Systematic Reviews
Copyright ©The Author(s) 2023.
World J Gastroenterol. Jan 7, 2023; 29(1): 200-220
Published online Jan 7, 2023. doi: 10.3748/wjg.v29.i1.200
Table 1 Literature review results
Ref.
Country
Cases (n)
Age (mean, range)
Sex
Type of autopsy
Pre-existing liver disease or other diseases
Laboratory findings
Macroscopic results
Microscopic results
Additional stainings
Cause of death
Medications
Hospitalization
Virus identification in liver
Aguiar et al[13], 2020Switzerland131FCompleteObesityNRNutmeg appearanceMicroabscessesNoneRespiratory failure in COVID-19NoneHome deathNo search
Arslan et al[14], 2021 Turkey756, 43-68M 6, F 1Partial3 obesity, 2 hypertension, 1 in hemodialysisNRNR4 mild steatosis, 1 biliary microhamartomaNoneRespiratory failure in COVID-19NR5 hospitalized, 2 NRNo search
Barton et al[15], 2020 United States259, 42-77M 2Complete2 obesity, 1 hypertension and 1 myotonic muscular dystrophyNRCase 1: weight: 2232 g, steatosis. Case 2: weight: 1683 g, cirrhosisNrNone1 respiratory failure in COVID-19, 1 complications of hepatic cirrhosis NR1 hospitalized and 1 home deathNo search
Beigmohammadi et al[16], 2021 Iran768, 46-84 M 5, F 2Core-biopsy4 hypertension, 1 immunocompromised and 1 valvular hearth diseaseNRNR7 congestion, 7 steatosis, 7 portal inflammation, 7 hepatitis, 4 ballooning degeneration of hepatocytes, 2 bile plugs, 7 focal confluent necrosis, 4 focal hepatocyte drop outMasson’s trichrome: 1 case of mild fibrosisNR7 were treated with hydroxycholorquine and 6 with antiviralsAll hospitalizedNo search
Bradley et al[17], 2020 United States1474, 42-84M 6, F 87 partial and 7 complete5 obesity, 8 hypertension, 4 heart failure, 8 CKD NRCongestion10 congestion, 9 steatosis, 1 toxic or metabolic disease, 4 centrilobular necrosis, 3 periportal inflammationNone12 respiratory failure in COVID-19, 2 cardiovascular failure NRAll hospitalized 2 positive and 1 negative PCR-test, 11 not tested. 14 negative IHC and TEM
Bryce et al[18], 2020 United States92NRNRComplete28 fatty liver diseaseNRNR8 cirrhosis, 57 early organizing thrombi in portal venules and terminal hepatic venules, 41 congestion with some cases showing hemophagocytosisNoneNRNRNRNo search
Bösmüller et al[19], 2020 Germany472, 59-79M 3, F 1Complete-no brain2 HIV, 2 hypertension3 NR 1 with normal values1 hepatosplenomegaly and 1 yellowish surfaceCase 1: congestion and activation of Kupffer cells. Case 2: macrophages activation with signs hemophagocytosisNone1 respiratory failure in COVID-19, 3 MOF1 had a MOF and was intubated, 1 was treated with meropenem, 1 was treated with ECMO3 hospitalized and 1 home deathNegative PCR-test
Bugra et al[20], 2021 Turkey10055, 7-98M 80, F 20PartialNRNRNR84 inflammation, 54 steatosis, 19 glycogenisation, 9 centilobulary necrosis, 18 autolysis, 45 congestion, 7 endotheliitis, 1 cirrhosis, 2 fibrin thrombosis, 2 bridging necrosis, 1 granulomatous inflammation, 23 cholestasisCD3+ in portal space74 respiratory failure in COVID-19 and 26 NRNR25 hospitalized, 55 home dead, 6 falling from height, 5 car accidents and 9 NR No search
