Browsing by Subject "Hepatitis C"
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Item Dihydropyridines Inhibit Translation and Early Replication of Hepatitis C Virus(2013-05-09) Klemashevich, CoryUp to 170 million people are infected with Hepatitis C Virus worldwide. Chronic HCV infection is the leading cause of fibrosis, cirrhosis and liver cancer. Treatment options are currently limited to interferon based therapies alone or in conjunction with direct acting antivirals (DAA) such as viral protease inhibitors. While the implementation of DAAs has increased the effective cure rate of HCV infected individuals, treatment is far from being complete or ideal. New DAAs with unique modes of action will be necessary to compliment our current repertoire of anti-HCV therapies. Previously our lab identified three dihydropyridines (DHP) as potent HCV replication inhibitors. We investigated and characterized the anti-HCV properties of nine additional DHP compounds. We also show that DHP compounds inhibit IRES dependent translation in full-length HCV. This inhibition of two separate steps of the viral life cycle may be a unique feature of DHPs making them superior DAAs. Among these DHPs, efonidipine emerged as the most effective HCV replication and translation inhibitor with the least toxicity. Using a real-time evolution strategy, we developed and characterized a mutant virus which was resistant to DHPs and several other drugs which modify intracellular calcium stores. Our results further the understanding of DHP inhibition of HCV providing a solid basis for investigation of more structurally related compounds as potent inhibitors of HCV.Item Healthcare costs and resource utilization in treated versus untreated chronically infected hepatitis C patients(2014-08) Kim, Yoona Amy; Rascati, Karen L.; Wilson, James P.Successful treatment of chronic hepatitis C virus (HCV) leads to significant benefits in both hepatic and extrahepatic morbidity and mortality. However, treatment is costly and onerous. The purpose of this study was to evaluate the resource utilization and healthcare costs of chronic HCV patients who are treated versus those who are not treated. Patients eligible for this study were Texas Medicaid patients ≥18 and ≤63 years who had evidence of chronic HCV during the identification period (1/1/07-9/30/11) and continuous enrollment throughout the analysis period. High dimensional propensity scoring techniques were used to match treated vs. untreated patients (1:2 ratio). Unadjusted and adjusted analyses compared the healthcare costs and utilization between patient cohorts at 6 and 18 months. For those treated, adherence was measured by proportion of days covered and persistence was evaluated as a gap in medication (of one fill) as determined by refill records. There were a total of 24,032 patients identified with chronic HCV. After high dimensional propensity scoring, there were no significant differences in key clinical and demographic characteristics between treated (n=939) and untreated (n=1878) cohorts. Over 97% of patients had evidence of end stage liver disease at baseline. Based on adjusted analyses of total costs using a generalized linear regression model, the mean difference in costs between the treated vs. untreated patients was $13,960 (SE $458, p<0.001). At 18 months of follow-up, the adjusted mean all-cause costs were $20,834 higher for treated patients (n=456) compared to those untreated (n=849) (p<0.001); however, mean outpatient costs were $1,894 (SE $274) less in treated vs. untreated patients. For those treated, the average HCV medication PDC was 71%, and by the end of 24 weeks, only 42.3% of patients remained on HCV therapy. This study did not show short-term cost offsets, but the sub-analysis following patients for 18 months showed trends in downstream cost offsets. Most patients had advanced liver disease, reducing the chances of successful treatment and averting liver disease sequelae. Earlier identification and treatment could bend the cost curve before these patients reached the more advanced stages seen in this costly cohort.Item Patient Perspectives on Barriers to Hepatitis C Treatment: Qualitative Analysis of Patient Focus Groups(2013-01-17) Devereaux, Robert Logan; North, Carol S., M.D., M.P.E.Much of the research to date on barriers to treatment for patients with hepatitis C (HCV) has approached the problem from either the perspective of either the medical provider or healthcare system. To better understand these barriers from the patientsÕ perspectives, exploratory focus groups were conducted with both mono-infected HCV and coinfected HCV/HIV patients. Nine focus groups with a total of 48 patients were conducted in 2008 and 2009. Transcribed focus group passages were categorized using qualitative analysis software. The category with the most passages was treatment knowledge (24%), which contained patientsÕ expressions of their personal understanding as well as requests for additional information. The category with the fewest passages was desire for treatment (6%). The treatment barriers category included frustration with medical provider communication and difficulty with physician-patient relationships as well as social stigma and lack of accurate disease knowledge. These areas of concern expressed by patients in focus groups have highlighted underexplored areas that may warrant future investigation as potential opportunities for development of intervention.