Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus.

Importance: Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. Objective: To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. Design, Setting, and Participants: The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. Interventions: The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Main Outcomes and Measures: Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). Results: The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. Conclusions and Relevance: These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.

Test characteristics for combining non-invasive liver fibrosis staging modalities in individuals with Hepatitis C virus.

Non-invasive methods have largely replaced biopsy to identify advanced fibrosis in hepatitis C virus (HCV). Guidelines vary regarding testing strategy to balance accuracy, costs and loss to follow-up. Although individual test characteristics are well-described, data comparing the accuracy of using two tests together are limited. We calculated combined test characteristics to determine the utility of combined strategies. This study synthesizes empirical data from fibrosis staging trials and the literature to estimate test characteristics for Fibrosis-4 (FIB4), APRI or a commercial serum panel (FibroSure®), followed by transient elastography (TE) or FibroSure®. We simulated two testing strategies: (1) second test only for those with intermediate first test results (staged approach), and (2) second test for all. We summarized empiric data with multinomial distributions and used this to estimate test characteristics of each strategy on a simulated population of 10,000 individuals with 4.2% cirrhosis prevalence. Negative predictive value (NPV) for cirrhosis from a single test ranged from 98.2% (95% CB 97.6-98.8%) for FIB-4 to 99.4% (95% CB 99.0-99.8%) for TE. Using a staged approach with TE second, sensitivity for cirrhosis rose to 93.3-96.9%, NPV to 99.7-99.8%, while PPV dropped to <32%. Using TE as a second test for all minimally changed estimated test characteristics compared with the staged approach. Combining two non-invasive fibrosis tests barely improves NPV and decreases or does not change PPV compared with a single test, challenging the utility of serial testing modalities. These calculated combined test characteristics can inform best methods to identify advanced fibrosis in various populations.

A Microsimulation Study of the Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis Centers.

BACKGROUND: National guidelines recommend twice-yearly hepatitis C virus (HCV) screening for patients receiving in-center hemodialysis. However, studies examining the cost-effectiveness of HCV screening methods or frequencies are lacking. METHODS: We populated an HCV screening, treatment, and disease microsimulation model with a cohort representative of the US in-center hemodialysis population. Clinical outcomes, costs, and cost-effectiveness of the Kidney Disease Improving Global Outcomes (KDIGO) 2018 guidelines-endorsed HCV screening frequency (every 6 months) were compared with less frequent periodic screening (yearly, every 2 years), screening only at hemodialysis initiation, and no screening. We estimated expected quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) between each screening strategy and the next less expensive alternative strategy, from a health care sector perspective, in 2019 US dollars. For each strategy, we modeled an HCV outbreak occurring in 1% of centers. In sensitivity analyses, we varied mortality, linkage to HCV cure, screening method (ribonucleic acid versus antibody testing), test sensitivity, HCV infection rates, and outbreak frequencies. RESULTS: Screening only at hemodialysis initiation yielded HCV cure rates of 79%, with an ICER of $82,739 per QALY saved compared with no testing. Compared with screening at hemodialysis entry only, screening every 2 years increased cure rates to 88% and decreased liver-related deaths by 52%, with an ICER of $140,193. Screening every 6 months had an ICER of $934,757; in sensitivity analyses using a willingness-to-pay threshold of $150,000 per QALY gained, screening every 6 months was never cost-effective. CONCLUSIONS: The KDIGO-recommended HCV screening interval (every 6 months) does not seem to be a cost-effective use of health care resources, suggesting that re-evaluation of less-frequent screening strategies should be considered.

"Meds-in-Hand" Intervention to Reduce Critical Process Delays in Pediatric Human Immunodeficiency Virus Post-Exposure Prophylaxis.

Pediatric human immunodeficiency virus post-exposure prophylaxis is frequently indicated, but delays in medication receipt are common. Using plan-do-study-act cycles, we developed a multidisciplinary collaboration to reduce critical process delays in our pediatric emergency department. Interruptions decreased from a median 1 per month pre-intervention to zero per month during the intervention.