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Safety and Efficacy of COVID-19 Vaccines in Patients with IBD or Liver Disease

Articles in the July issue of Clinical Gastroenterology and Hepatology report the efficacy and/or safety of coronavirus disease 2019 (COVID-19) vaccines in patients with inflammatory bowel diseases (IBD), chronic liver diseases, or who are recipients of liver transplants.

The serologic responses (production of antibodies) after severe acute respiratory syndrome coronavirus 2 (SARS-2) vaccines may be attenuated in immunocompromised individuals, including those receiving treatment for IBD. Annurag Jena et al performed a systematic review and meta-analysis of 46 studies of patients with IBD to determine seroconversion rates after complete vaccination for COVID-19.

In 31 studies of 9447 patients with IBD, the pooled rate of seroconversion after complete vaccination was good (0.96; 95% CI, 0.94–0.97) but slightly lower than that of individuals without IBD (controls; 0.98; 95% CI, 0.98–0.99).

The pooled seroconversion rates did not differ significantly among patients treated with different drug types. Drugs such as steroids and anti-tumor necrosis factor (TNF) agents combined with immunomodulators were associated with numerically (but not statistically) lower rates of seroconversion compared with patients on no treatment or those receiving anti-TNF alone, vedolizumab, ustekinumab, or JAK inhibitors.

The pooled relative risk of breakthrough infections in vaccinated patients with IBD patients was similar to vaccinated controls (0.60; 95% CI, 0.25–1.42). The studies reporting on durability of response indicated that antibody titers begin to decrease 4 weeks after complete vaccination; the decrease appears be faster among patients receiving anti-TNF drugs, immunomodulators, and combinations of these. An additional dose of COVID-19 vaccine elicited a serologic response in most nonresponders with complete vaccination. Jena et al state that their analysis indicates that the breakthrough infections can occur but the overall frequency is similar to the general population.

Jena et al conclude that complete COVID-19 vaccination produces effective seroconversion in patients with IBD. Durability of these responses is a concern, especially in patients receiving anti-TNF drugs and/or immunomodulators. In the subset of nonresponders to initial series of complete vaccination, an additional dose produced a serologic response in most. This finding, along with the fact that the majority of breakthrough infections did not require hospitalization, is reassuring to IBD patients and care takers.

Jingwen Ai et al performed a prospective study of 437 adult patients with chronic liver disease and 44 healthy volunteers (controls), at 15 sites in China, who received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines.

Most adverse reactions were mild and transient, with injection site pain (in 8.2% of patients) as the most frequently reported adverse event. Three participants had grade-3 increases in aminotransferases (>5-fold the upper limit of normal) after the second vaccine dose; only 1 was considered to be a severe adverse event potentially related to SARS-CoV-2 vaccination.

A significantly lower proportion of patients with chronic liver disease developed SARS-CoV-2 neutralizing antibodies than controls (338/437 [77.3%] in the CLD group and 130/144 [90.3%] in the healthy control group; P = .001). SARS-CoV-2 neutralizing antibodies were detected in 76.8% of patients without cirrhosis, 78.9% of patients with compensated cirrhosis, and 76.7% of patients with decompensated cirrhosis, 90.3% of the healthy controls (P = .008 vs patients with chronic liver disease). Male sex was found to be an independent risk factor for lack of serologic response to SARS-CoV-2 vaccination (odds ratio, 1.89; 95% CI, 1.12-3.90; P = .017) after the authors took age, cirrhosis, overweight, and compensation status into consideration.

Ai et al conclude that Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with chronic liver disease, although patients have lower immunologic responses than healthy individuals. Liver disease and fibrosis impair the synthesis of innate immunity proteins and pattern recognition receptors, although lower serum levels of these proteins are only evident in patients with advanced cirrhosis because of the large functional reserve of the liver). Liver diseases also affect B-cell and T-cell counts and functions via down-regulation of co-stimulation markers, loss of memory cells, and T-cell exhaustion. The authors propose that patients with CLD might need a boosting dose of SARS-CoV-2 vaccination to get a better response.

Maria Guarino et al performed a prospective study of responses of 492 liver transplant recipients and healthy individuals (controls) given the Pfizer-BioNTech BNT162b2 vaccine, administered in 2 doses 3 weeks apart, in Italy.

The authors observed an antibody response in a lower proportion of patients (77%) vs controls (98%).

The most frequent indication for liver transplantation was virus infection (76.4%), followed by hepatocellular carcinoma (39%). Overall, 293 patients (59.55%) received a single immunosuppressant agent; calcineurin inhibitors were the most common immunosuppressants (80.28%). Furthermore, 286 patients (58.13%) were on tacrolimus alone or in combination; 109 patients (22.15%) were on cyclosporine A alone or in combination, 168 patients (34.15%) were on mycofenolate mofetil alone or in combination, and 137 patients (27.85%) were on mTOR inhibitors (everolimus or sirolimus) alone or in combination. The median time from liver transplantation to COVID-19 vaccination was 14.08 years, and 386 patients (78.45%) had received a liver transplant more than 5 years before vaccination; 13 patients (2.64%) received transplantation within 1 year.

At 1 month after the 2-dose vaccination, antibodies were detected in serum samples from 333/444 patients (75%), with a median value of 99.05 AU/mL (IQR, 25.05–278 AU/mL) (median, 28 days; IQR, 28–31 days). At 3 months, antibodies were detected in 336/444 patients (75.67%), with a median value of 73.9 AU/mL (IQR, 25.75–156 AU/mL) (median, 88 days; IQR, 86–91 days).

Among patients with detectable antibody titer at 1 month, 16 of the 333 patients (4.8%) fell below the threshold of positivity at 3 months. Antibody titer increased in 20 of the 333 patients (6%), decreased in 142 of 333 patients (42.64%), and remained stable in 155 of 333 patients (46.54%). On the other hand, among those with undetectable titer at 1 month, 19 of 111 patients (17.1%) developed detectable antibody titers at 3 months. Among those with a high-positive titer at 1 month (>400 AU/mL), 17 of 83 patients (20.48%) dropped to a titer below 200 AU/mL, and 38/83 (45.78%) remained strongly positive at 3 months.

In multivariable analysis, older age (>40 years; P = .016), shorter time from liver transplantation (<5 years; P = .004), and immunosuppression with anti-metabolites (P = .029) were significantly associated with non-response to vaccination. The authors propose that these are features of liver transplant recipients at risk of non-response to vaccination who should be closely monitored.

Liver transplant recipients had antibody titers that were statistically lower than the control group (103 vs 261 AU/mL; P < .0001). In both groups, Guarino et al observed an inverse correlation between age and antibody titers (correlation coefficients: −0.2023 for patients and −0.2345 for controls).

Guarino et al state that the BNT162b2 vaccine is well tolerated by liver transplant recipients, with none reporting organ rejection or compromised graft function. Longer studies are needed of outcomes and to assess the cellular response in this group of patients.


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Kristine Novak

Kristine Novak

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About The Author:

Dr. Kristine Novak

Dr. Kristine Novak

Dr. Kristine Novak is a science writer and editor based in San Francisco. She has extensive experience covering gastroenterology, hepatology, immunology, oncology, clinical, and biotechnology research discoveries.

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