Vaccination against SARS-CoV-2 infection is currently approved and shows favorable outcomes, but little known about antibody responses in solid organ transplant recipients, since these patients are known to have an impaired immune response upon vaccination and have not been included in admission studies. We therefore analyzed immunogenicity in 43 liver transplant (LT) recipients in a median of 15 days (IQR, 12–24) after receiving two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol, and compared these results to a control group consisting of 20 healthcare workers (HCWs). Thirty-four of the 43 (79%) LT recipients developed antibodies, compared to 20 out of 20 (100%) in the control group (p = 0.047). The median SARS-CoV-2 IgG titer was significantly lower in the LT recipients compared to the control group (216 vs. >2080 BAU/mL, p = 0.0001). Age and sex distribution was similar in the LT patients that developed antibodies after vaccination compared to those who did not. Interestingly, the patients who received mycophenolate mofetil exhibited a reduced vaccination response compared to the other LT patients (5 of 11 (45.5%) vs. 29 of 32 (90.6%), p = 0.004). In conclusion, our data reveal lower immunogenicity of SARS-CoV-2 vaccine BNT162b2 in LT patients compared to the control group, but still show superior results compared to other solid organ transplant recipients reported so far.
SARS-CoV-2 infection is known to lead to severe morbidity and mortality in patients with liver cirrhosis. For this reason, vaccination of these patients against COVID-19 is widely recommended. However, data regarding immunogenicity in patients with liver cirrhosis is limited and even less is known about the kinetics of antibody response, as well as the optimal timing of booster immunization. We analyzed immunogenicity in 110 patients with liver cirrhosis after receiving two doses of the mRNA-based vaccine BNT162b2 following the standard protocol and compared these results to a control group consisting of 80 healthcare workers. One hundred and six patients with liver cirrhosis (96%) developed antibodies against SARS-CoV-2, compared to 79 (99%) in the control group (p = 0.400). Still, the median SARS-CoV-2 IgG titer was significantly lower in patients with liver cirrhosis compared to the control group (939 vs. 1905 BAU/mL, p = 0.0001). We also analyzed the strength of the antibody response in relation to the time between the second dose and antibody detection. Antibody titers remained relatively stable in the control group while showing a rapid and significant decrease in patients with liver cirrhosis. In conclusion, our data reveals a favorable initial outcome after vaccination with the COVID-19 vaccine BNT162b2 in cirrhotic patients but show a rapid deterioration of the antibody response after time, thereby giving a strong hint towards the importance of early booster immunization for this group of patients.
Primary sclerosing cholangitis (PSC) is characterized by inflammation of the whole bile duct system. Liver transplantation is only approved as a curative treatment when it comes to end-stage liver disease. The aim of our study was to assess morbidity, survival rates and PSC recurrence and the impact of donor characteristics in long-term follow-up. This was an IRB-approved retrospective study. A total of 82 patients were identified who were transplanted between January 2010 and December 2021 for PSC. Among these patients, 76 adult liver transplant PSC patients and their corresponding donors were analyzed. Three pediatric cases and three adult patients with a follow-up within 10 years (15 vs. 22, p = 0.004). Most patients (65%) passed in the first year following transplantation, with primary non-function (PNF), sepsis and arterial thrombosis being the most common causes of death. Donor characteristics did not affect patient survival. Patients with PSC show excellent 10-year survival rates. While the lab-MELD score significantly affected long term outcomes, donor characteristics did not affect survival rates.
The calcineurin inhibitor tacrolimus is included in most immunosuppressive protocols after liver transplantation. This retrospective, observational 24-month study investigated the tolerability of once-daily MeltDose® prolonged-release tacrolimus (LCPT) after switching from twice-daily immediate-release tacrolimus (IR-Tac) in a real-world cohort of 150 patients with previous liver transplantation. No graft rejection or new safety signals were observed. Only 7.3% of patients discontinued LCPT due to side effects. In the overall patient population, median liver transaminases, total cholesterol, triglycerides, glucose, and HbA1c remained constant after switching to LCPT. Total cholesterol significantly decreased (p ≤ 0.002) in patients with initially elevated levels (>200 mg/dL). A total of 71.8% of 96 patients maintained a glomerular filtration rate > 60 mL/min/1.73 m2 throughout the study, while 44.7% of patients were classified as fast metabolizers and 55.3% as slow metabolizers. Median daily tacrolimus dose could be reduced by 50% in fast metabolizers and by 30% in slow metabolizers, while trough levels were maintained in the target range (4–6 ng/mL). In conclusion, our observational study confirmed previous evidence of good overall tolerability and a favorable outcome for the patients after switching from IR-Tac to LCPT after liver transplantation.
Immunogenicity after SARS-CoV-2 vaccination is known to be impaired in liver transplant (LT) recipients, but the results after the application of a third dose show significant improvement in seroconversion rates. In the general population, the antibody response wanes over the course of time after two doses of the vaccination, but seems to be more robust after the application of three doses. Still, the durability of the antibody response in LT recipients who receive a third dose of SARS-CoV-2 vaccination has not been analyzed yet. We therefore assessed antibody responses in a total of 300 LT recipients and observed antibody titers for six months each after patients had received the second and the third doses of the vaccination, explicitly excluding all patients who had suffered from SARS-CoV-2 infection. The initial antibody response was compared to a control group of 122 healthcare workers. After the application of two doses of the vaccination, 74% of LT recipients (158 out of 213) developed antibodies against SARS-CoV-2; this result depended significantly on whether the patients were taking the medication mycophenolate mofetil, and on the age of the patients. Antibody titers declined significantly within six months from 407 BAU/mL (IQR: 0–1865) to 105 BAU/mL (IQR: 0–145) (p ≤ 0.001), but increased after the application of the third vaccine dose in 92% of patients (105 out of 114), showing an antibody response (p ≤ 0.001). After a further six-month period, despite showing a decline from 2055 BAU/mL (IQR: 500 to >2080) to 1805 BAU/mL (IQR: 517 to >2080), the waning of antibody titers was not significant (p = 0.706), and antibody durability appeared to be more robust than that after the second dose. In conclusion, our study confirms the high efficacy of the application of a third dose of SARS-CoV-2 vaccination in LT recipients, and a reasonably sustained humoral response with superior durability in comparison to antibody kinetics after the application of the second dose of the vaccination.