Graft-vs-Host Disease in a Liver Transplant Patient With COVID-19 Infection.

Graft-vs-host disease (GVHD) after liver transplant is a rare complication with high mortality outcomes. Because of the rarity of occurrence, there is no standardized consensus for treatment. Early recognition of symptoms and a multidisciplinary approach with input from transplant hepatology and hematology is important to determine a treatment plan and improve outcomes. We present a unique case of a 49-year-old woman who developed GVHD during a coronavirus disease 2019 (COVID-19) infection 3 months after receiving a liver transplant. More data are needed to determine whether COVID-19 infection itself correlates with a risk of developing GVHD.

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

Case report: One pediatric liver-transplant recipient with SARS-CoV-2 infection suffering unexplained mixed acidosis.

Background: The management of LT patients during COVID-19 pandemic is important. Immunosuppressants (IS) are key therapy agents after liver transplant. Different ISs have different side effects. Calcineurin inhibitor (CNI) may lead to metabolic acidosis while mycophenolate mofetil (MMF) showed rare nephrotoxicity. We report a post-liver transplant girl who was infected with SARS-CoV-2, developing a severe mixed acidosis 3 months after the transplantation. Her acidosis was improved after withdrawing of MMF, leading the suspicion that acidosis maybe a rare side effect of MMF. Case presentation: A girl was admitted to our hospital due to SARS-CoV-2 infection, 3 months before admission the patient received LT due to Niemann-Pick disease (NPD). During hospitalization, blood gas analysis showed severe mixed acidosis. To relieve mixed acidosis, the patient was given oral rehydration salt and liquid replacement therapy. Considering that immunosuppressants may cause metabolic acidosis, dose of CsA was decreased and MMF was discontinued. Results: However, liquid replacement therapy and decreased CsA dose cannot improve the condition. As an attempt, MMF was discontinued, and 3 days later, the girl's acidosis was relieved, the latest blood gas analysis was normal with the original dose of CsA and no use of MMF or other IS. In addition, we used Naranjo Scale to see if adverse drug reactions (ADRs) existed. The final score was 6 which means MMF contributes to acidosis probably. Conclusion: The girl's mixed acidosis cannot be explained by Niemann-Pick disease and SARS-CoV-2 infection. CNIs could cause metabolic acidosis but declining the dose of CsA didn't improve her acidosis while withdrawing MMF showed a good effect. Together with the Naranjo Scale result, we suspect that acidosis maybe a rare side effect of MMF.

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis.

BACKGROUND/AIMS: Data of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody. METHODS: We collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses. RESULTS: Twenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76-90%) and 91% (95% CI, 83-95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76-86%) in chronic hepatitis B, 96% (95% CI, 93-97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75-91%) in cirrhosis and 85% (95% CI, 78-90%) in non-cirrhosis, 86% (95% CI, 78-92%) for inactivated vaccine and 89% (95% CI, 71-96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55-75%) after two doses of mRNA vaccines and 88% (95% CI, 58-98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30-89%). Prevalence of adverse events was 27% (95% CI, 18-38%) and 63% (95% CI, 39-82%) among CLD and LT groups, respectively. CONCLUSION: CLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.

A cross-sectional study of knowledge, attitude, and practice toward COVID-19 in solid organ transplant recipients at a transplant center in the United States.

Objectives: Knowledge, attitude, and practices (KAP) have been widely used during times of pandemic to quantify and locate gaps of care during pandemics. Using this tool, we can identify and target populations who underwent solid organ transplant (SOT) to bolster preventative practices in these patients during COVID-19. Materials and methods: An institution-based cross-sectional study was conducted between June 1, 2020 and June 30, 2021 on patients who underwent a liver and/or kidney transplant at Methodist Dallas Medical Center in Dallas, Texas, USA. A KAP questionnaire of 26 questions about COVID-19 was designed based on the clinical and community management guidelines published by the WHO. The participant's overall KAP was categorized using Bloom's cut-off point. A KAP domain was considered sufficient if the score was between 60 and 100% and insufficient if the score was <60%. The strength of association was assessed by using odds ratio (OR); only significant independent factors in each tested area were assessed. Results: Respondents with children in the household were less likely to have sufficient practices than those who did not [OR = 0.2491, 95% Confidence Interval (0.0893-0.6120), p = 0.001]. We also found that sufficient levels of knowledge correlated with higher likelihood of sufficient levels of practices [OR = 4.94, 95% CI (1.646-14.2159), p < 0.005]. Interestingly, we found that sufficient levels of attitude did not correlate with sufficient levels of practice (p = 0.201). Conclusion: Our study found that knowledge and having children in the household correlated with higher levels of practice.

Comparison of the safety and immunogenicity of the BNT-162b2 vaccine and the ChAdOx1 vaccine for solid organ transplant recipients: a prospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials.