Journal of Autoimmunity 123 (2021) 102710 Available online 28 July 2021 0896-8411/© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ).

Autoimmune hepatitis triggered by SARS-CoV-2 vaccination

´

Elise Vuille-Lessard

a

, Matteo Montani

b

, Jaume Bosch

c

, Nasser Semmo

a

,

*

a

Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, Department of Biomedical Research, University of Bern, Bern, Switzerland

b

Institute of Pathology, University of Bern, Bern, Switzerland

c

Department of Biomedical Research, University of Bern, Bern, Switzerland

ARTICLE INFO

Keywords:

Autoimmune hepatitis

SARS-CoV-2

COVID-19

Vaccination

ABSTRACT

The development of autoimmune diseases has been reported after SARS-CoV-2 infection. Vaccination against

SARS-CoV-2 could also trigger auto-immunity, as it has been described with other vaccines. An aberrant immune

response induced by molecular mimicry and bystander activation, especially in predisposed individuals, is a

potential mechanism. We report the case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-

19 infection who developed severe autoimmune hepatitis (with typical features including strongly positive anti-

smooth muscle antibody and markedly elevated immunoglobulins G, as well as typical histological ndings)

following SARS-CoV-2 vaccination (mRNA-1273 SARS-CoV-2 vaccine, Moderna ® ). The link between SARS-CoV-

2 vaccination and the development of autoimmune diseases needs to be further investigated. Although a cau-

sality relationship cannot be proven, caution may be warranted when vaccinating individuals with known

autoimmune diseases.

Article

A 76-year-old woman was referred to our Hepatology outpatient

clinic with a 5-week history of dark urine, weight loss and fatigue,

associated with elevated liver enzymes. Symptoms began two to three

days after receiving the rst dose of the mRNA-1273 SARS-CoV-2 vac-

cine. The patient had a medical history of COVID-19 infection 3 months

prior (mild disease not requiring hospitalization), Hashimoto thyroiditis

and prior urothelial carcinoma. Liver enzymes were completely normal

in a routine check-up three years prior, as well as two months after the

COVID-19 infection. Drug history included levothyroxine, midodrine

(for a history of low blood pressure) and zolpidem, which are infre-

quently associated with drug-induced liver injury The patient did not

take herbal remedies.

On examination, the patient had discrete scleral and sublingual

icterus. Abdominal examination was remarkable for tender

hepatomegaly.

Laboratory investigations found a total bilirubin of 65

μ

mol/L,

elevated aspartate transaminase (811 U/L), alanine transaminase (579

U/L), alkaline phosphatase (124 U/L) and gamma-glutamyltransferase

(361 U/L). INR was 1.23 and albumin was 28 g/L. Immunoglobulins

G (IgG) were signicantly increased (39.4 g/L). Anti-nuclear antibody

(titer 1:1280, homogeneous, ne granular), anti-smooth muscle

antibody (titer 1:1280, against F-Actin, no specic immunouorescence

pattern observed), anti-actin antibody 84 U (negativity cut-off < 20 U)

and anti-neutrophil cytoplasmic antibodies (titer > 1:1280, perinuclear,

MPO and PR3 negative) were strongly positive. Anti-M2 antibody, liver

kidney microsome type 1 antibody and anti-soluble liver antigen anti-

body were negative. Complete blood count and creatinine were normal.

Serologies for hepatitis A, B and C viruses were negative. PCR for hep-

atitis B and E viruses and for cytomegalovirus were negative.

Abdominal ultrasound showed a slightly enlarged and hyper-

echogenic liver without biliary duct dilatation.

A liver biopsy showed a chronic markedly active hepatitis with

interface hepatitis, plasma cells, feathery degeneration and pseudoro-

settes ( Fig. 1 ), typical ndings of autoimmune hepatitis (AIH). The de-

gree of brosis could not be assessed given the signicant parenchymal

collapse. Simplied AIH Score was 8 (denite diagnosis of AIH).

Treatment with oral prednisolone 40 mg daily was started. Azathi-

oprine was added two weeks later as maintenance therapy. After four

weeks of treatment, the liver enzymes had completely normalized and

the patient ’ s symptoms had signicantly improved. A decision was

made to not administer the second dose of the vaccine. Prednisolone was

tapered over a total of eight weeks and then stopped. The patient dis-

continued azathioprine on her own after two months of therapy due to

* Corresponding author. University Clinic of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, MEM F809, Murtenstrasse 35, 3008,

Bern, Switzerland.

E-mail addresses: elise.vuille-lessard@insel.ch ( ´

E. Vuille-Lessard), nasser.semmo@insel.ch (N. Semmo).

Contents lists available at ScienceDirect

Journal of Autoimmunity

journal homepage: www.elsevier.com/locate/jautimm

https://doi.org/10.1016/j.jaut.2021.102710

Received 3 June 2021; Received in revised form 15 July 2021; Accepted 24 July 2021