INTRODUCTION:Disrupted linkage to care is a major barrier to hepatitis C virus (HCV) elimination leading to high attrition rates. This study aimed to describe (1) flow through the HCV care-cascade (2009-2020), and (2) monthly patterns in HCV care during the coronavirus disease 2019 (COVID-19) pandemic (2020) in Israel. METHODS:Data were obtained from Maccabi Healthcare Services, a 2.6-million-member healthcare provider in Israel. Flow through the HCV care-cascade in 2009-2020 was described from individuals' first positive HCV antibody (Ab+) test to sustained virological response (SVR), and monthly data were obtained on individuals newly attaining a given stage in the HCV care-cascade in 2020. RESULTS:Among 2809 new patients who were Ab+, 2651 (94.4%) had an HCV polymerase chain reaction (PCR) test, and 1417 (50.4%) were PCR+ during the study. Median time from Ab+ to PCR+ was 3.9 years, with 39.7% PCR+ within 12 months. Median time from PCR+ to HCV treatment was 3.3 years, with 639 (55.5%) of patients who were PCR+ purchasing direct-acting anti-viral agents (DAAs), and 413/416 patients attained SVR. A significant reduction was observed in the time from first HCV detection (Ab+) to HCV confirmation (PCR+) and from PCR+ test to HCV treatment purchase in the pre-DAA era compared to the post-DAA. Monthly data during 2020 (Part B) indicates a decline in the numbers of patients receiving HCV care during the first pandemic-related closure. CONCLUSION:Real-world data from a nationally representative healthcare provider database suggest that HCV linkage to care improved over time alongside increased access to DAAs, despite observed declines in access to care in 2020.

Introduction: Venetoclax has demonstrated consistent efficacy and manageable toxicity in patients with previously untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). However, evidence on venetoclax use in patients previously treated with Bruton tyrosine kinase inhibitors (BTKi) is limited. This real-world evidence (RWE) study assessed clinical outcomes of patients who received venetoclax after covalent BTKi (cBTKi) therapy, i.e., response rates, time to next treatment or death (TTNT-D), and progression-free survival (PFS), overall and stratified by line of therapy. Methods: The CLL Collaborative Study of Real-World Evidence (CORE), a retrospective, international, observational study (23 centers) provided data for this analysis. Adult patients diagnosed with CLL/SLL were included if they received a venetoclax-based regimen after discontinuation of a cBTKi-based regimen. Baseline characteristics at venetoclax initiation were summarized using descriptive statistics. Overall response rate (ORR) was calculated as the proportion of patients with complete response (CR) or partial response (PR) among patients with documented responses as recorded in the patients' medical charts based on physician assessment. TTNT-D was measured from date of venetoclax initiation to change of treatment/death (event) or end of follow-up, while PFS was measured from date of venetoclax initiation to disease progression/death (event) or end of follow-up. Outcomes were reported for the overall population and stratified by line of therapy (1L→2L and 2L→3L) and also by with and without CT/CIT exposure prior to cBTKi for 2L→3L. Results: Of the 2,020 patients included in CORE, 1,287 (63.7%) received a cBTKi-based regimen in ≥1 line of therapy; 184 patients (14.3%) discontinued cBTKi (intolerance: 83 [45.1%], progression: 78 [42.4%]) and initiated venetoclax-based therapy (115 venetoclax monotherapy; 69 venetoclax combined with rituximab or obinutuzumab). Mean age at venetoclax initiation was 68.6 (median: 68.2) years old, 69.0% were male, and 31.0% had Medicare. Among tested patients, 41/61 (67.2%) had unmutated IGHV, and 28/109 (25.7%) had 17p deletion or TP53 mutation at venetoclax initiation. Average follow-up time from initiation of venetoclax therapy was 19.6 months (median: 16.6). Of the 127 patients (69.0%) with a documented response, the ORR was 78.0% (CR: 43.3%, PR: 34.6%). The median TTNT-D for these patients was 39.5 months (95% CI: 30.4, not reached [NR]) with 12- and 18-month rates of 82.3% and 72.4%, respectively. The median PFS was 43.2 months (95% CI: 31.9, NR), with 12- and 18- month PFS rates of 82.8% and 75.1%, respectively. Among patients who started venetoclax-based therapy post-cBTKi as 1L→2L (n=65), the ORR was 84.1% (CR: 54.5%, PR: 29.5%, out of 44 documented). The median TTNT-D for these patients was NR (95% CI: 31.9, NR) but the 12- and 18-month rates were 85.0% and 73.9%, respectively. The median PFS was 43.2 months (95% CI: 39.5, NR) with 12- and 18- month rates of 86.4% and 81.8%, respectively. Among patients who started venetoclax-based therapy post-cBTKi as 2L→3L (n=67), the ORR was 78.3% (CR: 41.3%, PR: 37.0%, out of 46 documented). The median TTNT-D for these patients was 44.2 months (95% CI: 37.0, NR) with 12- and 18-month rates were 83.1% and 76.5%, respectively. The median PFS for these patients was 44.1 months (95% CI: 31.8, NR) with 12- and 18- months rates were 85.2% and 80.4%, respectively. The results for ORR, TTNT-D, and PFS were also similar for those with and without CT/CIT exposure prior to cBTKi. Conclusions: In this multicenter real-world study, results demonstrate that venetoclax is effective overall and also when used either in 2L or 3L following cBTKi therapy. Additionally, even with prior CT/CIT exposure, results support that venetoclax-based therapy remains effective as a therapeutic option. Thus, this study demonstrates that venetoclax-based therapy post-cBTKi is associated with durable remission. These results are especially timely as the CLL treatment paradigm continues to evolve with multiple treatment options available, providing clinicians with valuable evidence to inform modern clinical practice. Further analysis of this study with larger cohorts and longer follow-up time will be undertaken as part of future work to grow this body of evidence.

