Post-liver Transplant Recipients Research Articles

Changes in liver biochemistry and tacrolimus levels following the introduction of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and liver transplant

IntroductionElevated liver function tests (LFTs) are reported in individuals with cystic fibrosis (CF) starting elexacaftor/tezacaftor/ivacaftor (ETI). We report our experience with ETI in CF liver transplant patients. MethodAll CF liver transplant patients under the care of the Leeds CF team were commenced on ETI. Liver biopsies were performed when ALT >3 times upper limit of normal with or without bilirubin elevation. Treatment was guided by transplant hepatology and CF teams. Clinical data including lung function, LFTs and tacrolimus levels were collected. ResultsFour patients (3 male, 1 female) on tacrolimus were commenced on ETI. Median time post liver transplantation was 6.5 years. Three patients underwent liver biopsy. One biopsy was abnormal with immune-mediated liver injury, which responded to increased immunosuppression. Management of tacrolimus levels proved straightforward. ConclusionETI therapy in CF post liver transplant recipients was encouraging. Normal liver biopsy provides re-assurance to continue treatment despite elevated LFTs.

Gastroduodenal Ulcers in Liver Transplant Recipients under Immunosuppressive Therapy

Introduction: The proportion of gastroduodenal ulcers caused by drugs is increasing. However, the risk of gastroduodenal ulcer from drugs other than nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin is unclear. An association between immunosuppressive drugs and gastroduodenal ulcers has been suggested. We aimed to identify the immunosuppressive drugs and clinical characteristics associated with gastroduodenal ulcers in post-liver transplant patients. Methods: The study investigated 119 patients who underwent esophagogastroduodenoscopy after liver transplantation, and 2 patients were excluded. Clinical characteristics, medications, and endoscopic images were retrospectively reviewed. Results: Among 117 post-living donor liver transplant recipients, gastroduodenal ulcers were found in 10 (9.2%) patients. The ulcer group had endoscopic gastritis more frequently (40%) compared with the non-ulcer group (10%). Logistic regression analysis revealed gastritis, NSAID use, and mycophenolate mofetil were risk factors in the post-liver transplant patients. Among 103 patients not on NSAIDs, 8 (7.8%) had peptic ulcer. The most common ulcer site and ulcer shape were the gastric antrum and a circular shape, respectively. All patients in the ulcer group were taking mycophenolate mofetil, which was the only immunosuppressive drug that showed a significant difference between the two groups. Five out of 8 ulcer patients (63%) were taking gastric acid suppressants, and gastroduodenal ulcers in post-liver transplant recipients were suggested to be refractory. Conclusion: Patients treated with immunosuppressive drugs after liver transplantation can develop gastroduodenal ulcers, even with gastric acid suppressant medication. Mycophenolate mofetil may increase the risk of gastroduodenal ulcers compared with other immunosuppressive drugs.

Impact of Text Message Reminders on Drug Adherence in Post-Liver Transplant Patients

Non-adherence among post liver transplant recipients may lead to serious consequences. Hence, there is a dire need to improve medication adherence, particularly among post-liver transplant recipients. Till date, no sufficient data has been published related to our study from Sindh province or even from Pakistan. Therefore, this study will not only help highlight the rate of Medication non-adherence but also implementation of a particular method that could be more helpful to improve the adherence among the study population. The main objective of this study was to determine medication adherence in post-liver transplant recipients before and after text message remainders. A cross sectional study was conducted on 103 post liver transplant patients at Pir Abdul Qadir Shah Institute of Medical Sciences Gambat. BAASIS Scale was used to measure medication adherence among study subjects, after that text messages reminders were given to enrolled patients and adherence was measured again using the same scale to determine the impact of text message reminders on adherence. Among enrolled patients, majority of the study subjects were male, whereas only one participant was transgender. Mostly patients belong to rural areas. Majority of the patients were of matriculation pass, while minorities of the patients were primary pass. Majority of the patients were unemployed, while few had non-government jobs, whereas government job study subjects were in minority. Majority of the patients were of age from 41 to 50, where minority of the patients were aged from 61 to 70. Majority of the patients were prescribed four drugs, whereas no any patient was prescribed only one drug. Majority of the patients were prescribed two immunosuppressant drugs while only few study subjects were prescribed only one immunosuppressant drug. Initially 86% patients were non-adherent to therapy, but after text message reminders, adherence was improved from 24% to 80%. This study concluded that the rate of adherence was improved by giving text message reminders to the patients.

