Liver injury persists in patients with vaccine breakthrough COVID-19

Liver injury is not uncommon among patients with vaccine breakthrough COVID-19, indicating the importance of monitoring liver injury enzymes, according to a study presented at The Liver Meeting 2021 by the American Association for the Study of Liver Diseases (AASLD 2021).

“Although COVID-19 vaccines are effective, breakthrough cases are expected, especially with variants of concern and in patients with suboptimal immunogenicity,” the researchers said.

Markos Kalligeros from Brown University in the US presented the study. He and his colleagues analysed the patterns and incidence of liver injury in COVID-19 vaccine breakthrough cases admitted to their institution and compared them to those of unvaccinated individuals during the same period.

A total of 892 consecutive adult hospitalized patients who had a primary diagnosis of COVID-19, confirmed by a positive RT-PCR, and were admitted between 1 January and 1 May 2021 were included in the study. Those with known vaccination status and at least two liver injury panels (one on admission and one prior to discharge) were eligible for analysis.

The researchers measured liver injury by alanine transaminase (ALT), aspartate transaminase (AST), or total bilirubin elevation and graded it based on the Common Terminology Criteria for Adverse Events version 5.0.

The main objective was to estimate the incidence of liver injury among patients hospitalized with vaccine breakthrough COVID-19. Additionally, the researchers examined the link between liver injury and vaccination status through a multivariate logistic regression model adjusted for age, sex, race, comorbidities, hepatotoxic medication, and baseline COVID-19 severity based on the NEWS score.

Of the 892 patients, 107 (12 percent) had received at least one dose of a COVID-19 vaccine. Elevations in ALT, AST, and bilirubin were noted in 16 (16.7 percent), 13 (13.5 percent), and six (6.3 percent) partially vaccinated patients (<14 days after two doses of BNT162b2 Pfizer-BioNTech or Moderna mRNA-1273 COVID-19 mRNA based vaccines, or <14 days after one dose of the Ad26.COV2.S Janssen Biotech Inc. adenoviral vector vaccine), respectively. [ASSLD 2021, abstract 538]

Among those fully vaccinated (>14 days after either two doses of mRNA-based vaccine or one dose of adenoviral vaccine), ALT, AST, and bilirubin were elevated in one patient each (9 percent).

Multivariate analysis revealed that neither partial nor complete vaccination in hospitalized patients with COVID-19 correlated with protection against liver injury relative to unvaccinated patients (ALT: odds ratio [OR], 1.11, 95 percent confidence interval [CI], 0.63–1.99; AST: OR, 0.96, 95 percent CI, 0.52–1.78; bilirubin: OR, 0.80, 95 percent CI, 0.27–2.36).

“There is increasing interest in the study of COVID-19 vaccine breakthrough cases,” the researchers said. “In addition, COVID-19 has been associated with liver injury, while abnormal liver function tests have been associated with worse COVID-19 outcomes.”

For instance, a China study reported the association of AST abnormality with the highest mortality risk compared with other indicators of liver injury during hospitalization. Lymphocyte count decrease, neutrophil count increase, and male gender were associated with elevated liver injury. [Hepatology 2020;72:389-398]