SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes

다국어 초록 (Multilingual Abstract)

The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.

참고문헌 (Reference)

1 Zhou YJ, "Younger patients with MAFLD are at increased risk of severe COVID-19 illness : a multicenter preliminary analysis" 73 : 719-721, 2020

2 Ju-Yeon Cho ; Young-Sun Lee ; Soon Sun Kim ; Do Seon Song ; Jeong-Hoon Lee ; Ji Hoon Kim ; Korean Association for the Study of the Liver, "Update on liver disease management during the pandemic of coronavirus disease 2019 (COVID-19): 2021 KASL guideline" 대한간학회 27 (27): 515-523, 2021

3 National Center for Immunization and Respiratory Diseases (NCIRD), "Underlying medical conditions associated with higher risk for severe COVID-19: information for healthcare professionals" NCIRD

4 Kompaniyets L, "Underlying medical conditions and severe illness among 540, 667adults hospitalized with COVID-19, March 2020-March 2021" 18 : E66-, 2021

5 Moss M, "The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults" 275 : 50-54, 1996

6 GBD 2017 Cirrhosis Collaborators, "The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the global burden of disease study 2017" 5 : 245-266, 2020

7 Simou E, "The effect of alcohol consumption on the risk of ARDS : a systematic review and meta-analysis" 154 : 58-68, 2018

8 Shankar A, "The association among smoking, heavy drinking, and chronic kidney disease" 164 : 263-271, 2006

9 Kim NJ, "The COVID-19 pandemic highlights opportunities to improve hepatocellular carcinoma screening and diagnosis in a national health system" 117 : 678-684, 2022

10 Centers for Disease Control and Prevention (CDC), "Stay up to date with your COVID-19 vaccines including boosters" CDC

11 Qi F, "Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses" 526 : 135-140, 2020

12 Edwards K, "Secondary sclerosing cholangitis in critically ill patients : a rare disease precipitated by severe SARS-CoV-2 infection" 13 : e237984-, 2020

13 Bütikofer S, "Secondary sclerosing cholangitis as cause of persistent jaundice in patients with severe COVID-19" 41 : 2404-2417, 2021

14 Chong CR, "Safety of inactivated influenza vaccine in cancer patients receiving immune checkpoint inhibitors" 70 : 193-199, 2020

15 Wang J, "Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis : a prospective multicenter study" 16 : 691-701, 2022

16 Wang J, "Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease(CHESS2101) : a multicenter study" 75 : 439-441, 2021

17 Moon AM, "SARS-CoV-2infections among patients with liver disease and liver transplantation who received COVID-19 vaccination" 6 : 889-897, 2022

18 Pirola CJ, "SARS-CoV-2 virus and liver expression of host receptors : putative mechanisms of liver involvement in COVID-19" 40 : 2038-2040, 2020

19 Marjot T, "SARS-CoV-2 vaccination in patients with liver disease : responding to the next big question" 6 : 156-158, 2021

20 Boettler T, "SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis" 77 : 653-659, 2022

21 Wang Y, "SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19" 73 : 807-816, 2020

22 Marjot T, "SARS-CoV-2 infection in patients with autoimmune hepatitis" 74 : 1335-1343, 2021

23 Bangash MN, "SARS-CoV-2 : is the liver merely a bystander to severe disease?" 73 : 995-996, 2020

24 Issaka RB, "Real-world data on the impact of COVID-19 on endoscopic procedural delays" 12 : e00365-, 2021

25 Wegermann K, "Racial and socioeconomic disparities in utilization of telehealth in patients with liver disease during COVID-19" 67 : 93-99, 2022

26 Hartl L, "Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease" 76 : 1563-1575, 2022

27 Pose E, "Programmed death ligand 1 is overexpressed in liver macrophages in chronic liver diseases, and its blockade improves the antibacterial activity against infections" 74 : 296-311, 2021

28 Richardson S, "Presenting characteristics, comorbidities, and outcomes among 5700patients hospitalized with COVID-19 in the New York City area" 323 : 2052-2059, 2020

29 Kim D, "Predictors of outcomes of COVID-19 in patients with chronic liver disease : US multicenter study" 19 : 1469-1479, 2021

30 Roth NC, "Post-COVID-19 cholangiopathy : a novel entity" 116 : 1077-1082, 2021

31 Serper M, "Positive early patient and clinician experience with telemedicine in an academic gastroenterology practice during the COVID-19 pandemic" 159 : 1589-1591, 2020

32 Fan AZ, "Patterns of alcohol consumption and the metabolic syndrome" 93 : 3833-3838, 2008

33 Willuweit K, "Patients with liver cirrhosis show high immunogenicity upon COVID-19 vaccination but develop premature deterioration of antibody titers" 10 : 377-, 2022

34 Wiersinga WJ, "Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019(COVID-19) : a review" 324 : 782-793, 2020

35 Nardo AD, "Pathophysiological mechanisms of liver injury in COVID-19" 41 : 20-32, 2021

36 Xu Z, "Pathological findings of COVID-19 associated with acute respiratory distress syndrome" 8 : 420-422, 2020

37 Ge J, "Outcomes of SARS-CoV-2 infection in patients with chronic liver disease and cirrhosis : a national COVID cohort collaborative study" 161 : 1487-1501, 2021

