Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were ...not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population.
LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10–20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records.
Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group.
LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population.
The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.
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•Liver transplant recipients exhibited reduced response to the SARS-CoV-2 mRNA-based vaccine.•Neutralizing antibody was detected in only 47.5% of patients following vaccination.•Antibody titers were significantly lower compared to the control group.•Age, renal function and immunosuppression were associated with lower immunological response.
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of ...obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.
COVID‐19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS‐CoV‐2 vaccines. We ...analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer‐BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS‐CoV‐2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti‐spike level was higher in the controls (31.05 41.8 vs. 200.5 65.1 AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 95% confidence interval 1.17–2.69), high‐dose corticosteroids in the last 12 months (1.3 1.09–1.86), maintenance with triple immunosuppression (1.43 1.06–2.15), and regimen that includes mycophenolate (1.47 1.26–2.27). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID‐19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.
Most kidney transplant recipients do not mount an appreciable anti‐spike antibody response to the BNT162b2 (Pfizer‐BioNTech) SARS‐CoV‐2 vaccine.
AIM To assess the practice of caring for acute liver failure(ALF) patients in varying geographic locations and medical centers.METHODS Members of the European Acute Liver Failure Consortium completed ...an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed,treating between 300 and 500 ALF cases and performing over 100 liver transplants(LT) for ALF annually. The questions pertained to details of the institution and their clinical activity,standards of care,referral and admission,wardbased care versus intensive care unit(ICU) as well as questions regarding liver transplantation- including criteria,limitations,and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted,treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers,particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamolrelated ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals,lactulose,nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure(ICP). ICP monitoring was employed in 12 centers,with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT,with a 90% post transplant survival to hospital discharge,42% survived with medical management alone. CONCLUSION Alongside similarities in principles of care of ALF patients,major areas of divergence were present in key areas of diagnosis,monitoring,treatment and decision to transplant.
Majority of transplant recipients did not develop an appreciable humoral response following SARS‐CoV‐2 vaccine, in contrast to dialysis patients and healthy individuals. We analyzed the serologic ...response to BNT162b2 (Pfizer‐BioNTech) vaccine in a cohort of 19 kidney transplant recipients, vaccinated prior to transplantation, compare to 109 recipients vaccinated after transplantation, and to 39 healthcare workers, by determining the level of anti‐spike antibodies after transplantation. All controls and 17 of 19 (90%) of recipients vaccinated before transplant were seropositive, while only 49 of 109 (45%) recipients vaccinated post‐transplant had positive serology (P < .001). Median anti‐spike IgG in the group of kidney transplant recipients vaccinated after transplantation (10.7 AU/ml, IQR 0–62.5) was lower than the patients vaccinated before transplantation (66.2 AU/ml 21.6–138), which was significantly lower than in the controls (156 AU/ml 99.7–215.5). Negative humoral response was associated with vaccination post transplantation (odds ratio 22.4), older age (OR = 1.04), and longer time on dialysis (OR = 1.02), while higher lymphocyte count at time of vaccination was protective (OR = .52). Our findings of sustained superior humoral response to SARS‐CoV‐2 vaccine in kidney transplant recipients vaccinated prior to transplantation strongly support the recommendations of SARS‐CoV‐2 vaccination of transplant candidates, especially those younger than 60 years.
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