PURPOSE Venetoclax and Bruton's tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL. METHODS We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n = 193) or BTKi treatment (n = 1,577) in the frontline setting between June 01, 2019, and June 30, 2020. Discontinuation was defined as a consecutive 90-day gap in treatment at any point over an 18-month follow-up. BTKi patients were expected to receive treatment continuously; VEN-O patients were expected to complete 11 months of treatment (12 cycles × 28 days = 336 days). The rates of subsequent CLL treatment and all-cause/CLL-related hospitalization were assessed. RESULTS Over an 18-month follow-up, 102 (52.8%) VEN-O patients discontinued after completing the fixed-duration period; 597 (37.9%) BTKi and 57 (29.5%) VEN-O patients discontinued treatment prematurely. The median time to discontinuation was 11.9 months (VEN-O) and 4.0 months (BTKi patients), respectively. Few patients (n < 11) who discontinued VEN-O initiated another CLL treatment over a median postdiscontinuation follow-up period of 6.1 months. By contrast, 39.0% of discontinuers in the BTKi group had evidence of subsequent CLL treatment over a median 13.8-month postdiscontinuation follow-up period. Post-BTKi regimens included BCL-2 (35.6%), subsequent BTKi (31.8%), chemotherapy (14.6%), anti-CD20 monotherapy (9.9%), and other (8.2%). The rate of postdiscontinuation all-cause and CLL-related hospitalization per 100 patient-months was 2.0 and 1.5 for the VEN-O group and 3.3 and 2.9 for the BTKi group, respectively. CONCLUSION In this real-world study, early discontinuation was more common in patients initiating a BTKi in contrast to VEN-O. Patients who initiated a BTKi also had high rates of subsequent treatment and hospitalization.

