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COVID-19 vaccination does not increase the risk of acute liver injury, suggests a study that found that acute liver injury is far more common from SARS-CoV-2 infection.
In a population-based study, researchers in Hong Kong found that there was no increased risk of acute liver injury within 56 days among more than 2.3 million vaccine recipients, regardless of whether they received the BNT162b2 mRNA vaccine from Pfizer-BioNTech or the CoronaVac vaccine from Sinovac Biotech, the only two vaccines available in Hong Kong.
Moreover, vaccination was associated with a significantly reduced risk of acute liver injury compared with SARS-CoV-2 infection, at around 50%.
“Our findings show that the absolute risk of acute liver injury is very low following COVID-19 vaccination in our cohort of over 2 million vaccine recipients,” write Ian Chi Kei Wong, PhD, Center for Safe Medication Practice and Research, the University of Hong Kong, Hong Kong SAR, China, and colleagues.
“Based on all current available evidence from previous studies and our study, the potential benefit of mass vaccination far outweighs the potential acute liver injury risk from vaccination and SARS-CoV-2 infection,” they conclude.
The study was published online in the Journal of Hepatology.
Case Reports Prompt Safety Investigation
Acute liver injury, a rare outcome, was not reported in clinical trials of the vaccines, but following the widespread rollout of COVID-19 vaccination programs, cases of acute liver injury that mimic autoimmune hepatitis have been reported. In these cases, hepatotoxicity was evidenced by elevations in liver enzyme and bilirubin levels, the authors write.
Liver biopsies have revealed alterations typical of acute liver injury, such as those associated with interface hepatitis and portal inflammation. In addition, severe venous thrombosis in the portal and splenic veins has been reported, as well as immune thrombocytopenic purpura.
Such events have been observed in individuals receiving the Oxford-AstraZeneca adenovirus-based vaccine and the BNT162b2 mRNA vaccine, vaccines that have different mechanisms.
To assess the risk and severity of acute liver injury following COVID-19 vaccination, the researchers collated anonymized, population-wide vaccination records in the Hong Kong Special Administrative Region. These included the vaccination date and brand of vaccine used, as well as demographics, date of registered death, drug dispensing records, diagnoses, procedures, and laboratory test results.
For the study, the researchers used a self-controlled case series design, which was developed to test vaccine safety and controls for between-person confounders by comparing risk and reference periods for each participant.
They studied data from adults who had received at least one dose of COVID-19 vaccine between February 2021 and September 2021. Acute liver injury, identified from liver function test results extracted from the electronic medical records, was deemed to be related to vaccine exposure if it occurred within 56 days of the date of vaccination.
Among 3,981,696 individuals without a history of acute liver injury, 2,343,288 received either the BNT162b2 mRNA vaccine or the CoronaVac vaccine during the study period. Among these individuals, 94% and 92% received a second dose of the BNT162b2 mRNA vaccine or the CoronaVac vaccine, respectively.
Among those vaccinated during the study period, the researchers found that 4677 individuals experienced a first-incident acute liver injury. The median duration from vaccination to onset of acute liver injury was 20 days.
Among those vaccinated with the BNT162b2 mRNA vaccine, there were 307 events of acute liver injury that occurred within 56 days of the first dose and 521 within 56 days of the second dose, at a rate of 335 and 334 per 100,000 person-years, respectively.
For those vaccinated with the CoronaVac vaccine, there were 304 events of acute liver injury within 56 days of the first dose and 474 within 56 days of the second dose, at a rate of 358 and 403 per 100,000 person-years, respectively.
Of these 1606 vaccinated individuals who experienced an incident acute liver injury within 56 days after the first or second dose of COVID-19 vaccination, hospitalization was required by 42% of them. The median length of stay was 4 days, and 1.2% were admitted to the intensive care unit.
The team found that, compared with the exposure period, there was no increased risk of acute liver injury after the BNT162b2 mRNA vaccine. The incidence rate ratio after the first dose was 0.800 and after the second dose, 0.944.
There was also no increased risk with the CoronaVac vaccine, at an incidence rate ratio following the first dose of 0.689 and of 0.905 after the second dose.
SARS-CoV-2 Infection Linked to Higher Risk
As a comparator, the team assessed adults who tested positive for COVID-19 on polymerase chain reaction tests during September 2021 and who had no prior history of acute liver injury.
A total of 6353 patients were included in this second analysis. Of those patients, 309 developed acute liver injury within 56 days of infection, at an incidence rate of 32,997 cases per 100,000 person-years.
The median time to acute liver injury onset was 9 days. Patients spent a median of 13 days in hospital, and 19% required admission to the intensive care unit.
Propensity score weighting indicated that the rate of acute liver injury at 56 days was lower among vaccinated individuals than among those infected with SARS-CoV-2, at an incidence rate ratio of 0.052 for the BNT162b2 mRNA vaccine and of 0.051 for the CoronaVac vaccine.
The study was funded by a research grant from the Food and Health Bureau, the government of the Hong Kong Special Administrative Region, and was partly funded by AIR@InnoHK, as administered by Innovation and Technology Commission. Wong declares relationships with Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, and the National Health and Medical Research Council in Australia. Other authors have disclosed numerous relationships.
J Hepatol. Published online July 8, 2022. Full text