Infection with the SARS-CoV-2 virus frequently affects the liver. Liver injury, often detected through elevated liver enzyme levels in the blood, was noted in a significant percentage of hospitalized patients. Understanding the causes of this liver dysfunction is important for distinguishing between the direct effects of the virus and the body’s systemic response to severe illness. Liver inflammation during a COVID-19 infection results from three primary mechanisms: the virus directly attacking liver cells, the body’s excessive immune response, and the side effects of medications used for treatment.
Direct Viral Effects on Liver Tissue
The SARS-CoV-2 virus gains entry into human cells by binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor, which is found in the liver. Studies show that while ACE2 is present on hepatocytes (the main liver cells), it is expressed at much higher levels on cholangiocytes, the cells lining the bile ducts.
The virus’s preference for cholangiocytes suggests that direct injury may focus on the bile ducts rather than the main liver tissue. Damage to these bile duct cells can disrupt the normal flow of bile, subsequently impacting hepatocyte function and causing secondary liver cell dysfunction. This direct cytopathic effect contributes to the overall liver injury observed in some patients, though it is often considered a lesser cause compared to the systemic effects of a severe infection.
Immune System Overreaction and Liver Injury
The most common cause of liver enzyme elevation, especially in severe COVID-19 cases, is the body’s overwhelming systemic response to the infection. A massive release of pro-inflammatory signaling molecules, known as a cytokine storm, causes widespread damage to multiple organs, including the liver. This uncontrolled inflammatory cascade involves the overproduction of cytokines like Interleukin-6 (IL-6), which directly injure liver cells.
Systemic complications of severe COVID-19, such as hypoxia (low oxygen supply), also significantly contribute to liver damage. The liver is highly metabolically active and particularly susceptible to injury from low oxygen levels. This condition, sometimes called hypoxic hepatitis, causes rapid elevation of liver enzymes. Furthermore, severe inflammation can lead to microvascular dysfunction and blood clotting disorders, impairing blood flow within the liver and causing cell death.
Drug-Induced Hepatitis in COVID-19 Patients
A portion of the liver injury seen in hospitalized COVID-19 patients is caused by the medications administered during treatment. This is referred to as Drug-Induced Liver Injury (DILI). Since the liver is the primary site for metabolizing many drugs, it is vulnerable to toxic side effects, especially when multiple medications are used simultaneously.
Certain drug classes used to manage severe COVID-19 carry a risk of hepatotoxicity. Antiviral medications, such as remdesivir and lopinavir/ritonavir, have been associated with elevated liver enzymes. Systemic corticosteroids, often used to suppress the inflammatory response, can also contribute to liver dysfunction. The potential for DILI necessitates close monitoring of liver function tests, as discontinuing the offending medication is often the first step in management.
Diagnosis and Recovery Outlook
COVID-related hepatitis is identified through routine blood tests that measure liver enzymes, primarily Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST). Elevated levels of these enzymes indicate liver cell injury, with incidence rates ranging from 15% to over 50% in hospitalized patients. The severity of the enzyme elevation correlates with the overall severity of the COVID-19 illness, with higher levels observed in patients requiring intensive care.
Symptoms of liver involvement are usually mild, such as fatigue, but severe cases may involve jaundice (a yellowing of the skin and eyes caused by high bilirubin levels). The prognosis for COVID-related liver injury is favorable; the damage is transient in most cases. Liver enzyme levels decline and return to normal as the underlying viral infection and systemic inflammation resolve. While monitoring remains important, specific treatment for the liver injury is usually unnecessary, and the focus remains on treating the underlying COVID-19 infection.