The COVID-19 pandemic, caused by the SARS-CoV-2 virus, primarily impacts the respiratory system. However, the virus can also influence other organ systems, including the liver. This article explores how COVID-19 interacts with the liver, from initial infection to potential long-term implications.
How COVID-19 Affects the Liver
The SARS-CoV-2 virus can influence liver function through several biological mechanisms. One proposed pathway involves the direct infection of liver cells. While the virus primarily targets the respiratory tract, both hepatocytes (main liver cells) and cholangiocytes (bile duct cells) express the angiotensin-converting enzyme 2 (ACE2) receptor, which the virus uses to enter host cells. Studies suggest that SARS-CoV-2 can infect human hepatocytes and cholangiocytes, leading to viral replication and potential cell damage.
Beyond direct viral infection, systemic inflammation, often referred to as a “cytokine storm,” contributes significantly to liver injury during COVID-19. This exaggerated immune response releases a flood of pro-inflammatory molecules, such as interleukin-6 (IL-6), that can cause widespread tissue damage, including in the liver. This inflammatory state can lead to conditions like bystander hepatitis, where the liver is damaged as a secondary effect of the body’s overall immune overreaction.
Drug-induced liver injury (DILI) is another factor contributing to liver involvement in COVID-19 patients. Many medications used to treat COVID-19, including antiviral drugs like remdesivir and lopinavir/ritonavir, as well as anti-inflammatory agents, have been associated with hepatotoxicity. These drugs can cause elevations in liver enzymes, and their potential for liver damage necessitates careful monitoring, especially in patients with pre-existing liver conditions.
Severe respiratory illness from COVID-19 can also lead to hypoxia, a condition of insufficient oxygen supply to tissues. The liver is highly sensitive to oxygen deprivation, and prolonged hypoxia can cause liver cell damage and even cell death. This ischemic or hypoxic liver injury can be exacerbated by conditions like lung and cardiac failure, which are common in severe COVID-19 cases.
Liver Changes During Acute COVID-19
During an active COVID-19 infection, changes in liver function tests are common. Elevated levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), are frequently reported in COVID-19 patients. These elevations indicate varying degrees of liver cell damage or issues with bile flow.
Specifically, elevated ALT and AST levels typically suggest hepatocellular damage, meaning injury to the main liver cells. AST levels may sometimes be higher than ALT levels. The pooled incidence of elevated liver enzymes on presentation in COVID-19 patients has been reported to be around 23.1%.
Increases in ALP and GGT, along with bilirubin levels, can indicate a cholestatic pattern of injury, pointing to problems with bile ducts or bile flow. While liver enzyme abnormalities are common, they are often mild to moderate and transient, resolving as the patient recovers from the acute infection. The severity of these liver changes can correlate with the overall severity of COVID-19, with higher enzyme levels often seen in patients with more severe disease or those requiring intensive care unit admission.
Impact on Individuals with Pre-existing Liver Conditions
Individuals with chronic liver diseases face increased risks when infected with SARS-CoV-2. Conditions such as cirrhosis, non-alcoholic fatty liver disease (NAFLD), and autoimmune hepatitis can make patients more vulnerable to severe COVID-19 outcomes, including higher rates of hospitalization and mortality. This heightened susceptibility is partly due to a compromised immune system and reduced liver reserve in these individuals.
Patients with cirrhosis, particularly those with decompensated cirrhosis, are at a higher risk for severe COVID-19 disease and may experience new onset organ failures, such as acute-on-chronic liver failure. The presence of comorbidities like diabetes and hypertension, which are often seen alongside chronic liver disease, further increases the risk of severe outcomes.
Liver transplant recipients are also a group of concern due to their immunosuppressed state. While studies have yielded inconsistent findings, some research indicates that liver transplant recipients may have increased rates of inpatient mortality and transplant rejection during the pandemic compared to the pre-pandemic period. However, other studies have found no significant difference in death or hospitalization rates due to COVID-19 between liver transplant recipients and control groups.
Liver Health After COVID-19 Recovery
After recovering from the acute phase of COVID-19, some individuals may experience lingering or new liver issues, a phenomenon often associated with “long COVID.” Observations indicate that mild liver enzyme elevations can persist for weeks or even months after the initial infection. These persistent abnormalities, including elevated ALT, AST, GGT, and lactate dehydrogenase (LDH), may suggest ongoing inflammation or early-stage fibrosis.
New onset of conditions like fatty liver disease, specifically metabolic-associated fatty liver disease (MAFLD), has been observed in some individuals post-COVID-19 infection. A study found that MAFLD was highly prevalent in patients hospitalized for severe COVID-19, with rates increasing from 37.3% on admission to 55.3% during follow-up. This suggests a potential link between COVID-19 and the development or exacerbation of metabolic liver conditions.
While severe long-term liver damage directly attributable to COVID-19 is uncommon for the general population, monitoring is warranted, especially for those who experienced significant acute liver involvement. Persistent liver stiffness, which can indicate inflammation or scar tissue buildup (fibrosis), has been reported in COVID-19 patients months after infection, although the long-term clinical implications are still under investigation. For patients with cirrhosis, COVID-19 has been associated with long-term mortality even after recovery from the respiratory infection, and long COVID symptoms are seen in about a third of these survivors.