Short Communication: Fasting Increases Serum Concentrations of Bilirubin in Patients Receiving Atazanavir: Results from a Pilot Study

Abstract

Unconjugated hyperbilirubinemia resulting from therapy with atazanavir is physiologically related to hyperbilirubinemia in Gilbert's syndrome (GS). In patients with GS, changes in diet have a significant impact on bilirubinemia. Our aim was to investigate whether changes in diet affect the level of serum bilirubin in patients receiving atazanavir. Thirty patients on stable therapy with ritonavir-boosted atazanavir without evidence of GS were enrolled. Hemolysis and chronic hepatitis were excluded. After a baseline period of normal intake of calories, the patients were randomized to follow a 24-h 400-calorie diet (fasting), then a 48-h period of normal calorie intake and, afterward, a 24-h period of a high-calorie diet, or the same interventions in inverse order. Serum bilirubin concentrations were measured before and after each intervention. A high adherence to the recommended diet was observed. The mean unconjugated bilirubin concentration before the high-calorie diet was 2.79±1.53 mg/dl and after such intervention it was 2.70±1.40 mg/dl. The mean difference between preintervention and postintervention was -0.08±0.69 mg/dl (p=NS). The mean unconjugated bilirubin concentration before the fasting diet was 2.31±1.23 mg/dl and it was 3.84±1.90 mg/dl after. The mean difference between prefasting and postfasting was 1.53±1.17 mg/dl (p=0.001). According to these results, short periods of fasting seem to increase the unconjugated bilirubin concentration in patients on atazanavir. A high-calorie diet did not have any impact in bilirubin probably because most patients follow similar diets in their everyday life.

Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants

“…A study by Lopardo and colleagues in 2013 showed that fasting increases serum concentrations of Bilirubin in patients receiving atazanavir therapy for HIV 5. However, it should be noted that food affects atazanavir levels and the drug itself causes hyperbilirubinaemia 5.…”

“…A study by Lopardo and colleagues in 2013 showed that fasting increases serum concentrations of Bilirubin in patients receiving atazanavir therapy for HIV 5. However, it should be noted that food affects atazanavir levels and the drug itself causes hyperbilirubinaemia 5. Lopardo and colleagues propose that an increased hepatic uptake of non-esterified fatty acids interferes with the hepatic clearance of bilirubin and thus contributes to the unconjugated hyperbilirubinaemia of fasting 5.…”

“…However, it should be noted that food affects atazanavir levels and the drug itself causes hyperbilirubinaemia 5. Lopardo and colleagues propose that an increased hepatic uptake of non-esterified fatty acids interferes with the hepatic clearance of bilirubin and thus contributes to the unconjugated hyperbilirubinaemia of fasting 5. Similar mechanisms may be at work in healthy males.…”