Infections In Liver Transplant Recipients Research Articles

Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave.

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.

2112. Incidence and outcomes of infections in liver transplant recipients during the first year post-transplant.

Abstract Background Despite the use of antimicrobial prophylaxis in liver transplant recipients (LTR), infection remains the most likely cause of death (18.94%) in the first year. There is limited data describing the characteristics, &amp; infections of LTR while hospitalized in the first year post-transplantation. We aimed to review the incidence and outcomes of infections in LTR in the first year post-transplant during hospitalization or re-hospitalization. Graph 1.Y-axis; Number of cultures collected, X-axis; type of organism dived over time. Site of bacterial infection Table 1.Number of bacterial infections divided by site/system, involved compared to timing of infection. Methods We performed a single-center retrospective cohort study at The University of Rochester. Electronic medical records of 298 first time adult LTR between 03/5/2011 and 04/01/2020 were reviewed. Demographic and comorbidity data was obtained at time of transplant. Microbiologic data and outcomes were obtained during the first year post-transplant. We compared mortality between those with infection and those without using log-rank survival analysis. Graph 2. Y-Axis; Number of patients with diagnosed viral infection. X-axis virus divided over time. Results 160 (53.7%) patients suffered at least 1 infection while hospitalized in the first year post-transplant. There were 178 bacterial infections in 130 patients of which 115 were intra-abdominal (table 1). The most common organism was Enterococcus sp. (n=102), 65 were vancomycin resistant (VRE). The most common site of fungal infection was abdominal (n=13) and the most common organism was C. glabrata (n=9). The most common viral infection was CMV at 7-12 months although other viral infections occurred between 1-6 months (graph 2). In a univariate chi-square model, bacterial infection at any time was associated with all-cause mortality in the first year (CI 1.7-8.9 p-adj= 0.002). Fungal infection between 2-6 months was also associated with increased mortality (CI 2.7-12.2 p-adj= 0.0005). Conclusion Bacterial infections are the most common type of infection in LTR and occur more frequently during the first 6 months. Bacterial infection at any point was independently associated with increased mortality in the first year post-transplant. The most common organism was Enterococcus with a high rate of VRE which should be taken into consideration for empiric coverage at our institution. Fungal infection between 2 to 6 months was associated with increased mortality. We observed that early bacterial and fungal infections are markers of poor prognosis. Disclosures All Authors: No reported disclosures.

Withholding methotrexate after COVID-19 vaccination: different strategies, same results?

Withholding methotrexate after COVID-19 vaccination: different strategies, same results?

Risk factors and outcomes of early infection in liver transplant recipients with acute‐on‐chronic liver failure

Patients with acute-on-chronic liver failure (ACLF) have a high risk of infection after liver transplantation (LT). In this study, we aimed to evaluate the prevalence of early post-LT infection (within one month after LT) in recipients with ACLF, and to compare the survival rate between patients with or without post-LT infection. Patients with ACLF who underwent LT between January 2015 and December 2017 were retrospectively included. Characteristics of the patients, prevalence, site and pathogen of post-LT infection, and its risk factors were evaluated. A total of 62 patients with ACLF developed bacterial or fungal infection after LT. The 30-day, 90-day, and 1-year survival rates in the infected group were found to be significantly lower than those in the non-infected group (67.7% vs 98.5%, 64.5% vs 97.7%, and 48.4% vs 95.4%; all P < 0.001). The most common pathogens involved were carbapenem-resistant gram-negative organisms, including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter lwoffi. Multivariate analysis demonstrated that reoperation and length of intensive care unit stay were independently associated with post-LT infection. In addition, living donor LT and early allograft dysfunction were independently associated with 30-day all-cause mortality, whereas red blood cell transfusion and post-LT infection were independently associated with all-cause 30-day and 90-day mortality after LT. Early infection after LT is a major prognostic factor in patients with ACLF. Constant vigilance for the risk factors of early infection after LT is needed for timely diagnosis and prompt intervention.

249.10: COVID-19 Infection in Liver Transplant Recipients: Results From a Brazillian Multicentric Historical Cohort

249.10: COVID-19 Infection in Liver Transplant Recipients: Results From a Brazillian Multicentric Historical Cohort

COVID-19 infection in liver transplant recipients: Clinical features and outcomes from a Canadian multicentre cohort.

