The changing burden of hepatitis C virus infection in the United States: model-based predictions.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes a substantial health and economic burden in the United States. With the availability of direct-acting antiviral agents, recently approved therapies and those under development, and 1-time birth-cohort screening, the burden of this disease is expected to decrease. OBJECTIVE: To predict the effect of new therapies and screening on chronic HCV infection and associated disease outcomes. DESIGN: Individual-level state-transition model. SETTING: Existing and anticipated therapies and screening for HCV infection in the United States. PATIENTS: Total HCV-infected population in the United States. MEASUREMENTS: The number of cases of chronic HCV infection and outcomes of advanced-stage HCV infection. RESULTS: The number of cases of chronic HCV infection decreased from 3.2 million in 2001 to 2.3 million in 2013. One-time birth-cohort screening beginning in 2013 is expected to identify 487,000 cases of HCV infection in the next 10 years. In contrast, 1-time universal screening could identify 933,700 cases. With the availability of highly effective therapies, HCV infection could become a rare disease in the next 22 years. Recently approved therapies for HCV infection and 1-time birth-cohort screening could prevent approximately 124,200 cases of decompensated cirrhosis, 78,800 cases of hepatocellular carcinoma, 126,500 liver-related deaths, and 9900 liver transplantations by 2050. Increasing the treatment capacity would further reduce the burden of HCV disease. LIMITATION: Institutionalized patients with HCV infection were excluded, and empirical data on the effectiveness of future therapies and on the future annual incidence and treatment capacity of HCV infection are lacking. CONCLUSION: New therapies for HCV infection and widespread implementation of screening and treatment will play an important role in reducing the burden of HCV disease. More aggressive screening recommendations are needed to identify a large pool of infected patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

Predictors of consent to pharmacogenomics testing in the IDEAL study.

INTRODUCTION: Pharmacogenomic testing is important in developing individualized therapeutic approaches. In the phase 3 IDEAL (Individualized Dosing to Assess Optimal Pegylated Interferon Therapy) clinical trial, a subset of patients receiving peginterferon and ribavirin for treatment of chronic hepatitis C agreed to provide blood samples for genetic testing. Genome-wide association studies subsequently identified associations between IL28B polymorphism and sustained virologic response, and ITPA polymorphism and ribavirin-associated anemia. OBJECTIVE: To characterize the groups of patients who accepted or declined pharmacogenomic testing in the IDEAL study. METHODS: Clinical and demographic factors and treatment outcomes were compared at all sites that had approved pharmacogenomic testing. Differences between patients who consented to and declined pharmacogenomic testing were analyzed using Student's t-test and χ²-test. RESULTS: In total, 109 of 118 sites participated in the pharmacogenomic substudy, and 1674 of 2949 (57%) patients enrolled at these sites consented to pharmacogenomic testing. More patients treated in academic medical centers than in community centers (60 vs. 52%, P<0.001) provided consent. More men than women (58 vs. 54%, P=0.04) consented to pharmacogenomic testing. There was no significant difference in pharmacogenomic participation between patients from different racial groups, including whites and African Americans (58 vs. 54%, P=0.07). Treatment outcomes were also similar according to pharmacogenomic participation. CONCLUSION: In the IDEAL study, patient consent to pharmacogenomic testing did not introduce selection bias. Treatment at an academic center and male sex were associated with higher rates of pharmacogenomic testing consent. Efficacy and safety outcomes were similar in patients who accepted and declined pharmacogenomic testing.

Direct-acting antiviral medications for chronic hepatitis C virus infection.

Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Current standard therapy consists of pegylated interferon α and ribavirin, both of which have nonspecific and largely unknown mechanisms of action. New therapies are in development that act directly on the hepatitis C virus at various points in the viral life cycle. Published clinical trial data on these therapies are summarized in this paper. A new era of hepatitis C virus treatment is beginning, the ultimate goals of which will be directly targeting the virus, shortening the length of therapy, improving sustained virologic response rates, and minimizing side effects.

Emerging therapies in hepatitis C: dawn of the era of the direct-acting antivirals.

The HCV viral life cycle provides targets for drug development at virtually every step, and many new drugs aimed at these targets are currently being developed. Clinical practice takes a major step forward this year with the arrival of telaprevir and boceprevir, which will be added to the current standard of care of pegIFNα/RBV. Patients will need to be monitored closely and counseled extensively, and clinicians will need to learn the new response-guided therapy algorithms with these therapies. Although there remains work to be done in the field of HCV, these therapies will allow many more patients the opportunity to eradicate HCV infection.