Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals.

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. RESULTS: In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. CONCLUSIONS: The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Estimated Reductions in Opioid Overdose Deaths With Sustainment of Public Health Interventions in 4 US States.

Importance: In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs). Objective: To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo. Design, Setting, and Participants: This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic. Exposure: Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years. Main Outcomes and Measures: Projected reduction in number of OODs under different combinations and durations of sustainment of interventions. Results: Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained. Conclusions and Relevance: In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.

Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure.

OBJECTIVES: The aim of this study was to examine patterns of care and clinical outcomes among patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Canada. BACKGROUND: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial, the use of N-terminal pro-B-type natriuretic peptide-guided titration of guideline-directed medical therapy (GDMT) was compared with usual care alone for patients with HFrEF in the United States and Canada. It remains unknown whether the country of enrollment had an impact on outcomes or GDMT use. METHODS: A total of 894 patients at 45 sites across the United States and Canada with HFrEF (ejection fraction ≤40%) were enrolled in the trial. Kaplan-Meier survival estimates stratified by country of enrollment were developed for the trial outcomes, and log-rank testing was compared between the groups. GDMT use and titration were also compared. RESULTS: U.S. patients were more likely to be younger, to be Black, to have higher body mass index, and to have histories of defibrillator placement or sleep apnea. Use of ß-blockers was significantly higher in Canada at baseline (99.3% vs. 94.0%; p = 0.01) and 6 months (99.0% vs. 94.1%; p = 0.04), and use of mineralocorticoid receptor antagonists was higher in Canada at 6 months (68.3% vs. 55.1%; p = 0.01). Canadian patients were less likely to experience the primary study endpoint (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.93; p = 0.01) due to decreased rates of HF hospitalization (HR: 0.57; 95% CI: 0.38 to 0.86; p = 0.003). The differences in outcomes were driven by increased heart failure hospitalization among U.S. Black patients. CONCLUSIONS: In GUIDE-IT, patients with HFrEF in Canada were significantly less likely to be hospitalized for heart failure. Differences in GDMT use, along with differences in sociodemographics and care delivery structures, may contribute to these differences, highlighting the importance of increasing diversity in clinical trials. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Alcohol-Associated Liver Disease Mortality Rates by Race Before and During the COVID-19 Pandemic in the US.

This cross-sectional study examines the national- and state-level age-adjusted mortality rates for alcohol-associated liver disease in 4 racial groups, with a focus on the American Indian or Alaska Native population.