2. - COVID-19 (coronavirus disease 2019) is a disease caused
by a virus named SARS-CoV-2 and was discovered in December
2019 in Wuhan, China. It is very contagious and has quickly spread
around the world.
- COVID-19 most often causes respiratory symptoms that can
feel much like a cold, a flu, or pneumonia. COVID-19 may attack
more than your lungs and respiratory system. Other parts of your
body may also be affected by the disease.
CDC (2020) COVID-19 and Your Health, Centers for Disease Control and Prevention. Available at:
https://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19/basics-covid-19.html
(Accessed: 23 January 2023).
3. Indonesia: WHO Coronavirus Disease (COVID-19) Dashboard With Vaccination Data (no date). Available at:
https://covid19.who.int (Accessed: 23 January 2023).
4. COVID-19 and the liver
- Little cause for concern The largest study on COVID-19 to date
showed that the prevalence of elevated aminotransferases and
bilirubin in people faring worst was at least double that of others.
Although clinically significant liver dysfunction was not quantified, this
and other studies have led some to suggest that this finding might
present clinical challenges.
- A new study found that the SARS-CoV-2 virus may bind to
angiotensin-converting enzyme 2 (ACE2) on cholangiocytes, leading to
cholangiocyte dysfunction and inducing a systemic inflammatory
response leading to liver injury.7 As of March 10, 2020, 7 relatively
large-scale hospitalbased studies have reported the clinical
characteristics of patients with COVID-19, including some insights into
other factors, which may lead to COVID-19 induced liver damage.
Bangash, M.N., Patel, J. and Parekh, D. (2020) ‘COVID-19 and the liver: little cause for concern’, The Lancet. Gastroenterology & Hepatology,
5(6), pp. 529–530. Available at: https://doi.org/10.1016/S2468-1253(20)30084-4.
Cai, Q. et al. (2020) ‘COVID-19: Abnormal liver function tests’, Journal of Hepatology, 73(3), pp. 566–574. Available at:
https://doi.org/10.1016/j.jhep.2020.04.006.
5. SARS- CoV2 HOST RECEPTORS IN LIVER TISSUE
• The respiratory tract is not the unique tropism for SARS-CoV-2; it is also
founded in the kidneys, heart, liver and surprisingly, the brain. The ACE2
protein displays within the gastrointestinal (GI) tract and within the colon,
the biliary system, and the liver at high levels. Moreover, SARS-CoV2-
interacts with three receptors in liver tissue, the expression fluctuats
among cell types. ACE2, for illustration, is expressed in cholangiocytes,
along with hepatocytes. TMPRSS2 is expressed in hepatocytes,
cholangiocytes, erytroid cells, and sinusoidal endothelial cells.
These receptors' existence indicates the emergence of liver disease in
patients with COVID-19, the direct viral cytopathic effect. Several studies
revealed the relationship between COVID-19 and hepatic manifestation.
Dawood, D.R.M., Salum, G.M. and El-Meguid, M.A. (2022) ‘The Impact of COVID-19 on Liver Injury’, The American Journal
of the Medical Sciences, 363(2), p. 94. Available at: https://doi.org/10.1016/j.amjms.2021.11.001.
6. TRAJECTORY OF LIVER FUNCTION TESTS IN COVID 19 PATIENTS
• Chen et al was the first study that reported abnormal
liver tests in patients with COVID-19. Abnormal alanine
transaminase/aspartate transaminase (ALT/AST) levels
and slightly elevated bilirubin levels indicate liver
damage. In severe cases, the albumin is lessened and the
level of albumin ranges from 26.3 to 30.9 g/L
Chen, T. et al. (2020) ‘Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study’,
BMJ (Clinical research ed.), 368, p. m1091. Available at: https://doi.org/10.1136/bmj.m1091.
7. Mechanisms of hepatic injury in SARS-CoV-2 infection
Dawood, D.R.M., Salum, G.M. and El-Meguid, M.A. (2022) ‘The Impact of COVID-19 on Liver Injury’, The
American Journal of the Medical Sciences, 363(2), p. 94. Available at: https://doi.org/10.1016/j.amjms.2021.11.001.
8. Mechanisms of hepatic injury in SARS-CoV-2 infection
• Direct viral effect on the liver
• Systemic cytokine storm
• Effect of the drug on liver functions
• Hypoxic injury
Dawood, D.R.M., Salum, G.M. and El-Meguid, M.A. (2022) ‘The Impact of COVID-19 on Liver Injury’, The
American Journal of the Medical Sciences, 363(2), p. 94. Available at: https://doi.org/10.1016/j.amjms.2021.11.001.
