Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Unspoken Truths: Mental Health Among Academic Surgeons.

OBJECTIVE: To characterize the current state of mental health within the surgical workforce in the United States. BACKGROUND: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. METHODS: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. RESULTS: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. CONCLUSIONS: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

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.

The Rising Costs of Alcohol-Associated Liver Disease in the United States.

INTRODUCTION: Alcohol-associated liver disease (ALD) is rising in the United States because of an increase in high-risk drinking, but population-level ALD cost is unknown. Our aim was to project the direct and indirect costs associated with ALD in the US population through 2040. METHODS: We used a previously validated microsimulation model of alcohol consumption and ALD with model parameters estimated from publicly available data sources, including the National Epidemiologic Survey Alcohol and Related Conditions-III, the Center for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research, the Bureau of Labor Statistics, and published studies informing the impact of alcohol consumption on ALD severity in the United States resident population. The simulated scenario included current and projected ALD-associated costs. RESULTS: From 2022 to 2040, the ALD is projected to cost $880 billion, $355 billion in direct healthcare-related costs, and $525 billion in lost labor and economic consumption. The annual cost of ALD is projected to increase from $31 billion in 2022 to $66 billion (118% increase) in 2040. Although the female population makes up 29% of these costs in 2022, by 2040 on a per annum basis, female costs would be 43% of the total annual expenditure. DISCUSSION: Increased consumption of alcohol in the US population, especially in females, will cause a steep rise in the economic burden of ALD in the United States. These findings highlight the need for planners and policymakers to plan for the increased impact of liver disease in the United States.

Hepatitis C Elimination in Rwanda: Progress, Feasibility, and Economic Evaluation.

OBJECTIVES: In 2018, Rwanda launched a national program to eliminate the hepatitis C virus (HCV). We aim to assess the impact of the program to date and identify strategies to achieve the World Health Organization's HCV elimination goals by 2030. METHODS: We developed a microsimulation model to simulate Rwanda's HCV epidemic from 2015 through 2050 and evaluated temporal trends in HCV infection, prevalence, mortality, and the total cost of care for scenarios that could achieve HCV elimination by 2030. RESULTS: Between 2018 and 2022, over 7 million people were screened for HCV, and 60 000 were treated. The study projected that Rwanda could achieve HCV elimination as early as 2027. A feasible strategy of an annual screening rate of 15% and a treatment rate of 100% would achieve all World Health Organization elimination goals by 2028, requiring screening an additional 4 million people and treating 23 900 patients by 2030. The elimination strategy costs $25 million for screening and diagnosis and $21 million for treatment from 2015 to 2050. The national program would avert 4900 hepatocellular carcinoma cases and 6700 HCV-related deaths and save the health system $25.33 million from 2015 to 2050. CONCLUSIONS: Rwanda is poised to become one of the first countries in the world to eliminate HCV. Rwanda's program serves as a blueprint for other countries in the African region. By rapid screening and treatment scale-up (eg, by leveraging HIV platforms) and by drug price negotiations, HCV elimination is not only feasible but can be cost-saving in low-income settings.

Estimates of Hepatitis C Seroprevalence and Viremia in State Prison Populations in the United States.

BACKGROUND: Prior studies demonstrate that eliminating hepatitis C virus (HCV) in the United States (US) heavily depends on treating incarcerated persons. Knowing the scope of the carceral HCV epidemic by state will help guide national elimination efforts. METHODS: Between 2019 and 2023, all state prison systems received surveys requesting data on hepatitis C antibody and viremic prevalence. We supplemented survey information with publicly available HCV data to corroborate responses and fill in data gaps. RESULTS: Weighting HCV prevalence by state prison population size, we estimate that 15.2% of the US prison population is HCV seropositive and 8.7% is viremic; 54.9% of seropositive persons have detectable RNA. Applying prevalence estimates to the total prison population at year-end 2021, 91 090 persons with HCV infection resided in a state prison. CONCLUSIONS: With updated and more complete HCV data from all 50 states, HCV prevalence in state prisons is nearly 9-fold higher than the US general population. The heterogeneity in HCV prevalence by state prison system may reflect variable exposure before arrest and/or differences in treatment availability during incarceration. Elimination of HCV in the country depends on addressing the carceral epidemic, and one of the first steps is understanding the size of the problem.

