Table 1.
Background characteristics of the included studies
| Study | Country | Study duration | Participants | Age (years) | Male | Liver disease | Immunosup-pressants used | Vaccine type | Antibody type | Time interval of antibody measurement from second dose of vaccination | Method of antibody test | Cut-off of antibody level regarded as seropositive | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chronic liver disease | |||||||||||||
| Ai et al. [10] | China | January to August 2021 | 437 | Median (IQR): 47.0 (38.0–56.0) | 278 (63.6%) | Non-cirrhotic chronic liver disease: HBV, 260 (91.5%); HCV, 8 (2.82%); NAFLD, 9 (3.17%); ALD, 1 (0.35%); AIH/PBC/PSC, 1 (0.35%); others, 5 (1.76%) | NA | CoronaVac: NA | Neutralising Ab | ≥14 days | CLIA | >10.0 AU/mL | |
| BBIBP-CorV: NA | |||||||||||||
| Cirrhosis: HBV, 124 (81.0%); HCV, 12 (7.84%); NAFLD. 3 (1.96%); AIH/PBC/PSC, 7 (4.58%); others, 7 (4.58%) | WIBP-CorV: NA | ||||||||||||
| Bakasis et al. [11] | Greece | March to May 2021 | 87 | Median (range): cirrhosis, 67.0 (27–86); noncirrhotic liver disease, 65.0 (35–81) | 43 (49.4%) | Non-cirrhotic chronic liver disease: HBV, 23 (46.9%); HCV, 1 (2.04%); NAFLD, 7 (14.3%); AIH, 6 (12.2%); PBC, 11 (22.4%); PSC, 1 (2.04%) | MTX: 5 (5.75%) | BNT162b2: 81 (93.1%) | Antispike Ab, neutralising Ab | Cirrhosis: 24 days (IQR, 14–57) | ELISA | Anti-spike Ab: >1.1 OD ratio | |
| AZA: 7 (8.05%) | |||||||||||||
| RTX: 4 (4.60%) | |||||||||||||
| Cirrhosis: HBV, 7 (18.4%); HCV, 1 (2.63%); NAFLD, 9 (23.7%); ALD, 6 (15.8%); AIH, 8 (21.1%); PBC, 1 (2.63%); PSC, 3 (7.89%); HSC, 1 (2.63%); BCS, 1 (2.63%); DILI, 1 (2.63%) | MMF: 6 (6.90%) | mRNA-1273: 6 (6.90%) | Non-cirrhotic liver disease: 25 days (IQR, 15–45) | Neutralising Ab: >30% inhibitory concentration | |||||||||
| TNFI: 4 (4.60%) | |||||||||||||
| S: 14 (16.1%) | |||||||||||||
| He et al. [26] | China | July to August 2021 | 362 | Median (range): 45.0 (19.0–78.0) | 223 (61.6%) | HBV, 362 (100%); cirrhosis, 48 (13.3%) | NA | CoronaVac: NA | Antispike Ab, antispike RBD Ab, neutralising Ab | ≥21 days (range, 21–105) | ELISA | Anti-spike Ab, antispike RBD Ab: ≥2.1 OD ratio | |
| BBIBP-CorV: NA | Neutralising Ab: ≥20% inhibitory concentration | ||||||||||||
| Ruether et al. [15] | Germany | NA | 48 | Mean±SD: 53.8±9.5 | 108 (58.1%) | Cirrhosis: ALD, 23 (47.9%); VH, 3 (6.30%); AIH, 11 (22.9%); NAFLD, 4 (8.30%); CC, 5 (10.4%); ALF, 1 (2.10%); others, 1 (2.10%); HCC, 5 (10.4%)* | NA | mRNA/mRNA: 44 (91.6%) | Antispike RBD Ab, antispike trimer Ab | Median (IQR): 28 days (21–41) | CLIA | Anti-spike RBD Ab: >100 U/mL | |
| BNT162b2: 38 (79.2%) | ECLIA | ||||||||||||
| mRNA-1273: 6 (12.4%) | Anti-spike trimer Ab: >100 BAU/mL | ||||||||||||
| AZD1222/AZD1222: 1 (2.08%) | |||||||||||||