Two Cases of Possible Exacerbation of Chronic Rejection After Anti-SARS-CoV-2 Messenger RNA Vaccination: A Case Report

In post-liver transplant recipients, SARS-CoV-2 infection is a health threat, and novel messenger RNA vaccines such as Pfizer BioNTech BNT162b2 and Moderna mRNA-1273 are aggressively recommended. However, there are few reports on their adverse effects, some of which may be potentially fatal. We have experienced 2 post-liver transplant recipients with exacerbated chronic rejection after vaccination, one of whom had to undergo retransplant and the other who is still in the process of liver function without improvement. These alarming cases will be presented as case reports.

Study of Adherence to Medication in Pediatric Liver Diseases (“SAMPLD” Study) in Indian Children

Adherence to medication(s) is an essential component of holistic management in any chronic disease including in post liver transplant (LT) patients. Thus, this study aimed to assess adherence to medications in Indian pediatric liver disease patients (including post LT recipients) and to identify variables affecting its occurrence. A cross-sectional study was conducted amongpediatric (<18 years of age) subjects with Wilson disease (WD) and autoimmune liver disease (AILD) along with post LTrecipients from May 2021 to October 2021. Structured tools using prevalidated questionnaires (Medication adherence measureand the Child & Adolescent Adherence to Medication Questionnaire) were used to collect data related to nonadherence prevalence (based on missed and late doses) and factors influencing the adherence. A total of 152 children were included in the study (WD 39.5%, AILD 32.9%, and post LT 27.6%). Prevalence of missed and late dose nonadherence (at a cut-off of ≥20%) was 12.5% and 16.4%, respectively. Older age (odd's ratio/O.R 1.185), stay in a rural area (O.R 5.08), and barriers like bad taste of medication(O.R 4.728) and hard to remember the medication(O.R 7.180) were independently associated with nonadherence (P<0.05). Overall, nonadherence was seen in 12-16%, i.e., around one-sixth of the patients, with least nonadherence seen in post LT recipients (0-2.4%). Older age of the patient, rural place of stay and personal barriers like hard to remember/forgetfulness and bad medication taste were identified as factors independently leading to nonadherence.

P267 Candida in the biliary tract: extrapolative PK PD considerations

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Objective Candida norvegensis is an uncommon Candida species causing infection in immunocompromised hosts. It is intrinsically resistant to Fluconazole, which is commonly the empiric choice for therapy. A strong association with post-liver transplant status, as in this case and near-100% mortality, likely due to inappropriate antifungal therapy and lack of source control has been reported in the literature.Methods and ResultsMr. AK, a 32-year-old gentleman, 10 months post-liver transplant recipient, had stenting done for biliary stricture. A month later, he developed ESBL E. coli cholangitis and bacteremia for which he was treated with Meropenem. Flaky pus was seen during stent exchange which grew Candida norvegensis on culture with 97% probability of identification (Fig. 1). Suspecting cholangitic abscesses, patient would require at least 3 weeks of antifungals and Meropenem.Since there is limited data about antifungal susceptibilities of C. norvegensis, MICs were generated on VITEK by using names of other Candida species. Micafungin was found to show an MIC of 0.12 and voriconazole of 0.25. EUCAST breakpoints are only provided for certain species and for others treatment is based on PK/PD considerations. The PK PD indices for efficacy of voriconazole is AUC/MIC of 30 and of Echinocandins is Cmax/MIC of 1R, which prompted extrapolation in this case.The extrapolative PK PD considerations were as follows (Table 1).Micafungin dose of 150 mg generates a biliary trough level of 1.9 mcg/mlR, which will lead to Cmax/MIC (1.9/0.12) of 15.83, exceeding the required target Cmax/MIC for cidal therapy of echinocandins which is 1R. Micafungin and Meropenem were administered for 3 weeks and the patient responded well to treatment.ConclusionThis case highlights the importance of speciation of Candida spp, extrapolating MICs and breakpoints for species where data are not available, early source control and use of PK/PD considerations in choosing the appropriate antifungal agent on a case-by-case basis.

Editorial: Tuberculosis in Post-Liver Transplant Recipients—A Road Less Traveled!

Editorial: Tuberculosis in Post-Liver Transplant Recipients—A Road Less Traveled!

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

“SARS-CoV-2 Infection in Liver Transplant Recipients - Immunosuppression is the Silver Lining?”

