2 New HCV Abstracts regarding Anemia during treatment

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Hepatology. 2011 Feb;53(2):389-95. doi: 10.1002/hep.24068. Epub 2011 Jan 10.

Inosine triphosphatase genetic variants are protective against anemia during

antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or

increase SVR.

AJ, Santoro R, Piazzolla V, PJ, Naggie S, Tillmann HL, Patel K,

Muir AJ, Shianna KV, Mottola L, Petruzzellis D, Romano M, Sogari F, Facciorusso

D, Goldstein DB, McHutchison JG, Mangia A.

Duke Clinical Research Institute, Durham, NC, USA.

Abstract

Two functional variants in the inosine triphosphatase (ITPA) gene causing

inosine triphosphatase (ITPase) deficiency protect against ribavirin

(RBV)-induced hemolytic anemia and the need for RBV dose reduction in patients

with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3

HCV. We evaluated the association between the casual ITPA variants and

on-treatment anemia in a well-characterized cohort of genotype 2/3 patients

treated with variable-duration pegylated interferon alfa-2b (PEG-IFN-á2b) and

RBV. Two hundred thirty-eight Caucasian patients were included in this

retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3].

Patients were treated with PEG-IFN-á2b plus weight-based RBV (1000/1200 mg) for

12 (n = 109) or 24 weeks (n = 129). The ITPA polymorphisms rs1127354 and

rs7270101 were genotyped, and an ITPase deficiency variable was defined that

combined both ITPA variants according to their effect on ITPase activity. The

primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb

reduction over the course of therapy, the need for RBV dose modification, and

the rate of sustained virological response (SVR). The ITPA variants were

strongly and independently associated with protection from week 4 anemia (P =

10(-6) for rs1127354 and P = 10(-7) for rs7270101). Combining the variants into

the ITPase deficiency variable increased the strength of association (P =

10(-11) ). ITPase deficiency protected against anemia throughout treatment.

ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL

(hazard ratio = 0.25, 95% confidence interval = 0.08-0.84, P = 0.025) but not

with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL).

There was no association between the ITPA variants and SVR. Conclusion: Two ITPA

variants were strongly associated with protection against treatment-related

anemia in patients with genotype 2/3 HCV, but they did not decrease the need for

RBV dose reduction or increase the rate of SVR. American

Association for the Study of Liver Diseases.

PMID: 21274861 [PubMed - indexed for MEDLINE]

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Hepatology. 2011 Feb;53(2):415-21. doi: 10.1002/hep.24058. Epub 2011 Jan 18.

Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with

pegylated interferon, ribavirin, and telaprevir.

Suzuki F, Suzuki Y, Akuta N, Sezaki H, Hirakawa M, Kawamura Y, Hosaka T,

Kobayashi M, Saito S, Arase Y, Ikeda K, Kobayashi M, ma K, Kamatani N,

Nakamura Y, Miyakawa Y, Kumada H.

Department of Hepatology, Toranomon Hospital, Tokyo, Japan.

fumitakas@...

Abstract

Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during

pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects

during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple

therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49

patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA)

ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1.

Decreases in hemoglobin levels were greater in patients with CC than CA/AA

genotypes at week 2 (-1.63 ± 0.92 vs. -0.48 ± 0.75 g/dL, P = 0.001) and week 4

(-3.5 ± 1.1 vs. -2.2 ± 0.96, P = 0.001), as well as at the end of treatment

(-2.9 ± 1.1 vs. -2.0 ± 0.86, P = 0.013). Risk factors for hemoglobin <11.0 g/dL

at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC

at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was

smaller in patients with CC than CA/AA genotypes (52 ± 14% vs. 65 ± 21% of the

target dose, P = 0.039), but the total RBV dose was no different between them

(49 ± 17% and 54 ± 18% of the target, P = 0.531). Sustained virological response

(SVR) was achieved in 70% and 64% of them, respectively (P = 0.724). CONCLUSION:

ITPA polymorphism influences hemoglobin levels during triple therapy,

particularly during the first 12 weeks while telaprevir is given. With careful

monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved

comparably frequently between patients with CC and CA/AA genotypes.Copyright ©

2010 American Association for the Study of Liver Diseases.

PMID: 21246582 [PubMed - indexed for MEDLINE]

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