BACKGROUND: Prior studies have assessed risk factors and clinical outcomes in liver transplant (LT) recipients infected with COVID-19 globally; however, there is a paucity of Canadian data. Our multicentre study aims to examine the characteristics and clinical outcomes of LT patients with COVID-19 infection in Canada. METHODS: Adult LT recipients with reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19, from Canadian tertiary care centres between March 2020 and June 2021 were included. RESULTS: A total of 49 patients with a history of LT and COVID-19 infection were identified. Twenty-nine patients (59%) were male, median time from LT was 66 months (IQR 1-128), and median age was 59 years (IQR 52-65). At COVID-19 diagnosis, the median alanine transaminase (ALT) was 37 U/L (IQR 21-41), aspartate aminotransferase (AST) U/L was 34 (IQR 20-37), alkaline phosphatase (ALP) U/L was 156 (IQR 88-156), total bilirubin was 11 μmol/L (IQR 7-14), and international normalized ratio (INR) was 1.1 (IQR 1.0-1.1). The majority of patients (86%) were on tacrolimus (monotherapy or combined with mycophenolate mofetil); median tacrolimus level at COVID-19 diagnosis was 5.3 μg/L (IQR 4.0-8.1). Immunosuppression was modified in eight (16%) patients post-infection. Eighteen patients (37%) required hospitalization, and three (6%) required intensive care unit (ICU) admission and mechanical ventilation. Four patients (8%) died from complications related to COVID-19 infection. On univariate analysis, neither age, sex, comorbidities, nor duration post-transplant were associated with risk of hospitalization or ICU admission. CONCLUSIONS: LT recipients with COVID-19 have high rates of hospitalization but fortunately have low rates of ICU admission and mortality in this national registry.

SAT297 - Does m-RNA vaccination protect from Sars-Cov2 (asymptomatic) infection in liver transplant recipients?

SAT297 - Does m-RNA vaccination protect from Sars-Cov2 (asymptomatic) infection in liver transplant recipients?

Incidence and Impact of COVID-19 Cases in Brazilian Liver Transplant Recipients: An Academic, Single-center Experience

BackgroundCurrent literature reports diverge on the impact of COVID-19 in liver transplant (LT) recipients. Literature findings often report conflicting results, relying on small sample sizes, limited ethnic variability, and nonstandardized methodologies. Notably, there are no studies on this topic regarding Latin American populations. This study seeks to report the impact of COVID-19, disease characteristics, and progression in LT recipients in a Latin American academic center environment.MethodsThe study design was a historic cohort, including adult LT recipient patients with suspected or confirmed COVID-19 who sought care between December 2019 to October 2021. The primary end point was defined as COVID-19–related death. Demographic, clinical, and laboratory data was also collected.ResultsTwenty-seven patients were included, representing a 3.5% incidence within 752 patients in the follow-up. The mean age and years from transplantation were 54 (SD ± 11) and 6.3 years (SD ± 5.4), respectively. Most patients were white (23 - 85.2%) and male (21 - 25.2%). The hospitalization rate was 55.6%, and 5 patients (18.5%), all of whom subsequently died, were admitted to the intensive care unit. Neither the presence of comorbidities nor advanced age were related to lethality. Patients with immunosuppression modifications (P = 0.039) or isolated tacrolimus suspension (P = 0.006) were associated with increased mortality.ConclusionsThis study described COVID-19 infections in LT recipients in Latin American populations. This group was not affected by common factors associated with higher lethality, and displayed a tendency toward lower hospitalization rates. Our study concurred with previously reported evidence of a protective association of tacrolimus maintenance during treatment in LT recipients affected by COVID-19.

SARS-CoV-2 and Liver Transplant: How Has It Behaved in This Sixth Wave?

Background.Since the declaration of a new variant of concern (VOC), Omicron, by the World Health Organization in November 2021, a quick spread has been documented worldwide, being the main VOC in the sixth wave in Spain. The Omicron variant has more transmissibility, lower virulence, and less risk of severe disease than previously described VOC. Here we analyze the current wave of severe acute respiratory syndrome coronavirus 2 infection in liver transplant recipients (LTRs).Methods.A retrospective observational study of 355 LTRs was conducted in La Rioja and Cantabria regions of Spain. Epidemiological and clinical parameters were gathered on the basis of clinical records and telephone interviews.Results.In the current wave of infection, a higher number of LTRs have been found to be infected than the sum of the previous 5 waves (30 versus 16 LTRs). Of the 30 infected LTRs, 29 (96.6%) had received 3 vaccine doses (mRNA based), in a median of 93 d (interquartile range, 86–108) before infection. Eight of 30 LTRs (24.0%) were asymptomatic and 21 LTRs (67.8%) were with mild symptoms with a mean duration of 4.6 d (interquartile range, 2.5–7), whereas in the unvaccinated LTRs, the symptoms were fever, nausea, vomiting, and diarrhea. Moreover, in the sixth wave, intrafamiliar transmission was the main route of infection (17/30; 56.6%), and nosocomial transmission was confirmed in 2 LTRs (6.6%).Conclusions.In our series, increased transmissibility of the Omicron variant was confirmed, including nosocomial infection, with a lower risk of severe disease in LTRs. These findings could be supported by the universal vaccination of LTRs and less virulence of the Omicron variant.

