Jaundice is the yellowing of the skin and eyes that occurs when there is an excessive buildup of bilirubin, a yellowish pigment, in the blood. Human Immunodeficiency Virus (HIV) is a viral infection that attacks the immune system, gradually weakening the body’s defenses against other diseases. While HIV itself does not directly cause the sudden onset of jaundice, the chronic infection and the treatments used to manage it frequently lead to complications that result in liver injury and subsequent bilirubin accumulation. Therefore, jaundice in a person with HIV is typically a sign of an underlying liver issue stemming from the virus’s long-term effects, co-infections, or medication side effects.
The Direct Relationship Between HIV and Liver Function
Chronic HIV infection creates a state of persistent inflammation and immune activation, placing continuous stress on the liver. The virus can directly affect liver cells, including Kupffer cells and hepatic stellate cells. This ongoing systemic inflammation involves the release of specific signaling proteins called cytokines, which can promote subtle hepatotoxicity, or chemical-driven liver damage, over time.
This chronic activation often leads to fibrosis, which is the scarring of liver tissue. The HIV envelope protein, gp120, promotes this pro-fibrotic effect by activating hepatic stellate cells, which are the primary source of collagen in an injured liver. This accelerated scarring gradually diminishes the liver’s ability to function and process bilirubin effectively. Over years, this low-grade damage increases the risk of more severe liver disease.
Jaundice Caused by Viral Co-Infections
Viral co-infections, particularly with Hepatitis B (HBV) and Hepatitis C (HCV), are the most common and serious causes of severe liver disease and jaundice in people with HIV. These viruses share similar transmission routes, resulting in a high rate of co-infection; approximately one in four people with HIV have or have had HCV. HIV accelerates the progression of viral hepatitis because the compromised immune system is less effective at controlling the hepatitis viruses.
This immune dysfunction allows HBV and HCV to cause more rapid and extensive liver damage, resulting in faster progression to cirrhosis and liver failure. This rapid deterioration impairs the liver’s capacity to clear bilirubin from the bloodstream, leading to jaundice. Acute infections with Hepatitis A (HAV) or HBV can also cause severe liver inflammation and subsequent jaundice, which is often more prolonged and severe in a person with HIV. Screening for these viral co-infections is a standard component of HIV care.
Jaundice Caused by Antiretroviral Therapy
The life-saving medications used to manage HIV, known as Antiretroviral Therapy (ART), can sometimes cause drug-induced liver injury (DILI), which may manifest as jaundice. This hepatotoxicity is a side effect of certain antiretroviral drugs, which can lead to elevated liver enzymes and, in severe cases, liver damage. Older generations of drugs, such as certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some protease inhibitors (PIs), were historically associated with a higher risk of DILI.
A distinct mechanism of jaundice is specifically linked to certain protease inhibitors, notably atazanavir and indinavir. These drugs inhibit a liver enzyme called UDP-glucuronosyl transferase (UGT), which processes bilirubin. This inhibition leads to the accumulation of unconjugated bilirubin in the blood, a condition known as hyperbilirubinemia, causing visible jaundice. While visually concerning, this type of jaundice is often not associated with underlying liver cell damage, unlike DILI, and is functionally similar to a condition called Gilbert’s syndrome.
Monitoring and Treating Liver Issues in HIV Patients
Because liver complications are a leading cause of illness and death in people with HIV, routine monitoring of liver health is an important part of clinical management. Liver function tests (LFTs) and bilirubin levels are regularly checked through blood tests to detect early signs of hepatic impairment. Elevated liver enzymes, such as AST and ALT, signal injury to liver cells, while a rise in bilirubin indicates impaired processing or bile flow obstruction.
If jaundice is observed, the immediate goal is to determine the underlying cause, whether it is an acute viral infection, drug-related toxicity, or advanced cirrhosis. Treatment strategies are tailored to the specific diagnosis. For instance, drug-induced liver injury (DILI) may require adjusting the ART regimen or switching to a drug with a lower risk of hepatotoxicity. For viral co-infections, treating the hepatitis virus with specific medications, such as direct-acting antivirals for HCV, is crucial to prevent further liver damage and resolve the jaundice.