Phage Therapy for Cardiac Implantable Electronic Devices and Vascular Grafts: A Targeted Literature Review.

Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application.

Major Bleeding Events in Hospitalized COVID-19 Patients: A Retrospective Observational Study.

Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.

Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.

BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. OBJECTIVES: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. METHODS: A systematic review and individual patient data meta-analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. STUDY ELIGIBILITY CRITERIA: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. PARTICIPANTS: SOT recipients. INTERVENTION: TMP-SMX prophylaxis versus no prophylaxis. ASSESSMENT OF RISK OF BIAS: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. METHODS OF DATA SYNTHESIS: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100). CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

Rifampin Based Therapy for Patients With Staphylococcus aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-analysis.

BACKGROUND: Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. METHODS: We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). RESULTS: Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. CONCLUSIONS: Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

Traditional Cultures versus Next Generation Sequencing for Suspected Orthopedic Infection: Experience Gained from a Reference Centre.

(Background) The diagnosis and the antimicrobial treatment of orthopedic infection are challenging, especially in cases with culture-negative results. New molecular methods, such as next-generation sequencing (NGS), promise to overcome some limitations of the standard culture, such as the detection of difficult-to-grow bacteria. However, data are scarce regarding the impact of molecular techniques in real-life scenarios. (Methods) We included cases of suspected orthopedic infection treated with surgery from May 2021 to September 2023. We combined traditional cultures with NGS. For NGS, we performed a metagenomic analysis of ribosomal 16s, and we queried dedicated taxonomic libraries to identify the species. To avoid false positive results, we set a cut-off of 1000 counts of the percentage of frequency of reads. (Results) We included 49 patients in our study. Our results show the presence of bacteria in 36/49 (73%) and 29/49 (59%) cases studied with NGS and traditional cultures, respectively. The concordance rate was 61%. Among the 19/49 discordant cases, in 11/19 cases, cultures were negative and NGS positive; in 4/19, cultures were positive and NGS negative; and in the remaining 4/19, different species were detected by traditional cultures and NGS. (Conclusions) Difficult-to-grow microorganisms, such as slow-growing anaerobic bacteria, were better detected by NGS compared to traditional culture in our study. However, more data to distinguish between true pathogens and contaminants are needed. NGS can be an additional tool to be used for the diagnosis of orthopedic infections and the choice of appropriate antimicrobial therapy.

Cutibacterium acnes in spine tissue: characteristics and outcomes of non-hardware-associated vertebral osteomyelitis.

Cutibacterium acnes isolation from spine tissue can be challenging because the organism can represent a contaminant. There is a paucity of data regarding the role of C. acnes in non-hardware-associated vertebral osteomyelitis (VO). Herein we evaluate the clinical and microbiological characteristics, treatment, and outcome of patients with C. acnes VO. Data were retrospectively collected from adults with a positive spine culture for C. acnes at Mayo Clinic, Rochester (MN), from 2011 to 2021. Patients with spinal hardware and polymicrobial infections were excluded. Of the subjects, 16 showed radiological and clinical findings of VO: 87.5 % were male, the average age was 58 years (±15 SD), and back pain was the predominant symptom. Of the lesions, 89.5 % involved the thoracic spine. Of the subjects, 69 % had experienced an antecedent event at the site of VO. In five subjects, C. acnes was isolated after 7 d of anaerobic culture incubation. Thirteen subjects were treated with parenteral ß-lactams, and three with oral antimicrobials, without any evidence of recurrence. Twenty-one subjects were not treated for VO, as C. acnes was considered a contaminant; at follow-up, none had evidence of progressive disease. C. acnes should be part of microbiological differential diagnosis in patients with suspected VO, especially in the context of a prior spinal procedure. Anaerobic spine cultures should undergo prolonged incubation to enable recovery of C. acnes. C. acnes VO may be managed with oral or parenteral antimicrobial therapy. Without clinical and radiological evidence of VO, a single positive culture of C. acnes from spine tissue frequently represents contaminants.

Functional humoral and cellular response of monovalent COVID-19-vaccines against Omicron BA.2 variant of SARS-CoV-2 in patients with chronic lymphocytic leukemia.