Chornenkyy et al[21], 2021 United States858, 18-81M 3, F 5 Complete2 chronic liver disease (1 HCV and 1 autoimmune hepatitis), 6 obesity, 4 hypertensionPeak AST: 146 (20-1470) and ALT: 214 (10-9961)Yellowish surface and congestion3 periportal fibrosis, 2 necrosis, 5 inflammation, 7 portal inflammation, 6 congestion, 4 steatosis, 6 acute hepatitisNRNRNRAll hospitalized4 positive and 4 negative PCR-test
Danics et al[22], 2021 Hungary10075, 40-102M 50, F 50Complete36 obesity, 6 liver diseases, 85 hypertension41 elevated AST values and 27 elevated ALT valuesAverage weight 1544 g (range 520-3046 g)63 steatosis, 43 portal fibrosis, 4 cirrhosis, 11 centrolobular necrosis, 87 congestion, 52 hepatocellular cholestasisNoneNRNRAll hospitalizedNo search
Del Nonno et al[23], 2021Italy369, 63-76 M 2, F 1CompleteNRAdmission AST: 63 (31-128) and ALT: 41 (19-84) NRAll cases showed steatosis, portal inflammation, portal fibrosis, focal lobular inflammation, zonal necrosis and congestionIHC: CD8+ in portal inflammation, CD34 positive staining in the portal tract vasculature and sinusoids, Perl's staining for iron demonstrated iron deposits into hepatocytesAll respiratory failure in COVID-191 NR, one with immunosuppressor (tocilizumab) and one with antibiotics + morphine. All had O2 therapy (1 CPAP and 2 venturi mask)All hospitalizedNegative PCR-test and IHC detection (nucleocapsid and nucleoprotein)
Edler et al[24], 2020 Germany8079, 52-96M 46, F 34Complete6 obesity, 4 cirrhosisNRNRCongestionNone76 respiratory failure in COVID-19, 1 pericardial tamponade, 1 sepsis and 2 cardiovascular failure17 with NIV51 hospitalized, 13 in nursing care homes, 12 home deaths, 1 in a hotel and 3 NR No search
Elsoukkary et al[25], 2020 United States3268, 30-100M 22, F 10Partial17 hypertension, 12 obesityAST: 567 (18-6000) and ALT: 387 (12-4885)NR9 steatosis, 6 portal inflammation, 3 bridging fibrosis and/or cirrhosisNoneNR19 hydroxychloroquine and antibiotics, 9 only antibioticsAll hospitalizedNo search
Evert et al[26], 2021 Germany862, 44-73M 4, F 4Complete7 obesity, 1 liver cirrhosis, 5 hypertensionNRNR7 cholestasis, 7 single-cell necrosis, 5 fatty degeneration with 2 showing marked steatosis, 2 mild fibrosis, 1 cirrhosisNone8 MOFAll did NIV, dialysis and antibiotics. 5 had ECMOAll hospitalized3 positive PCR-test
Falasca et al[27], 2020 Italy2268, 27-92M 15, F 7Complete1 obesity NRCongestion11 inflammation, 10 congestion, 12 steatosisNoneAll respiratory failure in COVID-19NRAll hospitalizedNo search
Fassan et al[28], 2020 Italy2682, 61-97M 14, F 11Complete5 obesity, 1 HCV-related cirrhosisNRNR1 cirrhosis, 22 congestion, 5 centrilobular parenchymal atrophy, 2 fibrosis, 5 sinusoidal diffuse microthrombi, 3 portal vein thrombosis, 2 centroacinar necrosis, 26 activation of Kupffer cells, 1 portal inflammation, 9 steatosisNoneNRNRNRNegative ISH
Greuel et al[29], 2021 Germany635, 26-46M 3 F 3Complete1 obesity, 2 right cardiac insufficiency, 1 Ewing sarcoma4 elevated AST and ALT valuesNR1 severe cholestasis, 1 focal ischemic damage 2 steatosisNone3 MOF, 1 acute mesenteric ischemia, 1 cardiovascular failure, 1 hemorrhagic shock 5 had ECMO and NIVAll hospitalizedNegative PCR-test
