Key result
Patients with three or more mutations in the ISDR had significantly lower HCV viral loads than those with fewer than two mutations (192.2 vs. 1279.4 KIU/ml, P=0.0277).
Why the study?
Do mutations in the PePHD and ISDR regions correlate with viral load and interferon responsiveness in male patients with HCV genotype 3a?
Observational (n=21)
Do mutations in the PePHD and ISDR regions correlate with viral load and interferon responsiveness in male patients with HCV genotype 3a?
Absolute Event Rate: 192.2% vs 1279.4%
p-value: p=0.0277
The number of mutations in the ISDR is significantly associated with HCV viral load in patients with genotype 3a, suggesting it plays a role in regulating viral replication.
ISDR mutations associated with lower HCV-3a viral load; hypothesis-generating for replication regulation, requires prospective validation before clinical consideration.
Interferon (IFN) induces the double-stranded RNA-dependent protein kinase (PKR) to inhibit viral replication. Two motifs of the PKR-binding domain exist in the E2 and the NS5A regions of the hepatitis C virus (HCV). These regions are called the PKR-eukaryotic transcription factor (elF2-alpha) phosphorylation homology domain (PePHD), and the IFN sensitivity-determining region (ISDR). Both regions are inhibited by PKR. Thus, several studies have reported the relationship between these regions and IFN responsiveness and the HCV viral load. However, the data obtained from these studies remain controversial. The aim of this study was to investigate the genomic heterogeneity of the PePHD and the ISDR in patients with genotype 3a and how this impacts HCV replication and the response to IFN therapy. Twenty-one male patients infected with HCV genotype 3a were studied. The PePHD was well conserved, and mutations were found in only one amino acid position in two patients. Patients with three or more mutations in the ISDR had lower viral loads than those with fewer than two mutations (192.2 ± 176.7 vs. 1279.4 ± 997.6 KIU/ml, P = 0.0277). Ten (71.4%) of 14 patients achieved a sustained virological response to IFN therapy. No specific amino acid substitutions in the PePHD and the ISDR were associated with IFN responsiveness; however, the number of mutations in the ISDR was significantly associated with the HCV viral load. The findings from this study suggest that the ISDR plays an important role in regulating viral replication in patients infected with HCV genotype 3a.
No takes yet. Share an insight, caveat, or question.
Yokozaki et al. (2011) conducted an observational in Chronic hepatitis C genotype 3a (n=21). Three or more mutations in the ISDR vs. Fewer than two mutations in the ISDR was evaluated on HCV viral load (KIU/ml) (p=0.0277). Patients with three or more mutations in the ISDR had significantly lower HCV viral loads than those with fewer than two mutations (192.2 vs. 1279.4 KIU/ml, P=0.0277).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: