COVID-19-associated hepatic injury

Jump to: navigation, search


WikiDoc Resources for COVID-19-associated hepatic injury

Articles

Most recent articles on COVID-19-associated hepatic injury

Most cited articles on COVID-19-associated hepatic injury

Review articles on COVID-19-associated hepatic injury

Articles on COVID-19-associated hepatic injury in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on COVID-19-associated hepatic injury

Images of COVID-19-associated hepatic injury

Photos of COVID-19-associated hepatic injury

Podcasts & MP3s on COVID-19-associated hepatic injury

Videos on COVID-19-associated hepatic injury

Evidence Based Medicine

Cochrane Collaboration on COVID-19-associated hepatic injury

Bandolier on COVID-19-associated hepatic injury

TRIP on COVID-19-associated hepatic injury

Clinical Trials

Ongoing Trials on COVID-19-associated hepatic injury at Clinical Trials.gov

Trial results on COVID-19-associated hepatic injury

Clinical Trials on COVID-19-associated hepatic injury at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on COVID-19-associated hepatic injury

NICE Guidance on COVID-19-associated hepatic injury

NHS PRODIGY Guidance

FDA on COVID-19-associated hepatic injury

CDC on COVID-19-associated hepatic injury

Books

Books on COVID-19-associated hepatic injury

News

COVID-19-associated hepatic injury in the news

Be alerted to news on COVID-19-associated hepatic injury

News trends on COVID-19-associated hepatic injury

Commentary

Blogs on COVID-19-associated hepatic injury

Definitions

Definitions of COVID-19-associated hepatic injury

Patient Resources / Community

Patient resources on COVID-19-associated hepatic injury

Discussion groups on COVID-19-associated hepatic injury

Patient Handouts on COVID-19-associated hepatic injury

Directions to Hospitals Treating COVID-19-associated hepatic injury

Risk calculators and risk factors for COVID-19-associated hepatic injury

Healthcare Provider Resources

Symptoms of COVID-19-associated hepatic injury

Causes & Risk Factors for COVID-19-associated hepatic injury

Diagnostic studies for COVID-19-associated hepatic injury

Treatment of COVID-19-associated hepatic injury

Continuing Medical Education (CME)

CME Programs on COVID-19-associated hepatic injury

International

COVID-19-associated hepatic injury en Espanol

COVID-19-associated hepatic injury en Francais

Business

COVID-19-associated hepatic injury in the Marketplace

Patents on COVID-19-associated hepatic injury

Experimental / Informatics

List of terms related to COVID-19-associated hepatic injury

Main article: COVID-19

For COVID-19 frequently asked inpatient questions, click here

For COVID-19 frequently asked outpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2] Javaria Anwer M.D.[3]

Overview

According to 12 clinical studies, 14.8%-53% of COVID-19 patients have liver impairment, evidence of a COVID-19-associated hepatic injury, which has been a common complication observed among COVID-19 patients. With the number of COVID-19 cases increasing, abnormal liver function test results have been observed in some patients with COVID-19, making this organ the second most frequently damaged, next to the respiratory system. According to one study, serum ALT and AST levels increased up to 7590 U/L and 1445 U/L, respectively, in a severe COVID-19 patient. The diagnosis of COVID-19-associated hepatic injury is based on abnormal liver biochemical and function tests such as LDH, albumin, ALT, AST, total bilirubin, and INR. The mainstay of medical therapy is to target the viral infection using antivirals such as remdesivir, lopinavir/ritonavir, and darunavir/cobicistat, control and prevent inflammation, and symptomatic treatment. For severe hepatic injury, The Chinese Pharmaceutical Association recommends the use of jaundice-reducing, hepatoprotective and anti-inflammatory agents such as phosphatidylcholine, glycyrrhizin, bicyclol, and vitamin E. Maximum of one to two hepatoprotective or anti-viral drugs should be used to minimize drug interactions and possible liver damage. At this time, the only effective measures for the primary prevention of COVID-19 related liver damage include prevention of COVID-19 infection. Drug-induced liver injury can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with antiviral drugs.

To browse the complete page of COVID-19, click here.

Historical Perspective

To browse the historical perspectives of COVID-19, click here.

Classification

There is no formal classification of liver damage associated with COVID-19 but, we attempt to divide the disease classification based on the etiology and mechanism of liver damage:[22][23][9][24][25][26][27][28]

To browse the classification of COVID-19, click here.

Pathophysiology

The exact mechanism of liver injury is still unclear. There are several proposed mechanisms in an effort to understand the pathogenesis of hepatic injury but the hepatic complications in COVID-19 patients are described as multifactorial and heterogeneous. A few of the proposed mechanisms include:

Hepatic Injury through ACE2 receptors

Antibody-mediated Hepatic Injury

Cytokine-mediated Hepatic Injury

COVID-19 medical therapy-induced Hepatic Injury

Sepsis-induced COVID-19-associated Hepatic Injury

Ischemia-reperfusion-induced Hepatic Injury

To browse the pathophysiology of COVID-19, click here.