BackgroundCOVID-19 is associated with higher mortality among patients who have comorbidities. However, evidences related to COVID-19 among post liver transplant recipients are scarce and evolving.MethodsAdult Indian patients who had undergone liver transplantation at our centre since 2006 and were under regular follow-up, were contacted either telephonically or on email. Data were recorded related to symptoms and diagnosis of COVID-19, need for hospitalization, and need for ICU stay and mortality.ResultsEighty one (3.71%) of the 2182 adult Liver transplant (LT) recipients on regular follow-up reported SARS-CoV-2 infection between 1st April 2020 and 31st May 2021. Mean age was 51.3(±9.8) years, and 74(91.4%) were males. Thirty five (43.2%) patients had one or more comorbidities. Twenty one (25.9%) patients were transplanted less than 1 year ago. Forty four (54.3% ) patients had mild disease only while 23(28.4%) patients had severe COVID-19 disease. Of the 81 patients 14 patients died and overall mortality was 17.3%ConclusionUncomplicated liver transplant recipients without comorbidities who acquire SARS-CoV-2 do not have poor outcome.

Successful Management of COVID-19 Infection in 2 Early Post-Liver Transplant Recipients

BackgroundCoronavirus disease 2019 (COVID-19) has affected all facets of life and continues to cripple nations. COVID-19 has taken the lives of more than 2.1 million people worldwide, with a global mortality rate of 2.2%. Current COVID-19 treatment options include supportive respiratory care, parenteral corticosteroids, and remdesivir. Although COVID-19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID-19 infection in patients with organ transplants has not been well described in the literature. The treatment of COVID-19 differs based on the organ(s) transplanted. Preliminary data suggested that liver transplant patients with COVID-19 did not have higher mortality rates than untransplanted COVID-19 patients. Table 1 depicts a compiled list of current published data on COVID-19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID-19 within their posttransplant hospitalization course. This potential differentiation needs to be further explored. Here, we report 2 patients who underwent liver transplantation who acquired COVID-19 during their posttransplant recovery period in the hospital.Case DescriptionsTwo patients who underwent liver transplant and contracted COVID-19 in the early posttransplant period and were treated with hydroxychloroquine, methylprednisolone, tocilizumab, and convalescent plasma. This article includes a description of their hospital course, including treatment and recovery.ConclusionThe management of post-liver transplant patients with COVID-19 infection is complicated. Strict exposure precaution practice after organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID-19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low-dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID-19 pneumonia in post-liver transplant patients. Future studies and experiences from posttransplant patients are warranted to better delineate the clinical features and optimal management of COVID-19 infection in liver transplant recipients.

Risk factors predicting Cytomegalovirus infection in post liver transplant recipients

Abstract Background Liver transplantation is considered to be the only curative treatment for patients with end stage liver disease. Postoperative infection remains to be one of the most common causes of morbidity and mortality throughout the past years. Cytomegalovirus (CMV) infection although considered to be a weak viral infection that usually passes asymptomatic in immunocompetent patients, however, it is considered one of the most common pathogens causing morbidities and mortality in liver transplant recipients. Multiple studies have been done to assess the risk factors for developing CMV infection. Objective Identification of risk factors predicting Cytomegalovirus infection in liver transplant recipients following transplantation. Methods This retrospective study was conducted on 194 patients and their donors who underwent living donor liver transplantation operation at Ain Shams centre for organ transplantation (ASCOT) at Ain Shams specialized hospital in the period between January 2010 and December 2016 with at least one year follow up period after operation for the recipient group. Results In our study, 194 patients undergoing liver transplantation at Ain shams centre for organ transplantation over seven years from January 2010 to December 2016 have been followed to assess risk factors affecting CMV infection development. Chronic rejection was found to be the most common factor associated with CMV infection followed by Cyclosporin (Neoral) as main postoperative immunosuppressant following liver transplantation. Other factors that were found to carry risk for CMV infection included younger age, advanced MELD score, positive CMV IgM status of the donors and recipients. Conclusion Differentiation of Cytomegalovirus disease from Cytomegalovirus infection isn’t always available as it requires tissue invasive techniques. Multiple risk factors have been attributed to cause Cytomegalovirus infection (viremia) . In our study, rejection (chronic rejection) was the factor that carries highest risk for Cytomegalovirus infection development followed by Cyclosporin .