38 Marjot T, "Outcomes following SARS-CoV-2 infection in patients with chronic liver disease : an international registry study" 74 : 567-577, 2021

39 Ji D, "Non-alcoholic fatty liver diseases in patients with COVID-19 : a retrospective study" 73 : 451-453, 2020

40 Song Jeong Eun ; Kang Min Kyu ; Lee Yu Rim ; Lee Chang Hyeong ; Park Jung Gil ; Kweon Young Oh ; Tak Won Young ; Park Soo Young ; Jang Se Young ; Hwang Jae Seok ; Jang Byoung Kuk ; Jang Won Young ; Suh Jeong Ill ; 정우진 ; 김병석 ; Daegu-Gyeongbuk Liver Study Group, "Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment" 거트앤리버 소화기연관학회협의회 15 (15): 606-615, 2021

41 Butt AA, "Mortality is not increased in SARS-CoV-2 infected persons with hepatitis C virus infection" 41 : 1824-1831, 2021

42 Wanner N, "Molecular consequences of SARS-CoV-2 liver tropism" 4 : 310-319, 2022

43 Li J, "Mendelian randomization analysis reveals no causal relationship between nonalcoholic fatty liver disease and severe COVID-19" 20 : 1553-1560, 2022

44 Mao R, "Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19 : a systematic review and meta-analysis" 5 : 667-678, 2020

45 Ju-Yeon Cho ; Soon Sun Kim ; Young-Sun Lee ; 송도선 ; Jeong Hoon Lee ; Ji Hoon Kim ; Korean Association for the Study of the Liver, "Management of liver diseases during the pandemic of coronavirus disease-19" 대한간학회 26 (26): 243-250, 2020

46 Lei F, "Longitudinal association between markers of liver injury and mortality in COVID-19 in China" 72 : 389-398, 2020

47 Wang T, "Longitudinal analysis of the utility of liver biochemistry as prognostic markers in hospitalized patients with corona virus disease 2019" 5 : 1586-1604, 2021

48 Mohammed SA, "Liver injury with COVID-19 : laboratory and histopathological outcome-systematic review and meta-analysis" 12 : 9-, 2022

49 Yip TC, "Liver injury is independently associated with adverse clinical outcomes in patients with COVID-19" 70 : 733-742, 2021

50 Da BL, "Liver injury in patients hospitalized with coronavirus disease 2019 correlates with hyperinflammatory response and elevated interleukin-6" 5 : 177-188, 2020

51 Zhang Y, "Liver impairment in COVID-19 patients : a retrospective analysis of 115 cases from a single centre in Wuhan city, China" 40 : 2095-2103, 2020

52 Sonzogni A, "Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations" 40 : 2110-2116, 2020

53 Weber S, "Liver function test abnormalities at hospital admission are associated with severe course of SARS-CoV-2infection : a prospective cohort study" 70 : 1925-1932, 2021

54 Bloom PP, "Liver biochemistries in hospitalized patients with COVID-19" 73 : 890-900, 2021

55 Takeuchi O, "Innate immunity to virus infection" 227 : 75-86, 2009

56 Schütte A, "Influenza virus infection as precipitating event of acute-on-chronic liver failure" 70 : 797-799, 2019

57 Piano S, "Infections complicating cirrhosis" 38 (38): 126-133, 2018

58 Barnes E, "Infection of liver hepatocytes with SARS-CoV-2" 4 : 301-302, 2022

59 Calderwood AH, "Impact of the COVID-19 pandemic on utilization of EGD and colonoscopy in the United States : an analysis of the GIQuIC registry" 23 : 313-321, 2021

60 Kang E, "Impact of the COVID-19 pandemic on the health status and behaviors of adults in Korea : national cross-sectional web-based selfreport survey" 7 : e31635-, 2021

61 Dongsub Jeon ; Minkook Son ; Jonggi Choi, "Impact of liver cirrhosis on the clinical outcomes of patients with COVID-19: a nationwide cohort study of Korea" 대한내과학회 36 (36): 1092-1101, 2021

62 Gandhi M, "Impact of COVID-19on hepatocellular carcinoma management : a multicountry and region study" 8 : 1159-1167, 2021

63 Blach S, "Impact of COVID-19on global HCV elimination efforts" 74 : 31-36, 2021

64 Marjot T, "Humoral and cellular immune responses to SARS-CoV-2 vaccination across multiple vaccine platforms and liver disease types : an EASL registry multicentre prospective cohort study" 77 : S54-S55, 2022

65 Díaz LA, "High prevalence of hepatic steatosis and vascular thrombosis in COVID-19 : a systematic review and meta-analysis of autopsy data" 26 : 7693-7706, 2020

66 Moon AM, "High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis : preliminary results from an international registry" 73 : 705-708, 2020

67 Roca-Fernández A, "Hepatic steatosis, rather than underlying obesity, increases the risk of infection and hospitalization for COVID-19" 8 : 636637-, 2021