| AZD1222/mRNA: 3 (6.25%) | |||||||||||||
| Thuluvath et al. [21] | USA | NA | 171 | Mean±SD: noncirrhotic chronic liver disease, 60.4±13.9; liver cirrhosis, 63.8±11.1 | Noncirrhotic chronic liver disease: 37 (40.2%) | Non-cirrhotic chronic liver disease: AIH/PBC/PSC, 36 (39.1%); ALD, 2 (2.17%); HBV/HCV, 20 (21.7%); NAFLD, 36 (39.1%); others, 8 (8.70%) | AZA: 25 (14.6%) | BNT162b2: 80 (46.8%) | Antispike Ab | Mean±SD: non-cirrhotic chronic liver disease, 40.8±19.6; liver cirrhosis, 40.9±23.9 | ECLIA | >250 U/mL | |
| S: 19 (11.1%) | mRNA-1273: 77 (45.0%) | ||||||||||||
| Liver cirrhosis: 40 (50.6%) | Cirrhosis: AIH/PBC/PSC, 17 (21.5%); ALD, 17 (21.5%); HBV/HCV, 17 (21.5%); NAFLD, 33 (41.8%); others, 8 (10.1%) | TAC: 0 (0.00%) | |||||||||||
| Others: 11 (6.43%) | JNJ-78436735: 14 (8.19%) | ||||||||||||
| Wang et al. [12] | China | October 2020 to March 2021 | 381 | Median (IQR): 39.0 (33.0–48.0) | 179 (47.0%) | NAFLD: 381 (100%) | NA | BBIBPCorV: 381 (100%) | Neutralising Ab | 14 days | CLIA | NA | |
| Xiang et al. [25] | China | March to September 2021 | 149 | Median (IQR): 41.0 (33.0–49.0) | 108 (72.5%) | HBV: 284 (100%) | NA | CoronaVac: NA | Antispike RBD Ab, neutralising Ab | Median (IQR): 33 days (24–48) | CLIA | Anti-spike RBD Ab: 1 AU/mL | |
| BBIBP-CorV: NA | |||||||||||||
| WIBP-CorV: NA | Neutralising Ab: 0.05 AU/mL | ||||||||||||
| Liver transplant | |||||||||||||
| Rashidi-Alavijeh et al. [44] | Germany | February to March 2021 | 43 | Median (IQR): 47.0 (36.0–54.0) | 26 (60.5%) | HCC: 10 (23.3%); PSC: 7 (16.3%); AC: 6 (14.0%); HCV: 3 (6.98%); ALF: 3 (6.98%); WD: 3 (6.98%); CC: 2 (4.65%); AAD: 2 (4.65%); others: 7 (16.3%) | TAC+EVE: 22 (51.2%) | BNT162b2: 43 (100%) | Antispike Ab | 15 days (IQR: 12–24) | CLIA | ≥13.0 AU/mL | |
| TAC+MMF: 11 (25.6%) | |||||||||||||
| TAC: 7 (16.3%) | |||||||||||||
| CSA: 2 (4.65%) | |||||||||||||
| EVE: 1 (2.33%) | |||||||||||||
| Boyarsky et al. [45] | USA | December 2020 to March 2021 | 129 | NA | NA | NA | NA | BNT162b2: NA | Antispike Ab | Median (IQR): 29 days (28–31) | ECLIA | ≥0.8 U/mL | |
| mRNA-1273: NA | |||||||||||||
| Cholankeril et al. [16] | USA | January to February 2021 | 69 | Median (IQR): 63.0 (51–68) | 48 (69.6%) | ALD: 24 (34.8%); NAFLD: 13 (18.8%); HCC: 21 (30.4%) | TAC: 64 (92.8%) | BNT162b2: 69 (100%) | Antispike Ab | 30–75 days | ELISA | Titer ≥1 | |
| MMF: 23 (33.3%) | |||||||||||||
| S: 22 (31.9%) | |||||||||||||
| Davidov et al. [46] | Israel | January to May 2021 | 76 | Mean±SD: 59.0±15 | 43 (56.6%) | HBV: 7 (9.30%); HCV: 19 (25.3%); NAFLD: 13 (17.3%); PSC: 11 (14.7%); PBC: 3 (4.00%); others: 23 (30.3%) | CNI (TAC/CSA): 40 (52.6%) | BNT162b2: 76 (100%) | Antispike RBD Ab | Mean±SD: 38±24 days | ELISA | Titer ≥1.1 | |
