Objective Hyperbilirubinaemia (HB) is common in HIV and hepatitis C virus (HIV–HCV) co-infected patients and poses a unique challenge in management as it may be due to medications such as the protease inhibitors (PIs) or to hepatic dysfunction. There are no data on the relationship of HB to liver histology and PI use in this population. Clinicians caring for these patients are faced with the difficult task of determining whether increasing serum bilirubin is due to drug effects or progression of liver disease.

Methods To address this gap in knowledge, we performed a retrospective analysis of 344 consecutive HIV–HCV co-infected patients undergoing liver biopsy to identify factors associated with HB. Demographic, clinical, laboratory data were collected. Advanced fibrosis was defined as bridging fibrosis or cirrhosis. Those with hepatitis B virus, hepatic decompensation or hepatocellular carcinoma were excluded.

Results The prevalence of HB (range 1.3–9.4) was 33% and more common in those on a PI (46%) than those who were not (10%; p≤0.001) and mostly in those on indinavir (40%) or atazanavir (46%). Of the patients on these PIs, HB was not associated with fibrosis grade, demographics, or other clinical variables. Conversely, in those not on a PI, HB was associated with fibrosis grade (p≤0.0001) after adjusting for other clinical and demographic variables.

Conclusions In the setting of indinavir or atazanavir use, HB is common and unrelated to underlying disease severity and the medications can be continued safely. Conversely, HB in HIV–HCV co-infected patients not on a PI is due to their underlying liver disease and suggests these patients require closer monitoring.