COVID-19 vaccine responses are weaker in liver transplant patients

8 Jul 2021 Keith Alcorn
Originally published on www.infohep.org

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 vaccine.

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 drug.

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.