Liver injury after COVID-19 vaccination: Current status and future perspectives

Table 3 Case reports of specific liver injury associated with coronavirus disease 2019 vaccination

Ref.	Age/sex	Pre-existing diseases	Vaccine	Injury after 1st/2nd/3rd/4th dose	Pattern of injury (hep/chol/mixed)1	Autoantibodies/viral markers2	Liver pathological findings	Diagnosis	Complications	Therapy	Outcome
[45]	33/male	Type I DM	mRNA	2nd	Hep	Negative	NA	Immune-related liver dysfunction	Glycemic excursion and Raynaud’s phenomenon	Increased insulin dose	Improvement of glucose level and liver function at 4 weeks after vaccination
[46]	80/female	IgG4-RD and resected left kidney cancer	NA	1st	NA	Negative	Infiltration of IgG-4+ cells and elevated IgG4+/CD38+ cell ratio	IgG4-related hepatopathy	Multiple lymphadenopathy	None	Spontaneous regression with no recurrence
[47]3	46/male	FL, HC, GB polyps	mRNA	1st	Mixed	Negative	NA	Vaccine-related and/or thyrotoxicosis-associated liver injury	Subacute thyroiditis	Steroid	Improvement 4 weeks after liver injury diagnosis except γGTP
[48]	40/male	None	Vector	NA	NA	NA/Negative	NA	Live injury due to secondary HLH	Secondary HLH	Steroid	Improvement of liver function
[49]	21/male	None	mRNA	2nd	NA	Negative/HBsAb+: IgG-HBcAb+	NA	Live injury due to secondary HLH	Secondary HLH	Steroid	Improved to normal laboratory values
[50]	65/male	CLL, RA	NA	1st	Hep	RF/negative	NA	Live injury due to secondary HLH	Secondary HLH	Steroid, etoposide	Rapid clinical improvement including liver function but death due to neutropenia and pneumonia
[51]	33/male	HL, allergies	mRNA	2nd	NA	NA/negative	Significant hepatic inflammation	Acute liver failure due to secondary HLH	Secondary HLH	Steroid, etoposide	Multiorgan failure
[52]	24/female	None	mRNA	1st	NA	ANA+/negative4	NA	Live injury due to secondary HLH	Secondary HLH	IVIG, steroid, anakinra	Abdominal laboratory findings gradually resolved
[53]	14/female	None	mRNA	1st	NA	NA/EBV DNA+	NA	Live injury due to secondary HLH	Secondary HLH due to vaccine and EBV infection	IVIG, VA-ECMO, steroid	Hemogram and inflammatory markers normalized gradually
[54]	68/female	NA	Vector	1st	NA	NA/Negative	NA	Live injury due to secondary HLH	Secondary HLH	antibiotics	NA regarding liver injury but improved HLH
[55]	43/female	Chronic EBV infection	Inactivated	1st	NA	ANA-/EBV DNA+	NA	Live injury due to secondary HLH	Secondary HLH due to vaccine on chronic EBV infection	Steroid	Abdominal laboratory abnormalities improved gradually

¹Classification based on Ref. 35, although not cited in the main text.

²Findings as described in the paper.

³Of the two reported cases, one involved only mild liver damage, limiting assessment of causality.

⁴Elevated IgM and IgG levels were observed, with no significant change in titers after 10 days.

ANA: Anti-nuclear antibody; CD: Cluster of differentiation; Chol: Cholestatic injury; CLL: Chronic lymphocytic leukemia: DM: Diabetes mellitus; EBV: Epstein-Barr virus; FL: Fatty liver; GB: Gallbladder; γ-GTP: γ-glutamyl transpeptidase; HBsAg: Hepatitis B surface antigen: Hep: Hepatocellular injury; HC: Hypercholesterolemia; HL: Hyperlipidemia; HLH: Hemophagocytic lymphohistiocytosis; IgG4-RD: IgG4-related disease; IgG-HBcAb: Immunoglobulin G type hepatitis B core antibody; IVIG: Intravenous immunoglobulins; Mixed: Mixed injury; NA: Not available or not applicable; RA: Rheumatoid arthritis; RF: Rheumatoid factor; VA-ECMO: Venoarterial extracorporeal membrane oxygenation.