We designed a prospective study to evaluate the humoral (using a surrogate virus neutralization test) and cellular (using an IFN-γ ELISpot) immune response among patients with chronic lymphocytic leukemia (CLL) against Wuhan-Hu-1 and Omicron BA.2 strains of SARS-CoV-2, after mRNA-based vaccination. The proportion of patients with a functional humoral response was higher among untreated CLL patients compared to treated CLL patients against both Wuhan-Hu-1 and Omicron BA.2 after the second and the third dose of vaccination, and at 12 months after the first dose. The proportion of positive cellular response against the peptide pool covering the full-length Wuhan-Hu-1 spike protein was similar between untreated and treated CLL patients at all three timepoints. The cellular response to the mutated regions of BA.2 spike protein was lower than the response to the corresponding regions in the ancestral spike after the second dose, but this difference was eliminated after the third dose.

The use of MRI, PET/CT, and nuclear scintigraphy in the imaging of pyogenic native vertebral osteomyelitis: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Native vertebral osteomyelitis (NVO) is a severe infection with an increasing incidence globally. Although there is no widely agreed upon reference standard for diagnosis of the disease, imaging plays a crucial role. Magnetic resonance imaging (MRI) is currently the imaging modality of choice. In recent years, advances in imaging have allowed for a larger role for alternative imaging techniques in the setting of NVO. PURPOSE: Our aim was to evaluate the diagnostic accuracy of MRI, PET/CT, and nuclear imaging, namely 67Gallium and 99mTechnetium scintigraphy, in the diagnosis of pyogenic NVO. STUDY DESIGN/SETTING: We conducted a systematic review of five medical databases and included all studies from 1970 to September 2021 that compared imaging techniques and provided sufficient data for diagnostic test accuracy meta-analysis. METHODS: Abstract screening, full text review, and data extraction were done by a pair of independent reviewers. Nonnative and nonpyogenic patients were excluded. A bivariate random effect model was used for meta-analysis. RESULTS: Twenty studies were included in the meta-analysis, encompassing a total of 1,123 imaging studies. The meta-analysis sensitivity and specificity of MRI were 90% and 72% respectively; those of PET/CT were 93% and 80%; those of 67Ga were 95% and 88%; those of 99mTc were 86% and 39%; and the sensitivity and specificity of combined Ga and Tc were 91% and 92% respectively in the setting of suspected NVO. CONCLUSIONS: 67Ga has the highest sensitivity for NVO, and its specificity is augmented when combined with 99mTc. MRI and PET/CT are both highly sensitive modalities, although the specificity of PET/CT is slightly better. MRI remains an appropriate initial test depending on the availability of other modalities.

Early switch to oral antibiotic therapy for the treatment of patients with bacterial native vertebral osteomyelitis: a quaternary center experience, systematic review, and meta-analysis.

Recent data suggest that oral therapy can be effective for bone infections. We aim to assess the efficacy of an early switch to oral therapy ( < 2  weeks) compared to a non-early switch in bacterial native vertebral osteomyelitis. We conducted a cohort study at Mayo Clinic, Rochester (MN), between 2019-2021 combined with a systematic review, which queried multiple databases. Data were analyzed using a random-effects model. The cohort study included 139 patients: two received an early switch. Of 3708 citations, 13 studies were included in the final analysis. Meta-analysis demonstrated no difference in treatment failure (odds ratio  =  1.073, 95 % confidence interval 0.370-3.116), but many studies presented high risk of bias. Current evidence is insufficient to conclude the proportion of patients with failure or relapse is different in the two groups. High-quality studies are warranted before early switch can be routinely recommended.

Mortality among Italians and immigrants with COVID-19 hospitalised in Milan, Italy: data from the Luigi Sacco Hospital registry.

BACKGROUND: To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. METHODS: This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. RESULTS: The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58-79 vs 51 years, IQR 41-60; p < 0.001), and more frequently had one or more co-morbidities (79.1% vs 53.9%; p < 0.001). Mortality was significantly greater among the Italians than the immigrants as a whole (26.6% vs 12.8%; p < 0.001), and significantly greater among the immigrants from Latin America than among those from Asia, Africa or central/eastern Europe (21% vs 8%, 6% and 8%; p = 0.016). Univariable analysis showed that the risk of COVID-19-related death was lower among the immigrants (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.30-0.63; p < 0.0001], but the risk of Latin American immigrants did not significantly differ from that of the Italians (HR 0.74, 95% CI 0.47-1.15; p = 0.183). However, after adjusting for potential confounders, multivariable analysis showed that there was no difference in the risk of death between the immigrants and the Italians (adjusted HR [aHR] 1.04, 95% CI 0.70-1.55; p = 0.831), but being of Latin American origin was independently associated with an increased risk of death (aHR 1.95, 95% CI 1.17-3.23; p = 0.010). CONCLUSIONS: Mortality was lower among the immigrants hospitalised with COVID-19 than among their Italian counterparts, but this difference disappeared after adjusting for confounders. However, the increased risk of death among immigrants of Latin American origin suggests that COVID-19 information and prevention initiatives need to be strengthened in this sub-population.