Introduction: Venetoclax + obinutuzumab (VO) and Bruton tyrosine kinase inhibitor (BTKi) therapies used in the first line (1L) setting are highly effective for patients (pts) with chronic/small lymphocytic leukemia (CLL/SLL) but there are no reported comparative studies. This study compared real-world clinical outcomes of pts treated with VO vs BTKi therapy in 1L. Methods: Data from the CLL Collaborative Study of Real-World Evidence (CORE), an international, retrospective, multi-center chart review study (25 centers) were used. Adult pts who initiated approved 1L treatments of VO (VO cohort) or covalent BTKi (cBTKi cohort) therapy in 1L between 2019-2024 were included. Cohorts were balanced using entropy balancing on sex, age at 1L, year of 1L start, ECOG performance status, Rai stage, del(17p)/TP53 mutation, and comorbidities. Among pts with known mutation status, proportion of pts with unmutated IGHV was similar across cohorts; hence it was not included (VO: 54.8%; cBTKi: 57.6%). Weighted outcomes included overall response rate (ORR: proportion of pts with physician-reported clinical complete/partial response [CR/PR] out of pts with available response data), progression-free-survival (PFS: time from initiation of therapy to disease progression/death [event] or last follow-up [censor]), and time to next treatment or death (TTNT-D: time from initiation of therapy to the change of therapy (including cBTKi to cBTKi)/death [event] or last follow-up [censor]). Time-to-event data were assessed using Kaplan-Meier methods and Cox proportional hazards model at 12 and 18 months (mos). Given >20% of pts were still at risk 18-mos after 1L initiation, results for 18-mos rates were reported. Results: Of 2,309 total pts, 110 initiated VO and 242 a cBTKi (ibrutinib: 111 [45.9%], acalabrutinib: 102 [42.1%], zanubrutinib: 15 [6.2%], cBTKi+anti-CD20: 14 [5.8%]) in 1L. Before weighting, the VO cohort was younger at 1L initiation (median years VO: 64.5; cBTKi: 67.9) and median time to 1L start post-diagnosis was longer (39.1 vs 25.1 mos). The VO cohort had higher proportion of pts with ECOG 0-2 (among those with known ECOG: 99.0% vs 98.9%), lower proportion with del(17p)/TP53 mutation (6.7% vs 17.1%), and lower median number of comorbidities (1 vs 2). Common comorbidities for both cohorts included cardiovascular (43.6% vs 52.1%) and endocrine/metabolic conditions (20.9% vs 36.8%). Pt and treatment characteristics were well-matched between cohorts after weighting. After weighting, with a median follow-up of 10.2 mos (IQR: 5.6, 17.9) for the VO cohort and 10.7 mos (IQR: 4.9, 25.5) for the cBTKi cohort, median duration of treatment was 9.5 [IQR: 5.4, 17.3] vs 12.1 [IQR: 4.9, 18.3] mos, respectively; majority of pts were still on therapy at the time of analyses (63.6% vs 74.7%) but fewer pts in the VO cohort initiated a subsequent line of therapy (2.7% vs 18.8%). Among the 58 pts in the cBTKi cohort who sequenced to another therapy, largely due to intolerance (66.7%), 41.9% switched to another cBTKi (36.2% to acalabrutinib) and 58.1% to a different regimen (i.e., venetoclax-based: 45.7%; other: 12.4%). Only 3 pts in the VO cohort started another therapy (2 due to intolerance). The ORR was descriptively higher for the VO cohort (ORR: 89.2% [CR: 58.1%; PR: 31.1%], available response data for 67.3%) relative to the cBTKi cohort (ORR: 80.7% [CR: 8.8%; PR: 71.9%], available response data for 63.0%). The median PFS was not reached, however the 18-mos rate was trending higher for the VO cohort (92.2% vs 84.3%). Based on the Cox model, there was no statistically significant difference in PFS at 18-mos for the cBTKi cohort compared to the VO cohort (hazard ratio [HR]: 2.37 (confidence interval [CI]: 0.76, 7.44; p-value: 0.14). The median TTNT-D was not reached, however the 18-mos rate was higher for the VO cohort (89.4% vs 70.2%). Based on the Cox model, the cBTKi cohort had a statistically significant greater risk of sequencing to the next treatment/death at 18-mos compared to the VO-based cohort (HR: 3.27 (CI: 1.35, 7.94; p-value: <0.01). Conclusions: This study is one of the first to demonstrate advantages in clinical outcomes of pts using VO vs cBTKi therapy in 1L for TTNT-D. Considering that 19% of BTKi pts switched therapy, largely due to intolerance, this highlights the need for future studies to assess VO vs 2nd-generation BTKis in the 1L setting with longer follow-up time and larger cohorts.

