoperatively. There was no intraoperative awareness/recall or adverse events associated with remimazolam administered perioperatively. Conclusions. We safely managed general anesthesia for living donor liver transplantation with remimazolam using electroencephalogram monitoring. [ABSTRACT FROM AUTHOR]

Background. Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear. Methods. EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl4-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro. Results. EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the liver's microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea. Conclusions. These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering. [ABSTRACT FROM AUTHOR]

Background. Nonadherence to immunosuppression in liver transplant recipients (LTRs) leads to deterioration in health outcomes. Once-dailyextended-release tacrolimus (TAC-ER) may improve adherence when compared to twice-dailyimmediate-release tacrolimus (TAC-IR). Methods. We conducted a randomized controlled study to evaluate medication adherence, clinical efficacy, and safety of TAC-ER in stable LTR. All patients >18 years who underwent liver transplantation before 6 months were eligible. Patients were randomized 1 : 1 to continued TAC-IR or conversion to TAC-ER. The primary outcome was change in medication adherence from baseline to 9 months, assessed using BAASIS. Secondary outcomes were tacrolimus trough levels, safety, and quality of life. Results. Thirty-one patients were consented and randomized to either of the two groups: conversion to TAC-ER (n = 15) or continued TAC-IR (n = 16). Six patients in the TAC-ER group withdrew after randomization due to apprehension about switching medication (n = 2), unwillingness to travel (n = 2), and increased liver tests after conversion (n = 2, both were acute rejections despite therapeutic tacrolimus levels and were considered unrelated to TAC-ER). We compared the results of nine patients in the TAC-ER group that completed the study with those of sixteen in the TAC-IR group. At baseline, there was no difference in tacrolimus trough levels between groups. Improved adherence was observed in the TAC-ER group as 100% of patients reported at least one period of full adherence during the study period (100% vs. 62.6%, p = 0.035). Tacrolimus trough levels and liver tests were comparable between groups throughout the study. There were no differences in eGFR, HbA1c, or QoL between the groups. Conclusion. TAC-ER improved medication adherence while maintaining comparable trough levels, liver function, and QoL as TAC-IR in LTR. [ABSTRACT FROM AUTHOR]

Poorer than expected, living donor liver transplant outcomes are observed after recipient graft artery thrombosis. At grafting, the risk for later thrombosis is high if a dissected hepatic artery is used for standard reconstruction. Surgeon diagnosis of dissection requires nonstandard management with alternative technique in addition to microvascular expertise. Intimal flap repair with standard reconstruction is contingent on basis of a redo anastomosis. It is a suboptimal choice for living donor transplantation. Achieving goal graft arterial perfusion at first revascularization is crucial for superior outcomes. Managing dissection at grafting with nonstandard left gastric artery reconstruction is unreported. Our experience is limited, but this is our preferred alternative technique to standard hepatic artery reconstruction complicated by dissection. Here, we describe our two-case experience with left gastric arterialized grafts for management of dissection. Our living donor graft recipients with alternatively arterialized grafts are now 6- and 2-years posttransplant. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we sought to evaluate the prevalence and association of pre‐transplant atrial fibrillation (AF) on 30‐day postoperative outcomes in patients undergoing orthotopic liver transplant (OLT). Method: The National Inpatient Sample Database was queried from 2011 to 2017 for relevant ICD‐9 and ICD‐10 procedural and diagnostic codes. Baseline characteristics and in‐hospital outcomes were compared in patients who underwent OLT with AF and those without. Results: Among 45,357 patients who underwent OLT, women made up 35.8% of the overall population. The prevalence of AF before transplant was 2932 (6.5%) with a trend toward increasing prevalence, with an average annual change rate of 4.19%. Applying propensity score matching to control for potential confounding factors, there was no association between pre‐transplant AF and in‐hospital mortality in patients undergoing OLT, however there was a higher incidence of perioperative complications including: acute kidney injury, ventricular tachycardia, major bleeding, blood product transfusion, and septic shock. Conclusion: In patients undergoing OLT, pre‐transplant AF is increasing in prevalence and appears to be associated with similar in‐hospital mortality but worse perioperative outcomes. Greater emphasis should be placed on AF in the preoperative cardiovascular risk stratification of patients undergoing OLT. [ABSTRACT FROM AUTHOR]

Objectives. Tacrolimus is characterized by high pharmacokinetic variability in combination with a narrow therapeutic range. However, influence of donor CYP3A5 genotype and graft-to-recipient body weight ratio (GRWR) on tacrolimus' pharmacokinetics after pediatric living donor liver transplantation (LDLT) remains unclear. Methods. A total of 174 LDLT recipients (<6 y) were grouped according to donor CYP3A5 genotypes (nonexpressor (NEX) or expressor (EX)) and GRWR (<3.0% (SS, small-size) or ≥3.0% (LS, large-size)): SS/NEX (n = 40), SS/EX (n = 38), LS/NEX (n = 48), and LS/EX (n = 48). Pharmacokinetics of tacrolimus and clinical outcomes were analyzed. Results. The relationships between the concentration-dose ratio and donor CYP3A5 genotypes and graft size were examined 3, 7, 14, and 30 days after the transplantation. Tacrolimus C0 levels varied greatly among groups, although recipients started with the same initial dosage. LS/EX recipients had significantly lower C0 levels in comparison with those of other groups. The use of CYP3A5-EX-grafts and a greater GRWR both resulted in significantly higher TAC dose requirements and lower C/D ratios. However, the significance of GRWR no longer exists 3 months after transplantation. The multivariate generalized linear mixed model analysis showed that donor CYP3A5 genotypes (F = 11.876 ; P = 0.01) and GRWR (F = 4.631 ; P = 0.033) were independent impact factors for C/D ratios 3, 7, 14, and 30 days after transplantation. Donor CYP3A5-EX genotype was associated with significantly increasing risks of infectious complications and significantly lower Cylex ATP values. However, no significant difference was observed in acute rejections among 4 groups. Conclusions. Monitoring of C0 levels alone is not reliable to guide tacrolimus administration. Donor CYP3A5 and GRWR both significantly affect tacrolimus pharmacokinetics after pediatric LDLT. The use of Cylex ATP tests would be helpful to avoid overimmunosuppression. [ABSTRACT FROM AUTHOR]

