Bryce D. Smith

Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies

BACKGROUND Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). In the United States, this form of cancer occurs in approximately 15 000 persons annually. A systematic review of the evidence is needed to assess the benefits of treatment of HCV-infected persons on development of HCC. PURPOSE To systematically review observational studies to determine the association between response to HCV therapy and development of HCC among persons at any stage of fibrosis and those with advanced liver disease. DATA SOURCES MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science, and the Database of Abstracts of Reviews and Effectiveness from inception through February 2012. STUDY SELECTION English-language observational studies that compared therapy-derived sustained virologic response (SVR) with no response to therapy among HCV-infected persons, targeted an adult population, and had an average follow-up of at least 2 years. DATA EXTRACTION Two investigators independently extracted data into uniform relative risk measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. DATA SYNTHESIS Thirty studies fulfilled the inclusion criteria, and 18 provided adjusted effect estimates that were used to calculate pooled relative risks. Among HCV-infected persons, SVR was associated with reduced risk for HCC (relative risk for all persons, 0.24 [95% CI, 0.18 to 0.31], moderate-quality evidence; advanced liver disease hazard ratio, 0.23 [CI, 0.16 to 0.35], moderate-quality evidence). LIMITATION In the meta-analyses, some variables could not be controlled for because of the observational design of the included studies. CONCLUSION Sustained virologic response after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC. The evidence was determined to be of moderate quality.

The Cost-Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary Care Settings

BACKGROUND In the United States, hepatitis C virus (HCV) infection is most prevalent among adults born from 1945 through 1965, and approximately 50% to 75% of infected adults are unaware of their infection. OBJECTIVE To estimate the cost-effectiveness of birth-cohort screening. DESIGN Cost-effectiveness simulation. DATA SOURCES National Health and Nutrition Examination Survey, U.S. Census, Medicare reimbursement schedule, and published sources. TARGET POPULATION Adults born from 1945 through 1965 with 1 or more visits to a primary care provider annually. TIME HORIZON Lifetime. PERSPECTIVE Societal, health care. INTERVENTION One-time antibody test of 1945-1965 birth cohort. OUTCOME MEASURES Numbers of cases that were identified and treated and that achieved a sustained viral response; liver disease and death from HCV; medical and productivity costs; quality-adjusted life-years (QALYs); incremental cost-effectiveness ratio (ICER). RESULTS OF BASE-CASE ANALYSIS Compared with the status quo, birth-cohort screening identified 808,580 additional cases of chronic HCV infection at a screening cost of

Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention.

2874 per case identified. Assuming that birth-cohort screening was followed by pegylated interferon and ribavirin (PEG-IFN+R) for treated patients, screening increased QALYs by 348,800 and costs by

Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States ☆ ☆☆

5.5 billion, for an ICER of

The Cost-effectiveness, Health Benefits, and Financial Costs of New Antiviral Treatments for Hepatitis C Virus

15,700 per QALY gained. Assuming that birth-cohort screening was followed by direct-acting antiviral plus PEG-IFN+R treatment for treated patients, screening increased QALYs by 532,200 and costs by

Performance of Premarket Rapid Hepatitis C Virus Antibody Assays in 4 National Human Immunodeficiency Virus Behavioral Surveillance System Sites

19.0 billion, for an ICER of

Primary care-based interventions are associated with increases in hepatitis C virus testing for patients at risk

35,700 per QALY saved. RESULTS OF SENSITIVITY ANALYSIS The ICER of birth-cohort screening was most sensitive to sustained viral response of antiviral therapy, the cost of therapy, the discount rate, and the QALY losses assigned to disease states. LIMITATION Empirical data on screening and direct-acting antiviral treatment in real-world clinical settings are scarce. CONCLUSION Birth-cohort screening for HCV in primary care settings was cost-effective. PRIMARY FUNDING SOURCE Division of Viral Hepatitis, Centers for Disease Control and Prevention.

Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting.

DESCRIPTION The Centers for Disease Control and Prevention (CDC) and a group of governmental and private sector partners developed these evidence-based recommendations to increase the proportion of hepatitis C virus (HCV)-infected persons who know their status and are linked to appropriate care and treatment. The recommendations also address brief alcohol screening, as alcohol accelerates progression of liver disease among HCV-infected individuals. These recommendations augment CDCs 1998 and 1999 recommendations based on risk and medical indications and are not meant to replace those recommendations. METHODS These recommendations are based on systematic reviews of evidence published from 1995 through February 2012 in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Database of Abstracts of Reviews of Effects. Selected studies included cross-sectional and cohort studies that addressed either prevalence of hepatitis C in the United States or clinical outcomes (for example, hepatocellular carcinoma and serious adverse events) among treated patients and systematic reviews of trials that assessed effectiveness of brief screening interventions for alcohol consumption. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess quality of the evidence. RECOMMENDATION 1: Adults born during 1945-1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: All persons with identified HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Grade: strong recommendation; moderate-quality evidence).

Hepatitis C virus control among persons who inject drugs requires overcoming barriers to care.

BACKGROUND Without diagnosis and antiviral therapy, many patients with chronic hepatitis C infections will develop end-stage liver disease and die from complications. AIMS To evaluate the future impacts of preventive interventions and treatment advances, this paper forecasts a baseline estimate of the future morbidity and mortality of prevalent hepatitis C when left untreated. METHODS We simulated the future disease progression and death for all Americans with prevalent hepatitis C in 2005. To validate the model, we used past seroprevalence to forecast contemporary outcomes. We used the validated model to forecast future cases of end-stage liver disease, transplants, and deaths from 2010 to 2060, and we estimated credible intervals using Monte Carlo simulation. RESULTS When programmed with past data, our model predicted current levels of hepatitis C outcomes with accuracy between ±1% and 13%. Morbidity and mortality from hepatitis C will rise from 2010 to a peak between the years 2030 and 2035. We forecasted a peak of 38,600 incident cases of end-stage liver disease; 3200 referrals for transplant; and 36,100 deaths. CONCLUSIONS Because current rates of screening and treatment are low, future morbidity and mortality from hepatitis C are likely to increase substantially without public health interventions to increase treatment.

Effectiveness of a Risk Screener in Identifying Hepatitis C Virus in a Primary Care Setting

BACKGROUND New hepatitis C virus (HCV) treatments deliver higher cure rates with fewer contraindications, increasing demand for treatment and healthcare costs. The cost-effectiveness of new treatments is unknown. METHODS We conducted a microsimulation of guideline testing followed by alternative treatment regimens for HCV among the US population aged 20 and older to estimate cases identified, treated, sustained viral response, deaths, medical costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different treatment options expressed as discounted lifetime costs and benefits from the healthcare perspective. RESULTS Compared to treatment with pegylated interferon and ribavirin (PR), and a protease inhibitor for HCV genotype (G) 1 and PR alone for G2/3, treatment with PR and Sofosbuvir (PRS) for G1/4 and treatment with Sofosbuvir and ribavirin (SR) for G2/3 increased QALYs by 555 226, reduced deaths by 80 682, and increased costs by