Liver transplant recipients in Israel were less likely to
develop antibodies after a second dose of the Pfizer SARS-CoV-2 vaccine than
healthy volunteers, transplant specialists from Tel Aviv’s Sourasky Medical
Center report in the Journal of Hepatology.
The findings mirror those discussed by an Israeli transplant
specialist from Jerusalem during a recent International Liver Congress press
briefing. Professor Rifaat Safadi of Hadassah University Medical Centre reported
that 41% of a group of 90 liver transplant recipients failed to produce an
adequate antibody response after a second dose of the Pfizer vaccine.
Responses to vaccination tend to be weaker in older people and those receiving immunosuppressive treatment, including transplant recipients. Antibody responses to SARS-CoV-2 vaccines are uncertain in transplant recipients but authorities have recommended that transplant recipients should be prioritised for vaccination.
Israeli groups are among the first to report on vaccine responses
in large cohorts of transplant recipients because vaccination of solid organ
transplant recipients began in Israel in December 2020, with first and second
doses given three weeks apart. Israel has one of the highest rates of vaccine
coverage in the world (65%
by 6 July 2021, according to Our World in Data).
Dr Liane Rabinowich and colleagues tested antibody responses
in 80 people who had received a liver transplant at Sourasky Medical Center and
now receive outpatient care through the clinic. Recipients had undergone a
liver transplant a median of five years prior to vaccination and had an average
age of 60 years.
Three patients had received a transplant less than three months
prior to vaccination and nine patients in the previous year. Seventeen patients
were receiving a triple immunosuppressive regimen at the time of vaccination.
Nine patients were receiving high-dose prednisone or methyl prednisone as
treatment for acute organ rejection episodes in the previous year.
Transplant recipients were tested for antibodies to the
SARS-CoV-2 spike protein. Results below 12 AU/ml were classified as negative,
between 12 and 15 AU/ml as borderline and above 15 AU/ml as positive responses
to the vaccine. Antibody responses in live transplant recipients were compared to
those in 25 healthy volunteers (mean age 52 years) who also received the Pfizer
All participants in the study tested negative for SARS-CoV-2
N protein, indicating no prior infection with the virus. All volunteers in the
control group showed protective levels of antibodies after vaccination but 42
out of 80 transplant recipients failed to develop positive antibody responses.
Furthermore, antibody titres were significantly lower than the control group’s
in the 38 transplant recipients who had positive antibody responses to vaccination
(95 AU/ml vs 200 AU/ml, p<0.001).
Participants with negative antibody responses were
significantly older (63 years vs 57 years, p=0.04) and had lower eGFR (56
ml/min vs 75 ml/min, p=0.001). Thirty per cent of those with negative antibody
responses had received high-dose steroids in the previous year compared to 7%
of those with positive antibody responses (p=0.01). People with negative responses
had also received mycophenolate mofetil as an immunosuppressant more frequently
(59% vs 39%, p=0.069), although only half of study participants had received this
Vaccine response was not affected by the time that had
elapsed since transplantation.
Multivariate analysis showed that a negative antibody response
to vaccination was associated with older age (odds ratio 1.3, 95% CI 1.17-1.95),
use of high dose prednisone in the past year (OR 1.8, 95% CI 1.58-4.61),
treatment with mycophenolate mofetil (OR 1.8, 95%CI 1.15-3.47) or triple
immunosuppressive treatment (OR 1.73, 95% CI 1.21-2.52). Better kidney function
was associated with a reduced risk of a negative antibody response.
An important limitation of this study is the lack of data on
cellular immune responses. Speaking in a symposium on COVID-19 and chronic
liver disease at last month’s International Liver Congress, Christoph
Neumann-Haefelin, Head of the Liver Outpatient Center at the University
of Freiburg, Germany, said that while protection from infection
is generated after the second vaccine dose by neutralising antibodies, T-cell responses
emerge after the first vaccination and protect against severe illness. More
information is needed on T-cell responses to vaccination in patients with
chronic liver disease and transplant recipients, he said. T-cell responses may
be somewhat reduced, he said, offering less protection against new variants.
“There are quite good arguments to do
re-boosting earlier than for other patients,” he told the symposium. The
findings of the Israeli study also raise the question of whether or not immunosuppressive
treatment should be reduced prior to vaccination, he suggested.
The authors of the Israeli study say that
more research is needed on how to improve vaccine responses in liver transplant
recipients. They say that their findings emphasise the importance of vaccinating
people prior to undergoing a liver transplant, and advise that transplant recipients
should be counselled regarding ongoing protective measures against SARS-CoV-2
infection after vaccination.