Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

Delvaux, Nathália; Costa, Vanessa Duarte da; Costa, Maristella Matos da; Villar, Lívia Melo; Coelho, Henrique Sérgio Moraes; Esberard, Eliane Bordalo Cathalá; Flores, Priscila Pollo; Brandão‐Mello, Carlos Eduardo; Villela-Nogueira, Cristiane Alves; Almeida, Adílson José de; Lampe, Elisabeth

doi:10.1590/0074-02760150104

Cited by 6 publications

(7 citation statements)

References 36 publications

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“…This was in agreement with Delvaux et al [23] who reported that in Brazilian population the frequency of allelic dis tribution at rs7270101 and rs1127354 shows high rates of the genotypes AA (84%) and CC (94.3%), respectively. Also, Domingo et al [24], D'Avolio et al [25], Naggie et al [26] Rau et al [27] who demonstrated that the majority of European indi viduals carry AA and CC genotypes for rs7270101 and rs1127354, respectively.…”

Section: Resultssupporting

confidence: 92%

“…Additionally, most patients in our study exhibited the worst combina tion for both SNPs AA rs727010 , CC rs1127354 and AC rs7270101 , CC rs1127354 , which could explain why so many Egyptian patients developed RBV-induced anemia. This was in agreement with Delvaux et al [23] also found that, most Brazilian patients carried the worst combina tion for both SNPs and developed RBV-induced anemia.…”

Section: Resultssupporting

confidence: 92%

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Inosine Triphosphate Pyrophosphatase Gene Polymorphisms and Ribavirin-Induced Anemia in HCV Patients

Edel¹,

Hendy²,

Essa³

et al. 2017

J Mol Biomark Diagn

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In spite of the interferon (INF) redundancy in treating HCV, ribavirin (RBV) is still included with the new direct antiviral therapies. Ribavirin-induced hematological alterations had been referred to ITPA gene polymorphisms.Objective: Evaluate ITPA gene polymorphisms (rs1127354 and rs7270101) with development of anemia in chronic hepatitis C (CHC) Egyptian patients during treatment with pegylated-interferon (Peg-IFN) plus ribavirin (RBV).Methods: 100 Egyptian CHC patients treated with PEG-IFN/RBV were recruited, 55 patients developed anemia (Hb decline>2 g/dl), and other 45 would not developed anemia (Hb decline ≤ 2 g/dl) at week 12 throughout the treatment course. Routine laboratory investigations were done for all participates (HCV-Abs, HBs Ag, HCV-RNA levels, complete blood picture, liver and kidney function tests. Single nucleotide polymorphism (SNP) was done by ABI TaqMan allelic discrimination kit for ITPA polymorphisms (rs1127354 and rs7270101).Results: CC and AA were the most prevalent genotypes of SNPs rs1127354 and rs7270101 respectively among two studied groups. rs1127354 polymorphism was associated with Hb-decline at week 12 of treatment and with rs7270101 polymorphism for predicting platelet decline during treatment. Lower levels of platelet decline were detected with CC rs1127354 and AA rs7270101. Conclusion:While ITPA polymorphisms rs1127354 CC genotype carried a predilection of anemia occurrence in PEG-IFN/RBV HCV treated subjects, the minor allele rs1127354 AA plays a crucial role in their protection. Platelet decline was reported in both ITPA rs1127354 and rs7270101 polymorphisms. Screening for ITPA polymorphisms in Egyptian HCV patients would be of value in avoiding hematological disturbances and dose modulations in RBVbased therapies.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 92%

Inosine Triphosphate Pyrophosphatase Gene Polymorphisms and Ribavirin-Induced Anemia in HCV Patients

Edel¹,

Hendy²,

Essa³

et al. 2017

J Mol Biomark Diagn

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“…Lowering the RBV dosage may decrease the chance of sustained virologic response (SVR) and increase the rate of relapse . RBV‐induced anemia is likely to be dose‐dependent as most patients show improved hemoglobin (Hb) levels with the reduction of RBV dose and it is reversible after the end of treatment . The myelosuppressive action of PEG‐IFN may worsen RBV‐hemolytic anemia …”