Background. The incidence of chronic liver disease is increasing in the Nepalese population. Liver transplantation (LT) is the best option for patients with end-stage liver disease (ESLD). Nepal's first liver transplant was performed in 2016 in an international collaborative effort at Shahid Dharmabhakta National Transplant Centre (SDNTC), Bhaktapur, Nepal. We aim to report details of the first five patients who had undergone liver transplantation in SDNTC before the beginning of the COVID-19 outbreak in the history of transplantation in Nepal. Method. A descriptive analysis of the clinical data of five adult recipients of liver transplantation at SDNTC was done. We described the patient's demographics, length of stay, and survival of all the first five patients who had undergone four living donor liver transplantations and one brain-dead donor liver transplantation in SDNTC before the beginning of the COVID-19 outbreak. Results. Recipients were between 36 and 63 years old. The recipients of the four live donor liver transplants (LDLT) and one brain-dead donor liver transplant (DDLT) had alcoholic liver disease and cryptogenic liver disease, leading to end-stage liver disease. The model for end-stage liver disease (MELD) scores ranged from 23 to 34. Out of five, four recipients and four donors are doing well and relishing the prospect of a normal life, while the recipient of a brain-dead donor liver transplant passed away due to postoperative primary graft failure. Conclusion. Despite the small number of liver transplants that have been done, the success of these has created confidence in a sustainable liver transplantation program in Nepal. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Triazole antifungal‐associated severe skin allergy has received little attention. Here we report a case of an acute‐on‐chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. Case Summary: A 40‐year‐old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. What Is New and Conclusion: To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Only a few studies about polymyxin B (PMB) against multidrug‐resistant gram‐negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR‐GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30‐day all‐cause mortality. Methods: Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30‐day all‐cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. Results and Discussion: Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30‐day all‐cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016–1.423, p = 0.032) was an independent risk factor for 30‐day all‐cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019–0.860, p = 0.034) was an independent risk factor for clinical cure with PMB. What Is New and Conclusions: This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety. [ABSTRACT FROM AUTHOR]

Introduction. Orthotopic liver transplants are characterized by sudden changes in hemodynamics, intraoperative hemorrhage, metabolic and electrolyte derangements, and arrhythmias. Many of these features are also hallmarks of malignant hyperthermia episodes and make differentiation difficult intraoperatively. Additionally, the treatment for malignant hyperthermia, dantrolene, can cause hepatotoxicity in already damaged native livers and newly reperfused organ allografts. Thus, it is imperative to avoid a triggering anesthetic in these patients. Here we report on a successful total intravenous anesthetic in a malignant hyperthermia susceptible individual undergoing an orthotopic liver transplant for acutely decompensated end-stage liver disease. Case Presentation. A 49-year-old male with a past medical history significant for malignant hyperthermia episodes as a child was admitted with decompensated alcoholic cirrhosis. He underwent uneventful total intravenous general anesthesia with propofol and sufentanil continuous infusions for an orthotopic liver transplant. He required minimal vasoactive agents to maintain a mean arterial blood pressure >65 mmHg and was extubated on postoperative day 1. Conclusions. Total intravenous anesthesia is necessary for patients with a personal history of malignant hyperthermia. However, this type of general anesthesia is difficult in the setting of fluctuating hemodynamics, hemorrhage, and changes in drug metabolism and clearance during the anhepatic and reperfusion phases of an orthotopic liver transplant. Propofol and sufentanil continuous infusions provided stable hemodynamics and an excellent plane of anesthesia throughout the case and should be considered in other individuals undergoing this procedure who require a total intravenous anesthetic. [ABSTRACT FROM AUTHOR]

This study is aimed at reporting a rare and unusual focal choroidal excavation with a macular hole in a patient with Alagille syndrome (AGS). A 21-year-old woman with an established early-life AGS diagnosis was referred to our hospital prior to liver transplantation. Examination revealed best-corrected visual acuity of 16/20 and 20/20 in the right and left eye, respectively. Slit-lamp examination was positive for posterior embryotoxon in both eyes. Fundoscopy revealed diffuse choroidal hypopigmentation with increased visibility of the choroidal blood vessels and circumferential chorioretinal atrophy in the mid-peripheral and peripheral retina in both eyes. A full-thickness macular hole with underlying focal choroidal excavation was observed in the right eye. Optical coherence tomography through the macula confirmed choroidal excavation with a full-thickness macular hole in the right eye. To our knowledge, this is the first report describing focal choroidal excavation with a macular hole in an AGS patient. [ABSTRACT FROM AUTHOR]

