The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is primarily a respiratory illness, yet its effects extend far beyond the lungs. A significant number of patients experience systemic inflammation that impacts multiple organ systems, with the liver frequently affected. Observing abnormalities in liver function has become a common clinical finding during the acute phase of infection. While severe liver failure is rare, the correlation between infection and liver injury is an important area of study for understanding the full scope of the disease.
Indicators of Acute Liver Dysfunction
Liver injury during acute COVID-19 infection is typically identified through blood tests that measure the levels of liver enzymes. The two most common markers monitored are Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), which are released into the bloodstream when liver cells are damaged. Studies indicate that 15% to over 50% of patients show elevated liver enzymes during their illness.
These elevations are generally mild to moderate, often rising to less than five times the upper limit of normal. Patients with severe COVID-19 disease often exhibit higher levels of these markers, particularly AST, compared to those with milder cases. This suggests a link between the extent of liver injury and overall disease severity. Severe acute hepatitis or liver failure directly attributable to the virus remains an infrequent event.
Pathways Leading to Liver Injury
Liver injury in COVID-19 patients involves a combination of three distinct mechanisms. Understanding these separate pathways is essential for proper patient management and treatment.
Direct Viral Cytotoxicity
One proposed mechanism involves the virus directly infecting liver cells. The SARS-CoV-2 virus uses the Angiotensin-Converting Enzyme 2 (ACE2) receptor to gain entry into host cells. This receptor is expressed on both hepatocytes (the main liver cells) and cholangiocytes (cells lining the bile ducts). While ACE2 expression appears higher on cholangiocytes, the virus has the potential to directly damage liver tissue. Autopsy studies have occasionally shown evidence of viral components and mild tissue inflammation, supporting the possibility of a direct viral effect.
Immune-Mediated Damage
A widely accepted mechanism attributes liver injury to the body’s inflammatory response, often referred to as a “cytokine storm” in severe cases. The release of pro-inflammatory signaling molecules like interleukins and tumor necrosis factor can cause collateral damage to the liver. This systemic inflammation can also lead to microvascular changes and reduced oxygen supply to the liver, known as hypoxic hepatitis. Hypoxic hepatitis contributes to cell death and enzyme elevation.
Drug-Induced Liver Injury (DILI)
A third cause of enzyme elevation stems from the medications used to manage severe COVID-19. Many drugs administered in the intensive care setting, including certain antivirals and antibiotics, are processed by the liver and can place significant metabolic stress on the organ. This drug-induced liver injury (DILI) makes it a challenge for clinicians to differentiate the cause of the elevated enzymes. Identifying DILI is important because it may require adjustment of the patient’s medication regimen to prevent further liver stress.
Recovery and Long-Term Liver Health
For most individuals, acute liver enzyme elevations observed during the initial COVID-19 infection are transient and resolve as the patient recovers from the primary illness. The majority of affected patients see their liver function tests return to normal within weeks or a few months after hospital discharge. This resolution is typically observed once the systemic inflammation subsides and the viral load is cleared.
However, emerging evidence points to the possibility of persistent liver dysfunction in some patients experiencing “Long COVID.” Studies following survivors indicate that markers like ALT and AST may remain mildly elevated in a subset of people, particularly those who had a severe acute infection. COVID-19 may also be associated with increased liver stiffness, a marker of chronic injury or fibrosis, in the months following infection. Patients who experienced significant liver injury may require follow-up monitoring by a specialist to ensure full recovery and to detect any signs of long-term scarring. These findings underscore the need for continued surveillance to fully understand the long-term hepatic impact of the virus.
Pre-Existing Conditions and Vulnerability
The presence of pre-existing chronic liver disease (CLD) increases the risk of severe outcomes from COVID-19 infection. Patients with conditions like cirrhosis, chronic hepatitis, or Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) are at a higher risk of developing more pronounced liver injury. For those with cirrhosis, COVID-19 can trigger liver decompensation, leading to acute-on-chronic liver failure.
The severity of the underlying CLD is a strong predictor of poor outcomes, with patients who have higher scores on liver disease severity scales facing greater mortality rates. Systemic conditions that often coexist with liver disease, such as diabetes and obesity, also contribute to a worse prognosis. For this vulnerable population, close monitoring and early intervention are important for managing the dual threat of viral infection and liver deterioration.