68 Lagana SM, "Hepatic pathology in patients dying of COVID-19 : a series of 40 cases including clinical, histologic, and virologic data" 33 : 2147-2155, 2020

69 Williamson EJ, "Factors associated with COVID-19-related death using opensafely" 584 : 430-436, 2020

70 Brevini T, "FXR inhibition reduces ACE2 expression, SARS-CoV-2 infection and may improve COVID-19 outcome"

71 Gupta A, "Extrapulmonary manifestations of COVID-19" 26 : 1017-1032, 2020

72 Moon AM, "Elevated liver enzymes in patients with COVID-19 : look, but not too hard" 66 : 1767-1769, 2021

73 John BV, "Effectiveness of COVID-19 Viral Vector Ad. 26. COV2. S vaccine and comparison with mRNA vaccines in cirrhosis" 20 : 2405-2408, 2022

74 Cornberg M, "EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients" 74 : 944-951, 2021

75 Olry A, "Drug-induced liver injury and COVID-19 infection : the rules remain the same" 43 : 615-617, 2020

76 Walle T, "Cytokine release syndromelike serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy" 3 : 1039-1051, 2022

77 Yip TC, "Current and past infections of HBV do not increase mortality in patients with COVID-19" 74 : 1750-1765, 2021

78 Fu Y, "Clinical features of patients infected with coronavirus disease 2019 with elevated liver biochemistries : a multicenter, retrospective study" 73 : 1509-1520, 2021

79 Huang C, "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China" 395 : 497-506, 2020

80 Zhou F, "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China : a retrospective cohort study" 395 : 1054-1062, 2020

81 Wang D, "Clinical characteristics of 138hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China" 323 : 1061-1069, 2020

82 Ioannou GN, "Cirrhosis and severe acute respiratory syndrome coronavirus 2 infection in US veterans : risk of infection, hospitalization, ventilation, and mortality" 74 : 322-335, 2021

83 Moss M, "Chronic alcohol abuse is associated with an increased incidence of acute respiratory distress syndrome and severity of multiple organ dysfunction in patients with septic shock" 31 : 869-877, 2003

84 Laurent L, "Cholangiopathy in critically ill patients surviving beyond the intensive care period : a multicentre survey in liver units" 46 : 1070-1076, 2017

85 Faruqui S, "Cholangiopathy after severe COVID-19 : clinical features and prognostic implications" 116 : 1414-1425, 2021

86 Mahmud N, "Changes in hepatocellular carcinoma surveillance and risk factors for noncompletion in the Veterans Health Administration cohort during the coronavirus disease 2019pandemic" 160 : 2162-2164, 2021

87 Yoo HW, "COVID-19 morbidity and severity in patients with nonalcoholic fatty liver disease in South Korea : a nationwide cohort study" 20 : e1217-e1218, 2022

88 Kim HS, "COVID-19 case surge and telemedicine utilization in a tertiary hospital in Korea" 28 : 666-674, 2022

89 Jothimani D, "COVID-19 and the liver" 73 : 1231-1240, 2020

90 Marjot T, "COVID-19 and liver disease : mechanistic and clinical perspectives" 18 : 348-364, 2021

91 Cai Q, "COVID-19 : abnormal liver function tests" 73 : 566-574, 2020

92 Asrani SK, "Burden of liver diseases in the world" 70 : 151-171, 2019

93 Rüther DF, "Autoimmune hepatitis and COVID-19 : no increased risk for AIH after vaccination but reduced care" 77 : 250-251, 2022

94 Lopez-Mendez I, "Association of liver steatosis and fibrosis with clinical outcomes in patients with SARS-CoV-2 infection(COVID-19)" 20 : 100271-, 2021

95 John BV, "Association of BNT162b2 mRNA and mRNA-1273 vaccines with COVID-19 infection and hospitalization among patients with cirrhosis" 181 : 1306-1314, 2021

96 Muñoz-Martínez S, "Assessing the impact of COVID-19 on liver cancer management(CERO-19)" 3 : 100260-, 2021

97 Liu D, "Assessing causal relationships between COVID-19 and non-alcoholic fatty liver disease" 76 : 740-742, 2022

98 Fix OK, "American Association for the Study of Liver Diseases expert panel consensus statement : vaccines to prevent coronavirus disease 2019 infection in patients with liver disease" 74 : 1049-1064, 2021

99 Deutsch-Link S, "Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic" 20 : 2142-2144, 2022

100 Moon AM, "Alcohol-associated liver disease before and after COVID-19 : an overview and call for ongoing investigation" 5 : 1616-1621, 2021

101 Szabo G, "Alcohol's effect on host defense" 37 : 159-170, 2015

102 Boé DM, "Alcohol abuse and pulmonary disease" 86 : 1097-1104, 2009

103 Hundt MA, "Abnormal liver tests in COVID-19 : a retrospective observational cohort study of 1, 827 patients in a major U. S. hospital network" 72 : 1169-1176, 2020

104 Balderramo D, "Abnormal liver tests during hospitalization predict mortality in patients with COVID-19 : a multicenter study from South America" 2021 : 1622533-, 2021