Background. Liver transplantation (LT) is an effective treatment option for patients with end-stage liver disease; biliary complications are important cause of death in posttransplant patients. Endoscopic retrograde cholangiopancreatography (ERCP) has an irreplaceable role in the diagnosis and treatment of patients with biliary tract disease. Methods. The clinical data of patients with biliary strictures (BS) after LT treated with ERCP admitted to the Third Xiangya Hospital of Central South University from September 2016 to October 2021 were reviewed; the changes in temperature, bilirubin, and albumin before and after treatment and postoperative complications were analyzed. Results. A total of 41 patients were included in the study, and biliary stents were successfully placed in 37 cases (90.2%), while 4 cases (9.8%) were unsuccessful due to complete BS. Patients with ERCP guided biliary stenting had a significant improvement in bilirubin index compared to the preoperative period (P < 0.05). 27 patients (73.0%) had complete relief of symptoms after 1 ERCP-guided treatment, and 10 patients (27.0%) developed BS again at different times after the first ERCP treatment, among which 8 patients developed BS again within 1 year after the first treatment and 2 patients developed BS again after 1 year after the first treatment. The incidence of endoscopy-related adverse events was 35.14%, with no serious adverse events. Conclusion. ERCP-guided biliary stenting was an effective and safety treatment for BS after LT. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is characterized by uncontrolled progressive lung fibrosis with a median survival of 3 to 5 years. Although currently available pharmacotherapy cannot cure the disease, antifibrotics including pirfenidone and nintedanib were shown to slow disease progression and improve survival in IPF. Nevertheless, there is a knowledge gap on the safety of antifibrotics in patients after liver transplantation receiving concomitant immunosuppressive therapy. This case report of a 68-year-old male patient with IPF illustrates how a complex medical history has led to diagnostic and therapeutic challenges considerably affecting clinical decisions and impacting the patient's journey. The increasing severity of lung function impairment due to the progressive natural history of IPF ultimately led to severe respiratory failure. Double lung transplantation (LTx) was performed as the only therapeutic option in end-stage disease with the potential to improve quality of life and survival. To the best of our knowledge, this is the first case report describing the feasibility and safety of antifibrotic therapy with pirfenidone for IPF in a 68-year-old patient with a history of liver transplantation receiving concomitant immunosuppressive therapy with tacrolimus who underwent successful double lung transplantation when alternative medical interventions had been exhausted. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a frequent and serious complication of chronic liver disease. The mechanism of hepatic encephalopathy is not entirely clear. Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting. It manifests as a wide spectrum of neurological or psychiatric abnormalities, ranging from subclinical alterations, detectable only by neuropsychological or neurophysiological assessment, to coma. Liver transplant (LT) is the definitive treatment for refractory hepatic encephalopathy. In this case, we present a challenging case of refractory hepatic encephalopathy in a postliver transplant patient with portal vein thrombosis and a splenorenal shunt treated with a novel technique to address his complex anatomy. [ABSTRACT FROM AUTHOR]

Hepatic ischemia/reperfusion injury (HIRI) is a common complication of liver surgery requiring hepatic disconnection, such as hepatectomy and liver transplantation. The aim of this study was to investigate the effects of cordycepin on HIRI and to elucidate the underlying mechanisms. Balb/c mice were randomly divided into six groups: a normal control group, sham group, H-cordycepin group, HIRI group, L-cordycepin (25 mg/kg) + HIRI group, and H-cordycepin (50 mg/kg) + HIRI group. Mice were subjected to I/R, and cordycepin was intragastrically administered for seven consecutive days before surgery. Orbital blood and liver specimens were collected at 6 and 24 h after HIRI. Serum levels of ALT and AST were decreased in the cordycepin pretreatment groups. Notably, cordycepin attenuated the inflammatory response and the production of proapoptosis proteins, while increasing expression of antiapoptosis proteins and decreasing expression of autophagy-linked proteins. Furthermore, cordycepin inhibited activation of the MAPK/NF-κB signaling pathway. Collectively, these results indicate that cordycepin pretreatment ameliorated hepatocyte injury caused by HIRI. As compared with the HIRI group, cordycepin pretreatment mitigated the inflammatory response and inhibited apoptosis and autophagy via regulation of the MAPK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Glycogen storage disease (GSD) is a rare disease that can cause life-threatening problems owing to metabolic errors in storing or using glycogen. The disease course of GSD remains unknown, despite medical technology advances. We determined the prevalence and complications of GSD using data from the National Health Insurance Service database. Data were collected and analyzed for the entire South Korean population with GSD during 2007–2018. GSD was defined as a combination of disease code E74.0 and rare incurable disease insurance code V117, a unique disease code combination for GSD in South Korea. Overall, 23,055 patients had the E74 disease code; 404 had an additional V117 insurance code. Most GSD patients were aged <10 years. Many complications were identified, the most common being hepatomegaly, hyperuricemia, and elevated liver enzyme levels. The most prescribed drug was α-glucosidase, followed by allopurinol. Seventy-two percent of patients were treated in pediatrics. Twenty-five patients underwent liver transplantation, and 14 died after GSD diagnosis. In South Korea, more patients than expected had GSD diagnosis and were managed accordingly. GSD causes many complications and hospitalizations, resulting in high medical expenses. Serious complications can result in liver transplantation and, eventually, death in some cases. Although the patients' condition was identified only by the disease code, this is the first study to present the current situation of GSD patients in South Korea. Because GSD patients can have dangerous medical conditions, they should be managed consistently while minimizing various complications that may occur with optimal metabolic control. [ABSTRACT FROM AUTHOR]

