A Study to Evaluate the Erythropoietic Response in Hepatitis C Virus (HCV) Patients Receiving Combination Ribavirin (RBV)/Interferon (IFN) Therapy or RBV/PEG IFN (NATURAL HISTORY-HCV)
A Study to Evaluate the Erythropoietic Response in Hepatitis C Virus (HCV) Patients Receiving Combination Ribavirin (RBV)/Interferon (IFN) Therapy or RBV/PEG IFN (NATURAL HISTORY-HCV)
The purpose of this study was to describe the time course and extent of hemoglobin (Hb)
 changes and the erythropoietic response to PEG-IFN/RBV-induced anemia In HCV-infected
 subjects.
Patients receiving combination therapy for chronic hepatitis C virus (HCV) infection
 (standard or pegylated interferon alfa [PEG-IFN] in combination with ribavirin [RBV])
 frequently develop moderate to severe anemia. In large, prospective, clinical trials of
 PEG-IFN alfa-2b and PEG-IFN alfa-2a, the reported mean decreases in hemoglobin (Hb) were 2.5
 g/dL and 3.7 g/dL, respectively. Furthermore, in a retrospective study, 54% of standard
 interferon/RBV-treated patients had hemoglobin (Hb) decreases of at least 3 g/dL. It is
 important to understand the causes, natural history, and risk factors associated with HCV
 therapy-induced anemia, because such decreases in Hb can result in RBV dose reduction or
 discontinuation, which may adversely affect the likelihood of a virologic response.
 Erythropoietin is an endogenous hormone that acts in the bone marrow to increase the number
 of erythroid progenitor cells. Normally, a decrease in the Hb level is accompanied by an
 increase in the serum erythropoietin (sEPO) level, which will ultimately normalize the Hb
 level. The relationship between Hb and sEPO is less apparent in patients with chronic
 diseases such as cancer and human immunodeficiency virus (HIV) infection. It is not known
 whether HCV-infected patients receiving combination PEG-IFN/RBV therapy have a similarly
 diminished erythropoietic response to anemia.

 One hundred HCV-infected patients who are receiving combination RBV/IFN or RBV/PEG-IFN
 therapy will be enrolled in this multicenter study. No study medication will be administered
 during this study. Weekly blood samples will be collected at specified times during the
 initial 8 weeks of RBV/IFN or RBV/PEG-IFN therapy. Assessment of laboratory tests, vital
 signs, incidence and severity of adverse experiences will be obtained.

 The objective of this study is to document the pattern of hemoglobin changes and
 erythropoietic response (from baseline to final assessment, up to Week 8) in HCV-infected
 patients receiving combination therapy with RBV/IFN or RBV/PEG-IFN. N/A
Inclusion Criteria:

 -  Signed Informed Consent

 -  HCV- infected patients confirmed by PCR or branched DNA (b-DNA)

 -  Scheduled to commence combination RBV/IFN or RBV/PEG-IFN therapy on Day 1

 -  Normal serum creatinine

 -  Life expectancy > 6 months

 Exclusion Criteria:

 -  HIV-infected patients

 -  History of any primary hematologic disease

 -  Anemia attributable to factors such as iron or folate deficiency, pre-treatment

 -  hemolysis or gastrointestinal bleeding

 -  Has suspected or confirmed significant hepatic disease from an etiology other than

 -  HCV (e.g. alcohol, HBV, autoimmune disease etc)

 -  Current, active substance abuser

 -  Pregnant or breast feeding

 -  Women of childbearing potential not taking adequate birth control measures

 -  Exposure to Epoetin alfa within three (3) months prior to study enrollment or during
 study

 -  Transfusion within three (3) months prior to study entry