The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States

Abstract

Background: The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs).

Methods: To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040.

Results: Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%.

Conclusions: Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.

Keywords: direct-acting antivirals; hepatitis C; people who inject drugs; screening; treatment.

Figure 1.

Compartment diagram of injection drug use, hepatitis C virus (HCV) infection transmission dynamics, and liver disease progression. A, Individuals in the noninjecting population became people who inject drugs (PWIDs) at age-specific rates. Active PWIDs ceased injecting over time, with a fraction relapsing and the remainder returning to the noninjecting population. B, The compartmental model includes susceptible (S), acutely infected (I), recovered (R), acutely reinfected (J), undiagnosed chronic HCV Metavir stages 0–4 (F_0–4), diagnosed chronic HCV Metavir stages 0–4 (D_0–4), cirrhosis with sustained virologic response (SVR; sD₄), decompensated cirrhosis (DC), decompensated cirrhosis with SVR (sDC), hepatocellular carcinoma (HCC), hepatocellular carcinoma with SVR (sHCC), and post-liver transplant (L). HCC, sHCC, DC, sDC, and L experience increased mortality (dashed arrows).

Figure 2.

Hepatitis C virus (HCV)-associated health outcomes over time, predicted with annual treatment of the noninjecting population at a national treatment rate of 100 000 (solid), 200 000 (long-dashed), 300 000 (short-dashed), or 400 000 (dotted) patients annually. Health outcomes depicted are (A) total HCV prevalence, (B) annual number of patients treated, (C) new cases of compensated cirrhosis, (D) annual mortality, (E) new cases of decompensated cirrhosis (DC), (F) new cases of hepatocellular carcinoma (HCC), (G) annual liver transplants, and (H) new HCV infections. All scenarios assume treatment exclusively with direct-acting antivirals, 1-time birth-cohort screening, and no change to the risk-based screening rate or to people who inject drugs screening or treatment rates.

Figure 3.

Impact of current (solid), 5% (long-dashed), 10% (short-dashed), 20% (dash-dotted), and 30% (dotted) people who inject drugs (PWIDs) treatment rates on total hepatitis C virus (HCV) prevalence among PWIDs (A–D) and annual incidence among PWIDs of new HCV cases (E–H) at current, 10%, 20%, and universal PWID screening rates. All scenarios assume treatment exclusively with direct-acting antivirals, 1-time birth-cohort screening among the noninjecting population, and no change to routine risk-based screening or treatment of the noninjecting population. Results were insensitive to increased treatment of the noninjecting population.