Risk factors of invasive fungal infections in liver transplant recipients: A systematic review and meta-analysis

Invasive fungal infections (IFIs) remain one of the most common infectious complications after organ transplantation, and liver transplant recipients (LTRs) have the highest mortality rate. However, risk factors associated with IFIs have only been evaluated in small single-center studies. We performed a meta-analysis by conducting a comprehensive search using Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews, and Cochrane central register of controlled trials. All case-control and cohort studies evaluating risk factors for IFIs in adult LTRs were screened. Utilizing a random-effects model, a multivariate analysis was completed, and 28 studies were eligible for meta-analysis. Rates of IFIs ranged from 1.4% to 32.7%. Previous antibiotic use (OR 9.3; 95% CI 3.2-27.0) and bacterial infection (OR 4.3; 95% CI 2.1-8.6) were risk factors of invasive candidiasis. Yet for invasive aspergillosis, posttransplant renal replacement therapy (OR 9.2; 95% CI 4.2-20.4), reoperation (OR 8.0; 95% CI 2.9-21.7), and cytomegalovirus infection (OR 6.2; 95% CI 2.0-19.3) were risk factors. The top independent risk factors for IFIs during studies from 2010 to 2019 were previous fungal colonization (OR 9.19; 95% CI 4.92-17.16), reoperation (OR 5.45; 95% CI 2.93-10.15), and previous bacterial infections (OR 3.81; 95% CI 2.13-6.83). These risk factors may be targeted by antifungal prophylaxis in LTRs.

Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy.

BACKGROUNDPersistent inflammation on histology after successful hepatitis C (HCV) treatment has been reported. However, data regarding the long-term impact in liver transplant recipients is limited, particularly after using direct-acting antiviral (DAA) therapies. AIMTo evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.METHODSWe conducted a case series of 13 chronic HCV infected liver transplant recipients successfully treated with DAAs between December 2013 and May 2014. All patients were treated for 24 wk and had non-detectable serum HCV RNA by the time of biopsy. Only patients with at least one liver biopsy at or after treatment were included. We examined liver biopsies for evidence of residual inflammation and the presence of intrahepatic HCV RNA.RESULTSPersistent inflammation was seen in 12/13 patients on end of treatment biopsy. Inflammation was still seen in the available five follow-up biopsies (range 38-48 wk after the end of treatment). Intrahepatic HCV RNA was undetectable in all biopsies. All patients had preserved graft function for a mean follow-up of 2.5 years, except one that developed chronic rejection. CONCLUSIONAfter successful HCV treatment with DAAs, liver transplant recipients may have persistent inflammation on biopsy without evidence of intracellular RNA. The clinical outcome remained favorable in most patients. Further studies with a larger number and longer follow-up are needed to establish the implication of this finding on long-term graft function.

Clinical course and outcomes of COVID-19 infection in liver transplant recipients: single-center cross-sectional study

