transparent gif

 

Ej inloggad.

Göteborgs universitets publikationer

Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2/3.

Författare och institution:
Karolina Rembeck (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Jesper Waldenström (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Kristoffer Hellstrand (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik, Chalmers/GU); Kristina Nyström (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Anna Martner (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Magnus Lindh (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Gunnar Norkrans (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Johan Westin (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Court Pedersen (-); Martti Färkkilä (-); Nina Langeland (-); Mads Rauning Buhl (-); Kristine Mörch (-); Peer Brehm Christensen (-); Martin Lagging (Institutionen för biomedicin, avdelningen för infektionssjukdomar)
Publicerad i:
Hepatology (Baltimore, Md.), 59 ( 6 ) s. 2131–2139
ISSN:
1527-3350
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2014
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
The present study evaluated the impact of variations in the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) on treatment outcome in patients with hepatitis C virus (HCV) genotype 2/3 infection receiving peginterferon-α2a and lower, conventional 800 mg daily dose of ribavirin. Previous studies using higher, weight-based ribavirin dosing report that patients carrying polymorphisms encoding reduced predicted ITPase activity show decreased risk of ribavirin-induced anemia but increased risk of thrombocytopenia, with no impact on elimination of virus. Three hundred fifty-four treatment naïve HCV genotype 2/3 infected patients, enrolled in a phase III trial (NORDynamIC), were genotyped for ITPA (rs1127354 and rs7270101). Homo- or heterozygosity at Ars1127354 or Crs7270101, entailing reduced ITPase activity, was observed in 37% of patients and was associated with increased likelihood of achieving sustained virological response (SVR) (P=0.0003 in univariate and multivariate analyses) accompanied by a reduced risk of relapse among treatment-adherent patients. The association between ITPA variants and SVR remained significant when patients were subdivided by the 12- and 24-week treatment duration arms, HCV genotype, fibrosis stage and IL28B genotype, and was not secondary to improved adherence to therapy or less pronounced anemia. Gene variants predicting reduced predicted ITPase activity also were associated with decreased risk of anemia (P<0.0001), increased risk of thrombocytopenia (P=0.007), and lower ribavirin concentrations (P=0.02). Conclusion: These findings demonstrate a novel ribavirin-like association between polymorphisms at ITPA and treatment efficacy in chronic hepatitis C mediated by reduced relapse risk. We hypothesize that patients (63%) being homozygous for both major alleles, leading to normal ITPase activity, may benefit more from the addition of ribavirin to present and future treatment regimens for HCV in spite of concomitant increased risk of anemia.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Infektionsmedicin
Postens nummer:
194636
Posten skapad:
2014-03-07 11:42
Posten ändrad:
2016-06-29 13:19

Visa i Endnote-format

Göteborgs universitet • Tel. 031-786 0000
© Göteborgs universitet 2007