Hepatitis C Elimination in Moldova Is Feasible and Cost-Saving: A Modeling Study.

BACKGROUND: Moldova, an upper-middle-income country in Eastern Europe, is facing a high burden of hepatitis C virus (HCV). Our objective was to assist the National Agency of Public Health of Moldova in planning to achieve the World Health Organization's HCV elimination goals by 2030. METHODS: This study adapted a previously developed microsimulation model to simulate the HCV epidemic in Moldova from 2004 to 2050. Model outcomes included temporal trends in HCV infection, prevalence, mortality, and total cost of care, including screening and treatment. We evaluated scenarios that could eliminate HCV by 2030. RESULTS: Multiple strategies could lead to HCV elimination in Moldova by 2030. A realistic scenario of a 20% annual screening and 80% treatment rate would require 2.75 million individuals to be screened and 65 000 treated by 2030. Compared to 2015, this program will reduce HCV incidence by 98% and HCV-related deaths by 72% in 2030. Between 2022 and 2030, this strategy would cost $17.5 million for HCV screening and treatment. However, by 2050, the health system would save >$85 million compared to no investment in elimination efforts. CONCLUSIONS: HCV elimination in Moldova is feasible and can be cost saving, but requires resources to scale HCV screening and treatment.

Effect of increased alcohol consumption during COVID-19 pandemic on alcohol-associated liver disease: A modeling study.

BACKGROUND AND AIMS: Alcohol consumption increased during the COVID-19 pandemic in 2020 in the United States. We projected the effect of increased alcohol consumption on alcohol-associated liver disease (ALD) and mortality. APPROACH AND RESULTS: We extended a previously validated microsimulation model that estimated the short- and long-term effect of increased drinking during the COVID-19 pandemic in individuals in the United States born between 1920 and 2012. We modeled short- and long-term outcomes of current drinking patterns during COVID-19 (status quo) using survey data of changes in alcohol consumption in a nationally representative sample between February and November 2020. We compared these outcomes with a counterfactual scenario wherein no COVID-19 occurs and drinking patterns do not change. One-year increase in alcohol consumption during the COVID-19 pandemic is estimated to result in 8000 (95% uncertainty interval [UI], 7500-8600) additional ALD-related deaths, 18,700 (95% UI, 17,600-19,900) cases of decompensated cirrhosis, and 1000 (95% UI, 1000-1100) cases of HCC, and 8.9 million disability-adjusted life years between 2020 and 2040. Between 2020 and 2023, alcohol consumption changes due to COVID-19 will lead to 100 (100-200) additional deaths and 2800 (2700-2900) additional decompensated cirrhosis cases. A sustained increase in alcohol consumption for more than 1 year could result in additional morbidity and mortality. CONCLUSIONS: A short-term increase in alcohol consumption during the COVID-19 pandemic can substantially increase long-term ALD-related morbidity and mortality. Our findings highlight the need for individuals and policymakers to make informed decisions to mitigate the impact of high-risk alcohol drinking in the United States.

Cervical cancer geographical burden analyzer: An interactive, open-access tool for understanding geographical disease burden in patients with recurrent or metastatic cervical cancer.

OBJECTIVE: Cervical cancer (CC) disproportionately affects women based on socioeconomic status and racial/ethnic background. There is limited research in quantifying and visualizing whether substantial geographical disparities in the US exist with respect to CC burden, and especially with respect to recurrent or metastatic CC (r/mCC) disease burden. Identifying regions with higher r/mCC burden may help inform effective healthcare resource allocation and navigating patients to appropriate care. METHODS: We conducted a retrospective analysis of the 2015-2020 MarketScan® Commercial and Supplemental Medicare claims data; r/mCC burden was estimated as the number of patients initiating r/mCC systemic therapy over CC-diagnosed patients for each of the 410 metropolitan statistical areas (MSAs) considered. We developed a public, web-based tool, the Cervical Cancer Geographical Disease Burden Analyzer (Cervical Cancer Geo-Analyzer, http://www.geo-analyzer.org), that allows users to visualize r/mCC burden across MSAs over multiple years. RESULTS: There was considerable variation in r/mCC burden across MSAs, with a range of 0-83.3%. Burden increased in Boston-Cambridge-Newton, MA (r/mCC to CC ratio: 41% in 2018 to 50% in 2020), and Sacramento-Roseville-Arden-Arcade, CA (33% in 2018 to 50% in 2020). On the other hand, while r/mCC burden remained high, it decreased in Grand Rapids, MI (55% in 2018 to 31% in 2020) and San Francisco-Oakland-Hayward, CA (40% in 2018 to 26% in 2020). There were regions with sparse or no data, suggesting a need for more representative data capture. CONCLUSION: The Cervical Geo-Analyzer is a tool to visualize areas with high need for CC interventions. It also builds the foundation for further work to understand local risk factors of disease burden, identify populations of interest, characterize health disparities of CC or r/mCC and inform targeted interventions.

