Autoimmune liver diseases and SARS-CoV-2

Table 1 Cases of autoimmune hepatitis-like syndromes after the coronavirus disease 2019 vaccine

Ref.	Sex, age	Comorbidity	Vaccine	Time onset after vaccination	Symptoms	Antibodies	Histology	Treatment	Outcome
Bril et al[45]	F, 35	None	Pfizer-BioNTech	7 d after dose I	Jaundice, pruritus, choluria	ANA, anti- Ds-DNA	Compatible with AIH	Prednisone	Remission
Ghielmetti et al[49]	M, 63	Type II diabetes, ischemic heart disease	Moderna	7 d after dose I	Jaundice, fatigue, anorexia	ANA	Typical for AIH	Prednisone	Remission
Avci and Abasiyanik[50]	F, 61	Hashimoto thyroiditis, hypertension	Pfizer-BioNTech	30 d after dose I	Jaundice, malaise, fatigue,anorexia	ANA, ASMA	Compatible with AIH	Prednisone + AZA	Remission
Mahalingham et al[51]	F, 32	OLT post-AIH, hypertension	Pfizer-BioNTech	21 d after dose III	/	SLA/LP	Compatible with AIH	Methylprednisolone	Remission
Erard et al[52]	F, 80		Pfizer-BioNTech	10 d after dose II	All asthenia, pruritus, jaundice	ANA	Compatible with AIH	Steroids	Remission
	F, 73		Moderna	21 d after dose I		ANA		Steroids	Remission
	F, 68		AstraZeneca	20 d after dose I		ANA, ASMA		Listing for liver transplantation	Death after 3 d
Garrido et al[53]	F, 65	Polycythaemia Vera	Moderna	14 d after dose I	Abdominal pain, jaundice, pruritus, acholia, choluria	ANA	Compatible with AIH	Prednisolone	Remission
Goulas et al[54]	F, 52	/	Moderna	14 d after dose I	Malaise, jaundice	ANA, ASMA		Prednisolone + AZA	Remission
Cao et al[55]	F, 57	AIH	CoronaVac	14 d after dose I	Choluria, acholia, jaundice	ANA	Compatiblewith AIH	Methylprednisolone + AZA + UDCA	Remission
Vuille-Lessard et al[56]	F, 76	Hashimoto thyroiditis, urothelial ca.	Moderna	3 d after dose I	Choluria, fatigue, jaundice	ANA, ASMA, ANCA	Typical for AIH	Prednisolone + AZA	Remission
Suzuki et al[57]	F, 80	GERD	Pfizer-BioNTech	10 d after dose II	Jaundice	ANA	Compatible with AIH	Prednisone	Remission
	F, 75	Dyslipidemia	Pfizer-BioNTech	4 d after dose II	Choluria	ANA, AMA		Prednisone	Remission
	F, 78	Primary biliary cholangitis	Pfizer-BioNTech	7 d after dose I	Fever, malaise	ANA, AMA		Prednisone	Remission
Tan et al[58]	F, 56	/	Moderna	42 d after dose I	Jaundice, malaise, anorexia	ANA, AMA	Compatible with AIH	Budenoside	Remission
Zhou et al[59]	F, 36	Primary sclerosing cholangitis, ulcerative colitis	Moderna	11 d after dose I	/	ANA, Ds-DNA	Compatible with AIH	Prednisone + Azathioprine	Remission
Kang et al[60]	F, 27	/	Pfizer-BioNTech	8 d after dose II	Nausea, vomiting, headache, fever, dark urine	ANA	Compatible with AIH	Prednisolone	Remission
Rocco et al[61]	F, 80	Hashimoto thyroiditis Glomerulonephritis	Pfizer-BioNTech	7 d after dose II	Jaundice	ANA	Typical for AIH	Prednisone	Remission
Londoño et al[62]	F, 41	Premature ovarian failure	Moderna	7 d after dose II	Choluria, jaundice, epigastric pain, nausea, and vomiting	ANA, AMA, SLA/LP	Typical for AIH	Prednisone	Remission
McShane et al[63]	F, 71	/	Moderna	4 d after dose I	Jaundice	ASMA	Compatible with AIH	Prednisolone	Remission
Clayton-Chubb et al[64]	M, 36	Hypertension	AstraZeneca	26 d after dose I	Fever	ANA	Compatible with AIH	Prednisolone	Remission
Palla et al[65]	F, 40	Sarcoidosis	Pfizer-BioNTech	30 d after dose II	/	ANA	Compatible with AIH	Prednisolone	Remission
Rela et al[66]	F, 38	Hypothyroidism	AstraZeneca	20 d after dose I	Jaundice, fever, fatigue	ANA	Compatible with AIH	Prednisolone	Remission
	M, 62	Diabetes	AstraZeneca	16 d after dose I	Anorexia, fever, jaundice	/		Prednisolone	Death after 3 wk
Camacho-Domínguez et al[67]	M, 79	/	AstraZeneca	15 d after dose I	Abdominal pain, pruritus, acholia, choluria	ANA, ASMA	Compatible with AIH	Hydrocortisone; Prednisone; Prednisolone	Remission
Zin Tun et al[68]	M, 47	/	Moderna	3 d after dose I and 3 d after dose II	Malaise, jaundice	ANA	Compatible with AIH	Prednisolone	Remission
Torrente et al[69]	F, 46	Hypothyroidism	AstraZeneca	21 d after dose I	/	ANA	Compatible with AIH	Prednisone + AZA	Remission
Fimiano et al[70]	F, 63	Hypothyroidism	Pfizer-BioNTech	54 d after dose III	Abdominal pain, nausea, jaundice, choluria	-	Compatible with AIH	Methylprednisolone + AZA	Remission
Izagirre et al[71]	M, 72	Ischemic heart disease, 30 gr/day alcohol consumption	Pfizer-BioNTech	46 d after dose II	/	ANA	Compatible with AIH	Prednisone+ Azathioprine	Remission
	F, 62	Celiac disease	AstraZeneca	4 d after dose II	/	ANA		Prednisone+ AZA	Remission
	F, 72	/	Pfizer-BioNTech	14 d after dose II	/	ANA		Prednisone	Remission
	F, 59	Hypothyroidism	Pfizer-BioNTech	9 d after dose I	/	ANA	Not performed	No treatment received	Spontaneous improvement
Hasegawa et al[72]	F, 82	Hepatitis C virus	Pfizer-BioNTech	7 d after dose I	Malaise	ANA	Compatible with AIH	Prednisone	Remission
Shroff et al[73]	F, 59	/	Moderna	31 d after dose I	/	ANA	Compatible with AIH	Steroids	Remission
Efe et al[74]	M, 53	/	Pfizer-BioNTech	30 d after dose II	Abdominal pain, pruritus, erythematous skin eruption	/	Compatible with AIH	Prednisolone	Developed HE and liver transplantation
Shahrani et al[75]	F,59	Dyslipidemia	AstraZeneca	12 d after dose II	Jaundice	/	Compatible with AIH	Prednisolone	Remission
	F,72	/	Pfizer-BioNtech	10 d after booster	Jaundice	AMA	Compatible with AIH	Prednisolone	Remission
Nik et al[76]	F,63	Primary sclerosing cholangitis, ulcerative colitis	AstraZeneca	14 d after dose I	Jaundice, pruritus	ANA	Compatible with AIH	Prednisolone	Death after 2 wk for sepsis
Mekritthikrai et al[77]	F,52	Dyslipidemia, hypertension	Coronavac	After dose II	Jaundice	ANA, ASMA	Compatible with AIH	Prednisolone + AZA	Remission
Mathew et al[78]	F, late 20s	Headache	AstraZeneca	10 d after dose I	Jaundice	ANA	Compatible with AIH	Prednisolone	Remission

