An evaluation of antibody titers developed in response to the Pfizer-BioNTech mRNA COVID-19 vaccine appeared to show a correlation between low response and advanced liver fibrosis, researchers from Israel reported.

In a cohort of 140 patients with non-alcoholic fatty liver disease, the more advanced the fibrosis was, the less of a response patients had to the vaccine, reported Rifaat Safadi, MD, of Hadassah-Hebrew University Hospital in Jerusalem.

In patients with cirrhosis, for example, just 8% had an excellent response to the vaccine based on serum SARS-CoV-2 spike immunoglobulin levels (≥200 AU/mL), while 23% had only a good response (<200 AU/mL).

Additionally, among a cohort of 90 liver transplant patients who received both doses of the vaccine and were tested for serum SARS-CoV-2 spike immunoglobulins at least 7 days later, 58.9% developed satisfactory or excellent titers (≥19 AU/mL), while around 41.1% showed low titers.

Of the transplant patients with reduced response to the vaccine, five subsequently became infected with COVID-19 (one after the first dose and four after the second dose). Safadi said he could not be certain if the low percentage of breakthrough illness was due to some impact of the vaccine — despite low titer levels — or because of the overall success of the Israeli vaccination program.

“In Israel, we have vaccinated 96% of the population who are 16 and above,” Safadi said at a press briefing during the European Association for the Study of the Liver virtual meeting. “And just recently, a week ago we started to vaccinate young people between 12 years and 16 years.”

He noted that in the period prior to vaccination, 41 of his liver transplant patients were infected with COVID-19 and two died. After the vaccination rollout, the researchers followed 90 patients (72% men). Vaccine failure was defined as no response with antibodies or development of COVID infection. The failure to mount an antibody response may have been due to immune suppression.

As the Delta variant is gaining steam in Israel, Safadi said he is considering if a third booster shot of the vaccine may be needed for patients who don’t mount an adequate antibody response. “We have to think further about the booster or third vaccination. And I see that our Ministry of Health is now thinking about a third shot, especially for those with high risk for non-responsiveness,” Safadi said. “Now I’m just going to start to boost my patients who failed to develop response with a third vaccination.” He noted that one of the first patients who received a third inoculation did develop a strong titer response.

“This Israeli study may provide one answer as to who may need a third shot, or booster, of the mRNA vaccines,” David Bernstein, MD, of the Sandra Atlas Bass Center for Liver Diseases at Northwell Health in Manhasset, New York, told MedPage Today.

“Older people with more severe liver fibrosis do not appear to retain virus antibodies,” he said. “I am not surprised that advanced cirrhosis patients have a decreased vaccine response.”

Currently, antibody testing is not performed routinely in his institution, he noted. “I think a third shot makes sense in people with a poor antibody response,” Bernstein said. “This strategy would mean that we would need to introduce post-vaccine antibody testing into our algorithm in these patients.”