| Early
Bilirubin Elevation May Predict Severe Anemia during Interferon/ribavirin Treatment
for Chronic Hepatitis C By
Liz Highleyman  | Elevated
total bilirubin levels during the first few days of treatment with interferon
plus ribavirin can help predict which patients will develop severe hemolytic anemia
as a side effect of ribavirin, according to research presented at the 2009 Digestive
Disease Week meeting (DDW 2009) last month in Chicago. |
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. | 