Background. The novel coronavirus infection (COVID-19) pandemic has had a significant impact on all areas of health care system, including organ donation and transplantation. Despite this, there were no large Russian studies of COVID-19 course and outcomes in liver transplant recipients.The study purpose was to determine prevalence, clinical course, severity, outcomes of COVID-19, as well as to assess the safety and efficiency of vaccination for disease prevention in liver transplant recipients.Material and methods. 260 recipients (71% of all patients at risk of COVID-19 disease) who underwent liver transplantation at State Research Center – Burnasyan Federal Medical Biophysical Center from May 2010 to September 2021 were included in a single-center cross-sectional study. Data collection was performed during a telephone or face-to-face interview from September 6, 2021 to September 20, 2021. If patients were hospitalized with COVID-19, we also analyzed the results of laboratory and instrumental tests, other medical documentation.Results. By mid-September 2021, the incidence of COVID-19 after liver transplantation was 31% (75 cases in 260 recipients). Asymptomatic course was observed in 11 (15%) patients. Hospitalization was required in 18 (28%) cases. In one case, COVID-19 infection was the cause of death. Mortality and death rate in the study cohort were 1% (1/75) and 0.4% (1/260), respectively. Risk factors that statistically significantly increased the likelihood of infection with SARS-CoV-2 were contact with the patient (OR: 12.9; 95% CI: 6.6 - 25.0) and non-compliance with non-specific prophylaxis measures (OR: 2.0; 95 % CI: 1.1 - 3.7). The recipient's age of 60 years or more significantly increased the risk of severe infection (OR 5.0; 95% CI: 1.3 - 18.7). None of the immunosuppressive therapy regimens significantly increased the risk of severe disease. Tacrolimus monotherapy or in combination with other drugs reduced the risk of severe COVID-19 (OR: 0.2; 95% CI: 0.1 - 0.95). Vaccination against SARS-CoV-2, which was performed in 42 (17%) recipients, did not cause serious adverse events and significantly reduced the risk of COVID-19 disease (OR: 7.2; 95% CI: 1.7 - 31.3). The detection rate of specific IgG antibodies to SARS-CoV-2 was 94% in recipients who had undergone the disease and 45% among those vaccinated (p&lt;0.001). The achieved level of herd immunity against COVID-19 in the analyzed cohort was 48%. Conclusion. Adult liver transplant recipients are not at an excessive risk of COVID-19 disease. Compliance with preventive measures and vaccination can significantly reduce the risks of infection and severe infection. There is no objective evidence that immunosuppressive therapy increases the risk of severe COVID-19 in liver transplant recipients. In the context of the ongoing COVID-19 pandemic, tacrolimus monotherapy may be considered as a safe regimen of maintenance immunosuppression.

Daptomycin-Resistant Enterococcus Bacteremia Is Associated With Prior Daptomycin Use and Increased Mortality After Liver Transplantation.

BackgroundRisk factors for acquisition of vancomycin-resistant Enterococcus (VRE) include immunosuppression, antibiotic exposure, indwelling catheters, and manipulation of the gastrointestinal tract, all of which occur in liver transplant recipients. VRE infections are documented in liver transplantation (LT); however, only one single center study has assessed the impact of daptomycin-resistant Enterococcus (DRE) in this patient population.MethodsWe conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within 1 year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest.ResultsWe identified 139 cases of Enterococcus bacteremia following LT, of which 78% were VRE and 22% were DRE. When adjusted for total intensive care unit days in the first transplant year, liver-kidney transplantation, and calcineurin inhibitor use, patients with DRE bacteremia were 2.65 times more likely to die within 1 year of transplantation (adjusted odds ratio [aOR], 2.648; 95% CI, 1.025–6.840; P = .044). Prior daptomycin exposure was found to be an independent predictor of DRE bacteremia (aOR, 30.62; 95% CI, 10.087–92.955; P < .001).ConclusionsIn this multicenter study of LT recipients with Enterococcus bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared with VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.

Importance of daptomycin dosage on the clinical outcome in liver transplant recipients with vancomycin-resistant enterococci infection

We retrospectively studied 16 (3 colonization and 13 infections) early post-liver transplant (≤60-day after transplantation) patients with vancomycin-resistant enterococci (VRE) colonization/infection from 2016 to 2019. All VRE isolates were Enterococcus faecium. Of 13 patients with VRE infection, 12 (92.3%) underwent living-donor liver transplantation and 1 underwent deceased donor liver transplantation. Among these 13 patients, the median time from transplant to emergence of VRE infection was 12 days. The median interval from VRE infection to death was 27 days. Of these 13 patients, eleven patients (8 survived; 3 died) received daptomycin therapy for VRE. Among them, 4 (36.3%) received daptomycin doses <8 mg/kg. Non-survivors (n = 3) received significantly lower daptomycin dose than survivors (n = 8; p = .040). Daptomycin doses <8mg/kg were more frequently associated with non-survivors (n = 3) than with survivors (n = 8; p = .024). In summary, the suboptimal dosage of daptomycin may have contributed to a higher rate of in-hospital mortality. Doses ≥8 mg/kg may be needed to adequately treat VRE infection in liver transplant recipients.

