Early Treatment of Perinatally Acquired HCV More Cost-Effective Than DAA Deferral

Megan Rose Curtis, MD

Credit: Megan Rose Curtis on LinkedIn

Treating hepatitis C virus (HCV) at 3 years of age may be associated with significant cost savings and lead to improved health outcomes compared to deferring direct-acting antiviral (DAA) therapy, according to findings from a recent health economic study published in JAMA Pediatrics.¹

The state-transition model projected longer life expectancy, fewer cases of cirrhosis and hepatocellular carcinoma (HCC), and fewer liver-related deaths with treatment at 3 years of age versus deferral until age 6 years or older, further predicting substantial cost savings and reduced health care costs with early treatment compared to later treatment.¹

“Our model incorporates emerging data regarding the natural history of pediatric disease to validate projected HCV disease progression. It derives parameters for treatment costs and effectiveness specific to young children,” Megan Rose Curtis, MD, post-doctoral research fellow at Harvard Medical School and Massachusetts General Hospital, and colleagues wrote.¹ “This analysis is also, to our knowledge, the first to project the impact of early treatment at age 3 years old on life expectancy.”

According to the Centers for Disease Control and Prevention, approximately 6% of infants born to mothers with HCV will perinatally acquire the infection.² Although spontaneous clearance without treatment typically occurs in 20%–40% of children with perinatally acquired HCV, testing and linkage to care is of paramount importance in this patient population in order to prevent the potential development of clinical manifestations and complications from chronic HCV. Curative DAA therapy is FDA-approved for children ≥ 3 years of age, but little is known about the impact of treatment at this age.³

To project the clinical and economic outcomes of treating children with perinatally acquired HCV at various ages, investigators developed a state-transition model for simulating disease progression and costs in a hypothetical cohort of 1000 US children over a lifetime horizon. The model characterized disease progression through annual transitions between mutually exclusive health states reflecting key clinical conditions of HCV disease, including liver fibrosis stages, cirrhosis complications, and mortality from liver-related and age-adjusted competing risks of death.¹

The treatment strategies modeled included treating at 3 years, 6 years, 12 years, and 18 years of age with an 8-week course of glecaprevir/pibrentasvir. Treatment effectiveness, defined as sustained virologic response (SVR) at 12 weeks, reflected completion rates from a pediatric randomized clinical trial and a meta-analysis of real-world effectiveness of DAA therapy in adults, which both estimated 96% effectiveness.¹

The model simulated clinical outcomes including cases of cirrhosis, decompensated cirrhosis, HCC, liver-related mortality, and all-cause mortality. Outcomes of interest included life expectancy from 3 years and average lifetime per-person health care costs.¹

Without treatment, the model predicted a median age of cirrhosis of 35 years, which investigators noted fell within 6% of the predicted median age of cirrhosis in a validation cohort of 1049 individuals with pediatric hepatitis C (33 years). The median time from cirrhosis to first decompensation was 10 years in the model, which was within 8% of the median 10.8 years reported in prior HCV modeling studies and in a prospective study of patients with compensated HCV cirrhosis.¹

The model-predicted no-treatment strategy led to 926 cases of cirrhosis and 277 cases of HCC. Estimated life expectancy without treatment was 55.70 life years with 765 liver-related deaths. Investigators pointed out earlier treatment improved clinical outcomes with a monotonic trend in decreased cases of cirrhosis, decompensated cirrhosis, HCC, and life expectancy.¹

Indeed, projected life expectancy was longest when patients were treated at 3 years of age (78.36 life years) and decreased with treatment deferral until 6 years of age (76.10 life years), 12 years of age (75.99 life years), and 18 years of age (75.46 life years). Additionally, investigators pointed out treating at 3 years of age prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years of age.¹

Projected average per-person discounted lifetime health care costs ranged from $148,162 for treating at 3 years old to $279,252 in the no-treatment strategy. Lifetime health care costs were lower with earlier treatment compared with deferred treatment, with investigators noting treating HCV at 3 years of age was associated with lower mean lifetime per-person health care costs ($148,162) than deferring treatment until 6 years of age ($164,292), 12 years of age ($171,909), or 18 years of age ($195,374).¹

Of note, the clinical benefits and cost savings associated with early HCV treatment were significantly greater when investigators assumed higher loss to follow-up rates.¹

“This health economic study suggests that treating HCV at 3 years old costs less and leads to improved health outcomes compared to deferring treatment,” investigators concluded.¹

References:

1. ^{Curtis MR, Epstein RL, Pei P, Linas BP, Ciaranello AL. Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus. JAMA Pediatr. Published online March 11, 2024. doi:10.1001/jamapediatrics.2024.0114}
2. ^{Centers for Disease Control and Prevention. Hepatitis C Information. Viral Hepatitis. October 31, 2023. Accessed March 12, 2024. https://www.cdc.gov/hepatitis/hcv/cfaq.htm#transmission}
3. ^{Centers for Disease Control and Prevention. CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children — United States, 2023. November 3, 2023. Accessed March 12, 2024. https://www.cdc.gov/mmwr/volumes/72/rr/rr7204a1.htm}