کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5551867 | 1557805 | 2017 | 7 صفحه PDF | دانلود رایگان |
- ATP was significantly decreased in RBCs at day 28 and day 84 of RBV/SOF treatment.
- GTP and ITP were not significantly decreased over time on RBV/SOF.
- Individuals with â¤60% ITPA activity had a larger decrease in ATP at day 84.
- The mechanism of anemia protection is different in humans than expected from in-vitro studies.
Ribavirin (RBV), a purine analog, causes hemolytic anemia in some patients. In vitro, anemia appears to result from depletion of endogenous purines, but there are limited data in vivo. Single nucleotide polymorphisms in the gene encoding the inosine triphosphatase (ITPA) enzyme have been associated with protection against RBV-induced anemia and may mediate the effect of RBV treatment on endogenous purines. The purpose of this work was to determine the effect of RBV treatment on endogenous purine concentrations in individuals being treated for chronic hepatitis C virus (HCV) infection. Adenosine triphosphate (ATP), guanosine triphosphate (GTP), inosine triphosphate (ITP) and ribavirin triphosphate (RTP) were measured in whole blood obtained from 47 HCV-infected individuals at day zero (baseline), day three, day 28 and day 84 of RBV/sofosbuvir (SOF) treatment. ATP decreased â35.1% and â38.6% (p < 0.0001) at day 28 and day 84 of treatment, respectively compared to baseline. The decrease in ATP was greater in patients with â¤60% ITPA activity compared to those with 100% ITPA activity (â29.4% vs. â9.6%). GTP did not change during treatment but was 16.5% (p = 0.01) higher per 100 pmol/106 cells RTP in those with 100% ITPA activity. No significant change or effect of RTP or ITPA phenotype was noted for ITP. In summary, only ATP was reduced by RBV/SOF treatment and ITPA variants had larger reductions in ATP suggesting RBV-induced anemia is due to a different mechanism than predicted from in-vitro studies. These data emphasize the importance of characterizing the effect of nucleos(t)ide analog treatment on endogenous purines in-vivo.
Journal: Antiviral Research - Volume 138, February 2017, Pages 79-85