Evolving challenges with long-term care of liver transplant recipients.

The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.

Multidrug-resistant Gram-negative bacterial infections in solid organ transplant recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug-resistant (MDR) Gram-negative bacilli in the pre- and post-transplant period. MDR Gram-negative bacilli, including carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram-negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram-negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram-negative pathogens, especially in the setting of organ transplantation.

Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice.

Clinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High-level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2-5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.

Complications of Cardiac Transplantation.

PURPOSE OF REVIEW: Despite the improvement in medical therapy for heart failure and the advancements in mechanical circulatory support, heart transplantation (HT) still remains the best therapeutic option to improve survival and quality of life in patients with advanced heart failure. Nevertheless, HT recipients are exposed to the risk of several potential complications that may impair their outcomes. In this article, we aim to provide a practical and scholarly framework for clinicians approaching heart transplant medicine, as well as a concise update for the experienced readers on the most relevant post-HT complications. RECENT FINDINGS: While recognizing that most of the treatments herein discussed are based more on experience than on solid scientific evidence, significant step forward has been made in particular in the recognition and management of primary graft dysfunction, antibody-mediated rejection, and renal dysfunction. Complications after HT may vary according to the time from surgery and can be related to graft function and pathology or to diseases and dysfunctions occurring in other organs or systems, mainly as side effects of immunosuppressive drugs and progression of pre-existing conditions. Future research needs to focus on improving precision diagnostics of causes of graft dysfunction and on reaching an optimal and customized balance between efficacy and toxicities of immunosuppressive strategies.

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation.

BACKGROUND: The transmembrane glycoprotein CD30 contributes to regulate the balance between Th1 and Th2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection. METHODS: Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression. RESULTS: There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; <.001). Analogously, sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036). CONCLUSION: Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens.

Visceral leishmaniasis after orthotopic liver transplantation: a rare cause of infection.

Visceral leishmaniasis (VL) was known as an opportunistic infection associated with immunosuppression, particularly related to human immunodeficiency virus infection and rarely to solid organ transplant recipients. We report a case of VL, 6 months after liver transplantation, in a patient who presented with febrile pancytopenia. The diagnosis was made by demonstration of amastigotes in smears from bone marrow. VL is a very rare infection in patients who undergo liver transplantation and, to our knowledge, this is the first case diagnosed in Portugal.

Liver fluke-infested graft used for living-donor liver transplantation: case report and review of the literature.

Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke-infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living-donor liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and present a review of the literature. A 6-month-old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long-term follow-up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.

Preemptive treatment with voriconazole in lung transplant recipients.

BACKGROUND: Invasive fungal infection (IFI) is associated with high mortality in lung transplant (LTx) recipients. Data for voriconazole use in preemptive treatment remain scant. METHOD: A single-center, retrospective cohort study was conducted to investigate the efficacy and safety of voriconazole preemptive treatment for post-LTx colonization. RESULTS: We reviewed 62 adult LTx patients, who received their first course of voriconazole prophylaxis (i.e., as preemptive treatment) between July 2003 and June 2010. Outcomes were determined at 6 and 12 months after commencing therapy. Aspergillus fumigatus (75.8%) was the most common colonizing isolate. Median duration of voriconazole prophylaxis was 85 days. At 6 months, 1 LTx patient (1.6%) had IFI, 47 (75.8%) cleared their colonizing isolate, 3 (4.8%) had persistent colonization, 7 (11.3%) had recurrent colonization, 1 (1.6%) had new colonization, 2 (3.2%) had aspergilloma, and 1 (1.6%) was clinically unstable with no culture results. Sixteen (25.8%) had died by 12 months. Ten (16.1%) had likely drug-related hepatotoxicity. LTx patients with diabetes mellitus within 30 days before commencing prophylaxis were at higher risk of recurrent Aspergillus colonization at 6 months (P = 0.030). Chronic rejection within 30 days before prophylaxis was associated with 12-month mortality (P = 0.007). CONCLUSIONS: Voriconazole preemptive treatment resulted in low incidence of IFI and IFI-related mortality.

The Gut Microbiota in Kidney Transplantation: A Target for Personalized Therapy?

Kidney transplantation improves quality of life, morbidity, and mortality of patients with kidney failure. However, integrated immunosuppressive therapy required to preserve graft function is associated with the development of post-transplant complications, including infections, altered immunosuppressive metabolism, gastrointestinal toxicity, and diarrhea. The gut microbiota has emerged as a potential therapeutic target for personalizing immunosuppressive therapy and managing post-transplant complications. This review reports current evidence on gut microbial dysbiosis in kidney transplant recipients, alterations in their gut microbiota associated with kidney transplantation outcomes, and the application of gut microbiota intervention therapies in treating post-transplant complications.

Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis.

