Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients.

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.

Pleural Effusions Following Liver Transplantation: A Single-Center Experience.

INTRODUCTION: This was a single-center retrospective study to evaluate incidence, prognosis, and risk factors in patients with postoperative pleural effusions, a common pulmonary complication following liver transplantation. METHODS: A retrospective review was performed on 374 liver transplantation cases through a database within the timeframe of January 1, 2009 through December 31, 2015. Demographics, pulmonary and cardiac function testing, laboratory studies, intraoperative transfusion/infusion volumes, postoperative management, and outcomes were analyzed. RESULTS: In the immediate postoperative period, 189 (50.5%) developed pleural effusions following liver transplantation of which 145 (76.7%) resolved within 3 months. Those who developed pleural effusions demonstrated a lower fibrinogen (149.6 ± 66.3 mg/dL vs 178.4 ± 87.3 mg/dL; P = .009), total protein (5.8 ± 1.0 mg/dL vs 6.1 ± 1.2 mg/dL; P = .04), and hemoglobin (9.8 ± 1.8 mg/dL vs 10.3 ± 1.9 mg/dL; P = .004). There was not a statistically significant difference in 1-year all-cause mortality and in-hospital mortality between liver transplant recipients with and without pleural effusions. Liver transplant recipients who developed pleural effusions had a longer hospital length of stay (16.4 ± 10.9 days vs 14.0 ± 16.5 days; P = .1), but the differences were not statistically significant. However, there was a significant difference in tracheostomy rates (11.6% vs 5.4%; P = .03) in recipients who developed pleural effusions compared to recipients who did not. CONCLUSIONS: In summary, pleural effusions are common after liver transplantation and are associated with increased morbidity. Pre- and intraoperative risk factors can offer both predictive and prognostic value for post-transplantation pleural effusions. Further prospective studies will be needed to further evaluate the relevance of these findings to limit instances of postoperative pleural effusions.

Candida auris outbreak involving liver transplant recipients in a surgical intensive care unit.

Candida auris is a yeast that is difficult to eradicate and has caused outbreaks in health care facilities. We report a cluster of 5 patients in 1 intensive care unit who were colonized or infected in 2017. The initial 2 patients were recipients of liver transplants who had cultures that grew C auris within 3 days of each other in June 2017 (days 43 and 30 posttransplant). Subsequent screening cultures identified 2 additional patients with C auris colonization. Respiratory and urine cultures from a fifth patient yielded C auris. All isolates were fluconazole resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from New York/New Jersey strains, consistent with a separate introduction. However, no source or contact was found. Two of the 5 patients died. C auris infection likely contributed to 1 patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that although severe disease from C auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C auris to date.

Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre- and post-transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter-associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species-level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long-term multidrug regimens, and consideration of complex drug-drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.

Intensive Care of Pulmonary Complications Following Liver Transplantation.

Chronic liver disease has been associated with pulmonary dysfunction both before and after liver transplantation. Post-liver transplantation pulmonary complications can affect both morbidity and mortality often necessitating intensive care during the immediate postoperative period. The major pulmonary complications include pneumonia, pleural effusions, pulmonary edema, and atelectasis. Poor clinical outcomes have been known to be associated with age, severity of liver dysfunction, and preexisting lung disease as well as perioperative events related to fluid balance, particularly transfusion and fluid volumes. Delineating each and every one of these pulmonary complications and their associated risk factors becomes paramount in guiding specific therapeutic strategies.

Mycobacterium haemophilum infection in a renal transplant patient with inflammatory bowel disease.

A 61-year-old immunosuppressed renal transplant patient with inflammatory bowel disease presented with tender pink nodules on the trunk and extremities. An initial biopsy was suggestive of metastatic Crohn disease, but after disease persistence, a second biopsy revealed disseminated Mycobacterium haemophilum. Atypical mycobacterial infections should be considered in immunosuppressed patients. This case highlights the complexities of diagnosing such infections in patients with an underlying granulomatous condition and the particular growth requirements of M. haemophilum.

Phomopsis bougainvilleicola prepatellar bursitis in a renal transplant recipient.