Differentiating COVID-19-associated hepatic injury from other causes of hepatic injury

  • For further information about the differential diagnosis, click here.

To browse the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

Liver test abnormalities from various COVID-19 studies[10]
Author Group Number of patients Alanine

aminotransferase (IU)

Aspartate

aminotransferase (IU)

Prothrombin

time (s)

Bilirubin (μmol/L) Elevated lactate

dehydrogenase, creatinine kinase, or myoglobin

Mortality (%)
Guan et al (2020)[20] ICU or death 67 Not known Not known Not known Not known Yes 22% (day 51)
Huang et al (2020)[19] ICU 13 49 (29–115) 44 (32–70) 12·2 (11·2–13·4) 14·0 (11·9–32·9) Yes 38% (day 37)
Chen et al (2020)[5] Hospitalised 99 39 (22–53) 34 (26–48) 11·3 (1·9) 15·1 (7·3) Yes 11% (day 24)
Wang et al (2020)[48] ICU 36 35 (19–57) 52 (30–70) 13·2 (12·3–14·5) 11·5 (9·6–18·6) Yes 17% (day 34)
Shi et al (2020)[49] Hospitalised 81 46 (30) 41 (18) 10·7 (0·9) 11·9 (3·6) Unclear 5% (day 50)
Xu et al (2020)[50] Hospitalised 62 22 (14–34) 26 (20–32) Not known Not known Unclear 0% (day 34)
Yang et al (2020)[4] ICU 52 Not known Not known 12·9 (2·9)* 19·5 (11·6)* Not described 62% (day 28)
Extracted from all

studies above

Chronic liver

disease

42 Not known Not known Not known Not known Not known 0–2%†


In addition, abnormal liver function test in cases of COVID-19 is often transient and often simultaneously combined with increased enzymes from the cardiac muscle; these laboratory changes can return to normal without liver-related morbidity and mortality.

Gender

Although very limited data is available, the incidence of liver injury associated with COVID-19 is reported to be higher in males.[43]

To browse the epidemiology and demographics of COVID-19, click here.

Risk Factors

To browse the risk factors of COVID-19 clicking here.

Natural History, Complications and Prognosis

To browse the natural history, complications, and prognosis of COVID-19, click here.

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

  • The most common ultrasound findings associated with COVID-19-associated hepatic injury was fatty liver on the right upper quadrant abdominal ultrasound. Abnormal liver laboratory findings as indicated in Lab finding sections served as an indication to perform the abdominal ultrasound. Distended sludge-filled gallbladder suggestive of cholestasis has been reported in half of the patients studied (fig 1). Portal venous gas has also been identified in a few patients. [65]
  • However, echocardiography may be helpful in the diagnosis of cardiac complications of COVID-19 which include COVID-19-associated heart failure, or COVID-19-associated pericarditis. An abdominal ultrasound may be helpful in the case of COVID-19-associated abdominal pain.
  • The echocardiographic findings on COVID-19 can be viewed by clicking here.
    Fig 1 Upper abdominal ultrasound in an 83-year-old patient with raised enzymes on liver function tests and sepsis is suggestive of cholestasis. A distended gallbladder is marked by arrows and sludge by a (*) - [65]

CT scan

  • Portal venous gas on abdominal CT has been reported.[65]
  • Fig 2: A non-peer-reviewed retrospective cohort study mentions upper abdominal CT findings in 115 COVID-19 patients in China. The study reports homogeneous or heterogeneous hepatic hypodensity as the most common CT finding (26% patients) and pericholecystic fat stranding (21.3% cases). The study claims the correlation between CT signs and disease severity grading.[66]
  • Chest CT scan is helpful in suggesting lung involvement in patients with COVID-19 which is a multi-organ disease.
  • The CT scan findings in COVID-19 can be viewed by clicking here.
    Fig 2 Transverse upper abdomen non-contrast CT scan film showing:
    A and B: Lung consolidation with air bronchograms, ground-glass opacity, interlobular septal thickening, Crazy paving sign, and pleura effusion are visible in both lungs
    C: Liver hypodensity
    D: Pericholecystic fat stranding marked by yellow arrows - [66]

MRI

  • There is one liver MRI with gadolinium on a 3T MRI reported to have been performed in a patient with COVID-19-associated hepatic injury and abnormal liver biochemical tests.No specific findings have been reported.[65]
  • The MRI findings in COVID-19 can be viewed by clicking here.

Other Imaging Findings

  • There are no other imaging findings associated with COVID-19-associated hepatic injury.

Other Diagnostic Studies

  • There are no other diagnostic studies associated with COVID-19-associated hepatic injury.

