Liver Recipients Research Articles

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation.

Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients. We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients. Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE. These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

Impact of Hepatitis E Virus Screening in the UK Deceased Organ Donor Population.

Universal Hepatitis E Virus (HEV) screening of deceased organ donors was implemented by the UK national organ procurement organisation in October 2017. Donor testing for HEV infection is done post-transplant; detection of HEV ribonucleic acid (RNA) in donor plasma is therefore not a contra-indication for organ donation, with the result being used to inform recipient management. Immediate post-transplant detection of donor HEV viraemia triggers notification to transplant centres. Follow up of liver and kidney recipients has shown that transmission through solid organs is very efficient, particularly through liver grafts, as expected; no other organ types were transplanted in this cohort. Although donors with higher plasma viral load (VL > 103IU/mL) were invariably associated with recipient infection, transmission was also documented at lower VL levels. Knowledge of donor HEV status has led to identification of transmission of infection via solid organ grafts followed by close patient monitoring and informed clinical management decisions. The purpose of this strategy is to allow early detection of infection and recurrence and treatment to circumvent the risk of accelerated liver damage from chronic HEV infection due to undiagnosed, inadvertent donor-derived transmission of infection.

A PROSPECTIVE OBSERVATIONAL STUDY ON PRESCRIBING PATTERN IN LIVER TRANSPLANT RECIPIENTS


 
 
 The liver transplant is a surgical procedure in which the diseased liver of recipient is replaced with the healthy liver of donor. Our research involved 70 patients who underwent liver transplant and it was single centered. This study’s objective was to evaluate the medications used in liver transplantation. In our study we found that most common cause for liver transplantation is cryptogenic and second most cause is alcoholic related.
 Immunosuppressants and prophylaxis antimicrobials were primarily prescribed. In immunosuppressants, triple drug regimen was given for 74.28% and Quadruple regimen was prescribed for 18.5%. TDM immunosuppressants were performed during hospital stay. Meropenem is the major antibiotic used as prophylactic therapy, Valganciclovir is regularly prescribed antiviral whereas Fluconazole is usually prescribed antifungal. Immunosuppressants: 74.28% patients were prescribed with tacrolimus + mycophenolate mofetil + prednisolone (Triple therapy); Tacrolimus + Mycophenolate mofetil + prednisolone + Everolimus/Cyclosporine (18.5%). Antibiotics: 78.57% of patients were prescribed with Meropenem. Antiviral: 88.57% of patients were prescribed with Valganciclovir. Antifungal: 94.28% of patients were prescribed with Fluconazole. The length of hospital stay for many patients was 16-20 days.
 
 

CANLI DONÖR KARACİĞER NAKLİNİN ÖNGÖRÜSEL BİYOBELİRTEÇLERİ

Objective: Liver transplantation using a living donor (LDLT) is currently the most popular method used in the worldwide. Appropriate biomarkers that predict graft status should be used to detect early post-transplant complications that may lead to a rejection reaction. Material and Method: The study involved a total of 44 liver recipients and 44 liver donors, from whom preoperative blood samples were taken and immunoassay and spectrophotometric studies were carried out. The levels of serum neopterin, interferon-gamma (IFN- y), indoleamine-2,3 dioxygenase (IDO), and -glutathione S transferase (a-GST) were assessed using an enzyme-linked immunosorbent test. The activity of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) in erythrocytes was measured using spectrophotometry. Result and Discussion: “Neopterin, IDO, and G6PD levels were significantly higher in the recipient group than in the donor group. The differences in gender and blood groups were statistically insignificant. The rejection reaction developed in 25% of patients and none survived. These findings may facilitate the identification of novel predictive biomarkers for the diagnosis of acute rejection reactions after LDLT. The clinical use of novel non-invasive biomarkers may provide time and cost advantages.

Metabolic Profile of Liver Transplant Recipients and Determinants of their Body Fat Distribution

Obesity and diabetes mellitus epidemics exert a measurable impact on the liver transplant (Ltx) population. This study aimed to investigate the metabolic profile of Ltx recipients and its association with body fat distribution. Adults who underwent de novo elective cadaveric-donor Ltx were eligible. Metabolic syndrome (MS) was diagnosed based on the adapted International Diabetes Federation, the American Heart Association, and the National Heart, Lung, and Blood Institute guidelines. We recruited 100 patients with a mean age of 54 years, of whom 70% were men. Overall, 54% met the criteria for MS, most of which comprised new-onset cases. Excessive fat accumulation in liver donors was found to be associated with an increased metabolic risk in liver recipients. Haemoglobin A1C (OR: 8.962, 95% CI: 2.188–84.545, p = 0.013), ferritin (OR: 1.024, 95% CI: 1.005–1.054, p = 0.038), and de novo hypertriglycaeridemia (OR 27.957, 95% CI: 2.626–752.121, p = 0.014) were found to be independently associated with de novo MS. After a step-wise multivariate analysis, only the anthropometric obesity indices were significantly associated with abdominal fat distribution in Ltx recipients. Metabolic complications were common in liver recipients. Both pre- and post-Ltx factors impacted MS development in liver recipients and determined abdominal fat distribution.