Background. Venoocclusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening hematopoietic stem cell transplantation (HSCT) complication. Cases of mild and moderate VOD/SOS are self-limiting; however, the mortality for severe VOD/SOS has reached 80%. Recently, defibrotide became available and has been used for VOD/SOS; however, the outcome for patients with severe VOD/SOS is not satisfactory, and liver transplantation is attempted in these severe cases. Method. We describe a case of living donor liver transplantation (LDLT) for acute liver failure secondary to VOD/SOS that originates from HSCT. Result. Liver regeneration after LDLT was impaired, and several infections were developed before liver regeneration completion. Our patient suffered sepsis and finally died of multiorgan failure. Conclusion. Severe VOD/SOS originating from HSCT is associated with a very poor prognosis. The liver transplantation outcome for VOD/SOS has not been satisfied, but it may provide long-term survival if successful. We considered liver transplantation as a therapeutic option, especially in cases where sufficient graft volume is secured, considering impaired liver regeneration under bone marrow suppression after HSCT. [ABSTRACT FROM AUTHOR]

Background. Catastrophic antiphospholipid syndrome (CAPS) is an autoimmune thrombogenic disorder of small and large vessels caused by autoantibodies against phospholipids and phospholipid-binding proteins. This severe form of antiphospholipid syndrome (APS) presents clinically with simultaneous life-threatening multiorgan thrombosis and the presence of two or more persistent antiphospholipid antibodies (APL) confirmed on testing 12 weeks apart. Case Presentation. We describe a case report of a 66-year-old woman with detected antinuclear antibodies (ANA) pretransplant diagnosed with CAPS following orthotopic liver transplant. The patient had acute respiratory failure; Doppler ultrasound and CT angiogram confirmed thrombosis in the hepatic artery, subsequent occlusion of the jump graft, and a splenic infarct. Hypercoagulability workup showed elevated levels of anticardiolipin IgG and beta-2-glycoprotein IgG/IgM and positive lupus anticoagulant, treated with steroids and anticoagulation. The patient was discharged after one month and was transitioned from heparin to life-long warfarin. Conclusion. Our patient provided a standard presentation of CAPS with abnormal pretransplant levels of antinuclear antibodies (ANA). Although there have been studies investigating the relationship between anticardiolipin antibodies and lupus anticoagulants and APS, the relationship between pretransplant positive ANA or antimitochondrial antibodies (AMA) and CAPS has yet to be explored. Further studies will be needed to determine the significance of these antibodies. We recommend preoperative APL testing for patients with positive ANA and AMA at preliver transplant presentation. [ABSTRACT FROM AUTHOR]

Background and Aim: On the basis of previously published accounts, coupled with our own experience, we have assessed the surgical approaches to patients with isomeric atrial appendages. Methods: We reviewed pertinent published studies on surgical treatment of individuals with isomeric atrial appendages, with the pertinent surgical details provided by most of the manuscripts. Results: Half of patients with right isomerism, and two‐thirds of those with left isomerism have bilateral superior caval veins. Azygos extension of the inferior caval vein is reported in three‐quarters of those with left isomerism. The coronary sinus is universally absent in right isomerism, along with totally anomalous pulmonary venous connection, and is absent in two‐fifths of those with left isomerism. Univentricular atrioventricular connections are expected in up to three‐quarters of those with right isomerism. Atrioventricular septal defect is reported in up to four‐fifths, more frequently in right isomerism, with such patients typically having discordant ventriculoatrial connections or double outlet right ventricle. Reported mortalities extend to 85% for those with right, and 50% for those with left isomerism. In right isomerism, mortality is up to 54% for systemic‐to‐pulmonary arterial shunting, up to 75% for univentricular repair, and up to 95% for repair of totally anomalous pulmonary venous connection itself. No more than one‐quarter had undergone Fontan completion, with reported mortalities of 21%. Conclusion: Early surgical results are satisfactory in patients with left isomerism, but disappointing for those with right. Recent advances in cardiac and liver transplantation may offer improved survival. [ABSTRACT FROM AUTHOR]

Lung transplant recipients experience a high rate of invasive pulmonary aspergillosis infections, for which voriconazole is the treatment of choice. We report a patient who developed voriconazole-induced myositis that relapsed after one dose of isavuconazole. Our patient was a 38-year-old man who received a single sequential lung transplantation and liver transplantation because of end-stage cystic fibrosis. He presented to our emergency room with acute pain in both forearms at 3 weeks after voriconazole was initiated for invasive pulmonary aspergillosis infection. Levels of voriconazole were normal during the course of therapy. After stopping voriconazole, the symptoms decreased but relapsed after one dose of isavuconazole. Other causes of muscle pain and inflammation were excluded. Magnetic resonance imaging of both arms showed muscle edema in both arms, including involvement of the fascia, consistent with myositis. There were no signs of necrosis. Isavuconazole was discontinued, and the corticosteroid dose was temporarily increased, with rapid resolution of all complaints. Our patient is the fourth reported case of voriconazole-induced myositis, and the first whose symptoms relapsed after initiating isavuconazole. [ABSTRACT FROM AUTHOR]