Treatment

Medical Therapy

Currently there is no specific treatment for patients with COVID-19 associated liver injury. The mainstay of medical therapy is to target the viral infection using antivirals such as remdesivir, lopinavir/ritonavir and darunavir/cobicistat, control and prevent inflammation and symptomatic treatment. The recommended medical therapy is based upon expert opinion rather than randomized control trials and is as follows: [25][28][67][68]

Mild hepatic injury

In a COVID-19 patient with mild hepatic biochemical abnormalities, the mainstay of treatment is actively managing the primary infection. The administration of hepatoprotective and enzyme‐lowering therapy is not recommended but supportive as well as specific antiviral therapy to halt viral replication and to reduce inflammation.

Severe hepatic injury

In patients with severe COVID-19 infection and liver injury, hyperinflammatory responses such as cytokine storms and tissue ischemia are usual causal factors. Treatment should focus on maintaining optimal blood oxygen saturation. This can be achieved either by oxygen therapy or administering extracorporeal membrane oxygenation. The patient should be monitored closely with ongoing supportive and symptomatic treatment and correction of hypoproteinemia if required. The Chinese Pharmaceutical Association recommends administering jaundice-reducing, hepatoprotective and anti-inflammatory agents such as phosphatidylcholine, glycyrrhizin, bicyclol, and vitamin E. Maximum of one to two hepatoprotective or anti-viral drugs should be adminstered to minimize drug interactions and possible liver damage.[69]

Acute liver failure

In the case of acute liver failure in a COVID-19 patient, after the cause of liver failure has been established, hepatoprotective and enzyme‐lowering drugs are administered. It is important to choose lower doses and fewer types of drugs (not more than 2, in general) with known mechanism of action and composition as the hepatic drug metabolism may pose a potential risk of harming the organ. The patient should be closely monitored with frequent hepatic biochemical tests such as (AST, ALT, albumin, total bilirubin and INR). Acute liver injury should be managed with close monitoring, supportive and symptomatic treatment, and correction of hypoproteinemia.

Drug induced liver injury

It is important to assess the degree of liver damage and identify the drug responsible and then adjust the treatment accordingly. If possible completely stop the drug, reduce the amount, or administering an alternative drug. Anti‐inflammatory and hepatoprotective treatment should be provided.

Underlying chronic liver disease

Target the coronavirus infection and maintain the original therapy for chronic liver diseases.The American Association for the Study of Liver Diseases (AASLD) does not recommend to discontinue Hepatitis B and Hepatitis C antiviral treatments but recommends that large doses of hormones are not to be administered simultaneously. However, direct-acting antiviral therapy initiation for Hepatitis C patients may be delayed.

Liver transplant patients

Specific COVID-19 therapy administered in patients includes steroids (the study does not specify the type), hydroxychloroquine, antivirals (such as lopinavir/ritonavir, darunavir/cobicistat, and remdesivir). Some patients were administered antibiotics such as azithromycin and immunomodulatory therapies such as rituximab and tocilizumab. Immunosuppression has been reduced in the majority of patients and discontinued in some. It is also advised at some places to keep the immunosuppression to the minimal possible dosage.

Monitoring

  • There are no clear guidelines on the evaluation of response to COVID-19 associated hepatic injury. A review article on evidence-based management guidelines for the COVID-19 reports a raised CRP and low albumin to be associated with deterioration in patients' condition. Demonstration of viral clearance in two respiratory tract specimens (at least 24 hours apart) may also serve as a monitoring tool.[70]
  • Liver function tests can serve as indicators of disease progression. Treatment and prevention of inflammation in the early stages of the disease prevent severe disease.


To view medical treatment for COVID-19, click here.

Surgery

  • Surgical intervention is not recommended for the management of COVID-19-associated hepatic injury.

Primary Prevention

  • The disease itself is associated with COVID-19 infection so prevention of the infection is a promising primary prevention strategy at the moment.
  • There are no available vaccines against COVID-19 at the moment. There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.[71]
  • At this time, the only effective measures for the primary prevention of COVID-19 related liver damage include prevention of itself COVID-19. Drug induced liver injury can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with antiviral drugs.
  • The only prevention for COVID-19 associated hepatic injury is the prevention and early diagnosis of the coronavirus-19 infection itself. According to the CDC, the measures include:[72]
    • Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% ethyl alcohol. It is essential to be sure that the hand sanitizer is free of methanol (wood alcohol) as FDA recently warns that methanol is harmful to human skin.[73]
    • Staying at least 6 feet (approximately 2 arms’ length) from other individuals who do not live with you.
    • Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs.
    • Cleaning and disinfecting.

