Liver involvement is a common complication observed in patients with COVID-19, often manifesting as a sign of systemic distress. The presence of the SARS-CoV-2 virus can lead to various degrees of liver injury, which is frequently indicated by abnormal blood tests. These abnormalities suggest that the liver is under stress during the infection, whether from the virus itself or the body’s reaction to it. Liver dysfunction in patients with COVID-19 is a predictor of disease progression and severity.
How COVID-19 Affects the Liver
The SARS-CoV-2 virus causes acute liver damage through both direct and indirect mechanisms. The virus enters human cells by binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor, which is expressed on liver cells, including hepatocytes and cholangiocytes. Although ACE2 expression is lower in the liver than in the lungs, its presence allows for direct viral entry, which can lead to cellular damage and death, known as cytotoxicity.
A primary cause of liver injury is the body’s overwhelming inflammatory response, often called a cytokine storm. This severe systemic inflammation releases excessive signaling proteins that cause widespread tissue damage, including in the liver. The inflammatory state can cause hepatocellular apoptosis, or programmed cell death, and contribute to generalized sepsis that further stresses liver tissue.
Indirectly, the severe pneumonia and respiratory distress caused by COVID-19 can lead to hypoxia, or low oxygen levels, throughout the body. The liver is particularly vulnerable to this lack of oxygen, which results in hypoxic-ischemic liver injury. This acute injury is observed through elevated levels of liver enzymes, specifically Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST). These enzymes leak into the bloodstream when liver cells are damaged, signaling acute hepatocellular injury during the infection.
Pre-existing Liver Conditions and COVID Risk
Patients who already have chronic liver disease (CLD) face a significantly increased risk of severe outcomes from COVID-19 infection. Individuals with CLD have a heightened vulnerability driven by the liver’s already compromised state and the systemic effects of chronic illness. A meta-analysis showed that individuals with CLD had a risk of severe COVID-19 that was more than double the risk for those without liver disease.
Non-Alcoholic Fatty Liver Disease (NAFLD), also referred to as Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), is a common pre-existing condition posing a substantial risk for severe COVID-19 illness. Patients with NAFLD often have co-occurring conditions like diabetes and obesity, which combine to create a pro-inflammatory environment. The presence of advanced fibrosis in NAFLD patients is associated with more severe COVID-19 outcomes.
For patients with advanced liver scarring, known as cirrhosis, the risk is particularly high. A severe COVID-19 infection can trigger acute-on-chronic liver failure, a rapid deterioration of liver function that carries a high mortality rate. Immunosuppression in patients who have undergone liver transplants also increases the risk of severe COVID-19, requiring careful management of anti-rejection medications during the infection.
Drug-Induced Liver Injury During COVID Treatment
Medications used to treat COVID-19 can cause liver injury, known as Drug-Induced Liver Injury (DILI), separate from the viral-induced damage. DILI requires careful monitoring of liver function tests (LFTs) during treatment. Antiviral medications are a common cause of this injury; drugs like remdesivir and the combination of lopinavir/ritonavir are associated with elevated serum aminotransferase levels.
Immunomodulators, such as tocilizumab, used to control the cytokine storm, can also cause transient elevations in hepatic enzymes. Even supportive care medications, including high-dose acetaminophen (Tylenol), can become hepatotoxic if the patient is nutritionally compromised or the dosage is too high. The cumulative prevalence of acute liver injury in COVID-19 patients has been reported to be as high as nearly 24%, with medication being a major contributing factor.
The risk of DILI often correlates with the dosage and duration of treatments and is more pronounced in patients with pre-existing chronic liver disease. The injury mechanism for many antivirals involves interference with liver metabolism through the cytochrome P450 (CYP) enzyme system. Clinicians must balance aggressive COVID-19 treatment with the potential for medication-related harm to the liver, often necessitating frequent LFT checks.
Monitoring Liver Health After Infection
For the majority of patients who experience liver enzyme elevation during the acute phase of COVID-19, liver function typically resolves. Studies tracking recovery have shown that for many, elevated liver enzymes normalize within weeks to a few months after discharge. However, a subset of patients, particularly those with severe initial disease or pre-existing liver conditions, may show persistent abnormalities for six months or longer.
Follow-up Liver Function Tests (LFTs) are recommended for individuals with severe initial injury or those who continue to experience symptoms like persistent fatigue or jaundice. The continued presence of abnormal LFTs, such as elevated Alkaline Phosphatase (ALP) or Gamma-Glutamyl Transferase (GGT), may suggest ongoing issues and warrant further investigation. Persistent liver function abnormalities during follow-up are more frequently observed in patients who had pre-existing conditions.
To support liver recovery, general lifestyle recommendations are beneficial for all patients who had significant liver involvement. Avoiding alcohol consumption and managing diet to support a healthy weight can help the liver regenerate and reduce stress on the organ. Regular monitoring is important for those who had severe COVID-19, as liver injury can sometimes be a subtle component of post-acute sequelae.