Treatment with peginterferon alfa-2a and ribavirin for 48 weeks resulted in rates of sustained virologic response among patients infected with HCV genotype 1 that were lower among Latino whites than among non-Latino whites. Strategies to improve the sustained virologic response in Latinos are needed. (ClinicalTrials.gov number, NCT00107653.)
Hepatitis C virus (HCV) infection increases total healthcare costs but the effect of the severity of liver disease associated with chronic hepatitis C (CHC) on healthcare costs has not been well studied. We analyzed the demographics, healthcare utilization, and healthcare costs of CHC patients in a large U.S. private insurance database (January, 2002 to August, 2010 . Mean all-cause PPPM healthcare costs were 32% and 247% higher for patients with CC and ESLD compared to those with NCD ($1,870 and $4,931 versus $1,420; P < 0.001) and were independent of age or comorbid conditions. Pharmacy, ambulatory, and inpatient care collectively accounted for 90% of NCD costs and 93% of CC and ESLD costs. The largest cost components were inpatient costs for those with ESLD (56%) and ambulatory costs for those with CC and NCD (37% and 36%, respectively). Overall, 56% of costs were HCV-related and this proportion increased with severity (46%, 57%, and 71% for patients with NCD, CC, and ESLD, respectively). Conclusion: The direct healthcare costs associated with CHC are high, increase in association with the progression of liver disease, and are highest in those with ESLD.
The presence of Epstein-Barr virus (EBV) in the tumor cells of some EBV-associated malignancies may facilitate selective killing of these tumor cells. We show that treatment of an EBV ؉ Burkitt's lymphoma cell line with 5-azacytidine led to a dose-dependent induction of EBV lytic antigen expression, including expression of the viral thymidine kinase (TK) and phosphotransferase (PT). Azacytidine treatment for 24 h modestly sensitized the cell line to all nucleosides tested. To better characterize EBV TK with regard to various nucleoside analogues, we expressed EBV TK in stable cell clones. Two EBV TK-expressing clones were moderately sensitive to high doses of acyclovir and penciclovir (PCV) (62.5 to 500 M) and to lower doses of ganciclovir (GCV) and bromovinyldeoxyuridine (BVdU) (10 to 100 M) compared to a control clone and were shown to phosphorylate GCV. Similar experiments in a transient overexpression system showed more killing of cells transfected with the EBV TK expression vector than of cells transfected with the control mutant vector (50 M GCV for 4 days). A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU-or PCVmediated cell killing. Induction of EBV kinases in combination with agents such as GCV merits further evaluation as an alternative strategy to gene therapy for selective killing of EBV-infected cells.
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