Secondary prevention

References

  1. Chau, Tai-Nin; Lee, Kam-Cheong; Yao, Hung; Tsang, Tak-Yin; Chow, Tat-Chong; Yeung, Yiu-Cheong; Choi, Kin-Wing; Tso, Yuk-Keung; Lau, Terence; Lai, Sik-To; Lai, Ching-Lung (2004). "SARS-associated viral hepatitis caused by a novel coronavirus: Report of three cases". Hepatology. 39 (2): 302–310. doi:10.1002/hep.20111. ISSN 0270-9139.
  2. Alsaad, Khaled O; Hajeer, Ali H; Al Balwi, Mohammed; Al Moaiqel, Mohammed; Al Oudah, Nourah; Al Ajlan, Abdulaziz; AlJohani, Sameera; Alsolamy, Sami; Gmati, Giamal E; Balkhy, Hanan; Al-Jahdali, Hamdan H; Baharoon, Salim A; Arabi, Yaseen M (2018). "Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study". Histopathology. 72 (3): 516–524. doi:10.1111/his.13379. ISSN 0309-0167.
  3. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H; et al. (2020). "First Case of 2019 Novel Coronavirus in the United States". N Engl J Med. 382 (10): 929–936. doi:10.1056/NEJMoa2001191. PMC 7092802 Check |pmc= value (help). PMID 32004427 Check |pmid= value (help).
  4. 4.0 4.1 4.2 Yang, Xiaobo; Yu, Yuan; Xu, Jiqian; Shu, Huaqing; Xia, Jia'an; Liu, Hong; Wu, Yongran; Zhang, Lu; Yu, Zhui; Fang, Minghao; Yu, Ting; Wang, Yaxin; Pan, Shangwen; Zou, Xiaojing; Yuan, Shiying; Shang, You (2020). "Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study". The Lancet Respiratory Medicine. 8 (5): 475–481. doi:10.1016/S2213-2600(20)30079-5. ISSN 2213-2600.
  5. 5.0 5.1 5.2 5.3 5.4 Chen, Nanshan; Zhou, Min; Dong, Xuan; Qu, Jieming; Gong, Fengyun; Han, Yang; Qiu, Yang; Wang, Jingli; Liu, Ying; Wei, Yuan; Xia, Jia'an; Yu, Ting; Zhang, Xinxin; Zhang, Li (2020). "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study". The Lancet. 395 (10223): 507–513. doi:10.1016/S0140-6736(20)30211-7. ISSN 0140-6736.
  6. Liu C, Jiang ZC, Shao CX, Zhang HG, Yue HM, Chen ZH; et al. (2020). "[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study]". Zhonghua Gan Zang Bing Za Zhi. 28 (2): 107–111. doi:10.3760/cma.j.issn.1007-3418.2020.02.003. PMID 32077660 Check |pmid= value (help).
  7. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J; et al. (2020). "[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]". Zhonghua Jie He He Hu Xi Za Zhi. 43 (0): E005. doi:10.3760/cma.j.issn.1001-0939.2020.0005. PMID 32026671 Check |pmid= value (help).
  8. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J; et al. (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China". JAMA. doi:10.1001/jama.2020.1585. PMC 7042881 Check |pmc= value (help). PMID 32031570 Check |pmid= value (help).
  9. 9.0 9.1 9.2 Zhang C, Shi L, Wang FS (2020). "Liver injury in COVID-19: management and challenges". Lancet Gastroenterol Hepatol. 5 (5): 428–430. doi:10.1016/S2468-1253(20)30057-1. PMC 7129165 Check |pmc= value (help). PMID 32145190 Check |pmid= value (help).
  10. 10.0 10.1 Bangash MN, Patel J, Parekh D (2020). "COVID-19 and the liver: little cause for concern". Lancet Gastroenterol Hepatol. 5 (6): 529–530. doi:10.1016/S2468-1253(20)30084-4. PMC 7270582 Check |pmc= value (help). PMID 32203680 Check |pmid= value (help).
  11. Mao R, Liang J, Shen J, Ghosh S, Zhu LR, Yang H; et al. (2020). "Implications of COVID-19 for patients with pre-existing digestive diseases". Lancet Gastroenterol Hepatol. 5 (5): 425–427. doi:10.1016/S2468-1253(20)30076-5. PMC 7103943 Check |pmc= value (help). PMID 32171057 Check |pmid= value (help).
  12. Hu LL, Wang WJ, Zhu QJ, Yang L (2020). "[Novel coronavirus pneumonia-related liver injury: etiological analysis and treatment strategy]". Zhonghua Gan Zang Bing Za Zhi. 28 (2): 97–99. doi:10.3760/cma.j.issn.1007-3418.2020.02.001. PMID 32075364 Check |pmid= value (help).
  13. Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T; et al. (2020). "Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study". Chin Med J (Engl). 133 (9): 1015–1024. doi:10.1097/CM9.0000000000000722. PMC 7147275 Check |pmc= value (help). PMID 32004165 Check |pmid= value (help).