First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China: 5-year Experience at a High-volume Donor and Recipient Liver Transplant Center.

First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China: 5-year Experience at a High-volume Donor and Recipient Liver Transplant Center.

Shear wave elastography and shear wave dispersion correlated to biopsy at the scheduled follow-up of pediatric liver grafts.

It is unknown how shear wave dispersion (SWD) is displayed in pediatric liver transplant recipients and not fully elucidated how ultrasound shear wave elastography (2D-SWE) display within this cohort, which is important to determine to improve noninvasive surveillance of these patients. The study aimed to compare SWE and SWD values with histopathology in pediatric liver recipients. Forty-eight pediatric liver recipients were examined with SWE in conjunction with an elective liver biopsy (clinically without complication). Additionally, SWD values were measured in 21 children. SWE and SWD values were compared to histologically determined fibrosis graded as none-to-mild (F0-1) and moderate-to-severe (F2-4), and inflammation graded as low (grade 0-1) and high (grade 2-4). Two children were excluded due to SWE IQR/median > 30% kPa. The mean age across 46 included patients was 10.9 years (range 1.4-18). The number of patients and median (range) SWE value (kPa) for each stage of fibrosis were: F0-1 [n = 23; 5.8 (3.2-16.1)], F2 [n = 22; 6.0 (4.5-25.9)], F3 [n = 1; 33.3], and F4 [n = 0]. Significantly higher SWE values and greater variability were registered in F2-4 vs. F0-1 (p = .05). Grade of fibrosis correlated weakly to SWE values (r = .3; p = .05), but not to SWD values (r = .2; p = .27). In patients with low-grade inflammation, median SWD was 13.7 m/s KHz (10.7-17.6). Only one patient had high-grade inflammation. Uncomplicated transplanted liver grafts in a small pediatric cohort revealed slightly increased SWE and SWD values compared to previously reported values in healthy children. This likely reflect both the fibrotic and inflammatory elements in the grafts; however, other confounders impacting the liver's viscoelastic properties are also probable factors.

When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients.

There is an ongoing need to understand whether transplantation during acute Coronavirus disease 2019 (COVID-19) can be performed safely, especially when urgent transplant is required. We collected retrospective data of all consecutive non-lung transplant recipients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) on the day of planned deceased donor organ implantation. Data were collected from two large transplant centers from 01/01/2022 to 02/01/2023. Demographics, details regarding COVID-19 infection, waitlist priority, and details regarding transplantation were obtained. A descriptive analysis was performed. A total of 12 patients were identified: 7 renal, 4 liver, and 1 heart transplant recipient. All 12 patients were vaccinated for COVID-19. Ten were asymptomatic outpatients found positive on admission and transplanted immediately. Two were in-patients with mild COVID-19 symptoms and were reactivated on the waitlist following 3 days of remdesivir when no progression to severe COVID-19 occurred. Most patients (10/12) received remdesivir posttransplant. No complications attributed to COVID-19 were noted nor were any secondary family or healthcare worker infections observed. All recipients were managed with special isolation precautions befitting their potentially infectious state. Standard induction therapy was used in all recipients. After a median follow up period of 143 days (interquartile range: 96-201 days), 3 episodes of rejection were documented, 2/7 renal recipients experienced delayed graft function, and 2/4 liver recipients required renal replacement therapy. Graft and patient survival were 100%. Transplantation can safely proceed in select, minimally symptomatic, non-lung recipients with a positive SARS-CoV-2 PCR at the time of transplant.

Changes in Functional Outcomes After an Inpatient Rehabilitation Program for Solid-Organ Transplant Recipients.

