COVID-19-associated hepatic injury

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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]


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.


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.


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)


aminotransferase (IU)


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


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.


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.


Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings



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]


  • 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.


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.


  • 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.


  • 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


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