COVID-19, caused by the SARS-CoV-2 virus, primarily impacts the respiratory system. However, the virus can also affect other organs, including the liver. Liver involvement in COVID-19 patients has been noted since the early stages of the pandemic. This has led to investigations into how the virus might cause liver damage and what its potential long-term consequences could be.
Mechanisms of Liver Injury
Liver injury in COVID-19 patients can arise from several factors. One mechanism involves the direct interaction of the SARS-CoV-2 virus with liver cells. The virus uses ACE2 receptors to enter cells, and these receptors are present on cholangiocytes (cells lining the bile ducts) and, to a lesser extent, hepatocytes (main liver cells). While direct viral infection of liver cells is possible, it is not considered the sole or primary cause of liver damage.
The body’s systemic response to the infection is another contributor to liver injury. Severe COVID-19 can trigger an overactive immune response known as a “cytokine storm.” This uncontrolled release of inflammatory proteins leads to widespread inflammation, affecting organs like the liver. The liver is particularly susceptible to this inflammatory damage due to its anatomical position and exposure to circulating cytokines.
Medications used to treat COVID-19 can also cause liver damage. Drug-induced liver injury (DILI) is a known side effect of various antiviral drugs, antibiotics, and anti-inflammatory medications. Commonly implicated drugs include remdesivir, lopinavir/ritonavir, and tocilizumab. The risk of DILI can be higher in patients with pre-existing liver conditions or severe infections.
Additionally, severe COVID-19 can lead to reduced oxygen supply to tissues, known as hypoxia. The liver needs a consistent oxygen supply, and prolonged hypoxia can damage liver cells. Ischemic injury, resulting from reduced blood flow, can also contribute to liver dysfunction in critically ill patients.
Clinical Signs of Liver Involvement
Liver involvement in COVID-19 is often identified through laboratory findings. Elevated levels of liver enzymes in blood tests are a common indicator of liver injury. These enzymes include alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). An increase in these enzyme levels suggests damage to liver cells, causing them to release their contents into the bloodstream.
The pattern and extent of enzyme elevation can provide clues about the type of liver injury. High levels of ALT and AST typically point to hepatocellular injury or inflammation of the liver, often referred to as hepatitis. Elevated ALP and GGT can indicate cholestasis, a condition where bile flow from the liver is impaired. Liver injury, identified by abnormal liver function tests, has been reported in 15% to over 50% of hospitalized COVID-19 patients.
While liver involvement is frequently detected through blood tests, some patients may experience symptoms, particularly in more severe cases. These can include fatigue, abdominal pain, and jaundice (yellowing of the skin and eyes). However, many individuals with liver enzyme abnormalities due to COVID-19 do not exhibit any noticeable symptoms, making routine blood monitoring important for detection.
Factors Increasing Susceptibility
Several factors can increase the likelihood of liver damage during a COVID-19 infection. The severity of the COVID-19 illness is a primary factor. Patients with more severe forms of the disease, particularly those requiring hospitalization, intensive care unit (ICU) admission, or mechanical ventilation, have a notably higher incidence of liver involvement. Liver injury has been observed in a substantial percentage of severe cases, with some studies reporting rates as high as 58% to 78%.
Pre-existing liver conditions also increase vulnerability to COVID-19-induced liver injury. Individuals with chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD), cirrhosis, or chronic viral hepatitis (B or C), are at greater risk. For these patients, COVID-19 can exacerbate their underlying liver disease, potentially leading to a worsening of their condition or even liver decompensation. Patients with cirrhosis, for example, have shown a higher risk of severe COVID-19 and increased mortality.
Other underlying health conditions, such as diabetes, obesity, and cardiovascular disease, can also elevate the risk of liver damage. These conditions can contribute to systemic inflammation and metabolic dysfunction, making the liver more susceptible to COVID-19 effects. While age can play a role in overall COVID-19 severity, its direct impact on liver susceptibility is less clear, though older patients with pre-existing conditions may face higher risks.
Resolution and Persistent Effects
Liver enzyme abnormalities observed during acute COVID-19 are typically transient. As patients recover from the infection, these elevated enzyme levels usually return to normal. Studies show that a majority of patients experience normalization of their liver function tests within weeks to months after discharge. This suggests that for many, the liver injury associated with COVID-19 is temporary and self-limiting.
However, liver abnormalities can persist in some individuals, particularly as part of “Long COVID.” A proportion of patients may continue to have abnormal liver function tests for several months post-infection. For example, persistent elevations in GGT levels have been noted even after other liver enzymes normalize. The presence of pre-existing liver disease appears to increase the likelihood of these persistent abnormalities.
For individuals with pre-existing liver conditions or those who experienced severe COVID-19, ongoing monitoring of liver function may be advised. While severe, irreversible liver damage or acute liver failure as a direct consequence of COVID-19 is rare, the possibility of long-term fibrosis (scarring) has been suggested in some cases, particularly in individuals with pre-existing chronic liver disease. Consulting a healthcare professional for persistent symptoms or concerns related to liver health after COVID-19 is always recommended.