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OBJECTIVE: To evaluate the cost-effectiveness of combinations of different direct-acting antivirals(DAAs) for treatment-naive patients infected with chronic hepatitis C virus genotype 1b in China, which would provide pharmacoeconomic evidence for relevant health care decisions. METHODS: A Markov model was constructed based on the natural history of chronic hepatitis C to evaluate the quality-adjusted life years (QALYs) and direct medical costs for noncirrhotic patients and compensated cirrhotic patients from the payer perspective, and to further calculate incremental cost-effectiveness ratio (ICER) of different regimens. Lifetime horizon(100 years of age) and one year cycle length were adopted. A 5% discount rate was applied to both QALYs and costs. One-way sensitivity analysis and probabilistic sensitivity analysis were performed. RESULTS: Base-case analysis showed that six DAAs regimens not only gained QALYs but also reduced medical costs compared with no treatment and PR regimen. Among all the DAAs regimens, the combination of paritaprevir/ombitasvir/ritonavir+dasabuvir± ribavirin (POR+DAS±RBV) was the most cost-effective alternative for all the target population. The findings from the base-case analysis were confirmed by the sensitivity analyses. CONCLUSION: Among all the regimens, the combination of POR+DAS±RBV is the economically dominant regimen in the treatment of treatment-naive patients infected with chronic hepatitis C virus genotype 1b in China.
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<p><b>BACKGROUND</b>Idiopathic membranous nephropathy (IMN) is an autoimmune disease and the leading cause of adult nephritic syndrome. HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population. In this study, six single nucleotide polymorphisms (SNPs) in the promoter of HLA-DQA1 and other two SNPs with IgA nephropathy were included for the association analysis.</p><p><b>METHODS</b>The SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX. The quantification of anti-phospholipase A2 receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R ELISA (IgG) kit.</p><p><b>RESULTS</b>After analysis, four SNPs were significantly associated with IMN, with rs2187668 and rs28383345 as the top two signals (P = 8.42×10-5 and 2.48×10-5, respectively). Even under dominant model, the two SNPs were still significantly associated with IMN (P = 3.50×10-3 for rs28383345 and P = 6.55×10-5 for rs2187668). After conditional study with rs2187668, rs28383345 was the only variant significantly correlated with IMN after Bonferroni correction (P = 0.016). The minor alleles of the two SNPs were also mutually exclusive in our cohort. This indicated that the two SNPs were independently associated with IMN in Chinese Han population. Levels of anti-PLA2R autoantibodies were correlated with the genotypes of the two SNPs, but not significantly (P>0.05).</p><p><b>CONCLUSIONS</b>Our results revealed that a novel independent variant in the promoter of HLA-DQA1 was associated with IMN in Chinese Han population. The locus possessed regulatory role according to the data of RegulomeDB. The exact role of the SNPs on the expression of HLA-DQA1 needs further investigation.</p>