ANA: Antinuclear antibody; anti-Ds-DNA: Anti-double stranded DNA; AIH: Autoimmune hepatitis; ASMA: Anti-smooth muscle antibody; AZA: Azathioprine; OLT: Orthotopic liver transplantation; SLA/LP: Anti-soluble liver antigen/liver-pancreas; UDCA: Ursodeoxycholic acid; ANCA: Anti-neutrophil cytoplasmic antibodies; GERD: Gastroesophageal reflux disease; AMA: Anti-mitochondrial antibodies; HE: Hepatic encephalopathy.

Table 2 Cases of autoimmune hepatitis-like syndromes after coronavirus disease 2019 vaccine: Demographics, patient information, and disease presentation

Classification
Number of patients	40
Females, n (%)	32 (83)
Age (years, mean ± SD)	58.7 ± 16
Race/ethnicity, n (%)
Caucasian	11 (27)
Asian	3 (8)
Arabic	1 (3)
Unspecified	25 (62)
Predisposing conditions, n (%)
History of liver disease	6 (15)
History of autoimmune disease	11 (28)
Medications, n (%)
Acetaminophen	3 (8)
Other hepatotoxic drugs (statins, peg-IFN, AZT)	5 (13)
Vaccine, n (%)
Pfizer-BioNTech	17 (43)
Moderna	11 (28)
AstraZeneca	10 (25)
Coronavac	2 (5)
Symptom onset (days after a dose, mean ± SD)	16.6 ± 12.8
Symptoms, n (%)
Jaundice	24 (60)
Astenia/Malaise/Fatigue	13 (33)
Choluria	10 (25)
Pruritus	8 (20)
Abdominal pain	4 (10)
Fever	5 (13)
Loss of appetite	4 (10)
Nausea/vomiting	5 (13)

Peg-IFN: Pegylated interferon; AZT: Azathioprine.

Table 3 Cases of autoimmune hepatitis-like syndromes after coronavirus disease 2019 vaccine: Diagnostics, treatment, and clinical outcomes

Diagnostics
Peak laboratory values (mean ± SD)
AST (IU/l)	936 ± 523
ALT (IU/l)	1060 ± 567
GGT (IU/l)	312 ± 220
ALP (IU/l)	209 ± 95
Bilirubin (mg/dL)	9.8 ± 8.5
IgG (g/L)	21.7 ± 6.7
Antibodies, n (%)
ANA	33 (83)
ASMA	7 (18)
SLA/LP	2 (5)
AMA	5 (13)
Others (ANCA, DS-DNA)	3 (8)
Liver biopsy
Performed	39
Not performed	1
Morphologic characteristics, n (%)
Interface hepatitis	31 (78)
Lymphoplasmacellular infiltrates	36 (90)
Rosette formation	5 (13)
Treatment
First agent
Budesonide	1
Prednisone	15
Prednisolone	17
Methylprednisolone	3
Hydrocortisone	1
Steroids	3
No treatment	2
Second agent
Azathioprine	8
Prednisolone	2
Clinical outcomes
Time to the first improvement, days (mean ± SD)	4.6 ± 2.9
Time to resolution, days (mean ± SD)	44.6 ± 37
Alive	37
Dead	3

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; IgG: Immunoglobulin G; ANA: Antinuclear antibody; ASMA: Anti-smooth muscle antibody; SLA/LP: Anti-soluble liver antigen/liver-pancreas; AMA: Anti-mitochondrial antibodies; ANCA: Anti-neutrophil cytoplasmic antibodies; Ds-DNA: Anti-double stranded DNA.