Section: Introductionmentioning

confidence: 99%

ITPA gene polymorphism (94C>A) effects on ribavirin‐induced anemia during therapy in Egyptian patients with chronic hepatitis C

Raziky

Baki

Afify

et al. 2017

Journal of Medical Virology

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Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)-induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction, and treatment response in hepatitis C virus (HCV)-infected patients. This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated-interferon (PEG-INF) /RBV therapy. ITPA genotypes rs1127354 were determined by Real Time PCR melting curve analysis. Effects of ITPA polymorphism on hemoglobin (Hb) levels, RBV dose reduction and treatment response were analyzed. The homozygous wild genotype (CC) was associated with Hb reduction at week 4 (P = 0.004). The minor allele protected against Hb reduction. No association with sustained virological response was observed (P = 0.492). Female gender; lower baseline Hb and higher baseline WBC were associated with week 4 anemia (P = 0.04; P = 0.023; 0.033, respectively). The ITPA gene polymorphism rs1127354 heterozygous genotype (CA) may influence Hb levels and protect against hemolytic anemia during RBV-containing regimens for HCV. However, such findings were not significantly related to treatment outcomes. Patients with wild ITPA genotype (CC) experienced a more Hb drop and RBV dose reductions more frequently.

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“…Among monoinfected patients, 42% had anemia caused by ribavirin and 45% of coinfected patients presented this event. In a study performed by Delvaux et al [29] in Brazilian patients with HCV, the allelic distribution frequency of SNPs in rs7270101 and rs1127354 showed high rates of AA and CC genotypes, respectively, suggesting that the study population are greatly prone to develop RBV-induced anemia. To our knowledge, this is the first report of the frequency of ITPA gene polymorphisms in a cohort of Brazilian patients coinfected with HCV/HIV.…”

Section: Characteristicsmentioning

confidence: 87%

IL28B and ITPA Single Nucleotide Polymorphisms in a Cohort of Patients with HCV and HCV/HIV, Southern Brazil

VM¹,

BA²,

Mm³

et al. 2016

J AIDS Clin Res

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Objective: The aim of this study is to describe the single nucleotide polymorphisms (SNP) in human genes for IL28B and ITPA of HIV/HCV coinfected patients followed at a referral Hospital of Universidade Federal do Paraná (UFPR). Methods: A cross-sectional study was carried out. HIV/HCV coinfected and HCV monoinfected patients were enrolled. Clinical and epidemiological data from medical records were reviewed, and peripheral blood was collected to analyze the IL28B and ITPA SNPs. Results: A total of 37 HCV-and 41 HCV/HIV-positive subjects were included in the study, 13 (35.1%) monoinfected subjects were previously treated, 12 (92.3%) with PEG-INFα/RBV and of these, 8 (61.5%) had sustained virological response (SVR). Regarding HCV/HIV coinfected patients, 23 (56.1%) received treatment with PEG-INFα/RBV and 12 (52.1%) had SVR. IL28B CC genotype was found in all HCV monoinfected patients and in 56.5% of coinfected subjects. Regarding ribavirin-induced anemia, all patients showed the ITPA SNP favorable for this event, and anemia was present in 38.5% of monoinfected and in 65.2% of coinfected patients. Conclusion: With the availability of direct-acting antivirals (DAAs) for the treatment of chronic infection by the hepatitis C virus, free-INF regimens have been implemented worldwide. However, in the setting of HIV/HCV coinfection ribavirin will continue to compose some therapeutic schemes. Thus, tests related to genetic markers that influence the response to HCV treatment should be recommended in pretreatment, since results would benefit both the patient and the public healthcare system, guiding rational drug use in situations where responses to treatment are particularly low and adverse effects are high.

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Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

Cited by 6 publications

References 36 publications

Inosine Triphosphate Pyrophosphatase Gene Polymorphisms and Ribavirin-Induced Anemia in HCV Patients

Inosine Triphosphate Pyrophosphatase Gene Polymorphisms and Ribavirin-Induced Anemia in HCV Patients

ITPA gene polymorphism (94C>A) effects on ribavirin‐induced anemia during therapy in Egyptian patients with chronic hepatitis C

IL28B and ITPA Single Nucleotide Polymorphisms in a Cohort of Patients with HCV and HCV/HIV, Southern Brazil

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