Consensus report from the 10th Global Forum for Liver Magnetic Resonance Imaging: developments in HCC management.

The 10th Global Forum for Liver Magnetic Resonance Imaging (MRI) was held as a virtual 2-day meeting in October 2021, attended by delegates from North and South America, Asia, Australia, and Europe. Most delegates were radiologists with experience in liver MRI, with representation also from specialists in liver surgery, oncology, and hepatology. Presentations, discussions, and working groups at the Forum focused on the following themes: • Gadoxetic acid in clinical practice: Eastern and Western perspectives on current uses and challenges in hepatocellular carcinoma (HCC) screening/surveillance, diagnosis, and management • Economics and outcomes of HCC imaging • Radiomics, artificial intelligence (AI) and deep learning (DL) applications of MRI in HCC. These themes are the subject of the current manuscript. A second manuscript discusses multidisciplinary tumor board perspectives: how to approach early-, mid-, and late-stage HCC management from the perspectives of a liver surgeon, interventional radiologist, and oncologist (Taouli et al, 2023). Delegates voted on consensus statements that were developed by working groups on these meeting themes. A consensus was considered to be reached if at least 80% of the voting delegates agreed on the statements. CLINICAL RELEVANCE STATEMENT: This review highlights the clinical applications of gadoxetic acid-enhanced MRI for liver cancer screening and diagnosis, as well as its cost-effectiveness and the applications of radiomics and AI in patients with liver cancer. KEY POINTS: • Interpretation of gadoxetic acid-enhanced MRI differs slightly between Eastern and Western guidelines, reflecting different regional requirements for sensitivity vs specificity. • Emerging data are encouraging for the cost-effectiveness of gadoxetic acid-enhanced MRI in HCC screening and diagnosis, but more studies are required. • Radiomics and artificial intelligence are likely, in the future, to contribute to the detection, staging, assessment of treatment response and prediction of prognosis of HCC-reducing the burden on radiologists and other specialists and supporting timely and targeted treatment for patients.

Consensus report from the 10th global forum for liver magnetic resonance imaging: multidisciplinary team discussion.

The 10th Global Forum for Liver Magnetic Resonance Imaging was held in October 2021. The themes of the presentations and discussions at this Forum are described in detail in the review by Taouli et al (2023). The focus of this second manuscript developed from the Forum is on multidisciplinary tumor board perspectives in hepatocellular carcinoma (HCC) management: how to approach early-, mid-, and late-stage management from the perspectives of a liver surgeon, an interventional radiologist, and an oncologist. The manuscript also includes a panel discussion by multidisciplinary experts on three selected cases that explore challenging aspects of HCC management. CLINICAL RELEVANCE STATEMENT: This review highlights the importance of a multidisciplinary team approach in liver cancer patients and includes the perspectives of a liver surgeon, an interventional radiologist, and an oncologist, including illustrative case studies. KEY POINTS: • A liver surgeon, interventional radiologist, and oncologist presented their perspectives on the treatment of early-, mid-, and late-stage HCC. • Different perspectives on HCC management between specialties emphasize the importance of multidisciplinary tumor boards. • A multidisciplinary faculty discussed challenging aspects of HCC management, as highlighted by three case studies.

A multimorbidity model for estimating health outcomes from the syndemic of injection drug use and associated infections in the United States.

