COVID-19 Vaccinations May Be Weakened by Liver Disease

Laird Harrison

June 23, 2021

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Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah University Medical Center, in Jerusalem, Israel.

"If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them," Safadi told Medscape Medical News.

The suggestion contradicts the US Food and Drug Administration (FDA), which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Safadi said he is more convinced by the data, which he presented at the International Liver Congress (ILC) 2021, than by the FDA's recommendation.

"I'm not sure how scientific this recommendation is," he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer's and Moderna's mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.

New Data on Vaccine Efficacy in the Immunocompromised

To address this knowledge gap, Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG <19 AU/mL, the researchers' cutoff for a "good" antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose, and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Safadi said.

To determine the effectiveness of the vaccine in a larger population, Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers >19 AU/mL.

Another 8 (1.1%) had titers <12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, and cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers >19 AU/mL, Fibrosis–4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores <1.3, 68.0% had S IgG titers >200 AU/mL, and of those with Fib-4 scores >2, 44.2% had S IgG titers >200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.

Differing Opinions on Value of Antibody Titers, Third Doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Safadi said.

"I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time," he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, Geneva, Switzerland, questioned whether antibody titers can be used to estimate an individual's level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it's not clear to what degree, she said.

"There's no definitive cutoff," Vetter told Medscape Medical News. "I can't say if you have more than a titer of 5, then you're protected or you're more protected ― or if you have less, then you're not protected."

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

"There might be a benefit in these populations. But the question is, when and in which situations?" she said.

Vetter and Safadi have disclosed no relevant financial relationships.

International Liver Congress (ILC) 2021: Abstract OA-2854. Presented June 23, 2021.

Laird Harrison writes about science, health, and culture. His work has appeared in magazines, newspapers, and online publications. He is at work on a novel about alternate realities in physics. Harrison has taught writing at San Francisco State University, UC Berkeley Extension and the Writers Grotto. Visit him at or follow him on Twitter: @LairdH.

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