Abnormal Liver Function Tests in Patients With COVID-19: Relevance and Potential Pathogenesis

The study “Abnormal Liver Function Tests in Patients With COVID-19: Relevance and Potential Pathogenesis” provides a comprehensive analysis of liver function abnormalities in COVID-19 patients.

Here’s a detailed summary:

  1. Context of the Study: The study addresses the prevalence and potential causes of abnormal liver function tests (LFTs) in patients with COVID-19, noting that these abnormalities are frequently observed but their pathogenesis is not fully understood​​.
  2. Epidemiology of Abnormal LFTs: LFTs include markers of hepatocyte injury, bile duct injury, hepatic clearance, and synthetic capacity. Elevated aminotransferases in COVID-19 may originate from myositis rather than liver injury. Elevated muscle damage markers and hypoalbuminemia are associated with disease severity and mortality​​.
  3. Prevalence of LFT Abnormalities: ALT and AST elevations were observed in a significant proportion of COVID-19 patients, with the prevalence ranging from 4% to 58% in various cohorts. These elevations were generally mild​​. Additionally, elevated ALP and GGT were reported in 2%-54% of patients​​.
  4. Severity of COVID-19 and LFTs: More frequent and greater elevations in ALT and AST were seen in patients with severe COVID-19 compared to those with mild disease. This trend was also observed in patients with SARS during the 2002-2004 outbreak. However, the prognostic value of abnormal LFTs in COVID-19 is unclear, with some studies associating them with increased disease severity and mortality, while others found no such association​​.
  5. Pathogenesis of LFT Abnormalities: The direct infection of liver cells by SARS-CoV-2 is considered unlikely. The virus uses ACE2 as a receptor, mainly expressed in a subpopulation of cholangiocytes, not hepatocytes. Hence, the role of direct virus-induced liver injury is uncertain​​.
  6. Host Inflammatory Response: The host immune response to SARS-CoV-2 infection can result in complications like acute respiratory distress syndrome, coagulopathy, multi-organ failure (MOF), and death. An excessive release of inflammatory cytokines, particularly in severe cases, can lead to cytokine storm syndrome (CSS), affecting various organs including the liver​​.
  7. Coagulation Abnormalities: Disseminated intravascular coagulation (DIC) is observed in critical and nonsurvivor COVID-19 patients. Autopsy findings have shown pulmonary embolism and thrombotic microangiopathy in multiple organs​​.
  8. Endothelial Damage and Coagulopathy: Endothelitis in the liver and fibrin microthrombi in liver sinusoids were noted. These findings suggest that CSS, leading to shock and coagulopathy, could affect liver perfusion and result in liver cell death​​.
  9. COVID-19 Mild Cases and LFTs: In mild COVID-19 cases, LFT abnormalities may not relate to general inflammation, suggesting a specific inflammatory response caused by SARS-CoV-2. Whether LFT abnormalities are present in asymptomatic or paucisymptomatic cases is unknown​​.
  10. Medication-Induced Liver Injury: Drugs used for COVID-19 management, such as antivirals, antibiotics, corticosteroids, and immune-modulators, are potentially hepatotoxic. Some patients developed LFT abnormalities after hospital admission, possibly related to the use of these medications​​.
  11. Pre-Existing Liver Diseases and COVID-19: Pre-existing liver diseases were reported in 1%-11% of COVID-19 patients. It’s unclear whether such diseases affect COVID-19 severity or vice versa. Chronic liver disease can increase infection risk due to immune dysfunction​​.
  12. Obesity, NAFLD, and COVID-19 Severity: Obesity is a significant risk factor for COVID-19 severity, and nonalcoholic fatty liver disease (NAFLD) is associated with obesity. NAFLD may explain some LFT alterations in COVID-19 patients and is related to rapid disease progression and longer viral shedding​​.
  13. Hepatic Injury in Critical COVID-19 Patients: Hypoxic hepatitis can occur due to respiratory failure, shock, or cardiac failure in critically ill COVID-19 patients. Hemodynamic alterations in the liver, especially in mechanically ventilated patients, could affect LFTs​​.
  14. Conclusion: Abnormal LFTs in COVID-19, particularly mildly elevated AST and ALT, are commonly associated with severe disease and increased inflammatory markers. However, these abnormalities generally do not lead to significant liver impairment or failure, and liver-directed treatment is usually not required. The pathogenetic mechanisms for abnormal LFTs in COVID-19 are likely multifactorial, involving factors like microthrombotic endothelialitis, immune dysregulation, drug-induced liver injury, and hepatic ischemia related to hypoxia and MOF​​.

In summary, this study provides comprehensive insights into the abnormalities in liver function tests observed in COVID-19 patients, highlighting the multifactorial nature of these abnormalities and their association with disease severity. While direct infection of liver cells by SARS-CoV-2 appears unlikely, systemic effects of the infection and host immune response play significant roles in liver involvement in COVID-19.

Read More: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404414/

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