BACKGROUND: Fatal drug overdoses and serious injection-related infections are rising in the US. Multiple concurrent infections in people who inject drugs (PWID) exacerbate poor health outcomes, but little is known about how the synergy among infections compounds clinical outcomes and costs. Injection drug use (IDU) converges multiple epidemics into a syndemic in the US, including opioid use and HIV. Estimated rates of new injection-related infections in the US are limited due to widely varying estimates of the number of PWID in the US, and in the absence of clinical trials and nationally representative longitudinal observational studies of PWID, simulation models provide important insights to policymakers for informed decisions. METHODS: We developed and validated a MultimorbiditY model to Reduce Infections Associated with Drug use (MYRIAD). This microsimulation model of drug use and associated infections (HIV, hepatitis C virus [HCV], and severe bacterial infections) uses inputs derived from published data to estimate national level trends in the US. We used Latin hypercube sampling to calibrate model output against published data from 2015 to 2019 for fatal opioid overdose rates. We internally validated the model for HIV and HCV incidence and bacterial infection hospitalization rates among PWID. We identified best fitting parameter sets that met pre-established goodness-of-fit targets using the Pearson's chi-square test. We externally validated the model by comparing model output to published fatal opioid overdose rates from 2020. RESULTS: Out of 100 sample parameter sets for opioid use, the model produced 3 sets with well-fitting results to key calibration targets for fatal opioid overdose rates with Pearson's chi-square test ranging from 1.56E-5 to 2.65E-5, and 2 sets that met validation targets. The model produced well-fitting results within validation targets for HIV and HCV incidence and serious bacterial infection hospitalization rates. From 2015 to 2019, the model estimated 120,000 injection-related overdose deaths, 17,000 new HIV infections, and 144,000 new HCV infections among PWID. CONCLUSIONS: This multimorbidity microsimulation model, populated with data from national surveillance data and published literature, accurately replicated fatal opioid overdose, incidence of HIV and HCV, and serious bacterial infections hospitalization rates. The MYRIAD model of IDU could be an important tool to assess clinical and economic outcomes related to IDU behavior and infections with serious morbidity and mortality for PWID.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection.

INTRODUCTION: There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection. METHODS: We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status. RESULTS: Among 92,567 patients (32% cirrhosis), 3,247 cases of HCC were diagnosed during a mean follow-up of 2.5 years. In patients with cirrhosis, male sex (hazard ratios [HR]: 1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HR: 1.71, 1.79, and 1.34), varices (HR: 1.73, 1.60, and 1.56), baseline albumin (HR: 0.48, 0.47, and 0.49), and change in albumin (HR: 0.82 and 0.90) predicted HCC risk at each landmark time. HCV genotype 3, previous treatment, bilirubin, smoking, and race influenced HCC risk at baseline, but their effects attenuated over time. In patients without cirrhosis, diabetes (HR: 1.54, 1.42, and 1.47) and hypertension (HR: 1.59, 1.65, and 1.74) were associated with HCC risk at all landmark times. Changes in fibrosis-4 scores over time were associated with HCC risk both in patients with and without cirrhosis. DISCUSSION: Risk factors for HCC were different in patients with and without cirrhosis and some also evolved during follow-up. These factors can help with risk stratification and HCC surveillance decisions in patients with cured HCV.

Feasibility, effectiveness and cost of a decentralized HCV care model among the general population in Delhi, India.

BACKGROUND AND AIMS: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action. CONCLUSIONS: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times.

Cost-Effectiveness of a Core Antigen-Based Rapid Diagnostic Test for Hepatitis C.