Effect of Hepatitis C Virus Treatment on Rejection Incidence and Severity in Post-Liver Transplant Recipients

Abstract Background and Aims HCV is a worldwide cause of chronic liver disease, particularly in Egypt where the most prevalent is genotype 4. HCV-associated cirrhosis is the most common indication for orthotopic liver transplantation (OLT) among adults. HCV infection remains a problem after transplantation, and recurrent hepatic infection is the leading cause of graft failure. Little is known about the long-term effects of direct acting antiviral therapy in patients after liver transplantation. We examined the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with DAAs relative to the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with Interferon based therapy and patients who didn’t receive any treatment for HCV after transplantation. Patients and Methods The study was conducted on 90 patients who had underwent liver transplantation between 2010 and 2017 at Ain Shams Center for Organ Transplantation (ASCOT) with a minimum follow up period of 6 months. Patients were divided into three groups: group I included 16 patients that didn’t receive antiviral treatment after liver transplantation, group II included 20 patients that had received interferon based therapy after liver transplantation and group III included 54 patients that had received direct acting antivirals after liver transplantation. Results Amongst group I, 2 patients (12.5%) developed acute graft rejection while in group II 2 patients (10%) developed chronic graft rejection and in group III 6 patients (11.11%) developed chronic rejection. In group I, all the patients (100%) had developed rejection that was diagnosed within one year of liver transplantation. In group II, 2 patients (100%) developed chronic graft rejection which occurred after one year of liver transplantation, one of them was on treatment with peg interferon and the other had already completed treatment. In group III, 2 patients (40%) had developed chronic rejection within one year of transplantation, while 4 patients (60%) had developed chronic rejection after one year of transplantation. One patient (16.67%) had developed rejection on treatment while 5 patients (83.33%) had developed rejection after the end of treatment. Conclusion It was found that the incidence of chronic rejection was more in patients that had received antiviral treatment after liver transplantation, however no difference was noted between DAAs and peg-interferon. Chronic rejection was found to be more common when treatment was given over one year after liver transplantation (6 cases) as compared to within the 1st year (2 cases). This may be related to the withdrawal of immunosuppression treatment after one year of transplantation and maintenance on monotherapy.

Impact of direct-acting antivirals in the management of post-liver transplant recipients compared with the interferon-era

Introduction and Aims: Direct-acting antivirals (DAA) revolutionized HCV therapy, especially in liver transplant (LT) setting. We aimed to investigate the post-LT management during DAA-era compared with the interferon-one.

Incidence and Risk Factors for Diabetes, Hypertension and Hyperlipidemia after Liver Transplantation

Introduction and aim: Post-liver transplant recipients present a vast array of metabolic disturbances in the post-transplant period which impact on their morbidity and mortality. Post-transplant diabetes and hypertension were associated with increased risks of graft failure, infection, cardiovascular disease, and death. Therefore, predicting and preventing post-transplant metabolic complications would be a compelling objective for improving care of post-transplant recipients. The aim of this study was to identify the incidence and risk factors of metabolic complications after liver transplantation. Methods: Incidence and risk factors for new onset arterial hypertension, diabetes mellitus and hyperlipidemia were assessed progressively in 100 post- liver transplant recipients at least one year after transplantation (91% male; mean age 52 ± 7.7 y). Risk factors were assessed using logistic regression analysis according to demographic, clinical and laboratory variables. Results: The incidence of hypertension was 38.6%; diabetes, 39.7% and hyperlipidemia, 19% at one year post-liver transplantation (LTX). Independent risk factors for new onset of hypertension were family history of hypertension (OR: 4.85; 95% CI: 3.04-7.74), and cyclosporine use (OR: 6.33; 95%CI: 2.36-16.96). Risk factor for new onset of diabetes were HCV infection (OR: 2.54; 95%CI: 0.84-7.72) and cyclosporine use (12.63; 95%CI: 3.06-52.09). The incidence of hyperlipidemia after LTX was related to the use of cyclosporine (OR: 1.56; 95%CI: 1.04-1.98), or tacrolimus (OR: 1.34; 95%CI: 1.02-1.67). Conclusion: LTX was associated with significantly increased rates of hypertension, diabetes and hyperlipidemia. Furthermore, the incidences of these disorders were related to immunosuppressive therapy.

