Hepatitis C

Early Bilirubin Elevation May Predict Severe Anemia during Interferon/ribavirin Treatment for Chronic Hepatitis C

Hemolytic anemia, or blood cell destruction, is a well known side effect ribavirin used in combination interferon-based therapy for chronic hepatitis C virus (HCV) infection. Severe anemia may necessitate ribavirin dose reduction or discontinuation, but adequate ribavirin helps prevent relapse and ensure sustained response.

Bilirubin (a pigment produced during breakdown of red blood cells) may be a marker of both liver injury and hemolytic anemia. In this study, Japanese researchers noted that some patients starting interferon-based therapy had markedly elevated total bilirubin levels within just 1 week after starting treatment. The investigators looked at the characteristics of these patients and sought to determine whether early bilirubin elevation could be used as a predictive marker of hemolytic anemia.

The study included 253 patients who received conventional or pegylated interferon plus ribavirin. The researchers measured levels of hemoglobin, total bilirubin, ALT, AST, and gamma-GTP at baseline and at 1, 2, 4, 6, 8, 12, and 24 weeks after the treatment initiation.

Results

• 78 out of 253 patients (30.8%) experienced more than a 0.5 mg/dL elevation in total bilirubin 1 week after starting treatment.
• Hemoglobin levels dropped from 14.1 g/dL at baseline to 11.1 g/dL at week 4 in patients with total bilirubin elevation > 5 mg/dL.
• Hemoglobin decreased from 13.7 g/dL at baseline to 12.1 g/dL at week 4 in participants total bilirubin elevation < 0.5mg/dL.
• Hemoglobin levels at week 4 were significantly lower in patients with total bilirubin elevation > 0.5 mg/dL at 1 week (P < 0.0001).
• Total bilirubin levels rose from 0.92 mg/dL at baseline to 1.56 mg/dL at week 1 in patients with a hemoglobin decrease of > 3 g/dL within 4 weeks, but only rose to 0.97 mg/dL at week 1 in those with a smaller (< 3 g/dL) hemoglobin decrease.
• Total bilirubin levels at week 1 were significantly higher in patients with a hemoglobin decrease > 3 g/dL within 4 weeks (P < 0.0001).
• A total bilirubin elevation > 0.5 mg/dL at week 1 predicted a hemoglobin decrease > 3 g/dL at week 4 with 78.3% accuracy, 55.1% sensitivity, and 88.6% specificity.
• The positive predictive value was 68.3% and the negative predictive value was 81.6%.

Early elevation of total bilirubin levels during interferon plus ribavirin treatment could predict following severe hemolytic anemia within 4 weeks after start of treatment," the researchers concluded.

Although total bilirubin is determined only after starting treatment, they suggested, "this could be an easy and routine[ly]-used marker to determine the proper dose, especially for ribavirin."

Department of Gastroenterology, Nagoya University School of Medicine, Nagoya, Japan.

7/7/09

Reference

M Ishigami, K Hayashi, Y Katano, and others. Early Elevation of Total Bilirubin During Interferon (IFN) and Ribavirin (Rib) Combination Therapy Could Predict Early Phase Severe Hemolytic Anemia As a Critical Side Effect for Continuing Treatment. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract M1800.