rs1127354

This study evaluated add-on therapy with pitavastatin and eicosapentaenoic acid (EPA) combined with peginterferon and ribavirin for chronic hepatitis C 1b treatment. In patients with HCV-1b, the add-on group achieved significantly higher sustained virological response rates (54.7%) compared to standard therapy (30.1%, P<0.0001). Patients with IL-28B rs8099917 TT genotype had better responses overall, while those with TG+GG genotype benefited markedly from add-on therapy (37.9% vs 5.6%, P=0.007). IL-28B genotype remained the strongest independent predictor in multivariate analysis (OR 6.69, P=0.0019).

Model incorporating the ITPA genotype (rs1127354) identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C. In 446 genotype 1b HCV patients, ITPA CC genotype combined with baseline hemoglobin <14.0 g/dl predicted 57% anemia incidence, while patients with ITPA AA/CA and hemoglobin ≥14.0 g/dl had only 17% incidence. High-risk anemia was a significant negative predictor of sustained virological response.

This study examined ITPA gene polymorphisms (rs1127354 and rs7270101) in 121 patients with HIV/HCV coinfection (n=63) and HCV monoinfection (n=58) treated with pegIFN/RBV. ITPA deficiency was found protective against hemoglobin reduction >3 g/dl (P=0.020 at week 4 in coinfected patients) and was associated with rapid virologic response at week 4 (P=0.017) in HIV/HCV coinfected patients, but did not improve sustained virologic response.

In 381 Japanese patients with HCV genotype 2 treated with 24-week interferon plus ribavirin combination therapy, IL28B rs8099917 genotype TG+GG was identified as an independent predictor of non-sustained virological response (P=0.017, OR=3.95). Sustained virological response was achieved in 81.6% overall, with multivariate analysis identifying younger age, higher albumin, absence of prior IFN therapy, and lower viral load as additional significant predictors of treatment success.

Two functional ITPA gene variants (rs1127354 and rs7270101) were strongly protective against ribavirin-induced hemolytic anemia in 238 HCV genotype 2/3 patients treated with pegylated interferon and ribavirin (P=10^-6 and P=10^-7 respectively; combined P=10^-11). Despite protection from anemia, ITPA variants did not decrease the need for ribavirin dose reduction or improve sustained virological response.

This is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.

This study examined ITPA gene polymorphisms (rs1127354) and their influence on hemoglobin decreases during triple therapy with pegylated interferon, ribavirin, and telaprevir in 61 Japanese patients with hepatitis C virus genotype 1. Patients with the CC genotype at rs1127354 experienced significantly greater hemoglobin reductions (Δ-3.5 ± 1.1 g/dL at week 4, P=0.001) compared to CA/AA genotypes, required more RBV dose reductions during the first 12 weeks (52% vs 65% of target dose, P=0.039), and had higher risk for severe anemia (OR=36.8 for hemoglobin <11 g/dL). SVR rates were comparable between genotypes (71% vs 67%, P=0.736), demonstrating that with careful monitoring and dose adjustment, effective HCV treatment can be achieved despite genetic predisposition to RBV-induced anemia.