Introduction. Solid organ transplant graft-versus-host disease (SOT-GVHD) is a rare phenomenon in which recipients of solid organ transplant develop GVHD due to the presence of donor lymphocytes in the graft. SOT-GVHD most often occurs in patients receiving small bowel or liver transplants. Diagnosis is typically via identification of lymphocytic infiltration on histopathology and molecular demonstration of donor T cell chimerism in the target organ. The gastrointestinal (GI) system is the most common target of SOT-GVHD, and one estimate places long-term survival of patients with SOT-GVHD at 20% at 5 years. In this report, we present the case of a patient with sequential kidney and pancreas transplant who developed SOT-GVHD targeting host lymphocytes, skin, and liver, with a long period of stability before treatment with antithymocyte globulin. Peripheral blood chimerism testing was used to track response to therapy. Remarkably, he survived 1.5 years despite recurrent infections before dying of unrelated causes. [ABSTRACT FROM AUTHOR]

Background & Aims. The most dangerous complications of hepatocellular adenomas are hemorrhage and malignant transformation, both of which require surgical treatment. The surgical treatment strategy for patients with benign large or central tumors is challenging because complex liver resections are required. The strategy of using a live donor as a backup procedure is described in this series. Methods. We present a series of three patients with large hepatocellular adenoma lesions showing a central location, for which the living donor liver transplantation strategy was used as a backup procedure. Results. Hepatocellular adenoma was confirmed by biopsy in all patients. Surgical resection was indicated because of the patients' symptoms and lesion size and growth. All patients had a lesion that was central or in close contact with major vessels. The final decision to proceed with the resection was made intraoperatively. A live donor was prepared for all three patients. Two patients underwent portal vein embolization associated with extended hepatectomy, and a total hepatectomy plus liver transplantation with a living donor was performed in one patient. All patients had good postoperative outcomes. Conclusions. In the treatment of hepatocellular adenomas for which complex resections are necessary and resectability can only be confirmed intraoperatively, surgical safety can be improved through the use of a living donor backup. Center expertise with living donor liver transplantation is paramount for the success of this approach. [ABSTRACT FROM AUTHOR]

Objective. To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients. Methods. By searching CNKI and PubMed databases, we made a systematic analysis of the studies of postorgan transplantation complicating malignant tumors in the last decade. Results. There were 10 articles on malignant tumors after renal transplantation, 8 articles on liver transplantation, 2 articles on heart transplantation, and 1 article on lung transplantation. The incidence of malignant tumors complicating renal transplantation is 10.4% in Europe, with skin cancer and Kaposi's sarcoma being common; the incidence in the United States is 3.4%, with PTLD having the highest incidence; the incidence of malignant tumors is relatively lowest in Asia, with gastrointestinal malignancies being the main ones. The mean time to complication of malignancy after renal transplantation is 3.83 years. The incidence of concurrent malignancies after liver transplantation is 8.8% in Europe, where skin cancer and Kaposi's sarcoma are common; 5.6% in Asia, where gastrointestinal tract tumors are prevalent; and 4.5% in the United States, where gastrointestinal tract tumors, PTLD, and hematologic diseases are predominant. The mean time to complication of malignancy after liver transplantation is 4.79 years. The incidence of malignancy after heart transplantation is 6.8-10.7%. The incidence of malignancy after lung transplantation is about 10.1%. Minimization of immunosuppression or modification of immunosuppression regimens may be a key component of cancer prevention. mTOR inhibitors and phenolate (MMF) reduce the incidence of de novo malignancies in patients after solid organ transplantation. Surgical treatment improves survival in patients with early malignancies. The use of external beam radiation therapy in the treatment of hepatocellular carcinoma is limited due to the risk of radiation liver disease. Conclusions. The risk of concomitant malignancy needs to be guarded for 5 years of immunosuppressive therapy after organ transplantation surgery. Adjusting the immunosuppressive treatment regimen is an effective way to reduce concurrent malignancies. Systemic chemotherapy or radiotherapy requires vigilance against the toxic effects of drug metabolism kinetics on the transplanted organ. [ABSTRACT FROM AUTHOR]

What is known and objective: Tacrolimus (Tac) is an immunosuppressant that is widely used to prevent allograft rejection in patients after liver transplantation. Its metabolism mainly depends on the cytochrome P450 3A5 (CYP3A5), which has genetic polymorphisms. Recently, a Chinese herbal medicine known as Wuzhi Capsule (WZC) was shown to increase Tac blood concentrations by inhibiting the activity of CYP3A in animal studies in rats. To date, it remains unexplored whether WZC can be efficiently used to enhance the blood concentration of Tac in liver transplant patients with different donor‐recipient CYP3A5 genotypes. Methods: A total of 185 liver transplant patients were enrolled and two‐way ANOVA was carried out, then they were divided into four groups according to the combinations of donor‐recipient CYP3A5 phenotypes. WZC was given to patients when the dose of Tac was ≥4 mg, and the dose‐adjusted C0 (C0/D) of Tac measured twice in succession was ≤1 ng/ml/mg. The blood trough concentration of Tac (C0), C0/D, and dose‐ and body weight‐adjusted C0 (C0/D/W) was analysed on days 7 and 14 after liver transplantation. Results: The genotypes of donor and recipient or WZC had significant effects on C0, C0/D and C0/D/W. There were significant differences in the Tac blood concentrations between the groups. The recipient expression (*1)/donor expression (*1) (R+/D+) group had the lowest C0, C0/D and C0/D/W among the four groups. Furthermore, a larger proportion of patients in the CYP3A5 expression groups required Tac dose adjustment to achieve a therapeutic effect and were given Tac with WZC. Notably, the use of WZC significantly increased the blood concentrations of Tac in the CYP3A5 expression groups and greater increases in the C0/D and C0/D/W were significantly associated with higher doses of WZC in the CYP3A5 expression groups. What is more, WZC reduced the hospitalization cost of patients to a certain extent. What is new and conclusion: WZC significantly increased the C0, C0/D and C0/D/W in the CYP3A5 expression groups and reduced the hospitalization expenses of patients to a certain extent. What is more, greater increases in the C0/D and C0/D/W were significantly associated with higher doses of WZC. [ABSTRACT FROM AUTHOR]