Introduction: Outpatient exercise training has been shown to be beneficial for solid organ transplant recipients. Little is known about the effects of inpatient rehabilitation programs for recipients with a more complicated postoperative course. Research Question: This study was designed to (1) describe the changes in functional outcomes after an inpatient rehabilitation program, and (2) determine whether the changes in lower body strength and quadriceps strength are associated with changes in functional exercise capacity. Design: This was a single-arm prospective longitudinal study. The recipients participated in an inpatient rehabilitation program twice a day, 7 days a week for 3 to 4 weeks. Outcome Measures Included: 2-Minute Walking Test, Timed Up and Go, Berg Balance Scale, 30-Second Sit to Stand, biceps and quadriceps strength, Functional Independence Measure, SF-36, and Canadian Occupational Performance Measure. Results: Twenty-eight patients (54% female, mean age = 55 [11]) completed the study. Participants were mostly liver (42%) and lung recipients (35%). There were statistically significant improvements in all outcomes after the intervention. There was no relationship between changes in functional exercise capacity and quadriceps strength or lower body strength. Conclusion: An inpatient rehabilitation program may improve several functional outcomes and health-related quality of life in transplant recipients with a complicated postoperative course.

Characterization of the stanford integrated psychosocial assessment for transplant for heart, liver, and kidney transplant candidates in Japan

BackgroundThe Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive psychosocial assessment proven useful for predicting the outcomes of organ transplantation that is expected to be useful in Japan. However, the characteristics of organ-specific SIPAT scores for organ transplant recipient candidates in Japan are unclear and, to date, the SIPAT has not been properly utilized in clinical practice. The purpose of this study was to present basic data that can be used to establish the relation between SIPAT scores and post-transplantation psychosocial outcomes as well as organ-specific outcomes.MethodsThis study included 167 transplant recipient candidates (25 heart, 71 liver, and 71 kidney) who completed a semi-structured interview based on the Japanese version of SIPAT (SIPAT-J) prior to transplantation. The differences between organs in terms of SIPAT scores and differences in SIPAT scores based on demographic data were comparatively analyzed.ResultsThe total SIPAT scores were higher for liver recipient candidates than for heart recipient candidates (P = .019). Regarding the subscales, SIPAT B (social support system) scores were higher for liver and kidney recipient candidates than for heart recipient candidates (P = .021), whereas SIPAT C (psychological stability and psychopathology) scores were higher for liver recipient candidates than for kidney recipient candidates (P = .002). Recipient candidates with a history of psychiatric treatment and those who were unemployed had higher SIPAT scores, regardless of the transplant organ, than recipient candidates without a history of psychiatric treatment and those who were employed (P < .001, P = .016, respectively).ConclusionsThere were notable differences in the total SIPAT-J and subscale scores among the liver, heart, and kidney recipient candidates. Each organ was associated with specific psychosocial issues that should be addressed before transplantation. Interventions such as information provision and patient education based on SIPAT assessment results for each organ may improve recipient post-transplant outcomes.

Development of graft-versus-host disease in a liver recipient. Clinical observations and literature review

Graft-versus-host disease (GvHD) after liver transplantation (LT) occurs in 0.2–0.3% of liver transplant recipients. Each case is characterized by individual peculiarities of the clinical picture. There are no standards or clinical guidelines for the treatment of GvHD in solid organ recipients; mortality remains very high among these patients. We present two clinical cases of verified GvHD that developed early after LT, and we offer a brief review of the current state of the art in the study of this problem.

Prognostic significance of growth hormone in pediatric liver transplantation

Growth hormone (GH) plays a leading role in the regulation of cell and tissue metabolism and growth. Its effects are mediated through the so-called somatomedins, among which the most important is the liver-produced insulinlike growth factor 1 (IGF-1). It has been reported that serum GH levels in liver recipients is related to the clinical transplant outcomes.Objective: to evaluate the prognostic significance of GH in pediatric liver transplantation (LT).Materials and methods. The study enrolled 148 children (61 boys) aged 2 to 60 months (median, 8) with end-stage liver disease resulting from biliary atresia (n = 86), biliary hypoplasia (n = 14), Byler disease (n = 15), Alagille syndrome (n = 12), Caroli syndrome (n = 5), and other liver diseases (n = 16, cryptogenic cirrhosis, fulminant and autoimmune hepatitis, Crigler–Najjar and Budd–Chiari syndromes, alpha-1 antitrypsin deficiency, glycogenosis and hepatoblastoma). All the patients were transplanted with the left lateral segment of the liver from a living related donor. GH concentrations were measured by enzyme immunoassay before, at one month and at one year after transplantation.Results. Median plasma GH levels in children with liver disease were 4.3 [1.6–7.2] ng/mL, significantly higher than in healthy children of the same age at 1.2 [0.3–2.4] ng/mL, p = 0.001, while mean height and body weight were lower than in healthy controls. GH levels decreased significantly after transplantation. At one month and one year later, the levels did not differ from those of healthy children (p = 0.74, p = 0.67, respectively). One month after transplantation, GH concentrations were lower in 1-year survivors than in non-survivors (p = 0.02); the diagnostically significant threshold GH level was 1.8 ng/mL. Prior to LT, plasma GH levels did not differ between 1-year survivors and non-survivors. Children with GH levels below 1.8 ng/mL post-LT were 9 times more likely to survive one year post-transplant than patients with levels above the threshold.Conclusion. GH concentrations in pediatric liver recipients is a positive prognostic indicator of pediatric LT outcomes.