Prevalence and outcomes of Clostridioides difficile infection in liver transplant recipients.

Data are limited on whether Clostridioides difficile infection (CDI) in the first year after liver transplantation (LT) is associated with increased mortality. In an Australian setting without hypervirulent strain of C. difficile we investigated the prevalence, risk factors, and patient survival associated with CDI in LT. Consecutive patients who underwent deceased-donor LT from 2007 to 2017 were studied retrospectively. Prevalence and long-term outcomes of LT recipients with and without CDI were examined in the entire LT cohort. A case-control study was performed to investigate risk factors associated with CDI. Six hundred and forty-nine patients underwent LT, of which 32 (4.9%) were diagnosed with CDI within the first 12 months post-LT. There was no difference in patient survival in the overall LT cohort on Kaplan-Meier analysis when stratified by CDI status (log-rank test, p=.08). Furthermore, age was the only predictor of mortality on Cox regression (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, p=.03). On multivariable logistic regression, rifaximin pre-LT reduced risk (odds ratio (OR) 0.22, 95% CI 0.65-0.74, p=.01) whereas antibiotics pre-LT (OR 7.02, 95% CI 1.26-39.01, p=.03) and length of hospital stay after LT (OR 1.03, 95% CI 1.01-1.06, p=.02) were associated with increased risk of CDI. Within the local setting of our study, CDI within 12 months post-LT is of low severity, associated with pre-LT antibiotic exposure and longer hospital stay but no survival impact after LT. Rifaximin use pre-LT reduced the risk of CDI post-LT.

SARS-CoV-2 infection in liver transplant recipients: A complex relationship.

The recent manuscript reviewed investigations involving liver damage in coronavirus disease 2019 (COVID-19) patients, and COVID-19 in patients with previous chronic hepatological diseases, such as patients with liver graft. The literature presents several conflicting results concerning the anti-SARS-CoV-2 response in patients with solid organ transplants, in liver transplant recipients. Therefore, we would like to humbly state a few points for consideration involving liver transplant recipients and COVID-19, such as the time since transplantation, comorbidities, and immunosuppressive regimens.

Isavuconazole and Liposomal Amphotericin B as Successful Combination Therapy of Refractory Invasive Candidiasis in a Liver Transplant Recipient: A Case Report and Literature Review

Invasive fungal infections in liver transplant recipients are associated with elevated morbidity and mortality and pose a challenge to the treating physicians. Despite of lacking clinical data, the use of antifungal combination therapy is often considered to improve response rates in an immunocompromised patient population. We herein report a case of refractory invasive candidiasis in a liver transplant recipient treated successfully with a combination of isavuconazole und high-dose liposomal amphotericin B. The antimycotic combination treatment was able to clear a bloodstream infection with C. glabrata and led to regression of bilomas among tolerable side effects. The use of the above-mentioned antifungal combination therapy in a liver transplant recipient has not been reported previously. This case highlights the efficacy and safety of antifungal combination therapy in immunocompromised patients with refractory invasive candidiasis.

Impact of Living Donor Liver Transplantation on COVID-19 Clinical Outcomes from a Quaternary Care Centre in Delhi.

Background and AimsThe anticipated fear of serious outcomes in coronavirus infected liver transplant recipients led to disruption of transplant services globally. The aim of our study was to analyze COVID-19 severity in transplant recipients and to compare the difference of COVID-19 clinical outcomes in early (<1 year) vs. late (>1 year) post-transplant period.Methods41 post-living donor liver transplant recipients with COVID-19 infection were studied retrospectively from 1st April 2020 to 28th February 2021.ResultsThe median age was 49.00 years with a male preponderance (80.49%). Fifteen patients had infection within 1 year of transplant and 26 were infected after 1 year of transplant. The overall median interval between transplantation and COVID-19 diagnosis was 816.00 days. Fever and malaise were the common presenting symptoms. The most common associated comorbidities were diabetes mellitus (65.85%) and hypertension (46.34%). The severity of illness was mild in 28 (68.29%), moderate in 4 (9.76%), severe in 6 (14.63%) and critical in 3 (7.32%). To identify associated risk factors, we divided our patients into less severe and more severe groups. Except for lymphopenia, there was no worsening of total bilirubin, transaminases, alkaline phosphatase, and gamma-glutamyl transferase in the more severe group. Eight (19.51%) patients required intensive care unit admission and three (7.32%) died, while none suffered graft rejection. In recipients with early vs. late post-transplant COVID-19 infection, there were similar outcomes in terms of severity of COVID-19 illness, intensive care unit care need, requirement of respiratory support, and death.ConclusionLiving donor liver transplantation can be performed during the COVID-19 pandemic without the fear of poor recipient outcome in cases of unfortunate contraction of severe acute respiratory syndrome coronavirus-2.