Clinical periodontal and dental findings in liver transplant patients: a systematic review and meta-analysis

Objectives This systematic review aimed to investigate the oral health of post-liver transplant recipients (postLTx), in terms of dental and periodontal clinical results.Data sources Pubmed/MEDLINE and Cochrane Library databases were searched electronically.Data selection Prospective, cross-sectional and case-control studies comparing periodontal and dental health of postLTx patients with healthy and/or pre-liver transplant patients.Data extraction This was performed independently by two authors. Quality assessment was done by using tools from the National Heart, Lung, and Blood Institute.Data synthesis Nine studies were eligible for inclusion in the systematic review. A meta-analysis was performed on gingival inflammation, expressed by scores, on four studies including healthy controls. The gingival index scores were significantly higher in postLTx patients compared with healthy controls (p <0.001). The weighted mean difference was 0.91 (95% confidence interval, 0.44 to 1.38, heterogeneity I2 = 99.5%). Increased tendency of gingival enlargement was noticed in postLTx patients, especially after immunosuppression with Cyclosporine A. Controversial results were reported for the prevalence of caries in postLTx recipients, but there seems to be an increase.Conclusion The results suggest that patients with liver transplants, due to systemic condition and immunosuppressive therapy, exhibit a higher degree of gingival inflammation compared with unexposed patients.Prospero registration number: CRD42019121893.

Danis Ella Stent for the management of a non-variceal lower esophageal bleeding in a post liver transplant recipient- first case report

Danis Ella Stent for the management of a non-variceal lower esophageal bleeding in a post liver transplant recipient- first case report

Sa1521 - Healthcare Utilization, Risk Factors, and Outcomes of Patients with Takotsubo Cardiomyopathy in Post-Liver Transplant Recipients

Sa1521 - Healthcare Utilization, Risk Factors, and Outcomes of Patients with Takotsubo Cardiomyopathy in Post-Liver Transplant Recipients

Nutrition Management of Acute Postliver Transplant Recipients.

Aim:Acute post liver transplant (LT) phase is characterized by hypermetabolism and increased nutrient requirements. This study aimed to provide the cardinal data on nutrition progression in the management of acute post-LT patients.Methods:This exploratory study recruited 54 adult acute post-LT recipients. The information regarding patient stay, weight status, biochemical parameters, and route of feeding was gathered. Recipients' dietary and nutrient intake was computed by 24-h dietary recall method.Results:The data exhibited a significant trend of lower hemoglobin, platelet, and albumin levels and increased bilirubin (T), alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels (P < 0.05). In acute post-LT patients, a significant decrease in weight status (P < 0.001*) was observed. The recipients' information on daily nutrition progression showed significantly lower intake of calorie, protein, fats, calcium (P < 0.05) and lower percentage adequacy of other nutrients as compared to the recommended guidelines. The energy and protein intake from the parenteral route of feeding significantly decreased and that of through oral route significantly increased (P < 0.05) from postoperative day (POD) 2 to POD 9 and POD 12.Conclusion:There are scant data on nutrition management in acute post-LT phase. The present study provides the framework for the formulation of continuous, patient-centric, aggressive nutrition management interventions for acute post-LT recipients.

The Care of the Postliver Transplant Patient

Since 1988 nearly 150,000 liver transplants have been performed in the United States. Over the past 3 decades the indications for liver transplant have changed from end-stage liver disease from alcohol and cholestatic liver diseases to hepatitis C and most recently nonalcoholic fatty liver disease. Liver transplant recipients are living longer with 10-year survival rates exceeding 60%. Gastroenterologists are likely to encounter or consult on postliver transplant recipients as they live longer and seek care closer to home. Complications after liver transplant are related to immunosuppression, malignancy, recurrent disease, and conditions associated with metabolic syndrome. This review will discuss postliver transplant care and complications in liver transplant recipients.

Pegylated interferon plus ribavirin combination therapy in postliver transplant recipients with recurrent hepatitis C virus infection

Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated. Patients received either pegylated interferon α-2a 180 μg/wk or pegylated interferon α-2b 1.5 mg/kg/wk plus ribavirin for 24–48 weeks. The primary endpoint was the achievement of sustained virological response (SVR), defined as undetectable HCV RNA throughout 6 months of follow-up after the end of treatment. The safety profiles were also documented. The rates of rapid virological response, early virological response, end-of-treatment virological response, and SVR were 33%, 63%, 75%, and 56% respectively. Of the four patients who failed antiviral treatment, the treatment responses were nonresponse (n = 1), loss of follow-up (n = 1), and relapse (n = 2). Three patients terminated therapy early due to severe adverse events, including severe anemia, intra-abdomen infection, and hepatocellular carcinoma recurrence. One of the three patients who terminated treatment early at Week 6 experienced rapid virological response followed by SVR. Pegylated interferon/ribavirin combination allowed a chance for cure with a fair SVR rate in Taiwanese chronic hepatitis C patients postliver transplantation. Early identification of side effects and careful monitoring during therapy might enhance the treatment efficacy.