Development and validation of a nomogram model for predicting chronic kidney disease after liver transplantation: a multi-center retrospective study

Chronic kidney disease (CKD) is a frequent complication after liver transplantation (LT) and associated with poor prognosis. In this study, we retrospectively analyzed 515 adult patients who underwent LT in our center. They were randomly divided into a training set (n = 360) and an internal test set (n = 155). Another 118 recipients in other centers served as external validation set. Univariate and multivariate COX regression analysis were used to determine risk factors. A nomogram model was developed to predict post-LT CKD. The incidence of post-LT CKD in our center was 16.9% (87/515) during a median follow-up time of 22.73 months. The overall survival of recipients with severe CKD (stage IV and V) were significantly lower than those with non or mild CKD (stage III) (p = 0.0015). A nomogram model was established based on recipient’s age, anhepatic phase, estimated glomerular filtration rate and triglyceride levels at 30 days after LT. The calibration curves for post-LT CKD prediction in the nomogram were consistent with the actual observation in both the internal and external validation set. In conclusion, severe post-LT CKD resulted in a significantly reduced survival in liver recipient. The newly established nomogram model had good predictive ability for post-LT CKD.

Investigation of Ganciclovir Resistance in Cytomegalovirus Isolates by Phenotypic and Genotypic Methods

Ganciclovir-resistant cytomegalovirus (CMV) strains are reported following long-term antiviral agent use, especially for immune-suppressive patients. In this study, it was aimed to investigate the mutations in the UL97 gene of CMV, which causes ganciclovir (GCV) resistance by genotypic and phenotypic methods in patients who developed CMV infection following hematopoietic cell (HCT) or solid organ transplantation (SOT). Thirty patients who had HCT or SOT in Mediterranean University Hospital and developed CMV infection during routine follow-up with a viral load of CMV over 1000 copies/mL were included in the study. CMV DNA was analyzed by an automated system (Cobas Ampliprep/COBAS TaqMan CMV Test, Roche Diagnostics, Germany) quantitatively. DNA sequence analysis of the regions including codons 420-664 in the UL97 gene region was done by the Sanger sequencing method to detect mutations causing antiviral resistance and compared with defined mutations. In order to investigate antiviral resistance by phenotypic methods, heparinized blood samples of the patients were collected, 'buffy coat (leukocyte layer)' was inoculated into MRC-5 cells by centrifugation method and CMV growth in these cells was controlled with monoclonal antibodies when growth was detected, virus titer was determined and plaque reduction test was applied as recommended. It was determined that 22 of the 30 patients were HCT recipients and eight were SOT (five kidney, three liver) recipients. When the CMV serology pattern of the patients was evaluated before transplantation, 29 (96.7%) patients were found to be seropositive and one (3.3%) patient was found to be seronegative. Totally, nine CMV UL97 mutations were detected in seven (23.3%) pediatric patients who had HCT, including six seropositive and one seronegative case. In addition, one mutation (D605E) not known to cause GCV resistance was detected in a seronegative recipient and three previously unidentified mutations were detected (1474T, F499S, V559A) in a seronegative recipient. Five of the mutations defined were UL97 mutations with a defined clinical resistance against GCV in each of the five recipients (C603W, C592G, H520Q, M460V, A594T). In the plaque reduction test using 3 µM, 12 µM, 48 µM and 96 µM concentrations of GCV in CMV strains, the IC50 value was determined to be ≥ 8 µM for the five CMV strains, and the phenotypic presence of GCV resistance was shown. Clinical resistance associated with CMV UL97 mutation was detected in five (22.7%) of 22 patients who had HCT. GCV resistance was also demonstrated in these patients by phenotypic methods. No UL97 mutation was detected in the patients who had SOT.

Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor.

In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.

Balancing immunosuppression in pediatric liver transplantation: Playing the long game.

The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long-term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune-mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression-free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health.

