Impact of early elevation of serum bilirubin during treatment with pegylated interferon and ribavirin in patients with chronic hepatitis C

Aim: Hemolytic anemia is a well-known adverse effect of interferon and ribavirin combination treatment. Herein, we analyzed the impact of early elevation of serum bilirubin level as a marker for predicting severe anemia during treatment. Methods: We studied 245 chronic hepatitis C patients who received pegylated interferon and ribavirin combination treatment, and divided them using two different threshold levels: (i) elevation of total bilirubin of 0.5 mg/dL or more within 1 week of starting treatment; and (ii) drop of hemoglobin (Hb) by 3 g/dL or more within 4 weeks of starting treatment. We compared the dynamics in each group and then investigated independent factors for predicting a severe Hb drop (≥3 g/dL) at 4 weeks after beginning treatment and dose reduction of ribavirin. Results: Total bilirubin levels at 1 week were significantly higher in patients with a Hb drop of 3 g/dL or more as compared to those with a drop of less than 3 g/dL (P < 0.0001). Hb levels at 4 weeks were significantly lower in the group of 0.5 mg/dL or more increase of total bilirubin levels than in the group with a less than 0.5 mg/dL increase (P < 0.0001). Therefore, elevation of total bilirubin after 1 week of treatment was shown to be an independent factor for predicting severe Hb drop (≥3 g/dL) at 4 weeks (P < 0.0001), and dose reduction of ribavirin during treatment (P = 0.0321). Conclusion: Early elevation of serum bilirubin level was found to be a possible predictive marker of both a severe drop of Hb in the early phase of treatment and dose reduction of ribavirin.