  14. Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J; et al. (2020). "Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study". Lancet Infect Dis. 20 (4): 425–434. doi:10.1016/S1473-3099(20)30086-4. PMC 7159053 Check |pmc= value (help). PMID 32105637 Check |pmid= value (help).
  15. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL; et al. (2020). "Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series". BMJ. 368: m606. doi:10.1136/bmj.m606. PMC 7224340 Check |pmc= value (help). PMID 32075786 Check |pmid= value (help).
  16. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y; et al. (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. PMC 7159299 Check |pmc= value (help). PMID 31986264.
  17. Yao N, Wang SN, Lian JQ, Sun YT, Zhang GF, Kang WZ; et al. (2020). "[Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region]". Zhonghua Gan Zang Bing Za Zhi. 28 (3): 234–239. doi:10.3760/cma.j.cn501113-20200226-00070. PMID 32153170 Check |pmid= value (help).
  18. Guan WJ, Zhong NS (2020). "Clinical Characteristics of Covid-19 in China. Reply". N Engl J Med. 382 (19): 1861–1862. doi:10.1056/NEJMc2005203. PMID 32220206 Check |pmid= value (help).
  19. 19.0 19.1 19.2 19.3 19.4 19.5 Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
  20. 20.0 20.1 Guan, Wei-jie; Ni, Zheng-yi; Hu, Yu; Liang, Wen-hua; Ou, Chun-quan; He, Jian-xing; Liu, Lei; Shan, Hong; Lei, Chun-liang; Hui, David SC; Du, Bin; Li, Lan-juan; Zeng, Guang; Yuen, Kowk-Yung; Chen, Ru-chong; Tang, Chun-li; Wang, Tao; Chen, Ping-yan; Xiang, Jie; Li, Shi-yue; Wang, Jin-lin; Liang, Zi-jing; Peng, Yi-xiang; Wei, Li; Liu, Yong; Hu, Ya-hua; Peng, Peng; Wang, Jian-ming; Liu, Ji-yang; Chen, Zhong; Li, Gang; Zheng, Zhi-jian; Qiu, Shao-qin; Luo, Jie; Ye, Chang-jiang; Zhu, Shao-yong; Zhong, Nan-shan (2020). doi:10.1101/2020.02.06.20020974. Missing or empty |title= (help)
  21. 21.0 21.1 Cai, Qingxian; Huang, Deliang; Ou, Pengcheng; Yu, Hong; Zhu, Zhibin; Xia, Zhang; Su, Yinan; Ma, Zhenghua; Zhang, Yiming; Li, Zhiwei; He, Qing; Fu, Yang; Liu, Lei; Chen, Jun (2020). doi:10.1101/2020.02.17.20024018. Missing or empty |title= (help)
  22. Lee IC, Huo TI, Huang YH (June 2020). "Gastrointestinal and liver manifestations in patients with COVID-19". J Chin Med Assoc. 83 (6): 521–523. doi:10.1097/JCMA.0000000000000319. PMC 7176263 Check |pmc= value (help). PMID 32243269 Check |pmid= value (help).
  23. Kumar, Pramod; Sharma, Mithun; Kulkarni, Anand; Rao, Padaki N. (2020). "Pathogenesis of Liver Injury in Coronavirus Disease 2019". Journal of Clinical and Experimental Hepatology. doi:10.1016/j.jceh.2020.05.006. ISSN 0973-6883.
  24. 24.0 24.1 24.2 Li, Yueying; Xiao, Shu‐Yuan (2020). "Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications". Journal of Medical Virology. doi:10.1002/jmv.25973. ISSN 0146-6615.
  25. 25.0 25.1 25.2 25.3 25.4 Tian, Dandan; Ye, Qing (2020). "Hepatic complications of COVID‐19 and its treatment". Journal of Medical Virology. doi:10.1002/jmv.26036. ISSN 0146-6615.
  26. Shehu, Amina I.; Lu, Jie; Wang, Pengcheng; Zhu, Junjie; Wang, Yue; Yang, Da; McMahon, Deborah; Xie, Wen; Gonzalez, Frank J.; Ma, Xiaochao (2019). "Pregnane X receptor activation potentiates ritonavir hepatotoxicity". Journal of Clinical Investigation. 129 (7): 2898–2903. doi:10.1172/JCI128274. ISSN 0021-9738.
  27. 27.0 27.1 Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y, Liu Y, He Q, Chen J, Liu L, Xu L (April 2020). "COVID-19: Abnormal liver function tests". J. Hepatol. doi:10.1016/j.jhep.2020.04.006. PMC 7194951 Check |pmc= value (help). PMID 32298767 Check |pmid= value (help).
  28. 28.0 28.1 28.2 28.3 28.4 Su TH, Kao JH (June 2020). "The clinical manifestations and management of COVID-19-related liver injury". J. Formos. Med. Assoc. 119 (6): 1016–1018. doi:10.1016/j.jfma.2020.04.020. PMC 7180368 Check |pmc= value (help). PMID 32345544 Check |pmid= value (help).