This study is aimed at determining the ability of computed tomography- (CT-) based radiomic analysis to distinguish between grade 0/1 and grade 2/3 macrovesicular steatosis (MaS) in cadaveric donor liver transplantation cases. Preoperative noncontrast-enhanced CT images of 150 patients with biopsy-confirmed MaS were analyzed retrospectively; these patients were classified into the low-grade MaS (n = 100 , grade 0 or 1) and high-grade MaS (n = 50 , grade 2 or 3) groups. Three-dimensional spherical regions of interest of 40 pixel (2.5 cm) in diameter were placed in the right anterior and left lateral segments of the liver. Thereafter, 300 regions of interest (ROIs) were segmented and randomly assigned to the training and testing groups at a ratio of 7 : 3. A total of 402 radiomic features were extracted from each ROI. For MaS classification, a radiomic model was established using multivariate logistic regression analysis. Clinical data, including age, sex, and liver function, were collected to establish the clinical model at the patient level. The performances of the radiomic and clinical models, i.e., the diagnostic discrimination, calibration, and clinical utilities, were evaluated. The radiomic model, with seven selected features, depicted a good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.907 (95% confidence interval (CI): 0.869–0.940) in the training cohort and 0.906 (95% CI: 0.843–0.959) in the testing cohort. The calibration curve revealed good agreement between the predicted and observed probabilities in the training and testing cohorts (both P > 0.05 in the H-L test). Decision curve analysis revealed that the radiomic model was more beneficial than the treat-all or treat-none schemes for predicting the MaS grade. Alanine transaminase and gamma-glutamyl transferase were used for building the clinical model, and the AUC was 0.784 in the total cohort. The CT-based radiomic model outperforming the conventional clinical model could provide an important reference for MaS grading in cadaveric liver donors. [ABSTRACT FROM AUTHOR]

Background. The suspension of the surgical activity, the burden of the infection in immunosuppressed patients, and the comorbidities underlying end-stage organ disease have impacted transplant programs significantly, even life-saving procedures, such as liver transplantation. Methods. A review of the literature was conducted to explore the challenges faced by transplant programs and the adopted strategies to overcome them, with a focus on indications for imaging in liver transplant candidates. Results. Liver transplantation relies on an appropriate imaging method for its success. During the Coronavirus Disease 2019 (COVID-19) pandemic, chest CT showed an additional value to detect early signs of SARS-CoV-2 infection and other screening modalities are less accurate than radiology. Conclusion. There is an emerging recognition of the chest CT value to recommend its use and help COVID-19 detection in patients. This examination appears highly sensitive for liver transplant candidates and recipients, who otherwise would have not undergone it, particularly when asymptomatic. [ABSTRACT FROM AUTHOR]

Seizures after liver transplantation were previously thought to be a reliable harbinger of catastrophe, but more recent studies have found seizure activity to be relatively common, and most cases do not result in a poor outcome. Generalized seizures are the most common, and they typically occur de novo within the first two weeks after transplantation. The underlying cause for seizure activity in these patients may be complex, with potential etiologies including metabolic, infectious, cerebrovascular, and medication-induced causes. Identification of the underlying cause and the use of antiepileptic drugs (AEDs) is crucial for minimizing risk to the patient's neurologic and overall health. In this report, we present the case of a patient with refractory seizures unresponsive to conventional treatment, requiring prolonged barbiturate burst suppression with ventilator support. Seizure activity eventually ceased, and the patient made a full recovery. [ABSTRACT FROM AUTHOR]

The study focused on the clinical application value of artificial intelligence-based computed tomography angiography (CTA) in the diagnosis of orthotopic liver transplantation (OLT) after ischemic type biliary lesions (ITBL). A total of 66 patients receiving OLT in hospital were selected. Convolutional neural network (CNN) algorithm was used to denoise and detect the edges of CTA images of patients. At the same time, the quality of the processed image was subjectively evaluated and quantified by Hmax, Ur, Cr, and other indicators. Then, the digital subtraction angiography (DSA) diagnosis and CTA diagnosis based on CNN were compared for the sensitivity, specificity, positive predictive value, negative predictive value, and patient classification results. It was found that CTA can clearly reflect the information of hepatic aorta lesions and thrombosis in patients with ischemic single-duct injury after liver transplantation. After neural network algorithm processing, the image quality is obviously improved, the lesions are more prominent, and the details of lesion parts are also well displayed. ITBL occurred in 40 (71%) of 56 patients with abnormal CTA at early stage. ITBL occurred in only 8 (12.3%) of 65 patients with normal CTA at early stage. Early CTA manifestations had high sensitivity (72.22%), specificity (87.44%), positive predictive value (60.94%), and negative predictive value (92.06%) for the diagnosis of ITBL. It was concluded that artificial intelligence-based CTA had high clinical application value in the diagnosis of ITBL after OLT. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to determine the relationship between the care burden and burnout level of primary caregivers of patients undergoing liver transplantation. Design and Methods: The sample size of this descriptive and correlational was determined to be 202 primary caregivers via the power analysis. Findings: It can be asserted that the primary caregivers had high burnout and had moderate care burden. It was found that there was a statistically positive moderate correlation between the caregivers' care burden and burnout (p ˂ 0.05). Practice Implications: In the study, it was determined that primary caregivers of patients undergoing liver transplantation had higher burnout and moderate care burden. Also, care burden affected burnout. [ABSTRACT FROM AUTHOR]

