Overview of Liver Injuries

Clinical parameters and known mechanisms:

•     The main viral entry receptor of COVID19 is angiotensin converting enzyme 2 (ACE2). Because this receptor is expressed in different organs, like the liver, SARS-CoV-2 causes a systemic disease¹.
•     14% to 53%of hospitalized patients with COVID-19 show elevated serum liver biochemistries such as ALT, AST and bilirubin²
•     Liver biopsies show moderate microvascular steatosis and mild lobular and portal activity. Multiple mechanisms are suggested¹:
  • Immune mediated damage induced by severe inflammatory response
  • Direct cytotoxicity caused by viral replication in hepatic cells .
  • Hypoxic hepatitis secondary to respiratory failure
  • Drug toxicity from steroids, antibiotics and antivirals.
  • Reactivation of pre-existing liver disease.

•     Biopsy of one patient also showed overactivation of T cells with microvascular steatosis, suggesting that liver injury is likely immune mediated rather than the result of direct cytopathic damage³.
•     The pattern of liver injury is mostly hepatocellular rather than cholestatic³.

 

Recommended management for clinicians

•     Liver biochemistries should be verified in all COVID-19 patients regularly¹.
•     Safety data on drugs used to treat SARS-CoV-2 in patient with liver injury are missing¹.
•     Hepatitis B and C and other causes of liver disease should be investigated if patients have elevated liver biochemistries  (local epidemiology to be considered)^1,2.
•     Patients with liver damage should be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate².

 

Progression / Prognosis

•  Liver injury is associated with severe outcomes in patients with COVID-19 infection⁴.
• Alteration of liver enzymes seems to be transient¹.
•     Persistent liver injury were mostly seen with patients who had non-alcoholic fatty disease and high BMI³.
•     Patients with low albumin are more prone to develop severe infection and to have a poor prognosis^1,4.
• Higher serum levels of AST, ALT and total bilirubin are associated with a significant increase in the severity of COVID-10 infections⁴.
•     Patients with non-alcoholic fatty liver disease have higher risk of progression to severe COVID-19 and higher likelihood of abnormal liver function from admission to discharge³.
•     No death due to hepatic decompensation have been reported  in patients without pre-existing liver disease¹.

 

This data comes from 4 articles. The first is a schematic overview done by different institutions such as The Department of Infectious Diseases, Southern Medical University in Guangzhou, China, The Department of Gastroenterology in Humanitas Clinical and Reasearch Center in Rozzano, Italy and others.  The second is a literature review done by the Department  of  Infectious Diseases in Union  Hospital in Wuhan, China. They studied the characteristics and mechanisms of liver injury caused by the three different sources of corona virus to help further studies.The third is a retrospective study on 202 patients done by The Fifth Medical Center of Chinese General Hospital in Beijing, the China Fuyang Second People’s Hospital and the China Humanity and Health Clinical Trial Center in Hong Kong. They wanted to study the impact of Non-alcoholic fatty liver disease in patient with CODIV-19. Parohan M., et al present a systematic review and meta-analysis of retrospective studies about available findings on the association between liver injury and severity of COVID-19 infection. A total of 20 retrospective studies with 3428 COVID-19 infected patients were included.

 

 

Sources : 

1.   Sun J., Aghemo A., Forner A., Valenti L. (April 06, 2020). COVID-19 and liver disease. Wiley Online Library. https://doi.org/10.1111/liv.14470
2.     Xu L., Liu J., Lu M., Yang D., Zheng X., et al (March 14, 2020). Liver injury during highly pathogenic human coronavirus infections. Wiley online Library. https://doi.org/10.1111/liv.14435
3.     Ji D., Qin E., Xu J., et al. (April 8, 2020). Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study. Journal of Hepatology, ScienceDirect. https://doi.org/10.1016/j.jhep.2020.03.044
4. Parohan M., Yaghoubi S., Seraj A. (May 9, 2020). Liver Injury Is Associated With Severe Coronavirus Disease 2019 (COVID-19) Infection: A Systematic Review and Meta-Analysis of Retrospective Studies. Wiley Online Library. https://doi.org/10.1111/hepr.13510.