OBJECTIVES: Hepatitis C virus (HCV) affects 58 million worldwide and > 79% of people remain undiagnosed. Rapid diagnostic tests (RDTs) for HCV can help improve diagnosis and treatment rates. Nevertheless, the high price and infrastructure needed to use current molecular HCV RDT options present a barrier to widespread use-particularly in low- and middle-income countries. We evaluated the performance and cost-effectiveness of a theoretical core antigen (cAg) RDT for HCV viremia confirmation, which requires fewer resources. METHODS: We adapted a previously validated microsimulation model to simulate HCV disease progression and outcomes under different HCV testing algorithms in Georgia and Malaysia. We compared standard of care testing with laboratory-based ribonucleic acid HCV to a cAg-based RDT for HCV confirmation. We simulated a cohort of 10 000 adults in each country, with an HCV-ribonucleic acid prevalence of 5.40% in Georgia and 1.54% in Malaysia. We projected the cumulative healthcare costs, quality-adjusted life-years, and diagnosis coverage rates over a lifetime horizon. RESULTS: Compared with the standard of care testing, the cAg-based RDT would increase quality-adjusted life-years by 270 in Georgia and 259 in Malaysia per 10 000 people. The high diagnosis rate and treatment rate of the cAg-based RDT result in substantial cost savings because of averted HCV sequelae management costs. Cost savings are $281 000 for Georgia and $781 000 for Malaysia. CONCLUSIONS: We found that a cAg-based RDT for HCV could improve the diagnosis rate and result in cost savings. Such a test could have a substantial impact on the feasibility and cost of HCV elimination.

Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis.

BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.

Securing sustainable funding for viral hepatitis elimination plans.

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct-acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries' health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro-elimination approach in specific populations is less complex and less costly than country-wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO.

Cost-Effectiveness of Testing and Treatment for Hepatitis B Virus and Hepatitis C Virus Infections: An Analysis by Scenarios, Regions, and Income.

OBJECTIVES: Testing and treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are highly effective, high-impact interventions. This article aims to estimate the cost-effectiveness of scaling up these interventions by scenarios, regions, and income groups. METHODS: We modeled costs and impacts of hepatitis elimination in 67 low- and middle-income countries from 2016 to 2030. Costs included testing and treatment commodities, healthcare consultations, and future savings from cirrhosis and hepatocellular carcinomas averted. We modeled disease progression to estimate disability-adjusted life-years (DALYs) averted. We estimated incremental cost-effectiveness ratios (ICERs) by regions and World Bank income groups, according to 3 scenarios: flatline (status quo), progress (testing/treatment according to World Health Organization guidelines), and ambitious (elimination). RESULTS: Compared with no action, current levels of testing and treatment had an ICER of $807/DALY for HBV and -$62/DALY (cost-saving) for HCV. Scaling up to progress scenario, both interventions had ICERs less than the average gross domestic product/capita of countries (HBV: $532/DALY; HCV: $613/DALY). Scaling up from flatline to elimination led to higher ICERs across countries (HBV: $927/DALY; HCV: $2528/DALY, respectively) that remained lower than the average gross domestic product/capita. Sensitivity analysis indicated discount rates and commodity costs were main factors driving results. CONCLUSIONS: Scaling up testing and treatment for HBV and HCV infection as per World Health Organization guidelines is a cost-effective intervention. Elimination leads to a much larger impact though ICERs are higher. Price reduction strategies are needed to achieve elimination given the substantial budget impact at current commodity prices.

Reduction of COVID-19 Incidence and Nonpharmacologic Interventions: Analysis Using a US County-Level Policy Data Set.

BACKGROUND: Worldwide, nonpharmacologic interventions (NPIs) have been the main tool used to mitigate the COVID-19 pandemic. This includes social distancing measures (closing businesses, closing schools, and quarantining symptomatic persons) and contact tracing (tracking and following exposed individuals). While preliminary research across the globe has shown these policies to be effective, there is currently a lack of information on the effectiveness of NPIs in the United States. OBJECTIVE: The purpose of this study was to create a granular NPI data set at the county level and then analyze the relationship between NPI policies and changes in reported COVID-19 cases. METHODS: Using a standardized crowdsourcing methodology, we collected time-series data on 7 key NPIs for 1320 US counties. RESULTS: This open-source data set is the largest and most comprehensive collection of county NPI policy data and meets the need for higher-resolution COVID-19 policy data. Our analysis revealed a wide variation in county-level policies both within and among states (P<.001). We identified a correlation between workplace closures and lower growth rates of COVID-19 cases (P=.004). We found weak correlations between shelter-in-place enforcement and measures of Democratic local voter proportion (R=0.21) and elected leadership (R=0.22). CONCLUSIONS: This study is the first large-scale NPI analysis at the county level demonstrating a correlation between NPIs and decreased rates of COVID-19. Future work using this data set will explore the relationship between county-level policies and COVID-19 transmission to optimize real-time policy formulation.