Introduction. Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. Methods. Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. Results. All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. Conclusion. Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks. [ABSTRACT FROM AUTHOR]

Introduction. Systemic inflammation triggered by bacterial products like lipopolysaccharides (LPS) in the circulation is an important factor leading to decompensation in patients with chronic liver disease (CLD). High-density lipoprotein cholesterol (HDL-C) has a significant role in innate immune response to LPS in the circulation and could therefore increase the risk for decompensation in patients with CLD. In this study, we have explored the role of HDL-C as a prognostic marker for decompensation. Methods. This was a prospective, observational, cohort study where consecutive patients with CLD were included. Patients with cholestatic liver disease and hepatocellular carcinoma were excluded. Fasting lipids were measured in all patients at the time of recruitment. Each patient was carefully followed up for development of decompensation events such as new-onset/worsening ascites, hepatic encephalopathy, or variceal bleed during follow-up. Results. A total of 170 patients were included (mean age 60 ± 11.5 years, M : F = 6 : 1). At the end of follow-up, 97/170 patients (57%) had decompensation events. Mean HDL-C levels were significantly lower among patients with decompensation (27.5 ± 15 mg/dL vs. 43.5 ± 13.9 mg/dL; p value 0.004). Using ROC analysis, cut-off for HDL-C of 36.4 mg/dL was identified. On multivariate analysis, HDL-C (OR = 6.072 ; 95% CI 2.39-15.39) was found to have an independent association with risk of decompensation. Conclusions. HDL-C level (<36.4 mg/dL) is a reliable marker for risk of decompensation and can be a useful addition to existing prognostic scoring systems in CLD. It can be a valuable tool to streamline treatment protocols and prioritise liver transplantation. [ABSTRACT FROM AUTHOR]

Mucormycosis is caused by ubiquitous fungi and encompasses a variety of different opportunistic syndromes in humans that disproportionately affect immunocompromised patients. Mortality has been documented to range between 50 and 100%; however, location of infection greatly dictates likelihood of survival. Treatment of mucormycosis involves aggressive surgical intervention and combination therapy of antifungal agents. In solid organ transplant recipients, immunosuppressive agents used to prevent rejection of the transplanted organ pose additional obstacles in the treatment of invasive fungal infections. We report on 3 high models for end-stage liver disease (MELD-Na) score orthotopic liver transplant (OLT) recipients who all were diagnosed with Rhizopus spp. infections with positive, 1-year outcomes after aggressive, individualized treatment. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation. [ABSTRACT FROM AUTHOR]

Background. Liver inflammation indices reflect its inflammatory microenvironment, which may play a role in the proliferation, invasion, and migration of carcinoma. This study is aimed at exploring the prognostic significance of serum lactate dehydrogenase (LDH) levels and gamma-glutamyl transferase (GGT)/alanine aminotransferase (ALT) ratio in hepatocellular carcinoma after liver transplant (LT). Methods. We retrospectively analyzed data from 155 patients with a pathologically confirmed diagnosis of hepatocellular carcinoma who received LT between January 2013 and September 2017. We used receiver operating characteristics (ROC) curves to determine the optimal LDH and GGT/ALT ratio cut-off values. The Kaplan–Meier method and the logarithmic rank test were used to compare the survival curves without recurrence (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify factors associated with survival. Results. Serum LDH levels were significantly associated with the Child-Pugh score (P = 0.037), largest tumor size (<50 vs. ≥50 mm) (P = 0.017), tumor count (<3 vs. ≥3) (P = 0.009), microvascular invasion (P = 0.006), and the Milan criteria (P ≤ 0.001). The serum GGT/ALT ratio was significantly correlated with alpha-fetoprotein (AFP) levels (of <400 vs. ≥400 ng/ml) (P ≤ 0.001), largest tumor size (of <50 vs. ≥50 mm) (P ≤ 0.001), the Edmondson grade (I-II vs. III-IV) (P = 0.028), microvascular invasion (P ≤ 0.001), and the Milan (P = 0.002) and Hangzhou criteria (P = 0.018). The survival curves showed that the patients with high LDH and the GGT/ALT ratio were associated with poor RFS and OS (P < 0.05). Univariate and multivariate analyses showed that AFP levels of ≥400 ng/ml, largest tumor size of ≥50 mm, microvascular invasion, LDH levels of ≥213.5 U/l, and the GGT/ALT ratio of ≥3.1338 were factors independently associated with RFS. Conclusion. Elevated LDH levels and the GGT/ALT ratio before LT were associated with poor OS and RFS in the present study. These factors could be used in the prognostication of patients with hepatocellular carcinoma undergoing LT. [ABSTRACT FROM AUTHOR]