  29. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X; et al. (2020). "Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission". Sci China Life Sci. 63 (3): 457–460. doi:10.1007/s11427-020-1637-5. PMC 7089049 Check |pmc= value (help). PMID 32009228 Check |pmid= value (help).
  30. Letko M, Marzi A, Munster V (2020). "Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses". Nat Microbiol. 5 (4): 562–569. doi:10.1038/s41564-020-0688-y. PMC 7095430 Check |pmc= value (help). PMID 32094589 Check |pmid= value (help).
  31. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C; et al. (2020). "Pathological findings of COVID-19 associated with acute respiratory distress syndrome". Lancet Respir Med. 8 (4): 420–422. doi:10.1016/S2213-2600(20)30076-X. PMC 7164771 Check |pmc= value (help). PMID 32085846 Check |pmid= value (help).
  32. Tian S, Xiong Y, Liu H, Niu L, Guo J, Liao M; et al. (2020). "Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies". Mod Pathol. 33 (6): 1007–1014. doi:10.1038/s41379-020-0536-x. PMC 7156231 Check |pmc= value (help). PMID 32291399 Check |pmid= value (help).
  33. Chai, Xiaoqiang; Hu, Longfei; Zhang, Yan; Han, Weiyu; Lu, Zhou; Ke, Aiwu; Zhou, Jian; Shi, Guoming; Fang, Nan; Fan, Jia; Cai, Jiabin; Fan, Jue; Lan, Fei (2020). doi:10.1101/2020.02.03.931766. Missing or empty |title= (help)
  34. Tirado, Sol M. Cancel; Yoon, Kyoung-Jin (2003). "Antibody-Dependent Enhancement of Virus Infection and Disease". Viral Immunology. 16 (1): 69–86. doi:10.1089/088282403763635465. ISSN 0882-8245.
  35. Wang, Sheng-Fan; Tseng, Sung-Pin; Yen, Chia-Hung; Yang, Jyh-Yuan; Tsao, Ching-Han; Shen, Chun-Wei; Chen, Kuan-Hsuan; Liu, Fu-Tong; Liu, Wu-Tse; Chen, Yi-Ming Arthur; Huang, Jason C. (2014). "Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins". Biochemical and Biophysical Research Communications. 451 (2): 208–214. doi:10.1016/j.bbrc.2014.07.090. ISSN 0006-291X.
  36. Wong, C. K.; Lam, C. W. K.; Wu, A. K. L.; Ip, W. K.; Lee, N. L. S.; Chan, I. H. S.; Lit, L. C. W.; Hui, D. S. C.; Chan, M. H. M.; Chung, S. S. C.; Sung, J. J. Y. (2004). "Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome". Clinical & Experimental Immunology. 136 (1): 95–103. doi:10.1111/j.1365-2249.2004.02415.x. ISSN 0009-9104.
  37. Channappanavar, Rudragouda; Perlman, Stanley (2017). "Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology". Seminars in Immunopathology. 39 (5): 529–539. doi:10.1007/s00281-017-0629-x. ISSN 1863-2297.
  38. Mahallawi, Waleed H.; Khabour, Omar F.; Zhang, Qibo; Makhdoum, Hatim M.; Suliman, Bandar A. (2018). "MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile". Cytokine. 104: 8–13. doi:10.1016/j.cyto.2018.01.025. ISSN 1043-4666.
  39. Liu, Yanli; Sun, Wenwu; Li, Jia; Chen, Liangkai; Wang, Yujun; Zhang, Lijuan; Yu, Li (2020). doi:10.1101/2020.02.17.20024166. Missing or empty |title= (help)
  40. Wan, Suxin; Yi, Qingjie; Fan, Shibing; Lv, Jinglong; Zhang, Xianxiang; Guo, Lian; Lang, Chunhui; Xiao, Qing; Xiao, Kaihu; Yi, Zhengjun; Qiang, Mao; Xiang, Jianglin; Zhang, Bangshuo; Chen, Yongping (2020). doi:10.1101/2020.02.10.20021832. Missing or empty |title= (help)
  41. Diao, Bo; Wang, Chenhui; Tan, Yingjun; Chen, Xiewan; Liu, Ying; Ning, Lifeng; Chen, Li; Li, Min; Liu, Yueping; Wang, Gang; Yuan, Zilin; Feng, Zeqing; Wu, Yuzhang; Chen, Yongwen (2020). doi:10.1101/2020.02.18.20024364. Missing or empty |title= (help)
  42. . doi:10.3969/j.issn.1672-5069.2020.02.001. Missing or empty |title= (help)
  43. 43.0 43.1 43.2 43.3 43.4 43.5 43.6 43.7 Fan, Zhenyu; Chen, Liping; Li, Jun; Tian, Cheng; Zhang, Yajun; Huang, Shaoping; Liu, Zhanju; Cheng, Jilin (2020). doi:10.1101/2020.02.26.20026971. Missing or empty |title= (help)
  44. Wang, Fu‐Sheng; Fan, Jian‐Gao; Zhang, Zheng; Gao, Bin; Wang, Hong‐Yang (2014). "The global burden of liver disease: The major impact of China". Hepatology. 60 (6): 2099–2108. doi:10.1002/hep.27406. ISSN 0270-9139.