Prepatellar bursitis is typically a monomicrobial bacterial infection. A fungal cause is rarely identified. We describe a 61-year-old man who had received a renal transplant 21 months prior to presentation whose synovial fluid and surgical specimens grew Phomopsis bougainvilleicola, a pycnidial coelomycete.

A retrospective evaluation of completion rates, total cost, and adverse effects for treatment of latent tuberculosis infection in a public health clinic in central massachusetts.

Completion rates, total cost, and adverse effects were compared for patients in central Massachusetts treated for latent tuberculosis infection with 9 months of isoniazid or 4 months of rifampin. Although the adverse effects were similar between the 2 groups, 4 months of rifampin was associated with significantly better completion rates and less hepatotoxicity yet higher total cost.

Posaconazole as salvage therapy in patients with invasive fungal infections after solid organ transplant.

BACKGROUND: The incidence of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients has increased during the past 20 years and is associated with significant morbidity and mortality. In this post hoc analysis of a large, open-label, multicenter study, we evaluated efficacy and safety of posaconazole, a new extended-spectrum triazole, as salvage therapy for IFIs in SOT recipients. METHODS: Twenty-three SOT recipients with proven or probable IFI and evidence of disease refractory to, or intolerant of, standard antifungal therapies received posaconazole oral suspension (40 mg/mL) 800 mg daily in divided doses. An independent, blinded data-review committee assessed patient diagnosis and outcome. RESULTS: Complete or partial response was documented in 13 of 23 (57%) SOT recipients with proven or probable IFIs, including 1 of 2 (50%) refractory patients, 5 of 8 (63%) intolerant to prior therapy, and 7 of 13 (54%) who were both. Successes by type of IFI included 7 of 12 with invasive aspergillosis, 2 of 2 with invasive fusariosis, 1 of 1 with cryptococcosis, and 1 of 2 with zygomycosis. Treatment-related adverse events (TRAEs) were reported in 12 of 23 patients. Severe TRAEs occurred in 4 of 23 patients including increased levels of cyclosporine or tacrolimus requiring immunosuppressive dose adjustments in three patients and in one, termination of posaconazole. Severe TRAEs associated with renal and liver toxicities were uncommon. CONCLUSION: Posaconazole was well tolerated and effective against IFIs including invasive aspergillosis, zygomycosis, fusariosis, and cryptococcosis in SOT recipients intolerant of or failing other antifungal therapies. Calcineurin inhibitor levels should be closely monitored in patients treated concomitantly with posaconazole to avoid toxicity from drug interaction.

Preemptive strategy for ganciclovir administration against cytomegalovirus in liver transplantation recipients.

In utilizing a preemptive strategy to minimize the occurrence of symptomatic cytomegalovirus (CMV) infection following liver transplant, only patients with proven CMV activity by direct detection are treated. We applied the following preemptive strategy for CMV infection to 49 sequential liver transplant recipients between 1998 and 2001. Patients were monitored for CMV activity using CMV p65 antigen assay for the first 10 months of the study. Thereafter, we changed the detection method to a quantitative PCR for plasma CMV-DNA. All patients were monitored post transplant, weekly for the first 3 months and then monthly. Only patients with detected CMV activity were treated with ganciclovir. Patients were divided into four groups, based on donor (D) and recipient (R) CMV status. In seven out of 49 patients (14.3%) CMV activity was detected: four in group D+/R-, and three in group D-/R-. Five out of these seven patients had asymptomatic CMV infection. Symptomatic CMV infection developed only in two of these seven patients, to give total rate of 4.1% (2/49). All seven patients developed CMV IgG antibody. 'Transient' CMV replication detected by PCR in five patients in group D+/R+ was not defined as infection. No patients developed organ-invasive CMV disease. The cost of anti-CMV treatment using the preemptive strategy was $1000/patient/1st year. Using preemptive strategy, early detection of CMV infection was achieved, allowing timely treatment. The use of ganciclovir for CMV infection in only 4.3% of the patients should have a positive impact on minimizing the risk of ganciclovir-resistant virus, and should reduce the cost of CMV prevention strategies.