| CNI+MMF: 12 (15.8%) | |||||||||||||
| CNI+EVE: 10 (13.2%) | |||||||||||||
| CNI+S: 9 (11.8%) | |||||||||||||
| CNI+MMF+S: 4 (5.26%) | |||||||||||||
| SRL: 1 (1.32%) | |||||||||||||
| Erol et al. [47] | Turkey | April to June 2021 | 10 | NA | NA | NA | NA | BNT162b2: 4 (40.0%) | Antispike Ab | 28–42 days | CLIA | ≥50 AU/mL | |
| CoronaVac: 6 (60.0%) | |||||||||||||
| Fernández-Ruiz et al. [37] | Spain | April to June 2021 | 13 | NA | NA | NA | NA | mRNA-1273: 13 (100%) | Antispike Ab | 14 days | ELISA | OD ≥1.1 | |
| Guarino et al. [48] | Italy | May to August 2021 | 444 | Median (IQR): seronegative, 65.6 (59.4-71.0); seropositive, 65.2 (56.9-70.1) | 332 (74.8%) | VH: 342 (77.0%); ALD: 34 (7.66%); NAFLD: 8 (1.80%); AIH: 18 (4.05%); others: 43 (9.68%) | TAC/CSA: 357 (80.4%) | BNT162b2: 444 (100%) | Antispike Ab | Median (IQR): 1st collection, 28 days (28–31); 2nd collection, 88 days (86–91) | CLIA | >25 AU/mL | |
| MMF: 151 (34.0%) | |||||||||||||
| EVE/SRL: 118 (26.6%) | |||||||||||||
| Hall et al. [35] | Canada | March to April 2021 | 11 | NA | NA | NA | NA | mRNA-1273: 11 (100%) | Antispike RBD Ab, neutralising Ab | 28–42 days | ECLIA | Anti-spike RBD Ab: ≥0.8 U/mL | |
| ELISA | Neutralising Ab: >30% inhibitory concentration | ||||||||||||
| Herrera et al. [36] | Spain | NA | 58 | Median (range): 61.5 (18.0–88.0) | 40 (69.0%) | NA | CNI: 53 (91.4%) | mRNA-1273: 58 (100%) | Antispike RBD Ab | ≥28 days | CLIA | NA | |
| MMF: 15 (25.9%) | |||||||||||||
| S: 13 (22.4%) | |||||||||||||
| mTORI: 13 (22.4%) | |||||||||||||
| Holden et al. [17] | Denmark | From January 2021 | 13 | NA | NA | NA | NA | BNT162b2: NA | Antispike Ab | Median (IQR): 5.6 weeks (5.1–6.3) | ELISA | Titer ≥1.1 | |
| Huang et al. [18] | USA | January to April 2021 | 87 | NA | NA | NA | NA | BNT162b2: NA | Antispike Ab | ≥14 days | ELISA | Titer >1:50 | |
| mRNA-1273: NA | |||||||||||||
| Marion et al. [19] | France | January to April 2021 | 58 | NA | NA | NA | NA | BNT162b2: NA | Antispike Ab | 28 days | ELISA | NA | |
| mRNA-1273: NA | |||||||||||||
| Mazzola et al. [49] | France | January to April 2021 | 58 | Median (IQR): 64.0 (58.0–68.2) | 43 (74.1%) | NA | S: 15 (25.9%) | BNT162b2: 58 (100%) | Antispike Ab | 28 days | CLIA | ≥50 AU/mL | |
| CNI: 45 (77.6%) | |||||||||||||
| MMF: 33 (56.9%) | |||||||||||||
| mTORI: 13 (22.4%) | |||||||||||||
| Mulder et al. [50] | Netherlands | March to July 2021 | 476 | Median (IQR): BNT162b2, 71.0 (59.0–79.0); mRNA-1273, 59.0 (49.0–66.0); AZD1222, 63.0 (60.0–64.0) | 286 (60.1%) | PSC: 101 (21.2%); HCC: 103 (21.6%); ALF: 46 (9.66%); PBC/SSC/CBD: 37 (7.77%); NAFLD/ALD: 42 (8.82%); CC: 22 (4.62%); VH: 24 (5.04%); DC: 20 (4.20%); others: 50 (10.5%); retransplant: 31 (6.51%) | TAC: 243 (51.1%) | BNT162b2: 25 (5.25%) | Antispike Ab | Median (IQR): BNT162b2, 31 (29.0–40.0); mRNA-1273, 43.0 (33.0–56.3); AZD1222, 31.0 (26.0–38.0) | CLIA | NA | |