Brief Report: Impact of the COVID-19 Pandemic on Virological Suppression in People Living With HIV Attending a Large Italian HIV Clinic.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HIV suppression rates in people living with HIV (PLWH) attending a large Italian HIV clinic. SETTING: The HIV outpatient clinic of the Infectious Diseases Department of Luigi Sacco Hospital, Milan, Italy, which serves more than 5000 PLWH per year. METHODS: A before and after quasi-experimental study design was used to make a retrospective assessment of the monthly trend of HIV-RNA determinations of ≥50 among the PLWH attending our clinic, with "before" being the period from January 1, 2016 to February 20, 2020, and "after" being the period from February 21, 2020 to December 31, 2020 (the COVID-19 period). Interrupted time series analysis was used to evaluate any changes in the trend. RESULTS: During the study period, 70,349 HIV-RNA viral load determinations were made, and the percentage of HIV-RNA viral load determinations of <50 copies/mL increased from 88.4% in 2016 to 93.2% in 2020 (P < 0.0001). There was a significant monthly trend toward a decrease in the number of HIV-RNA determinations of ≥50 copies/mL before the pandemic (ß -0.084; standard error 0.015; P < 0.001), and this did not significantly change after it started (ß -0.039, standard error 0.161; P = 0.811). CONCLUSIONS: A high prevalence of viral suppression was maintained among the PLWH referring to our clinic, despite the structural barriers raised by the COVID-19 pandemic. The use of simplified methods of delivering care (such as teleconsultations and multiple antiretroviral treatment prescriptions) may have contributed to preserving this continuum.

Emerging drugs for the treatment of HIV/AIDS: a review of 2019/2020 phase II and III trials.

Introduction: The study of emerging drug trials to treat people living with HIV (PLWH) helps to understand any advantages and disadvantages of therapies that will be available on the market in the short-term future as well as the mechanisms underlying a better cure.Areas covered: This review analyzes phase 2 and 3 clinical trials published between 2019 and 2020 concerning six different emerging drugs. The majority of the trials focus on long acting drugs, but also on new orally administered compounds.Expert opinion: The biggest news in antiretroviral therapy (ART) is the approval of cabotegravir/rilpivirine as a complete long-acting (LA) therapeutic regimen. It paves the way for an innovation that may change the paradigms of HIV treatment in the long term, albeit it will not be obvious to implement and treatment adherence still needs to be fully evaluated. Results of phase 3 Islatravir trials are awaited. Lenacapavir may soon reach phase 3. These drugs may pave the way for 6-month ART in the next future. Fostemsavir has been recently approved. Albuvirtide, a fusion inhibitor approved in China, presents several limitations for its intravenous use only. UB-421 and VRC01 are monoclonal antibodies against HIV. This emerging technology has shown interesting results but needs further studies.

Short-term inhibition of SARS-CoV-2 by hydrogen peroxide in persistent nasopharyngeal carriers.

Asymptomatic and convalescent coronavirus disease 2019 (COVID-19) subjects may carry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for months in their upper respiratory ways. Desiring to permanently clean the mucosal surfaces, we investigated the chemical agents that fit to rapidly degrade the virus. Among these, hydrogen peroxide, initially tested by two of us for tolerability, showed both good performance and acceptable side effects (burning sensation for 15-20 s). We contacted circles of family physicians and the ATS Milano (Territorial Assistance and Prevention Service), and we tested this procedure on eight persistent carriers of SARS-CoV-2, performing swabs before the procedure and after it until the reappearance of the virus or until 14 days (the incubation period), keeping the surfaces clean with a hypertonic solution. Our patients had a median time from exposure or symptom onset of 111 days, and three had relapsed after being declared "cured" (two consecutive negative swabs after quarantine). One patient had a baseline negative swab and was excluded, and two successfully ended the 14 days' course, four suppressed viral elimination for 72 h, and one for 48 h, all rebounding to weak positive (cycle thresholds above 24). Although temporarily effective, such measures may have some place in the control of viral shedding to protect the most fragile subjects.

