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Hepatobiliary involvement in COVID-19 patients
Mohammad Amin Akbarzadeh1,2, Mohammad-Salar Hosseini2,3,4*
Available from: http://dx.doi.org/10.21931/RB/2021.06.02.3
As the new data emerges from the studies regarding COVID-19 infection, various complications are detected among the infected patients. Unlike its name, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not limited to the respiratory system1. Some studies have suggested the impact of COVID-19 on liver function2,3. Since the liver plays essential intoxication, enzyme activation, storage, and synthesis of necessary proteins, lipids, and carbohydrates, the potential liver complications may affect the body beyond ordinary expectations.
A chief hepatic injury is almost always determined by the elevated levels of liver enzymes, like alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). According to a study on 1099 patients with laboratory-confirmed SARS-CoV-2 infection, 22.2% and 21.3% of the patients with available data had elevated AST and ALT levels (>40 U/L), where only 23 patients had pre-existing liver conditions4. In another study, reporting clinical characteristics of 99 COVID-19 cases, 43 patients showed degrees of liver dysfunction with elevated levels of AST (>40 U/L) or ALT (>50 U/L)5. Also, another study showed that patients might even develop liver injury before demonstrating any changes in the blood level of AST and ALT6. Likewise, several findings suggest a potential association between the severity of the disease and elevation of liver enzymes7. Even a recently published retrospective cohort of 1827 COVID-19 patients showed that over 61% of the patients had abnormal serum levels of AST8. More importantly, the study showed that the abnormal liver test could be associated with poor prognosis and clinical outcomes.
The presence of liver damage among COVID-19 patients could be explained through many underlying mechanisms. First of all, like other viral infections, hepatocellular damage can be caused directly by the SARS-CoV-2, as its presence is reported from various systems, including the hepatic system. The virus uses angiotensin-converting enzyme 2 (ACE2) receptors as an entry gate to cells, and cells with ACE2 receptor expression are potential parts of the route underlying the pathophysiology of the infection9-11. Cholangiocytes express ACE2 molecules, and several reports suggest that this expression may have a role in complications such as cholestasis, provoke immune-related responses, which in severe conditions may lead to cytokine storm, and lead to liver injuries and significant hepatobiliary complications12.
The infection could affect the protein synthesis function of the liver. Besides, due to the lack of an effective and definite treatment regimen for managing COVID-19 patients, repurposing different drugs and using various treatment protocols has become quite common13. Since the liver plays the leading role in metabolizing chemicals and toxic compounds, consuming drugs without a definite knowledge of their side effects could place the liver in a devastating state, especially when the body power of endurance is remarkably reduced dealing with the bother of infection. Therefore, drug-induced hepatotoxicity should be taken into account seriously, and administration of various drugs – precisely, the herbal compounds – should be monitored more cautiously14-16.
Signs, symptoms, and conditions like abnormal liver function tests, elevated levels of bilirubin, and acute hepatitis can be presented in patients due to various reasons17,18. Considering the significantly high prevalence of hepatic complications in COVID-19 patients, different clinical features should be interpreted considering a possible presence of SARS-CoV-2 infection. This is especially important in patients with pre-existing liver conditions, such as patients with cirrhosis, chronic cholestatic liver disease (e.g., primary sclerosing cholangitis, primary biliary cholangitis), liver transplantation recipients, liver cancer, etc. There may also be a potential association between COVID-19 infection and comorbidities related to liver dysfunction, notably metabolic disorders (e.g., diabetes mellitus), fatty liver diseases, and viral hepatitis7,19. Chronic viral hepatitis may enhance the viral replication of the hepatocytes, which can contribute to the severe manifestation of COVID-19 infection.
Recent studies have shown a possible association between COVID-19 infection and liver-related complications. ALT and AST are the most utilized biomarkers which need to be monitored closely in all populations to avoid missing the potential relations with the pathophysiology of the SARS-CoV-2 infection. Further studies with a focus on evaluating the chief liver functions are strongly recommended. Most of the available findings only cover the blood levels of AST and ALT. Further studies should consider other liver enzymes, ultrasound, and even biopsy to determine the particular affection of the liver during this infection. Additional studies considering different ranges of liver enzymes may help us develop a prognostic scale for COVID-19 patients, which could be determinative in managing these patients. Also, assessing the patients with COVID-19 and viral hepatitis is mandatory, as so little information is available on the prognosis of patients with this co-infection. SARS-CoV-2 infection is a multi-system disease, and since the hepatic injury could cause permanent damages and even increase the risk of mortality independently, liver-related complications of COVID-19 should be observed strictly.
Funding information: Not Applicable.
Competing interest: The authors declare that they have no competing interests.
Keywords: Digestive system diseases, hepatic insufficiency, liver, SARS-CoV-2, COVID-19
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Mohammad Amin Akbarzadeh1,2, Mohammad-Salar Hosseini2,3,4*
1Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
3Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4Emergency Medicine Research Team, Tabriz University of Medical Sciences, Tabriz, Iran
Corresponding author: Mohammad-Salar Hosseini, Student Research Committee, Tabriz University of Medical Sciences, Golgasht Street, Postal code 5166/15731, Tabriz, EA, Iran. Telephone Number: +984133366581, Fax Number: +984133341994. Email: email@example.com
Mohammad Amin Akbarzadeh: 0000-0002-9589-104X,
Mohammad-Salar Hosseini: 0000-0003-2765-5018
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