| MMF: 27 (5.67%) | |||||||||||||
| CSA: 5 (1.05%) | mRNA-1273: 430 (90.3%) | ||||||||||||
| SRL: 2 (0.42%) | |||||||||||||
| EVE: 1 (0.21%) | AZD1222: 21 (4.41%) | ||||||||||||
| AZA: 1 (0.21%) | |||||||||||||
| S: 39 (8.19%) | |||||||||||||
| TAC+MMF: 113 (23.7%) | |||||||||||||
| TAC+S: 27 (5.67%) | |||||||||||||
| TAC+SRL: 16 (3.36%) | |||||||||||||
| CSA+EVE: 6 (1.26%) | |||||||||||||
| TAC+AZA: 7 (1.46%) | |||||||||||||
| TAC+EVE: 5 (1.05%) | |||||||||||||
| MMF+EVE: 3 (0.63%) | |||||||||||||
| MMF+SRL: 2 (0.42%) | |||||||||||||
| AZA+S: 1 (0.21%) | |||||||||||||
| CSA+AZA: 1 (0.21%) | |||||||||||||
| MMF+S: 1 (0.21%) | |||||||||||||
| TAC+MMF+S: 8 (1.68%) | |||||||||||||
| TAC+SRL+S: 1 (0.21%) | |||||||||||||
| Nazaruk et al. [51] | Poland | January to June 2021 | 55 | Mean±SD: 58.4±13.3 | 44 (80.0%) | NA | S: 20 (36.4%) | BNT162b2: 55 (100%) | Antispike Ab | 28–56 days | CLIA | >50 AU/mL | |
| MMF: 16 (29.1%) | |||||||||||||
| AZA: 5 (9.10%) | |||||||||||||
| CSA: 11 (20.0%) | |||||||||||||
| TAC: 43 (78.2%) | |||||||||||||
| SRL: 2 (3.60%) | |||||||||||||
| EVR: 2 (3.60%) | |||||||||||||
| CNI/MMF: 24 (43.6%) | |||||||||||||
| CNI+S/MMF/AZA/mTORI: 18 (32.7%) | |||||||||||||
| CNI/mTORI+S+MMF/AZA: 13 (23.6%) | |||||||||||||
| Rabinowich et al. [20] | Israel | From December 2020 | 80 | Mean±SD: 60.1±13.3 | 56 (70.0%) | HBV: 13 (16.3%); HCV: 26 (32.5%); NAFLD: 16 (20.0%); ALD: 3 (3.75%); AIH: 6 (7.50%); PBC: 3 (3.75%); PSC: 7 (8.75%); ALF: 2 (2.50%); CC: 3 (3.75%); WD: 1 (1.25%); SSC: 1 (1.25%); CHF: 1 (1.25%); HCC: 26 (32.5%)* | S: 24 (30.0%) | BNT162b2: 80 (100%) | Antispike Ab | 10–20 days | CLIA | ≥15 AU/mL | |
| TAC: 65 (81.3%) | |||||||||||||
| CSA: 10 (12.5%) | |||||||||||||
| EVE: 18 (22.5%) | |||||||||||||
| AZA: 4 (5.00%) | |||||||||||||
| MMF: 40 (50.0%) | |||||||||||||
| Ruether et al. [15] | Germany | NA | 138 | Mean±SD: 55.0±13.2 | 79 (57.2%) | ALD: 28 (20.3%); VH: 17 (12.3%); AIH: 40 (29.0%); NAFLD: 7 (5.10%); PLD: 5 (3.60%); CC: 13 (9.4%); ALF: 5 (3.60%); others: 23 (16.7%); HCC: 25 (18.1%)* | S: 43 (31.2%) | mRNA/mRNA: 121 (87.7%) | Antispike RBD Ab, antispike trimer Ab | Median (IQR): 29 days (25–39) | CLIA | Anti-spike RBD Ab: >100 U/mL | |
| TAC: 95 (68.8%) | ECLIA | ||||||||||||
| CSA: 33 (23.9%) | BNT162b2: 110 (79.7%) | Anti-spike trimer Ab: >100 BAU/mL | |||||||||||
| CNI: 33 (23.9%) | |||||||||||||
| CNI+S: 19 (13.8%) | mRNA-1273: 11 (7.97%) | ||||||||||||
| CNI+mTORI: 17 (12.3%) | |||||||||||||
| CNI+MMF: 48 (34.8%) | AZD1222/AZD1222: 6 (4.35%) | ||||||||||||
| CNI+AZA: 9 (6.50%) | |||||||||||||
