Factors Affecting Treatment-Induced Anemia and Virologic Responses in Chronic Hepatitis C Patients
Date Issued
2012
Date
2012
Author(s)
Hsu, Shih-Jer
Abstract
Background
Chronic hepatitis C (CHC) is a major cause of chronic liver disease both domestically and on a global scale. Pegylated interferon (Peg-IFN) in combination with ribavirin constitutes the current standard of care for CHC in most Asian countries. More than 60% of Asian CHC patients achieved sustained virologic response with combination therapy. Ribavirin-related hemolytic anemia is a common side effect of combination therapy and often leads to dose reduction or treatment discontinuation. Ribavirin dose reduction may compromise treatment responses. Noteworthy that recent studies revealed CHC patients with treatment-induced anemia achieved better virologic responses than those without. The association of treatment-induced anemia with virologic responses needs further investigation. Aim of the study The aim of this study was to evaluate the association between treatment-induced anemia and treatment outcomes in CHC patients. Factors predictive of virologic responses and treatment-induced anemia respectively will be analyzed as well. Methods We retrospectively enrolled naive HCV genotype 1 CHC patients who received Peg-IFN and ribavirin therapy. The treatment duration of enrolled patients was at least 4 weeks. The baseline demographics and patient characteristics were recorded, as well as on-treatment hemoglobin changes and ribavirin dosage. The virologic responses were evaluated. Genetic polymorphisms in the IL28B gene (rs8099917) and ITPA gene (rs1127354) were determined. Statistical analyses were performed to analyze factors predictive of treatment-induced anemia and treatment outcomes. Results A total of 313 patients were enrolled. All patients finished treatment except three who lost to follow-up before treatment completed. On-treatment virologic responses were determined for all patients in an intent-to-treat fashion. Sustained virologic response (SVR) was determined for 295 patients who finished posttreatment follow-up. The overall rapid virologic response (RVR) and SVR rates were 63% and 72%, respectively; the relapse rate was 23%. One hundred patients (32%) had hemoglobin decline >3 g/dL from baseline at week 4 of treatment. Thirty-eight patients (12%) had hemoglobin level <10 g/dL at week 4. The factors predictive of RVR included male gender (OR 2.11; P =0.006), baseline platelet count >180 ×103/μL (OR 1.96; P =0.021), baseline viral load <800,000 IU/mL (OR 4.35; P <0.001), rs8099917 genotype TT (OR 4.31; P <0.001), and rs1127354 genotype CC (OR 2.23; P =0.005). The predicting factors of SVR were male gender and achievement of RVR. Patient categories at risk of hemoglobin decline >3 g/dL at week 4 were age >55 years (OR 2.70; P =0.001), baseline hemoglobin >16 g/dL (OR 4.07; P <0.001), and rs1127354 genotype CC (OR 15.85; P <0.001). Age >55 years (OR 2.55; P =0.042), baseline hemoglobin <14 g/dL (OR 5.88; P <0.001), estimated glomerular filtration rate <60 ml/min/1.73m2 (OR 2.71; P =0.037), and rs1127354 genotype CC (OR 28.10; P =0.002) were predicting factors of hemoglobin level <10 g/dL at week 4. The magnitude of hemoglobin decline at week 4 was correlated with RVR rate. Conclusion For chronic hepatitis C patients receiving PegIFN plus ribavirin therapy, factors predictive of treatment-induced anemia are ITPA genetic polymorphism, baseline hemoglobin level, age, and renal function. ITPA genetic polymorphism is an independent factor of RVR. Treatment-induced anemia is also associated with treatment responses.
Chronic hepatitis C (CHC) is a major cause of chronic liver disease both domestically and on a global scale. Pegylated interferon (Peg-IFN) in combination with ribavirin constitutes the current standard of care for CHC in most Asian countries. More than 60% of Asian CHC patients achieved sustained virologic response with combination therapy. Ribavirin-related hemolytic anemia is a common side effect of combination therapy and often leads to dose reduction or treatment discontinuation. Ribavirin dose reduction may compromise treatment responses. Noteworthy that recent studies revealed CHC patients with treatment-induced anemia achieved better virologic responses than those without. The association of treatment-induced anemia with virologic responses needs further investigation. Aim of the study The aim of this study was to evaluate the association between treatment-induced anemia and treatment outcomes in CHC patients. Factors predictive of virologic responses and treatment-induced anemia respectively will be analyzed as well. Methods We retrospectively enrolled naive HCV genotype 1 CHC patients who received Peg-IFN and ribavirin therapy. The treatment duration of enrolled patients was at least 4 weeks. The baseline demographics and patient characteristics were recorded, as well as on-treatment hemoglobin changes and ribavirin dosage. The virologic responses were evaluated. Genetic polymorphisms in the IL28B gene (rs8099917) and ITPA gene (rs1127354) were determined. Statistical analyses were performed to analyze factors predictive of treatment-induced anemia and treatment outcomes. Results A total of 313 patients were enrolled. All patients finished treatment except three who lost to follow-up before treatment completed. On-treatment virologic responses were determined for all patients in an intent-to-treat fashion. Sustained virologic response (SVR) was determined for 295 patients who finished posttreatment follow-up. The overall rapid virologic response (RVR) and SVR rates were 63% and 72%, respectively; the relapse rate was 23%. One hundred patients (32%) had hemoglobin decline >3 g/dL from baseline at week 4 of treatment. Thirty-eight patients (12%) had hemoglobin level <10 g/dL at week 4. The factors predictive of RVR included male gender (OR 2.11; P =0.006), baseline platelet count >180 ×103/μL (OR 1.96; P =0.021), baseline viral load <800,000 IU/mL (OR 4.35; P <0.001), rs8099917 genotype TT (OR 4.31; P <0.001), and rs1127354 genotype CC (OR 2.23; P =0.005). The predicting factors of SVR were male gender and achievement of RVR. Patient categories at risk of hemoglobin decline >3 g/dL at week 4 were age >55 years (OR 2.70; P =0.001), baseline hemoglobin >16 g/dL (OR 4.07; P <0.001), and rs1127354 genotype CC (OR 15.85; P <0.001). Age >55 years (OR 2.55; P =0.042), baseline hemoglobin <14 g/dL (OR 5.88; P <0.001), estimated glomerular filtration rate <60 ml/min/1.73m2 (OR 2.71; P =0.037), and rs1127354 genotype CC (OR 28.10; P =0.002) were predicting factors of hemoglobin level <10 g/dL at week 4. The magnitude of hemoglobin decline at week 4 was correlated with RVR rate. Conclusion For chronic hepatitis C patients receiving PegIFN plus ribavirin therapy, factors predictive of treatment-induced anemia are ITPA genetic polymorphism, baseline hemoglobin level, age, and renal function. ITPA genetic polymorphism is an independent factor of RVR. Treatment-induced anemia is also associated with treatment responses.
Subjects
ITPA (Inosine Triphosphatase)
Pharmacogenomics
Ribavirin
SNP (Single Nucleotide Polymorphism)
Hemolytic Anemia
Hepatitis C
SDGs
Type
thesis
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