S1140 Practical Consideration for Drug Monitoring of Tacrolimus in Liver Transplant Recipients With SARS-CoV-2 Infection

Introduction: Previous studies have shown that infection-related cytokine increase of interleukins can cause suppression of cytochrome P450.. SARS-CoV-2 infection has been associated with increased cytokine levels which may suggest suppression of CYP3A4 enzymes and downstream interaction with CYP-mediated drug metabolism including calcineurin inhibitors. Tacrolimus is a calcineurin inhibitor metabolized via CYP3A4. This potential effect of CYP3A4 inhibition on immunosuppression management with tacrolimus in liver transplant recipients with SARS-CoV-2 infection has yet to be evaluated. Methods: We retrospectively evaluated data between June 1, 2020 through December 31, 2020. All patients had confirmed SARS-CoV-2 and among those on tacrolimus-based therapy, serial tacrolimus trough levels were collected during the hospitalization were analyzed. Results: 18 OLT recipients were hospitalized with SARS-CoV-2.14 patients had tacrolimus trough levels throughout hospitalization, 12 of which were on stable immunosuppression therapy. 9 (64.3%) patients had elevated liver enzymes at time of admission. All patients experienced a decrease in baseline albumin levels and 7 out of 10 had an elevated ferritin level within 72 hours from admission.13 (92.8%) patients on tacrolimus had an increase from their baseline levels after testing positive, with an average increase of 105.6% (SD, 81%.7). 9 patients (64.3%) had at least a 50% increase from baseline trough levels. Among these patients, tacrolimus dose was subsequently reduced by an average of 45%. Steroid use did show a positive correlation (Pearson coefficient=0.57, P=0.03) with a rise above baseline tacrolimus trough. Conclusion: We found that most patients on tacrolimus had a supratherapeutic trough goals. There was an average two-fold increase in tacrolimus trough levels compared to baseline, with 64% (n=9) of patients experiencing at least a 50% increase. As expected, these supratherapeutic levels in trough levels in the setting of SARS-CoV-2 infection led to considerable change in immunosuppressive therapy with an approximately 50% reduction in daily tacrolimus dosing. These observations may suggest that SARS-CoV-2 infection in liver transplant recipients should be taken into special consideration when managing immunosuppression. This is the first study to describe these findings. Our study provides compelling evidence to closely monitor tacrolimus levels during acute infection and adjust dosing accordingly.Figure 1.: Pathophysiologic Mechanisms of Liver Injury in COVID-19Table 1.: Characteristics of Patients with Cirrhosis and Clinically Significant Portal Hypertension (CSPH) Based on SARS-CoV-2 Infection. Abbreviations: IQR, interquartile range; BMI, body mass index; CAD, coronary artery disease; BMI, body mass index; MELD-Na, Model for End-stage Liver Disease; CTP, Child Turcotte Pugh; HgbA1C, hemoglobin A1c; COPD, chronic obstructive pulmonary disease

Clinical efficacy of Direct Acting Antivirals (DAAs) for Treatment of Recurrent Hepatitis C Virus infection After Liver Transplantation

Abstract BACKGROUND &amp; AIMS Recurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Directacting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown. In this study, we aimed to demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients. METHODS A total of 106 LT recipients given DAAs for recurrent HCV infection from 2015 to 2019 were identified (68 with and 38 without HCC). Descriptive statistics and logistic regression models were used to estimate the multivariate odds ratios and respective 95% confidence intervals for predictors of treatment failure and HCC recurrence. RESULTS Six patients (6%) experienced DAA therapy failure and 100 (94%) had a sustained virologic response at follow-up week 12 (SVR12). A high alanine transaminase level &amp;gt;35 U/L at treatment week 4 was a significant predictor of treatment failure. DAA failure at follow-up week 12 was significantly associated with post-transplantation HCC recurrence, (odds ratio, 10.6 [95% confidence interval, 1.0-121.6]; P = .05). CONCLUSIONS DAAs are effective and safe in the treatment of recurrent HCV infection in LT recipients with history of HCC. Lack of SVR12 is a predictor of post-transplantation HCC recurrence.