New Study Shows 1 in 2,600 Had Acute Liver Injury After COVID-19 Vaccination
“The frequency of liver injury after vaccine was no different between mRNA and viral-vector vaccines (0.038% vs. 0.024%, p = 0.26). Liver injury was observed after the first dose in 14% and second dose in 86%.“
No population-based studies investigating the risk and characteristics of liver injury following SARS-CoV-2 vaccination exist. We investigated the frequency and pattern of liver injury after SARS-CoV-2 vaccination across vaccine types, injury time course, and recovery using the Indiana University Health Enterprise Data Warehouse. Analysis was conducted following institutional review board (IRB) approval.
Our vaccine-exposed cohort included (a) patients receiving SARS-CoV-2 vaccination between December 2020 and October 2021 (3,546,047 patients) and (b) without pre-existing liver disease, defined as alanine aminotransferase (ALT) <45 U/L, aspartate aminotransferase (AST) <45 U/L, alkaline phosphatase (ALP) <150 U/L, and total bilirubin (TB) <1.2 mg/dl on 2 consecutive occasions with no ALT/AST >45 U/L, ALP >150 U/L, and TB >1.2 mg/dl within 24 months prior to the first SARS-CoV-2 vaccine dose (470,274 patients). For comparison, we identified a control group including patients receiving the influenza vaccine in 2019 at Indiana University Health and Eskenazi Health (130,067 patients) with no pre-existing liver disease (21,784 patients). Data collection ended on 10/29/2021.
Using published criteria for investigating drug-induced liver injury (DILI) in epidemiological studies, 4, 5, 6 we defined “liver injury after vaccination” as ALT >200 U/L and/or ALP >250 U/L and/or TB >2.5 mg/dl on at least 2 consecutive occasions within 12 weeks after the first or second vaccine dose, in the absence of positive hepatitis B virus surface antigen or hepatitis C virus antibody, alcohol consumption, exposure within 3 months to common DILI drugs (amoxicillin-clavulanate, isoniazid, diclofenac, nitrofurantoin, sulfamethoxazole/trimethoprim, minocycline, infliximab, azathioprine, ibuprofen, rifampin, pyrazinamide), heart failure (ICD-10 codes I50.xx, I11.0, I13.0, I97.13, I09.8), or hospitalization within previous 3 months. Qualifying labs were collected as part of routine clinical care. R-value was calculated using initial qualifying data to identify the pattern of liver injury.
 We compared liver injury frequencies after vaccine among SARS-CoV-2 (mRNA, viral-vector) and influenza vaccines.
Among 470,274 individuals in the vaccine-exposed cohort, 177 individuals (0.038%) met liver injury criteria after SARS-CoV-2 vaccination. Sixty percent were female, 90% White and average age at first vaccine was 70 years. The frequency of liver injury after vaccine was no different between mRNA and viral-vector vaccines (0.038% vs. 0.024%, p = 0.26).
Liver injury was observed after the first dose in 14% and second dose in 86%. Average time to injury after the first dose was 29 ± 21 days and second was 45 ± 25 days. Liver injury pattern was hepatocellular in 45%, cholestatic in 35%, and mixed in 20%. Peak mean for AST, ALT, ALP and TB were 800 IU/L, 553 IU/L, 405 IU/L, and 3.1 mg/dl, respectively. 29% of patients ever had TB >2.5 mg/dl. Follow-up liver biochemistries were available in 42 patients with liver injury after vaccination and liver tests normalized in 48% of them (defined as serum ALT <45 U/L, ALP <250 U/L and TB <2.5 mg/dl). Mean duration between first abnormal to first normal TB was 8 ± 14 days. Compared to influenza control, SARS-CoV-2 vaccination was associated with a lower frequency of liver injury after vaccination (0.038% vs. 0.069%, p = 0.04)