The cost-effectiveness of screening for chronic hepatitis B infection in the United States

Abstract

Background: Hepatitis B virus (HBV) continues to cause significant morbidity and mortality in the United States. Current guidelines suggest screening populations with a prevalence of ≥2%. Our objective was to determine whether this screening threshold is cost-effective and whether screening lower-prevalence populations might also be cost-effective.

Methods: We developed a Markov state transition model to examine screening of asymptomatic outpatients in the United States. The base case was a 35-year-old man living in a region with an HBV infection prevalence of 2%. Interventions (versus no screening) included screening for Hepatitis B surface antigen followed by treatment of appropriate patients with (1) pegylated interferon-α2a for 48 weeks, (2) a low-cost nucleoside or nucleotide agent with a high rate of developing viral resistance for 48 weeks, (3) prolonged treatment with low-cost, high-resistance nucleoside or nucleotide, or (4) prolonged treatment with a high-cost nucleoside or nucleotide with a low rate of developing viral resistance. Effectiveness was measured in quality-adjusted life years (QALYs) and costs in 2008 US dollars.

Results: Screening followed by treatment with a low-cost, high-resistance nucleoside or nucleotide was cost-effective ($29,230 per QALY). Sensitivity analyses revealed that screening costs <$50,000 per QALY in extremely low-risk populations unless the prevalence of chronic HBV infection is <.3%.

Conclusions: The 2% threshold for prevalence of chronic HBV infection in current Centers for Disease Control and Prevention/US Public Health Service screening guidelines is cost-effective. Furthermore, screening of adults in the United States in lower-prevalence populations (eg, as low as .3%) also is likely to be cost-effective, suggesting that current health policy should be reconsidered.

Figure 1.

A, decision tree model showing the 5 screening and treatment strategies at the initial square decision node. As indicated at the first round chance node, at the time of screening patients may have chronic hepatitis B virus (HBV) infection, be immune, or not be infected. Patients with chronic HBV infection may or may not have abnormal liver function tests (LFTs); HBeAg status may be positive or negative, and viral load may be elevated or not in those with abnormal LFTs. After initial screening, all patients proceed to the Markov simulation. B, Simplification of the actual Markov model, which contains 52 states of health. During each monthly cycle, patients face a series of different chance events that depend on the state of health in which they started that cycle. In general, these events include elevation or normalization of alanine aminotransferase (ALT), increase or decrease in HBV DNA load, HBeAg seroconversion, development of compensated cirrhosis, progression to decompensated cirrhosis, development of hepatocellular carcinoma (HCC), and liver transplantation. We assume that disease progresses in a linear fashion, such that only patients with compensated cirrhosis may develop decompensated cirrhosis. The risk of developing cirrhosis or HCC is dependent on HBV DNA load. HCC can develop at any stage of chronic HBV infection. Patients with decompensated cirrhosis or HCC may be eligible for liver transplantation. In any cycle patients may die from disease-related causes or nonexplicitly modeled causes based on life tables stratified by age, sex, and race.

Figure 2.

Tornado diagram of 1-way sensitivity analyses for the strategy of screening followed by prolonged treatment with the low-cost, high-resistance nucleoside or nucleotide and salvage therapy with the high-cost, low-resistance nucleoside or nucleotide if resistance develops. The marginal cost-effectiveness ratio (mCER) in dollars per quality-adjusted life year (QALY) is shown on the horizontal axis ranging between $0 and $100,000 per QALY. For each parameter examined, the upper and lower limits of the sensitivity analysis (labels appear at either end of each band) are based on either the 95% confidence intervals or a clinically reasonable range.

Figure 3.

Probabilistic sensitivity analysis showing a cost-effectiveness acceptability curve comparing no screening with screening followed by prolonged treatment with a low-cost, high-resistance nucleoside or nucleotide followed by salvage therapy with the high-cost, low-resistance nucleoside or nucleotide in those who develop resistance. We calculated the marginal cost-effectiveness ratios for this comparison based on 10,000 second-order Monte Carlo simulations. Values were varied simultaneously based on picks from their respective distributions. Screening cost <$50,000 per quality-adusted life year (QALY) in >49% of the simulations and cost <$100,000 per QALY >99% of the time.

Figure 4.

Prevalence of chronic hepatitis B virus (HBV) infection. The marginal cost-effectiveness ratio (mCER) of screening followed by prolonged treatment with the low-cost, high-resistance nucleoside or nucleotide decreases as the prevalence in the screening population increases. The mCER is <$50,000 per quality-adjusted life year (QALY) above a screening population prevalence of 0.3%.

Figure 5.

Three-way sensitivity analysis: relative hazard of compensated cirrhosis and relative hazard of hepatocellular carcinoma in patients receiving prolonged treatment with high-cost, low-resistance nucleoside or nucleotide. The 3 lines represent willingness-to-pay thresholds of $50,000, $75,000, and $100,000 per quality-adjusted life year (QALY). For points falling above each line, the cost-effectiveness of this strategy exceeds the willingness-to-pay threshold, and the less costly screening followed by prolonged treatment with the low-cost, high-resistance nucleoside or nucleotide is preferred.