Positive association between severity of COVID-19 infection and liver injury: a systematic review and meta-Analysis COVID-19 Infection and Liver Injury
Gastroenterology and Hepatology from Bed to Bench,
,
20 September 2020
https://doi.org/10.22037/ghfbb.v13i4.2129
Abstract
Aim: Current study aimed to report a pooled analysis of the association of the circulating levels of liver enzymes and total bilirubin with severe and non-severe COVID-19.
Background: The ongoing novel coronavirus outbreak is an important threat to health worldwide. Epidemiological data representing greater risk of liver failure in patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).
Methods: Electronic databases were comprehensively searched using Medline, ISI Web of Science, EMBASE and Cochrane Library up to July 2020. Outcomes from each relevant study were pooled using random-effects model. Heterogeneity was analysed by Q test and I2 statistics. Sensitivity analysis was also evaluated.
Results: A total of 24 studies were included (4,246 patients). We found a significant association of COVID-19 severity with increased levels of ALT [SMD: 1.40 U/L; 95% CI (0.93, 1.88); P<0.05, I2=96.5%, PHeterogenity= 0.000 ], AST [SMD: 2.11 U/L; 95% CI (1.40, 2.83); P<0.05, I2 = 97.9%, PHeterogenity= 0.000], LDH [SMD: 3.88 U/L; 95% CI (2.70, 5); P<0.05, I2 = 98.7%, PHeterogenity= 0.000] and TBil [SMD: 1.08 mmol/L ; 95% CI (0.44, 1.72); P = 0.001, I2=97.7, PHeterogenity= 0.000], whereas, ALP values [SMD: 0.31; 95% CI (-1.57, 2.20); P = 0.74] was not significant between severe and non-severe COVID-19 patients. Moreover, elevated liver enzymes were found in males [OR: 1.52, (95% CI 1.26, 1.83), P<0.05] with severe COVID-19 infection than females.
Conclusion: The alterations of liver function indexes caused by SARS-CoV-2 infection, suggested as potential prognosis biomarkers for screening of severe patients at early stages of disease.
Keywords:
- COVID-19, Coronavirus, Liver injury, Liver enzymes, Meta-analysis
References
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22. Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. The American journal of gastroenterology. 2020;115.
23. Jin X, Lian J-S, Hu J-H, Gao J, Zheng L, Zhang Y-M, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020.
24. Liu C, Jiang Z, Shao C, Zhang H, Yue H, Chen Z, et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study. Zhonghua gan zang bing za zhi= Zhonghua ganzangbing zazhi= Chinese journal of hepatology. 2020;28(2):148-52.
25. Cai Q, Huang D, Ou P, Yu H, Zhu Z, Xia Z, et al. COVID‐19 in a Designated Infectious Diseases Hospital Outside Hubei Province, China. Allergy. 2020.
26. Cao W. Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei. medRxiv. 2020.
27. Qian Z, Mei X, Zhang Y, Zou Y, Zhang Z, Zhu H, et al. Analysis of baseline liver biochemical parameters in 324 cases with novel coronavirus pneumonia in Shanghai area. Zhonghua gan Zang Bing za zhi= Zhonghua Ganzangbing Zazhi= Chinese Journal of Hepatology. 2020;28:E005-E.
28. Qian G-Q, Yang N-B, Ding F, Ma AHY, Wang Z-Y, Shen Y-F, et al. Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series. QJM: An International Journal of Medicine. 2020.
29. Xie H, Zhao J, Lian N, Lin S, Xie Q, Zhuo H. Clinical characteristics of Non‐ICU hospitalized patients with coronavirus disease 2019 and liver injury： A Retrospective study. Liver international. 2020.
30. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. Bmj. 2020;368.
31. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H. Clinical and immunologic features in severe and moderate forms of Coronavirus Disease. J Clin Invest. 2019;137244.
32. Deng Y, Liu W, Liu K, Fang Y-Y, Shang J, Wang K, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chinese medical journal. 2020.
33. Liu W, Tao Z-W, Wang L, Yuan M-L, Liu K, Zhou L, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chinese medical journal. 2020.
34. Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clinical Infectious Diseases. 2020.
35. Qu R, Ling Y, Zhang Yh, Wei Ly, Chen X, Li X, et al. Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with Corona Virus Disease‐19. Journal of medical virology. 2020.
36. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive care medicine. 2020:1-3.
37. Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al. Clinical Features and Treatment of COVID‐19 Patients in Northeast Chongqing. Journal of medical virology. 2020.
38. Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020.
39. Zhou B, She J, Wang Y, Ma X. The clinical characteristics of myocardial injury in severe and very severe patients with 2019 novel coronavirus disease. J Infect. 2020.
40. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020.
41. Wu C, Chen X, Cai Y, Zhou X, Xu S, Huang H, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA internal medicine. 2020.
42. Zhang X, Cai H, Hu J, Lian J, Gu J, Zhang S, et al. Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings. International Journal of Infectious Diseases. 2020.
43. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020;395(10229):1033-4.
44. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-13.
45. Huang Y, Zhou H, Yang R, Xu Y, Feng X, Gong P. Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. medRxiv. 2020.
46. Nasiri MJ, Haddadi S, Tahvildari A, Farsi Y, Arbabi M, Hasanzadeh S, et al. COVID-19 clinical characteristics, and sex-specific risk of mortality: Systematic Review and Meta-analysis. medRxiv. 2020.
47. Luedde T, Kaplowitz N, Schwabe RF. Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology. 2014;147(4):765-83. e4.
48. Humar A, McGilvray I, Phillips MJ, Levy GA. Severe acute respiratory syndrome and the liver. Hepatology (Baltimore, Md). 2004;39(2):291.
49. Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. International Journal of Infectious Diseases. 2014;29:301-6.
50. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020.
51. Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. MedRxiv. 2020.
52. Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. BioRxiv. 2020.
53. Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, et al. Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arteriosclerosis, thrombosis, and vascular biology. 2005;25(1):193-7.
54. Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2).
55. Yao X, Li T, He Z, Ping Y, Liu H, Yu S, et al. A pathological report of three COVID-19 cases by minimally invasive autopsies. Zhonghua bing li xue za zhi= Chinese journal of pathology. 2020;49:E009-E.
56. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clinical Infectious Diseases. 2020.
57. Li J, Fan J-G. Characteristics and mechanism of liver injury in 2019 coronavirus disease. Journal of Clinical and Translational Hepatology. 2020;8(1):13.
58. Fan Z, Chen L, Li J, Cheng X, Yang J, Tian C, et al. Clinical features of COVID-19-related liver damage. Clinical Gastroenterology and Hepatology. 2020.
59. Chang H-L, Chen K-T, Lai S-K, Kuo H-W, Su I-J, Lin RS, et al. Hematological and biochemical factors predicting SARS fatality in Taiwan. Journal of the Formosan Medical Association. 2006;105(6):439-50.
60. Al Ghamdi M, Alghamdi KM, Ghandoora Y, Alzahrani A, Salah F, Alsulami A, et al. Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC infectious diseases. 2016;16(1):174.
61. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of medicine. 2020:1-8.
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