Disseminated Cryptococcosis in a Patient With Metastatic Prostate Cancer Who Died in the Coronavirus Disease 2019 (COVID-19) Outbreak.

We report the case of a 61-year-old patient with a history of prostate cancer affected by bone metastasis. He presented to our attention for ulcerous and necrotic cutaneous lesions unresponsive to antibiotics. The spread of cutaneous lesions and the onset of neurological symptoms suggested a cryptococcal disease, which was confirmed by lumbar puncture and cutaneous biopsy. We present the diagnostic and therapeutic approach to this case.

30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: A prospective cohort study.

Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6 %) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1 %) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7 % (95 % CI 14.6-24.9 %) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95 % CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95 % CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95 % CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95 % CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95 % CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20 %. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.

Are direct-acting antivirals safe and effective in hepatitis C virus-cryoglobulinemia? virological, immunological, and clinical data from a real-life experience.

OBJECTIVES: Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Direct-acting antivirals (DAAs) have markedly changed the therapeutic outcomes in the treatment of patients with HCV. We evaluate the efficacy, safety, immunological, and clinical response of different DAA regimens in HCV-cryoglobulinemia. PATIENTS AND METHODS: Ninety-three cryoglobulinemic patients, divided into symptomatic [symptomatic cryoglobulinemic patients (SCP; n=35)] and asymptomatic [nonsymptomatic cryoglobulinemic patients (NSCP; n=60)], underwent DAAs. Eighty-nine comparable noncryoglobulinemic patients were selected as a control group. We evaluated the sustained virological response (SVR), the adverse effects, and the immune and symptomatic response. RESULTS: Percentages of patients who achieved SVR and experienced adverse effects were not statistically different between the three groups (100, 95, 93.3% and 57.1, 53.3, 48.3%). In 68.5% of SCP and in 76.7% of NSCP, cryoglobulins disappeared at SVR. No risk factor was associated with the persistence of cryoglobulins. An increase was observed both in C4 (P=0.002; P=0.018) and in C3 (P=0.0037; P=0.031) in SCP and NSCP. About 70% of symptomatic patients showed a complete or partial symptomatic remission: persistence of symptoms is correlated to the type of clinical picture. CONCLUSION: DAA regimens are safe and effective in patients with HCV-cryoglobulinemia. The achievement of SVR is necessary, but not sufficient, to achieve a complete immunological and clinical response.

Entecavir or tenofovir monotherapy prevents HBV recurrence in liver transplant recipients: A 5-year follow-up study after hepatitis B immunoglobulin withdrawal.

BACKGROUND: Recent data suggest that oral third-generation nucleos(t)ide analogs (NA) monoprophylaxis following hepatitis B immunoglobulin (HBIg) withdrawal may be effective to prevent HBV reinfection after liver transplantation (LT). PATIENTS AND METHODS: Between 01/2010 and 03/2012, all HBV monoinfected and HBV/HDV co-infected LT patients followed in our centre withdrew HBIg ±â€¯NA and were commenced on either ETV or TDF as monotherapy. RESULTS: Seventy-seven patients were included in the study (55% TDF, 45% ETV). Group A comprised 69 HBV monoinfected patients and Group B 8 HBV/HDV co-infected patients. After HBIg withdrawal, Groups A and B patients were followed for 69 (range 13-83) months and 61 (range 31-78) months, respectively. No Group B patients had HBsAg or HBV DNA recurrence, while 6 (9%) Group A patients became HBsAg-positive after a median of 18 (range 1-40) months. The cumulative 5-year incidence of HBsAg recurrence was 9%. All 6 patients demonstrated undetectable HBV-DNA levels and stable graft function during 30 months of additional follow-up. In 3/6 patients, seroconversion was transitory, while the remaining 3 showed HBsAg levels <0.13 IU/mL over the entire period of observation. Pre-LT HCC emerged as the strongest predictor of HBsAg recurrence. CONCLUSION: HBIG can be safely discontinued in HBsAgpositive LT recipients and replaced by ETV or TDF monotherapy.