9. Direct viral effect on the liver
• SARS-CoV-2 might enter the liver cells via ACE2
receptor, which is expressed in the liver and bile duct
cells.
• Recent data showed ACE2 expression in 2.6% of
hepatocytes and 59.7% of cholangiocytes, the level
of ACE2 expression in cholangiocytes was like that in
type 2 alveolar cells of the lungs, interpreting that
SARS-CoV-2 may directly attach to ACE2 found on
cholangiocytes and causing liver dysfunction.
10. Systemic cytokine storm
• Cytokine storm is a hyperinflammatory response of
the host body triggered by viral infection, which
recruits a persistent activation and generation of
lymphocytes and macrophages that will produce
massive quantities of inflammatory cytokine.
• Inflammatory cytokine storm gives an order to
pulmonary and non-pulmonary organs failure as
(kidneys, liver, and cardiac muscle).
11. Effect of the drug on liver functions
• A variety of antiviral drugs, steroids and antibiotics
are utilized in treatment of COVID-19 patients. The
liver plays a master function in the metabolism of all
these drugs; accordingly, these drugs may cause
hepatotoxicity.
12. Hypoxic injury
• Ischemic hepatitis, also named, hypoxic hepatitis, is
occasionally observed in severe patients and declares
a sign of cardiac, respiratory, or circulatory failure,
causing passive congestion or lessened perfusion of
the liver.
14. Cirrhotic Cardiomyopathy
• Cirrhotic cardiomyopathy is characterized by an
impaired cardiac response to stress, which results
from a combination of autonomic dysfunction,
alterations in cell membrane composition, ion
channel defects, and an overproduction of cardio
depressant factors.
Lyssy, L.A. and Soos, M.P. (2022) ‘Cirrhotic Cardiomyopathy’, in StatPearls. Treasure Island (FL): StatPearls Publishing.
Available at: http://www.ncbi.nlm.nih.gov/books/NBK556089/ (Accessed: 8 January 2023).
15. Myositis Liver Injury
• Akin to most other sites predisposed to SARS-CoV-2, the
muscle tissue expresses ACE-2 receptors as well.
Extrapulmonary manifestations of COVID-19 are thought to
occur through ACE-2 receptor–mediated facilitation of virus
entry into small vessel endothelium, organs like the bowel,
synovial tissue, and both smooth and skeletal muscles.
• In effect, this may be the reason behind multisystem
involvement with COVID-19. It has been speculated that
COVID-19 induced myositis may also transpire via direct
muscle entry of the virus through these receptors on the
muscle cells.
Saud, A. et al. (2021) ‘COVID-19 and Myositis: What We Know So Far’, Current Rheumatology Reports, 23(8), p. 63.
Available at: https://doi.org/10.1007/s11926-021-01023-9.
16. Systemic inflammatory Liver Injury
• COVID-19 associated liver injury is defined as any liver
damage occurring during disease course and treatment
of COVID-19 patients, with or without pre-existing liver
disease.
• This includes a broad spectrum of potential path
mechanisms including direct cytotoxicity from active viral
replication of SARS-CoV-2 in the liver, immune-mediated
liver damage due to the severe inflammatory
response/systemic inflammatory response syndrome
(SIRS) in COVID-19
https://onlinelibrary.wiley.com/doi/10.1111/liv.14730
17. Diagnostic work up of the patient and treatment
• The risk of drug-induced liver injury is heightened in COVID-19 patients
with pre-existing elevated transaminase levels. Hence, antipyretic
consumption, antiviral or herbal drugs must be under physician
monitoring to prevent drug-induced liver injury.
• The elevation of ALT/AST >5 times the normal amount should be
followed by drugs cessation. Also, the extensive usage of corticosteroids
(methylprednisolone) can reactivate chronic hepatitis B.
• Therefore, patients that have positive HBsAg must be treated with
antiviral drugs. Also, there is a recommendation for screening for the
hepatitis B core antibody and, if positive, treating patients with
antivirals along with steroid therapy.
• Moreover, it was observed that the introduction of lopinavir combined
with ritonavir could accelerate liver damage in hepatitis C or hepatitis B
infected patients
18. CONCLUSIONS
• Abnormal Liver tests are reasonably more frequent in severe
patients with COVID-19 infection. Liver function abnormalities
require clinical monitoring, continuous observations and, possibly,
specific treatment.
• Liver test biomarkers (especially AST and GGT) as well as viral
hepatitis markers should be regularly observed and monitored
through hospitalization. More consideration should be paid to
minimize liver damage in patients with pre-existing liver disease.
• Cautious usage of antiviral therapies in liver disease patients and
drug-drug interactions in post-liver transplanted patients must be
considered.
