Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is correlated to the development of autoimmune processes. Various studies have suggested molecular mimicry as a potential mechanism for these relations.

An in vitro study demonstrated that antibodies against the spike protein S1 of SARS-CoV-2 had high affinity against transglutaminase 3, transglutaminase 2, anti-extractable nuclear antigen, nuclear antigen, and myelin basic protein. Moreover, these are the same viral protein that the vaccine mRNA codes for, there is good possibility that these vaccines may reveal autoimmune diseases in predisposed patients.

The investigators treated a 35-year-old female in her third month postpartum, who developed autoimmune hepatitis after COVID-19 vaccination. She was diagnosed with gestational hypertension and was initiated with labetalol 100 mg bid. C-section was done without any complications, and patient was discharged from the hospital on labetalol for blood pressure control. She resumed her job as a healthcare and received her first dose of Pfizer-BioNTech COVID-19 vaccine on January 4^th. However, post 1 week, she started developing generalized pruritus, choluria, and then jaundice, and presented to the emergency room on day +13 after COVID-19 vaccination.

She had a normal physical exam, except for scleral icterus, jaundice and palpable hepatomegaly. Laboratories investigations showed significant elevation for bilirubin 4.8 mg/dl, AST 754 U/L, ALT 2,001 U/L, alkaline phosphatase 170 U/L, and ammonium 61 mg/dl. Laboratory results were negative for hepatitis A, B, and C, Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV) type 1 and 2, and HIV. HEV was been tested at the time of submission. Antinuclear antibody (ANA) was positive (1:1,280; homogeneous pattern). Double-stranded DNA antibodies were also positive (1:80) whereas other antibodies (i.e. anti-mitochondrial, anti-smooth muscle, liver-kidney microsomal, antineutrophil cytoplasmic antibodies) were negative. Total IgG was 1,081 mg/dl (normal range: 694–1,618 mg/dl). Abdominal ultrasound with Doppler showed hepatomegaly without cirrhotic morphology, and no intra- or extra-hepatic biliary dilation.

Endoscopic ultrasound reported no evidence of biliary lithiasis or biliary dilation. Transduodenal liver biopsies were done and finding was consistent with drug/toxin related liver injury, autoimmune hepatitis or infectious related etiologies. Other than the COVID-19 vaccine and labetalol, no other drugs, herbal supplements or toxins were reported in the medical history. The Revised Original Score for autoimmune hepatitis pretreatment was 18 (results >15 suggest definite autoimmune hepatitis). 

This is the first seen episode of autoimmune hepatitis developing post-COVID-19 vaccination. This raises significant alarms regarding the possibility of vaccine-induced autoimmunity.

Although healthcare providers should not be discouraged from prescribing COVID-19 vaccines, it is important to raise awareness about potential side effects that can occur due to vaccination.

Source: Bril F, Al Diffalha S, Dean M, Fettig DM. Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty? J Hepatol. 2021 Jul;75(1):222-224.