In recent solid organ transplant recipients, acute febrile illness is usually a source of grave concern and a diagnostic dilemma, especially if no response is noted after initiation of broad antimicrobial therapy. Human Monocytic Ehrlichiosis (HME) is a tick-borne illness caused by Ehrlichia chaffeensis and is not considered an opportunistic infection in immunocompromised patients such as solid organ transplant patients. Ehrlichiosis in immunocompromised patients can be life-threatening, and a strong index of suspicion is needed, especially in patients who live in endemic areas, for proper treatment initiation with doxycycline. We report a case of a 40-year-old male who received an orthotopic liver transplant six months earlier secondary to primary sclerosing cholangitis, on chronic immunosuppressive medication, who presented with complaints of sudden onset fever associated with nausea, vomiting, and diarrhea. Initial extensive infectious workup was negative and no response to empiric antimicrobials. There was suspicion for ehrlichiosis prompting empiric doxycycline use. Subsequently, E. chaffeensis polymerase chain reaction (PCR) was positive, and the antibiotic regimen was de-escalated to only doxycycline with complete resolution of his symptoms and progressive improvement in previously abnormal biochemical indices. [ABSTRACT FROM AUTHOR]

Background. In Oman, the first liver transplant was performed at the Royal Hospital (RH) in September 2017. Since then, thirteen cases have been operated on at the RH. All of these cases were living-donor liver transplants (LDLT), and the remaining cases were treated in India with a total of approximately 193 recipients. To provide an in-depth overview of donor experiences, challenges, and perceptions, a cross-sectional study was conducted. Methods. A cross-sectional study was conducted at one tertiary hospital in 2019. The survey was designed to collect data composed of closed and open-ended questions to reveal a thorough knowledge of the topic. Results. A total of 50 of 120 donors responded to the survey with male dominance in the sample (68%) and 64% were aged 28 to 38 years. 66% of the respondents came to know about the donation through hospital staff. Interestingly, respondents (n = 8/12) who reported that fear of operation is the cause that prevents people from donating are among the male gender, while more men believe that the main cause is lack of knowledge. 90% of the respondents felt satisfied after donation. More men reported ambiguous feelings before donation. Moreover, married donors reported ambiguous feelings before donation (p = 0.008). The younger age group reported anxiety and doubt as a challenge through their donation experience. Conclusion. This study revealed that donors have a positive feeling after donating as they have saved a life, as well as being empowered by family and community. The donors encourage individuals to donate a portion of their liver. Some crucial questions arose, such as anxiety before surgery, ambiguous feelings before surgery, and fatigue after surgery. These findings underscore the importance of a holistic approach that would enable donors to be well informed prior to surgery. [ABSTRACT FROM AUTHOR]

Introduction. It is of great significance to confirm reliable indicators for the guidance of pretransplant radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). In this study, we aim to investigate whether circulating tumor cell (CTC) status is a clinical indicator for RFA before liver transplantation (LT) in HCC patients. Method. CTC analyses were measured in 79 HCC patients. Clinical outcomes including progression-free (PFS) and overall survival (OS) were compared and analyzed between patients with and without pretransplant RFA. Result. Forty-two patients were detected as CTC-positive and 18 patients received pretransplant RFA. Recurrence was correlated with CTC count (P = 0.024), tumor number (P = 0.035), liver cirrhosis (P = 0.001), Milan criteria (P = 0.003), and University of California San Francisco (UCSF) criteria (P = 0.001). Kaplan–Meier analysis revealed that patients with CTC-positive had a lower PFS rate (P = 0.0257). For CTC-positive patients, the PFS rate of the pretransplant RFA group was significantly higher than the non-pretransplant RFA group (100% vs. 46.7%, P = 0.0236). For CTC-negative patients, both PFS rate and OS rate were similar and without significant differences. In multivariate analysis, pretransplant RFA was the independent factor for PFS (P = 0.025). Conclusion. Pretransplant CTC status can guide the administration of pretransplant RFA in HCC patients which can improve PFS in CTC-positive HCC patients. [ABSTRACT FROM AUTHOR]

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors with widespread distribution throughout the body and unpredictable clinical behavior. Recently, a subset of these tumors has been reported to harbor Transcription Factor E3 (TFE3) gene rearrangement with distinct morphologic and immunophenotypic features. Although limited, these tumors may represent a separate entity from the conventional PEComas and may require different treatment approaches. Surgery is the main treatment option with no clear consensus on systemic therapy. Here, we present the first case of a malignant pediatric colonic TFE3-associated PEComa with isolated liver metastasis leading to liver transplantation for the local control. [ABSTRACT FROM AUTHOR]

Liver fibrosis resulting from chronic liver injury is a key factor to develop liver cirrhosis and risk of hepatocellular carcinoma (HCC) which are major health burden worldwide. Therefore, it is necessary for antifibrotic therapies to prevent chronic liver disease progression and HCC development. There has been tremendous progress in understanding the mechanisms of liver fibrosis in the last decade, which has created new opportunities for the treatment of this condition. In this review, we aim to make an overview on information of different potential therapies (drug treatment, cell therapy, and liver transplantation) for the liver fibrosis and hope to provide the therapeutic options available for the treatment of liver fibrosis and discuss novel approaches. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia is a consumptive coagulopathy that can be either idiopathic or associated with infectious or autoimmune etiologies. Here, we present a case of immune thrombocytopenia in the setting of acute liver failure due to coexisting diagnoses of hepatitis B virus and autoimmune hepatitis. Our patient underwent orthotopic liver transplantation and recovered hemostatic platelet counts after treatment with romiplostim, a thrombopoietin receptor agonist, 51 days after transplantation. To our knowledge, this is the first case report of immune thrombocytopenia secondary to both hepatitis B virus and autoimmune hepatitis in a patient with acute liver failure. [ABSTRACT FROM AUTHOR]