From the Guidelines
Methamphetamines can cause hyperbilirubinemia, which is an elevated level of bilirubin in the blood, primarily through their toxic effects on the liver, as evidenced by studies on drug-induced liver injury 1. This occurs through methamphetamine's direct hepatotoxic effects, which can damage liver cells, and the metabolic stress, hyperthermia, and oxidative damage associated with methamphetamine use, further compromising liver function. Additionally, methamphetamine can cause rhabdomyolysis (muscle breakdown), which releases myoglobin that can damage the liver and kidneys, potentially contributing to hyperbilirubinemia. Users of methamphetamine who develop symptoms like yellowing of the skin or eyes (jaundice), dark urine, light-colored stools, or abdominal pain should seek immediate medical attention, as these may indicate liver dysfunction and hyperbilirubinemia. Some key points to consider in the evaluation of hyperbilirubinemia include:
- Determining whether the hyperbilirubinemia is conjugated (direct) or unconjugated (indirect) 1
- Evaluating patients with evidence of hyperbilirubinemia and cholestasis when serum bilirubin and alkaline phosphatase elevations are in excess of the aminotransferase elevations
- Considering the patient's clinical scenario and performing elective radiologic and serologic evaluations as necessary
- Being aware of the potential for methamphetamine use to cause liver injury or exacerbate existing liver conditions, leading to impaired bilirubin processing and clearance. Treatment typically involves cessation of methamphetamine use and supportive care for liver function. It is essential to closely monitor patients with cholestatic liver disease for signs of DILI, especially those with underlying synthetic function impairment, as persistent isolated elevations of direct bilirubin may be a sign of DILI 1.
From the Research
Methamphetamines and Hyperbilirubinemia
- Methamphetamines can cause liver damage, which may lead to hyperbilirubinemia, as seen in a case study where a 41-year-old man presented with psychosis, hyperthermia, rhabdomyolysis, and liver dysfunction after intravenous methamphetamine use, with total serum bilirubin peaking at 8.6 mg/dL 2.
- Hyperbilirubinemia is a common finding in individuals with a history of substance abuse, and it may not always indicate a serious disorder of liver function 3.
- Drug-induced hyperbilirubinemia can occur through various mechanisms, including inhibition of the enzyme UDP-glucuronosyl transferase-1A1, which is responsible for conjugating bilirubin with glucuronic acid, as seen with the antiretroviral drug atazanavir 3.
- Methamphetamine-induced hepatotoxicity may involve mitochondrial dysfunction, with reactive oxygen species formation, lipid peroxidation, and rapid glutathione depletion, leading to mitochondrial membrane damage and release of cytochrome c into the cytosol 4.
- Methamphetamine can cause acute hyperthermia-dependent liver damage, with changes in hepatocellular morphology and functional liver damage, including increased plasma ammonia concentrations, which can be prevented by blocking methamphetamine-induced hyperthermia 5.
Key Findings
- Methamphetamines can cause liver damage and hyperbilirubinemia through various mechanisms.
- Hyperbilirubinemia is a common finding in individuals with a history of substance abuse.
- Methamphetamine-induced hepatotoxicity may involve mitochondrial dysfunction and hyperthermia-dependent liver damage.
- The exact cellular and molecular mechanisms involved in methamphetamine-induced hepatotoxicity have not yet been completely understood, but studies suggest that oxidative stress and mitochondrial damage play a role 2, 4, 5.