COVID-19 vaccination and liver disease

Table 2 Literature review of the efficacy and safety of coronavirus disease 2019 vaccines in patients with liver disease

Ref.	Design	Vaccine	Country/region	Number of participants	Value	Major findings (efficacy)	Major findings (safety)
Cirrhosis
John et al[45], 2021	Multicentre retrospective cohort study	BNT162b2 and mRNA-1273	United States	Cirrhosis group (n = 20037); Control (n = 20037)	Efficacy	64.8% decrease in the development of COVID-19 infection after the first dose and a 78.6% decrease after the second dose	NA
Thuluvath et al[46], 2021	Prospective cohort study	BNT162b2, mRNA-1273, and AZD1222	United States	LT (n = 62); Cirrhosis (n = 79); CLD (n = 92)	Immunogenicity	Antibody was detectable in 82.2% of LT recipients, 96.2% of cirrhosis and 95.7% of CLD without cirrhosis. 61.3% of LT recipients and 24% CLD with/without cirrhosis had poor antibody responses	No patient had any serious AEs
Ruether et al[47], 2022	Prospective cohort study	BNT162b2, mRNA-1273, and AZD1222	Germany	LT (n = 138); Cirrhosis (n = 48); Control (n = 52)	Immunogenicity	Immunological response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively	NA
Willuweit et al[48], 2022	Prospective cohort study	BNT162b2	Germany	Cirrhosis (n = 166); Control (n = 79)	Immunogenicity	Antibody was detectable in 96% of cirrhosis and 99% of controls. The median SARS-CoV-2 IgG titer was significantly lower in cirrhosis compared to the controls (939 vs 1905 BAU/mL, P = 0.0001)	NA
Wang et al[49], 2022	Multicentre retrospective cohort study	Inactivated vaccine	China	Compensated-cirrhosis (n = 388); Decompensated cirrhosis (n = 165)	Immunogenicity	Antibodies were detectable in 71.6% and 66.1% in compensated-cirrhosis and decompensated-cirrhosis	The vaccines were well tolerated, most AEs were mild and transient
Ai et al[50], 2022	Multicentre prospective cohort study	Inactivated vaccine	China	CLD (n = 284); Compensated cirrhosis (n = 123); Decompensated cirrhosis (n = 30)	Immunogenicity	Antibody detection rates were 76.8% in noncirrhotic CLD group, 78.9% in compensated cirrhotic group, 76.7% in decompensated cirrhotic group, and 90.3% in controls (P = 0.008 vs CLD)	There was no significant difference in AE among subgroups
Liver transplant recipients
Rabinowich et al[51], 2021	Multicentre retrospective cohort study	BNT162b2 mRNA vaccine	Israel	LT patients (n = 80); Control (n = 25)	Immunogenicity	Immunogenicity among LT recipients was significantly lower [47.5% (LT) vs 100% (control), P < 0.001]	No patient had any serious AEs
Herrera et al[52], 2021	Multicentre prospective cohort study	mRNA-1273	Spain	LT recipients (n = 58)	Immunogenicity	93% of patients developed immunologic responses to mRNA-1273 vaccine	No serious AEs were reported in LT recipients
Strauss et al[53], 2021	Multicentre retrospective cohort study	BNT162b2 and mRNA-1273	United States	LT recipients (n = 161)	Immunogenicity	Antibody was detectable in 34% (95%CI: 27%-42%) of participants after first dose, and in 81% (95%CI: 74%-87%) after second dose	NA
Nazaruk et al[54], 2021	Retrospective cohort study	BNT162b2 mRNA vaccine	Poland	LT recipients (n = 65)	Immunogenicity	Antibody detection rate was 88.9% in LT recipients after the second dose	NA
Timmermann et al[55], 2021	Retrospective cohort study	mRNA vaccines	Germany	LT recipients (n = 118)	Immunogenicity	The seroconversion rate was 78.0% in LT recipients. MMF for immunosuppression was risk factors for seronegativity	NA
D'Offizi et al[56], 2022	Retrospective cohort study	BNT162b2 and mRNA-1273	Italy	LT patients (n = 61); Control (n = 51)	Immunogenicity	Immunological response rates 2 wk after 2nd dose were 47.5% (LT) and 100% (control) (P < 0.001)	NA
John et al[57], 2022	Multicentre retrospective cohort study	BNT162b2 and mRNA-1273	United States	LT patients (n = 1133); Control (n = 791)	Efficacy	Vaccination with 2 doses of an mRNA vaccine was associated with a 64% decrease in COVID-19 infection and 87% decrease in COVID-19–related death in LT recipients	NA
Davidov et al[58], 2022	Retrospective cohort study	BNT162b2 mRNA vaccine	Israel	LT patients (n = 76); Control (n = 174)	Immunogenicity	Immunological response rates 2 wk after 2nd dose were 72.0% (LT) and 94.2% (control) (P < 0.001)	AEs were reported by 51% LT recipients. No serious events were reported
Sakai et al[59], 2022	Retrospective cohort study	BNT162b2	Japan	LT patients (n = 56); Control (n = 42)	Immunogenicity	LT recipients showed a lower seroconversion rate (44/56; 78.6%) than healthy controls (41/42; 97.6%)	NA
Calleri et al[60], 2022	Retrospective cohort study	BNT162b2 and mRNA-1273	Italy	Pre-LT patients (n = 89)	Immunogenicity	In the 89 pre-LT patients, seroconversion rate was 94.4% (23 d after vaccination), and 92.0% (68 d after vaccination)	No serious AEs were reported in participants
Viral hepatitis and NAFLD
Xiang et al[61], 2021	Retrospective cohort study	Inactivated vaccine	China	CHB patients (n = 149)	Immunogenicity	The seroconversion rate was 87.2% in CHB	No serious AEs were reported in participants
He et al[62], 2022	Cross-sectional observational study	Inactivated vaccine	China	CHB patients (n = 362); Control (n = 87)	Immunogenicity	The seroconversion rates of SARS-CoV-2 antibodies were similar between CHB patients and healthy controls	The incidence was similar between CHB patients and controls. No serious AE
Wang et al[63], 2021	Multicentre retrospective cohort study	Inactivated vaccine	China	NAFLD patients (n = 381)	Immunogenicity	The inactivated COVID-19 vaccine was good immunogenicity (95.5%) in patients with NAFLD	AEs within 7 d and within 28 d totaled 95 (24.9%) and 112 (29.4%), respectively. No serious AEs were recorded
Autoimmune liver disease
Duengelhoef et al[64], 2022	Prospective cohort study	BNT162b2, mRNA-1273, and AZD1222	Germany	AIH (n = 103); PSC (n = 64); PBC (n = 61); Control (n = 95)	Immunogenicity	Seroconversion was measurable in 97% of AIH and 99% of PBC/PSC patients, respectively. In 14% of AIH patients antibody levels were lower compared to PBC/PSC or controls	NA
Schneider et al[65], 2022	Prospective cohort study	BNT162b2 mRNA vaccine	Austria	AIH (n = 12); Control (n = 24)	Immunogenicity	Patients of AIH and healty controls acquired sufficient antibodies after third vaccination	NA

AE: Adverse event; AIH: Autoimmune hepatitis; CHB: Chronic hepatitis B; CLD: Chronic liver disease; LT: Liver transplant; MMF: Mycophenolate mofetil; NA: Not available; NAFLD: Non-alcoholic fatty liver disease; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; CI: Confidence interval.