Roles of ITPA and IL28B Genotypes in Chronic Hepatitis C Patients Treated with Peginterferon Plus Ribavirin

Abstract

It has been reported that inosine triphosphatase (ITPA) gene variants protect against ribavirin-induced anemia in patients treated for chronic hepatitis C. IL28B variants also influence the treatment response of peginterferon plus ribavirin treatment in these patients. In the present study, we examined how ITPA and IL28B genotypes have clinical impacts on treatment-induced hematotoxicities and treatment response in HCV-infected patients treated with peginterferon plus ribavirin. ITPA genotypes (rs1127354 and rs6051702) and IL28B genotype (rs8099917) were determined by TaqMan SNP assay. We compared clinical background, treatment course and treatment response in terms of these genotypes. Only IL28B rs8099917 major type could predict sustained virological response. ITPA rs1127354 major type leads to significantly greater ribavirin-induced anemia than ITPA rs1127354 minor type between days 0 and 84. We noticed that IL28B rs8099917 minor genotype was associated with higher reduction of neutrophils and platelets. ITPA rs1127354 is useful for the prediction of ribavirin-induced anemia in the early phase after the commencement of peginterferon plus ribavirin treatment and IL28B rs8099917 is useful for the prediction of sustained virological response. Use of the combination of these two genotypes could lead to safe and effective treatment of chronic hepatitis C patients.

IL28B Genotyping: A Step towards HCV-Personalized Therapy

“…The presence of functional ITPA gene variant has been found to be associated with a significant reduction in haemoglobin levels, ~3gdl -3 at week 4; while reduced ITPA activity was found to have a protective outcome against RBVinduced anemia (Hitomi, 2011). Similar results have been documented in other primary studies including mono-HCV infected patients, which led to a modification in RBV dosage but did not contribute to SVR (Miyamura, 2012;Ochi, 2010).…”

Different effects of three interferons L on Toll-like receptor-related gene expression in HepG2 cells

“…IFNL3 genotypes have been shown to be associated with hepatitis C spontaneous and treatment-induced viral clearance [13][14][15][16][17][18]. IFNL1 is capable of antiviral activity against HCV in vivo [19].…”

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

“…The patients were eligible if they met the following inclusion criteria: (1) infection with HCV; (2) age ≥ 20 years; (3) no absolute contraindications for peginterferon plus ribavirin therapy such as pregnancy, severe heart disease, abnormal hemoglobinemia, chronic renal failure, mental disorders, severe liver failure, or autoimmune diseases; (4) absence of HIV infection; (5) no currently active drug abuse; and (6) no drug allergy to interferon or nucleos(t)ide analogues. Some of these patients had previously been included in other studies [19,25,26] . Among these 278 HCV RNA-positive patients, 178 had ALT elevation (each value exceeding the higher limit of the normal range was considered abnormal) [7] , and 100 exhibited normal ALT levels at least 3 times during a 24-mo period (considered as PNALT patients).…”

“…SNP rs8099917 was examined in plasma by allelic discrimi-nation using TaqMan minor groove binding (MGB) probes as described previously [26] . Briefly, we used DNA Extract All Reagents Kit (Applied Biosystems Inc., Foster City, CA, United States) to prepare the DNA sample from fresh plasma.…”