Objective Assess treatment characteristics and outcomes of patients with CLL treated with a venetoclax+BTKi-based (venetoclax+BTKi) combination therapy. Methods Data on adult CLL patients initiating venetoclax+BTKi came from 24 centers of the global CLL Collaborative Study of Real-World Evidence (CORE). Treatment characteristics and outcomes assessed were: overall response rate (ORR; ie, proportion of patients with physician-defined complete or partial response, among those with a recorded response), progression-free survival (PFS; ie, time from venetoclax+BTKi initiation to disease progression/death or end of follow-up), and time to next treatment/death (TTNT-D; ie, time from venetoclax+BTKi initiation to subsequent treatment/death or end of follow-up). Results were reported overall and stratified by line of therapy (ie, first line [1L], second line and later [2L+]) and type of combination BTKi (not mutually exclusive; ie, venetoclax+ibrutinibbased [VI-based], venetoclax+acalabrutinib-based [VA-based], venetoclax+other BTKi-based [VOther-based]). Results Of 2296 total patients, 65 initiated venetoclax+BTKi (in clinical trial: 73.8%; median age: 64.1 years; male: 66.2%, unmutated IGHV: 59.0%; del[17]p/TP53 mutation: 17.5%; cardiovascular comorbidities: 44.6%). The median follow-up was 16.7 months (treatment duration: 14.0 months). Venetoclax+BTKi combinations included VI-based (69.2% patients), VA-based (26.2%), and VOther-based (6.2%). Dose reductions (23.1%) and/or treatment interruptions (36.9%) occurred mostly due to intolerance; 40.0% of patients discontinued treatment within a median 13.9 months (VI-based: 13.9 months; VA-based: 14.8; VOther-based: 22.2), commonly for completion of scheduled duration of therapy (61.5%), disease progression (15.4%), and intolerance (11.5%). Of 7 with subsequent treatments, 42.9% were from 1L VI-based and 57.1% from 2L+ VI-based. The ORR was 90.4% (1L: 96.6%; 2L+: 82.6%; VI-based: 94.9%; VA-based: 72.7%; VOther-based: 100.0%). Median PFS was 60.3 months (1L: not reached [NR]; 2L+: 60.3; VI-based: 60.3; VA-based: NR; VOther-based: no events [NE]), with an 18-month rate of 89.5% (1L: 89.3%; 2L+: 88.5%; VI-based: 91.7%; VAbased: 80.0%; VOther-based: NE). TTNT-D was 67.1 months (1L: NR; 2L+: 67.1; VI-based: 67.1; VA-based: NR; VOther-based: NE), with an 18-month rate of 86.1% (1L: 86.9%; 2L+: 84.1%; VI-based: 87.1%; VA-based: 80.0%; VOther-based: NE). Conclusions Venetoclax+BTKi regimens were well tolerated across 1L/2L+, and most patients had no treatment interruptions/reductions. Strong response rates and durable remission support venetoclax+BTKi combination use for CLL management. Funding This study was funded by AbbVie.

Direct-acting antiviral (DAA) therapy is highly effective in curing hepatitis C virus (HCV) infection in people who inject drugs (PWID). Previous studies showed declining persistence to DAA therapy over the course of treatment. This study compares real-world medication persistence to prescription refills for 8- versus 12-week DAA in treatment-naïve PWID with chronic HCV with compensated cirrhosis or without cirrhosis. Symphony Health’s claims database was used to collect data from patients with chronic HCV aged ≥ 12 years who were prescribed 8- or 12-week DAA therapy between August 2017 and November 2020 and had a diagnosis of addicted drug use within 6 months prior to index date. Eligible patients had medical/pharmacy claims in the 6 months before and 3 months after the first index medication fill date (i.e., index date). Patients completing all refills (8-week = 1 refill, 12-week = 2 refills) were deemed persistent. The percentage of persistent patients in each group, and at each refill step, was determined; outcomes were also assessed in a subgroup of Medicaid-insured patients. This study assessed 7203 PWID with chronic HCV (8-week, 4002; 12-week, 3201). Patients prescribed 8-week DAA treatment were younger (42.9 ± 12.4 vs 47.5 ± 13.2, P < 0.001) and had fewer comorbidities (P < 0.001). Patients receiving 8- versus 12-week DAA had greater refill persistence (87.9

The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1–6 can achieve a 98

Background The objective of this study was to examine differences in healthcare utilization among patients receiving eight vs. 12-weeks of treatment for infection with the Hepatitis C Virus (HCV). Methods We conducted a retrospective cohort study among 282 treatment-naïve, HCV-infected patients. Those eligible were uninfected with the Human Immunodeficiency Virus, non-cirrhotic, and treated between 2016 and 2019 as part of an extensive, urban, university-affiliated healthcare system. Electronic medical data were abstracted starting from HCV treatment initiation and up to one year post-initiation or achievement of post-treatment sustained virologic response, whichever occurred first. The primary outcome of interest was healthcare utilization, defined by the number and type of healthcare encounters. Differences in healthcare utilization between those receiving eight vs. 12-weeks of treatment were examined using Student’s t-test, Fisher’s exact test, Pearson’s chi-square test, and the Wilcoxon rank-sum test. Results A total of 282 eligible patients were analyzed. At baseline, the average age was 59 years (standard deviation=12), and the majority were male (55%) and white/Caucasian (58%). There were no baseline demographic or clinical differences between those completing 8 (n=59) or 12 (n=223) weeks of treatment. While no overall difference in healthcare encounters was observed between those receiving the 8-weeks (median encounters 6; IQR 4-11) and 12-weeks of treatment (median encounters 8; IQR 5-12; P value=0.07), a notable difference was seen in the number of laboratory visits between the groups (median 1 vs. 2; P value=0.04). Conclusions Our findings indicate modest reductions in healthcare utilization among those receiving shorter treatment regimens for HCV infection, specifically regarding laboratory testing. These findings suggest that shorter treatment regimens may improve treatment expansion in settings that are otherwise too resource-constrained to deliver HCV care successfully.