| Biologics: 8 (5.8%) | AZD1222/mRNA: 11 (7.97%) | ||||||||||||
| Strauss et al. [52] | USA | January to April 2021 | 161 | Median (IQR): 64.0 (48.0–69.0) | 69 (42.9%) | NA | TAC: 81 (50.3%) | BNT162b2: 85 (52.8%) | Antispike Ab, antispike RBD Ab | Median (IQR): 30 days (28–31) | ECLIA | >250 U/mL | |
| MMF: 35 (21.7%) | |||||||||||||
| S: 22 (13.7%) | mRNA-1273: 76 (47.2%) | ||||||||||||
| SRL: 11 (6.83%) | |||||||||||||
| CSA: 8 (4.97%) | |||||||||||||
| AZA: 6 (3.73%) | |||||||||||||
| ERL: 3 (1.86%) | |||||||||||||
| Thuluvath et al. [21] | USA | NA | 62 | Mean±SD: 65.7±8.7 | 41 (66.1%) | AIH/PBC/PSC: 8 (12.9%); ALD: 13 (21.0%); HBV/HCV: 26 (41.9%); NAFLD: 15 (24.2%); others: 16 (25.8%) | AZA: 2 (3.23%) | BNT162b2: 24 (38.7%) | Antispike Ab | Mean±SD: 38.9±19.6 days | ECLIA | >250 U/mL | |
| S: 8 (12.9%) | |||||||||||||
| TAC: 41 (66.1%) | mRNA-1273: 33 (53.2%) | ||||||||||||
| Others: 29 (46.8%) | JNJ-78436735: 5 (8.06%) | ||||||||||||
| Timmermann et al. [53] | Germany | May to July 2021 | 118 | Mean (range): 66.1 (28.0–89.0) | 75 (63.6%) | ALD: 25 (21.1%); VH: 28 (23.7%); LT: 26 (22.0%); AIH: 18 (15.3%); CC: 4 (3.4%); other: 17 (14.4%) | TAC: 42 (35.6%) | BNT162b2: 114 (96.6%) | Antispike Ab | Mean (range): 44.6 days (21–132) | ELISA | NA | |
| MMF: 16 (13.6%) | |||||||||||||
| TAC+MMF: 24 (20.3%) | mRNA-1273: 3 (2.54%) | ||||||||||||
| TAC+EVE: 15 (12.7%) | |||||||||||||
| EVR: 1 (0.85%) | JNJ-78436735: 1 (0.85%) | ||||||||||||
| CSA+MMF: 3 (2.54%) | |||||||||||||
| CSA: 2 (1.69%) | |||||||||||||
| TAC+AZA: 1 (0.85%) | |||||||||||||
IQR, interquartile range; HBV, hepatitis B virus; HCV, hepatitis C virus; NAFLD, non-alcoholic fatty liver disease; ALD, alcoholic liver disease; AIH, autoimmune hepatitis; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; NA, not available; Ab, anti-body; CLIA, chemiluminescence immunoassays; HSC, hepatic sarcoidosis; BCS, Budd-Chiari syndrome; DILI, drug induced liver injury; MTX, methotrexate; AZA, azathioprine; RTX, rituximab; MMF, mycophenolate mofetil; TNFI, tumour necrosis factor inhibitor; S, steroid; OD, optical density; RBD, receptor binding domain; ELISA, enzyme-linked immunosorbent assay; SD, standard deviation; VH, viral hepatitis; CC, cryptogenic cirrhosis; ALF, acute liver failure; HCC, hepatocellular carcinoma; ECLIA, electrochemiluminescence immunoassay analyzer; TAC, tacrolimus; AC, alcoholic cirrhosis; WD, Wilson’s disease; AAD, α-1 antitrypsin deficiency; EVE, everolimus; CSA, cyclosporin A; CNI, calcineurin inhibitors; SRL, sirolimus; mTORI, mTOR inhibitors; SSC, secondary sclerosing cholangitis; CBD, congenital biliary disease; DC, dysmetabolic cirrhosis; CHF, congenital hepatic fibrosis; PLD, pediatric liver disease; LT, liver tumour.
*
Concomitant condition.