Effect of COVID-19 Vaccines on the Prevention and Severity of Omicron Strain in Liver Transplant Patient

Background: Because it is still not possible to accurately determine whether the injected vaccines affect the disease incidence and mortality or not in the newly diagnosed strains, the present study aimed to investigate the effect of injected coronavirus disease 2019 (COVID-19) vaccines on the mortality rate among liver transplant patients infected with COVID-19 in Mashhad, Iran. Methods: This prospective cross-sectional study was conducted on liver transplant patients with moderate to severe COVID-19 referred to Montaseriyeh Hospital, Mashhad, Iran, from December 2021 to March 2022. The relationship between mortality due to Omicron strain was assessed with various variables. Results: In general, 97 liver transplant recipients were entered into the present study. Vaccine failure was reported in 43.5% of liver recipients. About 30% of the patients had not received any COVID-19 vaccination, and 2.9%, 40%, and 27.1% had received one, two, and three dosages of COVID-19 vaccination, respectively. Infection with COVID-19 was the cause of mortality in 11.3% of patients. No significant relationship was reported between mortality and the consumption of immunosuppressive agents (P &gt; 0.05). Multiple linear regression showed that the number of received vaccine dosages was predictive of mortality due to infection with the Omicron variant in liver recipients (β = 0.13; P &lt; 0.005). Conclusions: It was found that mortality due to COVID-19 vaccination was higher among the patients with fewer COVID-19 vaccination dosages and, consequently, could be related to vaccine-induced immunity in liver transplant recipients. However, due to the high vaccine failure rate, it seems that neutralizing antibody activity against Omicron variants is high.

The Italian data on SARS-CoV-2 infection in transplanted patients support an organ specific immune response in liver recipients.

The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.

Peripheral neuropathy secondary to a ‘domino’ liver transplant: a case report

BackgroundPeripheral neuropathy caused by amyloidosis is one of the well-recognised sequelae of mutations in the transthyretin gene (TTR).Case presentationWe describe a case of peripheral neuropathy in a White British 74 year old man with wild-type TTR, 8 years following receipt of a ‘domino’ liver transplant (from a donor with a TTR mutation). The clinical phenotype and neurophysiology, coupled with presence of ATTR amyloid deposits on fat biopsy, established the diagnosis of ATTR amyloid neuropathy, as a consequence of receipt of a variant-TTR secreting liver. A nerve biopsy was not clinically appropriate for this patient. Such cases are rare since recipients of such livers are typically restricted to people whose natural lifespan is unlikely to stretch into the anticipated symptomatic period of ATTR amyloidosis. However, novel “gene silencing” therapeutics are now available which can dramatically alter the course of this disorder, by reducing the proportion of abnormal proteins.ConclusionsThis represents a rare but predictable iatrogenic side effect, and doctors should be aware of this eventuality occurring in a shorter time span than previously anticipated.

1398-P: Contribution of New-Onset Diabetes after Organ Transplantation on the Incident Cardiovascular Disease and Malignancy in Korea—A Nationwide Population-Based Study

Background: In Korea, the number of solid organ transplantation (TPL) has been markedly increased; however, there has been limited data on the adverse effect on the cardiovascular disease and malignancy of new onset diabetes after transplantation (NODAT) in solid organ TPL other than kidney. Methods: Using the National Health Insurance Service (NHIS) database which covers the claims of 97.0% of the population in Korea, the recipients of kidney, liver, and heart TPL in 2009-2015 were identified and categorized into 3 groups: without NODAT (reference), with NODAT, and pre-existing diabetes mellitus (DM). The incidence of myocardial infarction (MI), stroke, and malignancy till December 2018 in each group were compared using Cox-regression analysis. Results: Among the entire 18,763 cases of TPL identified, NODAT was detected in 29.8% (27.2% [2,903 out of 10,687], 43.4% [3,247 out of 7,747], and 41.5% [250 out of 602] in kidney, liver, and heart TPL, respectively); and 77.3% of NODAT cases were detected within 3 months after TPL. NODAT increased the risk of MI, but not of stoke, by 2.3 times compared to the reference group after adjustment for age, sex, hypertension, dyslipidemia, and immunosuppressants (hazard ratio [HR], 2.34; 95% CI, 1.61-3.51), which was observed only in kidney TPL (HR, 2.44; 95% CI, 1.52-3.91) but not in liver TPL. A significant increment of the risk of malignancy by NODAT was found only in kidney TPL (HR, 1.30; 95% CI, 1.04-1.64), whose statistical significance was lost after adjusting confounders. During the same period, no association between pre-existing DM and malignancy was found, neither. Conclusion: NODAT independently increased the risk of MI after organ transplantation, which was more evident in the recipient of kidney TPL. There was no additional increased risk of stroke or malignancy by NODAT in solid-organ TPL. Disclosure B.Koo: None. M.Moon: None. S.Park: None. K.Han: None.