Grosse et al[30], 2020 Austria1482, 55-94M 9, F 5Complete1 liver cirrhosis, 8 hypertensionAdmission AST: 49 (12-98) and ALT: 25 (7-87) NR13 steatosis, 14 congestion, 12 portal lymphoid infiltration, 4 portal fibrosisNone2 bronchopneumonia, 12 NR12 had antibioticsAll hospitalizedNo search
Hanley et al[31], 2020 United Kingdom1073, 52-79M 7, F 3Complete5 obesity, 4 hypertensionNRAverage weight 1432 g (range 1012-2466) and 3 hepatomegaly 7 steatosis, 3 cirrhosis or bridging fibrosisNoneNR4 NIVAll hospitalized3 positive PCR-test (e gene)
Hirayama et al[32], 2021United Kingdom1971, 42-94M 11, F 8Complete5 obesity, 8 hypertension NRNR12 steatosis, 5 congestion, 4 cirrhosis, 3 portal inflammationNoneNRNRAll hospitalizedNo search
Hooper et al[33], 2021 United States-Brazil13561M 80, F 5536 core-biopsy and 99 partial 34 obesity, 5 liver disease, 86 hypertension NRNR41 necrosis, 37 steatosis, 19 inflammation, 7 fibrosis, 6 congestion, 5 cirrhosis, 3 cholestasisNone101 respiratory failure in COVID-19, 6 cardiovascular failure, 28 NR NRAll hospitalizedNo search
Ihlow et al[34], 2021 Germany188FCompleteNonePeak AST: 1690 and ALT: 1632 Subtotal liver dystrophyNecrosis, cirrhosis, portal inflammation IHC for ACE2, TMPESS2 and cathepsin L: strong membranous signals in intrahepatic bile duct epitheliumAcute liver failureAntibioticsHospitalizedISH positive in the bile duct epithelium and positive PCR-test
Lacy et al[35], 2020 United States158FCompleteObesityNRWeight 1990 gSteatosis and congestionNoneRespiratory failure in COVID-19NRHome deathNo search
Lagana et al[36], 2020 United States4070, 66-80M 28, F 12NR2 chronic liver disease, 1 alcohol-related cirrhosis, 1 liver transplant with acute rejection and 1 with anti-HBV core antibody positivityn = 33 Admission AST: 63 (43-92) and ALT: 32 (19 - 55). Peak AST: 102 (54-294) and ALT: 68 (32-258)2 fibrosis and 1 had abscesses, 37 with steatosis and congestion20 lobular necroinflammation, 20 portal inflammation, 10 lobular apoptosis, 30 steatosis, 32 congestion, 16 centrilobular necrosis, 15 cholestasisNoneNR22 steroids, 19 hydroxychloroquine, and 6 received tocilizumabAll hospitalized11 positive and 9 negative PCR-test
Lax et al[37], 2020 Austria1182, 75-91M 8, F 3Partial 2 obesity, 9 hypertension, 1 Hodgkin lymphoma and 1 bladder carcinomaAST: 66 (17-189) and ALT: 41 (19-98)NR11 steatosis, 8 congestion, 7 necrosis, 10 Kupffer cell proliferation, 6 portal fibrosis, 8 inflammation, 8 ductular proliferationNonePulmonary arterial thrombosis2 NIV, 9 AIRVO and 9 had antibioticsAll hospitalizedNo search
Malik et al[38], 2021 India131FCompleteNoneNRCongestionCongestion, mild chronic inflammatory infiltrate in some portal tract, and occasional lymphocytic aggregate adjacent to central veinNoneRespiratory failure in COVID-19NoneHospitalizedPositive PCR-test
Menter et al[39], 2020 Switzerland2176, 53-96M 17, F 417 complete and 4 partial2 chronic liver disease, 21 hypertension, 6 obesityn = 10 AST: 67.2 (22-214)NR7 steatosis, 5 necrosis, 3 ASH/NASH NoneRespiratory failure in COVID-19NRAll hospitalizedNo search
Nunes et al[40], 2021 South Africa7560, 49-68M 29, F 46Core- biopsy41 hypertension, 20 HIVNRNR33 portal inflammation, 24 steatosis, 40 sinusoidal inflammation, 10 lobular hepatitis, 9 Kupffer cell activation, 11 spotty necrosis, 4 confluent necrosis, 6 fibrosis, 26 congestion, 7 fibrin-platelet thrombiNoneNRNRAll hospitalizedNo search
