people with non-alcoholic fatty liver disease (NAFLD), those with more advanced
liver fibrosis did not respond as well to the Pfizer-BioNTech COVID-19 vaccine,
according to study results presented at the 2021 International Liver Congress.
These and other findings from liver transplant recipients raise the question of
whether a third booster dose could improve immune response.
Prior studies have shown that people with liver
disease, including advanced cirrhosis and alcoholic liver disease, are more
likely to develop severe COVID-19 and die from it. Another study found that fatty
liver disease may help explain the greater
likelihood of severe COVID-19 among people with obesity.
Given this increased risk, experts recommend that people with liver disease
should be prioritised for COVID-19 vaccination. But questions remain about
vaccine effectiveness in this population.
Cell of the liver.
type of tumour affecting the lymph nodes.
Abnormal fat deposits in the liver.
Prof. Rifaat Safadi of Hadassah-Hebrew
University Medical Centre in Jerusalem and colleagues evaluated the impact of chronic
liver disease on the effectiveness of the Pfizer-BioNTech messenger RNA (mRNA)
In one study, the researchers analysed a
cohort of 719 HMO employees who received the vaccine and were tested for IgG
antibodies against SARS-CoV-2 at least seven days after the second dose; 98.5%
had a good response.
Two of the eleven non-responders had received
kidney transplants. Transplant recipients take immunosuppressive drugs to
prevent organ rejection, which could interfere with immune response. Five were
taking immunosuppressive medications for rheumatoid arthritis, multiple
sclerosis or lymphoma; other studies have shown that people with
blood cancers to not respond as well to COVID-19 vaccines. Four had metabolic
syndrome, characterised by abdominal obesity,
high blood pressure and abnormal blood sugar, cholesterol and triglyceride
In this cohort, 501 responders and 10 non-responders had lab test data available
to calculate FIB-4 scores, a measure used to estimate liver fibrosis. 360 (70.5%) had a FIB-4 score below 1.3, 137 (26.8%) had a FIB-4 score between 1.3 and 2.67, and 14 (2.7%) had a FIB-4 score above 2.67). Among the
responders, 68.0% of those with a FIB-4 score below 1.3 (ruling out advanced
fibrosis) had an excellent response (an antibody titre of 200 AU/ml or higher)
compared with 44.2% of those with a score above 2 (predictive of advanced
The researchers also evaluated 140 people
with NAFLD who underwent liver biopsies. All but two (98.6%) responded to the
vaccine, including 87 (62.1%) with an excellent response. Those who had an
excellent response were younger, on average, than those with a weaker response (53.7
vs 61.5 years). Body mass index was similar in both groups.
People with more advanced fibrosis did not
respond as well to vaccination, Safadi reported. Among those with mild fibrosis
(stage F1), 39% had an excellent response while 28% had a weaker response. However,
among those with advanced fibrosis (stage F3), just 14% had an excellent
response and 17% had a weaker response. For those with cirrhosis (stage F4),
the corresponding figures were 8% and 23%, respectively.
But liver steatosis, or fat accumulation, was
actually associated with better vaccine response. Among those with grade 0
steatosis (<5% liver fat), 14% had an excellent response and 19% had a
weaker response. For those with grade 1 (5-33% liver fat), the corresponding
figures were 33% and 45%. Conversely, people with more liver fat were more
likely to have an excellent response: 36% excellent vs 26% weak among those
with grade 3 (33-66% liver fat) and 17% excellent vs 9% weak among those with
grade 4 (>66% liver fat). Hepatocyte 'ballooning' and liver inflammation
were similar in both groups.
"Older age, advanced fibrosis with
decreased steatosis are risk factors for lower vaccine response for Pfizer’s
BNT162b2 vaccine," the researchers concluded. "A third dose vaccine
booster in those risk factor populations should be evaluated in future trials."
Speaking at a conference press briefing,
Safadi also reported findings from a cohort of 90 liver transplant
recipients who were tested for SARS-CoV-2 antibodies after receiving two doses
of the vaccine. Of these, 52 (58.9%) produced an adequate immune response, with
antibodies titres of at least 19 AU/ml, while 37 (41.1%) were
non-responders. Five patients (5.6%) had breakthrough
COVID-19, one after the first vaccine dose and four after the second dose. He
noted that people who received transplants more recently had poorer responses,
likely due to use of stronger immunosuppressive regimens.
Safadi noted that COVID-19 outcomes for liver
transplant recipients improved after the vaccine rollout. Since June 2020, 41
transplant patients contracted COVID-19, including two who died; 36 of them were
not vaccinated. There were no cases reported in April, May or June 2021. This
may indicate that patients were protected by the vaccine despite some having
low antibody levels, or it may reflect the fact that Israel has achieved
population immunity thanks to high vaccine uptake. "Was that a
result of their vaccination or the result of the population vaccination?,"
he asked. "That was the question."
EASL vice secretary Prof. Thomas Berg, who moderated
the press briefing, brought up the point that antibody levels do not give a
full picture of immunity, as memory B-cell and T-cell responses also play a
Safadi noted that the Israeli Ministry of Health is
thinking now about third booster doses for people who have a lower antibody
response or are at higher risk for non-response. Advanced fibrosis, as assessed
by FIB-4 or biopsy, is a strong predictor of non-response.
"Now I'm just going to start to boost my
transplant patients who failed to develop a serological response with a third vaccination,"
he said, adding that one person who had already received a third dose saw an
elevation from zero to a "very nice titre."
Two recent studies published in Annals of Internal Medicine and the New England Journal of Medicine found that an extra booster dose improved antibody responses among
organ transplant recipients, including about a dozen who received liver
transplants. Further studies are underway to determine if the third dose
strategy could also help people with immunosuppression due to other causes and people
with liver disease, cancer and other co-morbidities associated with poor vaccine