  45. Lelubre, Christophe; Vincent, Jean-Louis (2018). "Mechanisms and treatment of organ failure in sepsis". Nature Reviews Nephrology. 14 (7): 417–427. doi:10.1038/s41581-018-0005-7. ISSN 1759-5061.
  46. Strnad, Pavel; Tacke, Frank; Koch, Alexander; Trautwein, Christian (2016). "Liver — guardian, modifier and target of sepsis". Nature Reviews Gastroenterology & Hepatology. 14 (1): 55–66. doi:10.1038/nrgastro.2016.168. ISSN 1759-5045.
  47. Li J, Li RJ, Lv GY, Liu HQ (2015). "The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury". Eur Rev Med Pharmacol Sci. 19 (11): 2036–47. PMID 26125267.
  48. 48.0 48.1 48.2 Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
  49. Shi, Heshui; Han, Xiaoyu; Jiang, Nanchuan; Cao, Yukun; Alwalid, Osamah; Gu, Jin; Fan, Yanqing; Zheng, Chuansheng (2020). "Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study". The Lancet Infectious Diseases. 20 (4): 425–434. doi:10.1016/S1473-3099(20)30086-4. ISSN 1473-3099.
  50. Xu, Xiao-Wei; Wu, Xiao-Xin; Jiang, Xian-Gao; Xu, Kai-Jin; Ying, Ling-Jun; Ma, Chun-Lian; Li, Shi-Bo; Wang, Hua-Ying; Zhang, Sheng; Gao, Hai-Nv; Sheng, Ji-Fang; Cai, Hong-Liu; Qiu, Yun-Qing; Li, Lan-Juan (2020). "Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series". BMJ: m606. doi:10.1136/bmj.m606. ISSN 1756-1833.
  51. 51.0 51.1 51.2 51.3 51.4 Alqahtani, Saleh A; Schattenberg, Jörn M (2020). "Liver injury in COVID-19: The current evidence". United European Gastroenterology Journal. 8 (5): 509–519. doi:10.1177/2050640620924157. ISSN 2050-6406.
  52. 52.0 52.1 52.2 Li J, Fan JG (March 2020). "Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease". J Clin Transl Hepatol. 8 (1): 13–17. doi:10.14218/JCTH.2020.00019. PMC 7132021 Check |pmc= value (help). PMID 32274341 Check |pmid= value (help).
  53. Su, Tung-Hung; Kao, Jia-Horng (2020). "The clinical manifestations and management of COVID-19-related liver injury". Journal of the Formosan Medical Association. 119 (6): 1016–1018. doi:10.1016/j.jfma.2020.04.020. ISSN 0929-6646.
  54. 54.0 54.1 54.2 Olry A, Meunier L, Délire B, Larrey D, Horsmans Y, Le Louët H (July 2020). "Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same". Drug Saf. 43 (7): 615–617. doi:10.1007/s40264-020-00954-z. PMC 7279629 Check |pmc= value (help). PMID 32514859 Check |pmid= value (help).
  55. 55.0 55.1 Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M (June 2020). "COVID-19 and Liver". J. Hepatol. doi:10.1016/j.jhep.2020.06.006. PMC 7295524 Check |pmc= value (help). PMID 32553666 Check |pmid= value (help).
  56. 56.0 56.1 56.2 56.3 Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T (June 2020). "Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper". JHEP Rep. 2 (3): 100113. doi:10.1016/j.jhepr.2020.100113. PMC 7128473 Check |pmc= value (help). PMID 32289115 Check |pmid= value (help).
  57. Andrade, Raúl J.; Aithal, Guruprasad P.; Björnsson, Einar S.; Kaplowitz, Neil; Kullak-Ublick, Gerd A.; Larrey, Dominique; Karlsen, Tom H. (2019). "EASL Clinical Practice Guidelines: Drug-induced liver injury". Journal of Hepatology. 70 (6): 1222–1261. doi:10.1016/j.jhep.2019.02.014. ISSN 0168-8278.
  58. Li, Jie; Fan, Jian-Gao (2020). "Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease". Journal of Clinical and Translational Hepatology. 8 (1): 1–5. doi:10.14218/JCTH.2020.00019. ISSN 2225-0719.
  59. 59.0 59.1 59.2 Gholizadeh P, Safari R, Marofi P, Zeinalzadeh E, Pagliano P, Ganbarov K, Esposito S, Khodadadi E, Yousefi M, Samadi Kafil H (2020). "Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19)". J Inflamm Res. 13: 285–292. doi:10.2147/JIR.S257078. PMC 7335895 Check |pmc= value (help). PMID 32669866 Check |pmid= value (help).
  60. 60.0 60.1 Cardoso FS, Pereira R, Germano N (May 2020). "Liver injury in critically ill patients with COVID-19: a case series". Crit Care. 24 (1): 190. doi:10.1186/s13054-020-02924-4. PMC 7198236 Check |pmc= value (help). PMID 32366282 Check |pmid= value (help).
