Medication-Induced Hyperbilirubinemia

Antiviral Medications

Simeprevir commonly causes indirect bilirubin elevations without ALT elevations, requiring monitoring during treatment, as recommended by the American Association for the Study of Liver Diseases 1, 2
Paritaprevir (especially when ritonavir-boosted) causes transient increases in indirect serum bilirubin through inhibition of bilirubin transporters OATP1B1 and OATP1B3, according to the European Association for the Study of the Liver 3, 4

Ribavirin causes hemolysis which contributes to indirect hyperbilirubinemia, as reported by the American Association for the Study of Liver Diseases 5, 1
Combination therapy with ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir can cause indirect bilirubin increases, particularly in patients with cirrhosis, as noted by the European Association for the Study of the Liver 3, 4

Estrogen-containing medications are associated with greater risk of ALT elevations when used with certain antivirals, potentially affecting bilirubin metabolism, as suggested by the European Association for the Study of the Liver 3
Experimental drugs for COVID-19 (remdesivir, chloroquine, hydroxychloroquine, tocilizumab) may induce liver toxicity potentially affecting bilirubin levels, according to the Clinical and Molecular Hepatology journal 6

Cirrhosis increases the risk of medication-induced bilirubin elevations, with greater frequency of total bilirubin increases observed in patients with cirrhosis taking certain antivirals, as reported by the European Association for the Study of the Liver 3, 4

For patients receiving medications known to affect bilirubin, monitor liver function tests regularly, particularly when starting therapy, as recommended by the American Association for the Study of Liver Diseases 5, 1
For patients with elevated bilirubin, determine whether hyperbilirubinemia is predominantly unconjugated or conjugated to help narrow the differential diagnosis, as suggested by the American Association for the Study of Liver Diseases 1, 2