Introduction: Organ transplant recipients are at increased risk of developing pulmonary cryptococcosis (PC) due to weakened cell-mediated immunity caused by immunosuppressors. However, the nonspecific symptoms associated with PC can often lead to misdiagnosis and inappropriate treatment. Methods: We conducted a retrospective analysis of data from 23 kidney transplant recipients with PC between April 2006 to January 2021. Results: The median time from transplantation to the diagnosis of pathology-proven PC 4.09 years. Seventeen patients presented respiratory symptoms, including sputum-producing cough and dyspnea. Additionally, three patients also developed central nervous system (CNS) infections. Chest CT scans frequently revealed nodule-shaped lesions, which can mimic lung carcinoma. Serological tests did not demonstrate any specific changes. Nine patients received surgical resection as treatment. Fourteen patients were treated with antifungal medication only. No recurrence was observed in all 23 patients. Conclusion: Our study suggests that fever and sputum-producing cough are common symptoms of PC, and cryptococcal meningitis should not be excluded if corresponding symptoms occur. Fluconazole is a common and effective antifungal agent. Surgical resection should be considered for patients who do not respond well to antifungal therapy. Clinicians should be aware of these findings when evaluating transplant recipients with respiratory symptoms.

Parvovirus B19-Associated Severe Anemia in Adult Liver Transplant Recipients: A Case Series and Review of the Literature.

Background: Parvovirus B19 (B19V) infection is a rare cause of severe anemia in liver transplant recipients. However, few studies have systematically reviewed reported cases and summarized experience in managing this disease. Objective: We described a retrospective case series of eight adult liver transplant recipients with B19V-associated severe anemia and performed a literature review of epidemiology, etiology, clinical courses, diagnosis, treatment options available, and outcomes of B19V-associated anemia in adult liver transplant recipients. Patients and Methods: We systematically reviewed articles describing adult liver transplant recipients with B19V-associated anemia from PubMed and ScienceDirect databases from database inception to May 2022. Results: Eight articles containing 23 cases were identified in addition to eight cases from our center for a total of 31 patients (mean age, 45.7 ± 9.7 years; 74.2% male). Eighty-seven percent developed transfusion-dependent anemia within two months after liver transplantation (LT). Fever and progressive anemia are among the major manifestations. Intravenous immunoglobulin (IVIG)-based therapy was given to all patients and the treatment protocols varied among different centers. Except for two cases who died of comorbidities, 17 patients obtained long-term recovery from anemia after one course of treatment and six (19%) experienced relapses that were reversed by repeated courses of IVIG therapy. Two recipients presented with IVIG-associated side effects and two developed acute cellular rejection (ACR) after reduction of immunosuppression. Conclusions: B19V infection should be suspected early as a cause of severe anemia of unknown etiology in adult liver transplant recipients. The clearance of B19V typically lags behind recovery of anemia, and inadequate clearance of virus after cessation of IVIG appears to be a potential risk of anemia recurrence. Moreover, more attention should be paid to the side effects of high-dose IVIG infusion and ACR because of reduction of immunosuppression.

Clinical impact and economic burden of post-transplant infections following heart transplantation: A retrospective nationwide cohort study.

BACKGROUND: Post-transplant infections are associated with high mortality rates. This retrospective nationwide cohort study examined the incidence and risk factors of infections requiring hospitalization after heart transplantation and the associated economic burden. METHODS: The entire heart transplant recipients' data from the Korean Health Insurance Review and Assessment Service between 2013 and 2020 was used. We estimated the annual incidence of post-transplant infections and adjusted incidence rate ratios (aIRR) of risk factors for reported infections using the poisson generalized linear model. RESULTS: Among 1,030 heart transplant recipients (324 with and 706 without post-transplant infections), 0.45 post-transplant infections were reported annually, with respiratory tract infections constituting the highest proportion (0.16). The risk of post-transplant infections was high in recipients with renal failure (aIRR = 1.35; 95% confidence interval [CI], 1.05-1.75) or nosocomial infection (aIRR = 1.47; 95% CI, 1.15-1.87). Combination regimens, including mammalian target of rapamycin inhibitor (mTORi), did not differ significantly from the standard 3 drug regimen (aIRR = 1.16; 95% CI, 0.80-1.67). The risk of death was higher among recipients with post-transplant infections than in uninfected recipients (adjusted hazard ratio = 4.59; 95% CI, 2.19-9.65). The mean follow-up cost per patient per month was 2-fold higher in recipients with post-transplant infections than in uninfected recipients ($5,096 and $2,532, respectively; p < .001). CONCLUSIONS: mTORi combination, which reportedly maintains renal function, can be considered, as it does not increase the infection risk. Post-transplant infections present clinical and economic burdens, warranting careful observation of at-risk patients.

Microbiota Manipulation With Prebiotics and Probiotics in Patients Undergoing Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that often comes at the cost of complications such as graft-versus-host disease and post-transplant infections. With improved technology to understand the ecosystem of microorganisms (viruses, bacteria, fungi, and microeukaryotes) that make up the gut microbiota, there is increasing evidence of the microbiota's contribution to the development of post-transplant complications. Antibiotics have traditionally been the mainstay of microbiota-altering therapies available to physicians. Recently, interest is increasing in the use of prebiotics and probiotics to support the development and sustainability of a healthier microbiota. In this review, we will describe the evidence for the use of prebiotics and probiotics in combating microbiota dysbiosis and explore the ways in which they may be used in future research to potentially improve clinical outcomes and decrease rates of graft-versus-host disease (GVHD) and post-transplant infection.