Oprinca[41], 2020 Romania359, 27-79M 31 complete and 2 partial1 choledochal preampular intraluminal obstructionNRCase 1: choledochal preampullary intraluminal obstruction, case 2: normal, case 3: hepatomegaly and cirrhosisCase 1: congestion, steatosis, periportal fibrosis and portal inflammation, case 2: nothing, case 3: bridging fibrosis and portal inflammationNone2 respiratory failure in COVID-19, 1 shock hemorrhagicCase 1: antibiotics, corticosteroids and assisted oxygenation. Case 2: none (home death). Case 3: none2 hospitalized, 1 NRNo search
Rapkiewicz et al[42], 2020 United States7NR, 44-65M 3, F 4Complete5 obesity and 7 hypertensionNRNR6 steatosis, 1 cirrhosis, 6 platelet-fibrin microthrombi in sinusoids, 2 necrosis NoneCardiovascular failure 5 azithromycina and hydroxychloroquine and O2 NIV5 hospitalized, 2 home deathsNo search
Remmelink et al[43], 2020 Belgium1772, 62-77M 12, F 5Complete2 cirrhosis, 1 liver transplant, 10 hypertension NR5 hepatomegaly7 congestion, 1 steato-necrosis, 10 steatosis, 1 cholestasis, 3 chronic hepatitis, 2 cirrhosis, 1 centro-obular necrosis None9 respiratory failure in COVID-19, 7 MOF and 1 NR11 had mechanical ventilationAll hospitalized14 positive and 3 negative PCR-test
Ren et al[44], 2021 China153FCompleteNoneAdmission AST: 27 and ALT: 24. Peak AST: 83 and ALT: 93NormalNothing remarkableNoneRespiratory failure with bacterial infectionShe treated herself at home with Chinese herb medicine. In hospital intensive oxygen and supportive measurements, extensive antibiotics and antiviralHospitalizedPositive PCR-test
Schmit et al[45], 2020 Belgium1463, 50-83M 10, F 4Complete1 HIV, 1 non-alcoholic steatohepatitis, 1 HCV-hepatitis, 6 obesityAdmission AST: 54 (15-188) and ALT: 30 (7-62). Peak AST: 2610 (15-24176) and ALT: 854 (10-7245)Average weight 1988 g (range 1280-3220 g). 8 cases yellowish appearance 6 nutmeg appearance, 2 indurated consistency, 1 hepatocellular carcinoma, 1 normal11 centrilobular necrosis, 9 steatosis, 8 lobular inflammation, 12 portal inflammation, 4 fibrosis, 5 bile duct proliferation, 5 cholestasis, 5 iron overloadNone13 NR and 1 acute mesenteric ischemia8 hydroxychloroquine and antibiotics, 4 with antibiotics, 2 with hydroxychloroquineAll hospitalizedNo search
Schweitzer et al[46], 2020 Switzerland150MCompleteHIVNRReduced consistencySteatosis and liver dystrophy NoneRespiratory failure in COVID-19NoneHome deathNo search
Shishido-Hara et al[47], 2021 Japan175MCompleteNoneNRNormalPortal inflammationNoneSevere hemorrhageAnti-viral therapy, antibiotics, O2 therapyHospitalizedNo search
Sonzogni et al[48], 2020 Italy4871, 32-86M 22, F 830 partial and 18 complete - no brain7 obesity47 elevated valuesNR24 lobular inflammation, 32 portal inflammation, 18 confluent necrosis 18, 26 steatosis, 48 vascular thrombosis (35 portal, 13 sinusoidal), 37 fibrosisNoneNRNRAll hospitalizedNo search
Suess et al[49], 2020 Switzerland159MCompleteNoneNRNRSteatosis and some single necrotic hepatocytes NoneRespiratory failure in COVID-19NRHome deathNo search