  61. 61.0 61.1 61.2 Huang, Wei; Li, Chenze; Wang, Zhiquan; Wang, Hong; Zhou, Ning; Jiang, Jiangang; Ni, Li; Zhang, Xin A.; Wang, Dao-Wen (2020). "Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases". Science China Life Sciences. doi:10.1007/s11427-020-1733-4. ISSN 1674-7305.
  62. Ali, Nurshad; Hossain, Khaled (2020). "Liver injury in severe COVID-19 infection: current insights and challenges". Expert Review of Gastroenterology & Hepatology. doi:10.1080/17474124.2020.1794812. ISSN 1747-4124.
  63. Chen D, Li X, Song Q, Hu C, Su F, Dai J, Ye Y, Huang J, Zhang X (June 2020). "Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China". JAMA Netw Open. 3 (6): e2011122. doi:10.1001/jamanetworkopen.2020.11122. PMC 7290402 Check |pmc= value (help). PMID 32525548 Check |pmid= value (help).
  64. Alfano, Gaetano; Ferrari, Annachiara; Fontana, Francesco; Perrone, Rossella; Mori, Giacomo; Ascione, Elisabetta; Riccardo, Magistroni; Venturi, Giulia; Pederzoli, Simone; Margiotta, Gianluca; Romeo, Marilina; Piccinini, Francesca; Franceschi, Giacomo; Volpi, Sara; Faltoni, Matteo; Ciusa, Giacomo; Bacca, Erica; Tutone, Marco; Raimondi, Alessandro; menozzi, marianna; Franceschini, Erica; Cuomo, Gianluca; Orlando, Gabriella; Santoro, Antonella; Di Gaetano, Margherita; Puzzolante, Cinzia; Carli, Federica; Bedini, Andrea; Milic, Jovana; Meschiari, Marianna; Mussini, Cristina; Cappelli, Gianni; Guaraldi, Giovanni (2020). doi:10.1101/2020.06.14.20131169. Missing or empty |title= (help)
  65. 65.0 65.1 65.2 65.3 Bhayana, Rajesh; Som, Avik; Li, Matthew D; Carey, Denston E; Anderson, Mark A; Blake, Michael A; Catalano, Onofrio; Gee, Michael S; Hahn, Peter F; Harisinghani, Mukesh; Kilcoyne, Aoife; Lee, Susanna I; Mojtahed, Amirkasra; Pandharipande, Pari V; Pierce, Theodore T; Rosman, David A; Saini, Sanjay; Samir, Anthony E; Simeone, Joseph F; Gervais, Debra A; Velmahos, George; Misdraji, Joseph; Kambadakone, Avinash (2020). "Abdominal Imaging Findings in COVID-19: Preliminary Observations". Radiology: 201908. doi:10.1148/radiol.2020201908. ISSN 0033-8419.
  66. 66.0 66.1 Lei, Ping; Zhang, Lan; Han, Ping; Zheng, Chuansheng; Tong, Qiaoxia; Shang, Haitao; Yang, Fan; Hu, Yu; Li, Xin; Song, Yuhu (2020). doi:10.21203/rs.3.rs-28692/v1. Missing or empty |title= (help)
  67. Becchetti, Chiara; Zambelli, Marco Fabrizio; Pasulo, Luisa; Donato, Maria Francesca; Invernizzi, Federica; Detry, Olivier; Dahlqvist, Géraldine; Ciccarelli, Olga; Morelli, Maria Cristina; Fraga, Montserrat; Svegliati-Baroni, Gianluca; van Vlierberghe, Hans; Coenraad, Minneke J; Romero, Mario Cristobal; de Gottardi, Andrea; Toniutto, Pierluigi; Del Prete, Luca; Abbati, Claudia; Samuel, Didier; Pirenne, Jacques; Nevens, Frederik; Dufour, Jean-François (2020). "COVID-19 in an international European liver transplant recipient cohort". Gut: gutjnl-2020–321923. doi:10.1136/gutjnl-2020-321923. ISSN 0017-5749.
  68. Wu J, Song S, Cao HC, Li LJ (May 2020). "Liver diseases in COVID-19: Etiology, treatment and prognosis". World J. Gastroenterol. 26 (19): 2286–2293. doi:10.3748/wjg.v26.i19.2286. PMC 7243650 Check |pmc= value (help). PMID 32476793 Check |pmid= value (help).
  69. Zha L, Li S, Pan L, Tefsen B, Li Y, French N, Chen L, Yang G, Villanueva EV (May 2020). "Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19)". Med. J. Aust. 212 (9): 416–420. doi:10.5694/mja2.50577. PMC 7262211 Check |pmc= value (help). PMID 32266987 Check |pmid= value (help).
  70. Nicola M, O'Neill N, Sohrabi C, Khan M, Agha M, Agha R (May 2020). "Evidence based management guideline for the COVID-19 pandemic - Review article". Int J Surg. 77: 206–216. doi:10.1016/j.ijsu.2020.04.001. PMC 7151371 Check |pmc= value (help). PMID 32289472 Check |pmid= value (help).
  71. "NIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)".
  72. "How to Protect Yourself & Others | CDC".
  73. "FDA Updates on Hand Sanitizers with Methanol | FDA".
  74. "Contact Tracing for COVID-19 | CDC".