David B. Rein

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

BACKGROUND With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS We estimated mortality using natural history models for acute hepatitis infections and GBDs cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING Bill & Melinda Gates Foundation.

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

The global burden of hepatitis E virus genotypes 1 and 2 in 2005

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 Age-Related Macular Degeneration Through the Year 2050 The Potential Impact of New Treatments

5.5 billion, for an ICER of

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

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

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

19.0 billion, for an ICER of

Cost-effectiveness of routine childhood vaccination for hepatitis A in the United States.

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.

The cost-effectiveness of routine office-based identification and subsequent medical treatment of primary open-angle glaucoma in the United States.

We estimated the global burden of hepatitis E virus (HEV) genotypes 1 and 2 in 2005. HEV is an emergent waterborne infection that causes source‐originated epidemics of acute disease with a case fatality rate thought to vary by age and pregnancy status. To create our estimates, we modeled the annual disease burden of HEV genotypes 1 and 2 for 9 of 21 regions defined for the Global Burden of Diseases, Injuries, and Risk Factors Study (the GBD 2010 Study), which represent 71% of the worlds population. We estimated the seroprevalence of anti‐HEV antibody and annual incidence of infection for each region using data from 37 published national studies and the DISMOD 3, a generic disease model designed for the GBD Study. We converted incident infections into three mutually exclusive results of infection: (1) asymptomatic episodes, (2) symptomatic disease, and (3) death from HEV. We also estimated incremental cases of stillbirths among infected pregnant women. For 2005, we estimated 20.1 (95% credible interval [Cr.I.]: 2.8‐37.0) million incident HEV infections across the nine GBD Regions, resulting in 3.4 (95% Cr.I.: 0.5‐6.5) million symptomatic cases, 70,000 (95% Cr.I.: 12,400‐132,732) deaths, and 3,000 (95% Cr.I.: 1,892‐4,424) stillbirths. We estimated a probability of symptomatic illness given infection of 0.198 (95% Cr.I.: 0.167‐0.229) and a probability of death given symptomatic illness of 0.019 (95% Cr.I.: 0.017‐0.021) for nonpregnant cases and 0.198 (95% Cr.I.: 0.169‐0.227) for pregnant cases. Conclusion: The model was most sensitive to estimates of age‐specific incidence of HEV disease. (HEPATOLOGY 2012)

The Economics of Routine Childhood Hepatitis A Immunization in the United States: The Impact of Herd Immunity

OBJECTIVE To forecast age-related macular degeneration (AMD) and its consequences in the United States through the year 2050 with different treatment scenarios. METHODS We simulated cases of early AMD, choroidal neovascularization (CNV), geographic atrophy (GA), and AMD-attributable visual impairment and blindness with 5 universal treatment scenarios: (1) no treatment; (2) focal laser and photodynamic therapy (PDT) for CNV; (3) vitamin prophylaxis at early-AMD incidence with focal laser/PDT for CNV; (4) no vitamin prophylaxis followed by focal laser treatment for extra and juxtafoveal CNV and anti-vascular endothelial growth factor treatment; and (5) vitamin prophylaxis at early-AMD incidence followed by CNV treatment, as in scenario 4. RESULTS Cases of early AMD increased from 9.1 million in 2010 to 17.8 million in 2050 across all scenarios. In non-vitamin-receiving scenarios, cases of CNV and GA increased from 1.7 million in 2010 to 3.8 million in 2050 (25% lower in vitamin-receiving scenarios). Cases of visual impairment and blindness increased from 620 000 in 2010 to 1.6 million in 2050 when given no treatment and were 2.4%, 22.0%, 16.9%, and 34.5% lower in scenarios 2, 3, 4, and 5, respectively. CONCLUSION Prevalence of AMD will increase substantially by 2050, but the use of new therapies can mitigate its effects.

The Cost-Effectiveness of Three Screening Alternatives for People with Diabetes with No or Early Diabetic Retinopathy

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.