Tehrani et al[50], 2022 Iran571, 55-85M 3, F 2Partial NoneAST: 275 (106-528) and ALT: 392 (168-978)NRCongestion, hepatocytes mildly expanding and bile plugsNone4 respiratory failure in COVID-19 and 1 cardiovascular failure 1 hydroxychloroquine and antibiotics, 2 with hydroxychloroquine and anti-viral therapy, 1 only anti-viral therapy, 1 anti-viral therapy + antibioticsAll hospitalizedNo search
Tian et al[51], 2020 China473, 59-81M 3, F 1Core-biopsy1 cirrhosis and 1 hypertensionAST: 36,4 (30-48.8) and ALT: 16 (11-25.5)NRCase 1: congestion, glycogen accumulation and focal steatosis, case 2: regenerative nodules and fibrous bands, lobular inflammation and Kupffer cell activation, cases 3: Kupffer cell activation, case 4: periportal and centrilobular necrosis NoneRespiratory failure in COVID-19Antibiotics, antiviral therapy assisted oxygenationAll hospitalized1 positive and 2 negative PCR-test, 1 was not tested
Varga et al[52], 2020 Switzerland158FNRObesity and hypertensionNRNREndotheliitis and necrosisNoneMOFDialysisHospitalizedNo search
Wang et al[53], 2020 China250 and 79M 1, F 1Core-biopsyNRCase 1 peak ALT and AST of 70 U/L and 111 U/L, respectively. Case 2 peak ALT and AST of 76 and 236 U/LNRCase 1: apoptotic hepatocytes, steatosis, lobular inflammation, portal inflammation, case 2: apoptotic bodies, steatosis, portal inflammationIHC: case 1 increased CD68 + cells in hepatic sinusoids and infrequent CD4+. Case 2: many CD68+ cells in sinusoids1 respiratory failure in COVID-19 and 1 septic shockBoth had antiviral therapy and antibioticsAll hospitalized2 positive TEM (viral particles exist without membrane-bound vesicles)
Wang et al[54], 2020 China175FCore-biopsyChronic cardiac insufficiency, hypertensionElevated AST and ALT valuesNRNecrosis, activated histiocytes, occasional apoptotic hepatocytes, steatosis and cholestasisNoneMOFNRHospitalizedNegative ISH
Xu et al[55], 2020 China150MCore-biopsyNRNRNRSteatosisNoneRespiratory failure in COVID-19Antibiotics, antiviral therapy and oxygenationHospitalizedNo search
Yadav et al[56], 2022India2161, 25-84 M 15, F 6Complete6 obesity, 1 hepatitis B, 1 multiple myelomaAdmission AST: 95.4 (18.9-760.4) and ALT: 52,1 (13,2-229,2). Peak AST: 162,6 (19,8-760,4) and ALT: 75 (21.8-229.2) NR20 portal inflammation, 17 steatosis, 9 lobular inflammation, 1 fibrosis, 1 vascular thrombosis, 1 necrosisNone10 MOF, 1 multiple injuries, 6 septic shock, 3 cardiovascular failure, 1 respiratory failure in COVID-1911 treated with antibiotics, 7 antibiotics and antiviral therapy All hospitalized11 positive, 9 negative PCR-test, 1 not tested
Youd et al[57], 2020United Kingdom972, 33-88M 4, F 5Complete3 obesityNR4 congestion, 1 steatosis and 4 normalNRNoneRespiratory failure in COVID-19NR9 deaths in community settingsNo search
Zhao et al[58], 2020United States1765, 44-85M 10, F 7Complete5 hyperlipidemia, 1 cirrhosis12 elevated AST and ALT values. Peak AST: 1903 (24-13592) and ALT 1059 (13-6136) Weight 17694 g (1000-2600 g)12 platelet-fibrin microthrombi, 5 histiocyte activation, 12 steatosis, 5 lobular inflammation, 8 portal inflammation, 10 necrosisCD68 stain confirmed histiocytic hyperplasiaNRNRAll hospitalized5 positive IHC (spike protein) in the histiocytes in the portal tracts. Negative IHC in endothelial cells and hepatocytes