When a person becomes ill, doctors often look at liver enzyme levels to check for cellular stress or damage in the body. The two primary enzymes measured are Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), which are usually housed within liver cells. When liver cells are injured, these enzymes leak into the bloodstream, signaling a potential problem. Like many viral infections, the SARS-CoV-2 virus that causes COVID-19 can affect various organ systems beyond the lungs. This systemic impact includes the liver, leading to noticeable changes in a patient’s enzyme profile.
The Confirmed Link Between COVID-19 and Liver Changes
Clinical evidence established a clear association between COVID-19 infection and the elevation of liver enzymes. Studies estimated the overall pooled incidence of elevated liver enzymes to be around 23.1% of patients presenting with the infection.
The severity of the enzyme elevation often correlated directly with the severity of the respiratory disease. Patients with moderate or severe cases of COVID-19 were more likely to have enzyme abnormalities than those with mild illness. In severe cases, high levels of AST were frequently observed, sometimes disproportionately higher than ALT. This suggests a wider involvement of organs beyond the liver, since AST is also produced in muscle and heart tissue. This pattern is associated with poorer clinical outcomes, including increased risk of intensive care unit admission.
How the Virus Causes Liver Enzyme Elevation
The elevation of liver enzymes in COVID-19 patients is due to a combination of three distinct biological processes.
One mechanism involves the direct interaction between the SARS-CoV-2 virus and liver cells. The virus uses the Angiotensin-Converting Enzyme 2 (ACE2) receptor to enter cells, and these receptors are present on cells within the liver, particularly on bile duct cells, known as cholangiocytes. This direct viral invasion can lead to a cytopathic effect, where the virus damages the infected liver cells, causing the release of ALT and AST into the bloodstream.
Microscopic examinations of liver tissue from deceased COVID-19 patients have revealed signs of cellular damage consistent with viral infection. However, the direct viral effect is considered only one part of the injury, as the virus’s presence does not always correlate with the degree of enzyme elevation.
A second, often more pronounced, cause is the systemic inflammation triggered by the infection, commonly referred to as a cytokine storm. When the immune system overreacts, it releases inflammatory signaling molecules, such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α). These circulating cytokines can cause widespread damage to various organs, including the liver, even if the virus has not directly infected every cell.
This severe inflammatory response can lead to hypoxic injury, a form of damage resulting from a lack of sufficient oxygen, which is common in patients with severe respiratory distress.
The third contributing factor is Drug-Induced Liver Injury (DILI) resulting from the treatments used for severe COVID-19. Medications administered to manage the infection, such as certain antivirals, can sometimes strain the liver as the organ processes them. In these cases, the elevated enzymes are a side effect of the treatment rather than a direct consequence of the virus itself. Medical professionals must distinguish which of these three mechanisms is the primary driver of the liver enzyme elevation.
Typical Severity and Recovery Timeline
For the majority of patients, the liver enzyme elevations observed during the acute phase of a COVID-19 infection are mild to moderate. Most cases of liver injury fall into the mild category and do not require specific liver-focused treatment. The injury typically follows a hepatocellular pattern, meaning the liver cells themselves are affected rather than the bile ducts.
The enzyme levels usually peak during the height of the acute illness, correlating with the period of highest inflammation and systemic stress. As the patient recovers from the viral infection, the enzyme levels decrease and often return to their normal range. For most, this normalization occurs within a few weeks of recovery from the acute illness.
Some studies following patients post-discharge have noted that elevated enzyme levels, particularly for GGT and ALP, can persist for a longer duration, sometimes for up to two months. Instances of severe acute hepatitis or liver failure directly linked to COVID-19 are documented but remain rare occurrences. The persistence of abnormal enzymes beyond eight to twelve weeks signals that further investigation for a pre-existing or chronic liver condition is warranted.
Patient-Specific Risks and Continued Monitoring
Certain patient characteristics and pre-existing health conditions increase the risk of severe liver changes during COVID-19 infection. Individuals with metabolic dysfunction, including non-alcoholic fatty liver disease (NAFLD), obesity, or diabetes, are more predisposed to severe liver injury. These conditions make the liver more vulnerable to the systemic effects of COVID-19.
Patients with chronic liver diseases, including cirrhosis, face a higher risk of severe COVID-19 outcomes and death if infected. Older age and male gender have also been identified as independent risk factors for liver enzyme elevation.
Given the potential for delayed recovery, continued monitoring is recommended, especially for those recovering from a severe case. Follow-up blood tests after recovery are an important part of post-COVID care, particularly for individuals who report persistent symptoms. Regular checks help ensure that liver function returns to baseline and that any long-term issues are identified promptly.