Introduction Progress towards achieving hepatitis C virus (HCV) elimination in Florida has been hampered by barriers to screening, linkage to care, and treatment. This study aims to describe the HCV care cascade and patient characteristics in Florida. Methods This analysis combined HCV-related laboratory data and patient characteristics from two, large US laboratory datasets that included individuals tested for HCV antibody (Ab) and HCV ribonucleic acid (RNA) viral load between January 2015 and December 2019. A decline in sequential HCV RNA viral loads was used to impute HCV treatment. Machine-learning algorithms were used to identify cured patients. The actual number of individuals with HCV Ab screening, and the number and percentage of persons who were HCV RNA-positive and treated, were calculated. Results The number of persons in Florida diagnosed as HCV RNA-positive was 31,659 in 2019. The number of individuals HCV Ab screened in 2019 was 1,024,379, an increase of 82.5% from 2015. The percentage of HCV Ab-positive individuals was 4.1%, demonstrating a 16.2% decrease from 2015. The percentage of HCV RNA-positive patients who were treated was 27.0%, a 10.5% decrease from 2015 to 2019. Conclusion An Ab positivity rate > 4-times higher than national estimates with increased screening among baby boomers, but decreased screening among younger individuals, suggests risk-based screening is still common practice in Florida, despite universal screening recommendations. Public health efforts to decrease barriers to screening, linkage to care, and treatment are needed to reduce the burden of HCV in Florida and to ensure progress toward virus elimination.

Introduction Hepatitis C virus (HCV) is the most common bloodborne chronic infection in the US. Following approval of highly effective, direct-acting antivirals in 2014, the diagnostic and treatment rates for HCV infection in the US have evolved. This study assessed the number of individuals with HCV screening or diagnostic testing and the clinical characteristics and treatment of HCV-infected individuals between 2017 and 2019. Methods Individuals screened for HCV antibody and/or tested for HCV ribonucleic acid (RNA) from 2017 to 2019 by two large US laboratory companies were included in this analysis. Clinical characteristics, such as HCV genotype, fibrosis stage, HIV coinfection and demographics, were assessed in HCV RNA-positive individuals. HCV treatment and subsequent achievement of sustained virologic response were imputed using data-driven algorithms based on successive viral load decline and negativity. Results From 2017 to 2019, the number of individuals tested for HCV antibody increased by 5.7%, from 7,580,303 in 2017 to 8,009,081 in 2019. The percentage of individuals tested who were HCV antibody positive was stable, ranging from 5.0% in 2017 to 4.9% in 2018 and 2019. The number of HCV RNA-positive individuals decreased by 5.0% from 382,500 in 2017 to 363,532 in 2019. Of HCV RNA-positive individuals, the proportions with genotype (GT) 3 and minimal fibrosis increased over time; proportions of individuals aged < 40 years increased, while the proportion aged 50 to 59 years decreased. Treatment rates increased from 23.4% in 2017 to 26.8% in 2019. Conclusions The percentage of HCV antibody-positive individuals remained stable from 2017 to 2019. The number of individuals tested HCV RNA positive decreased over the years. Demographics shifted toward a younger population with less fibrosis and higher rates of GT3. More than 70% of diagnosed individuals were not treated during this interval, highlighting a need for unfettered access to treatment.

Glecaprevir/pibrentasvir (G/P) was approved on 26 September 2019 by the US Food and Drug Administration for 8-week duration in treatment-naïve (TN) hepatitis C virus (HCV)-infected patients with compensated cirrhosis (CC). Evidence from the EXPEDITION-8 study demonstrated that 8 weeks of G/P achieved a 98% intent-to-treat (ITT) sustained virologic response rate 12 weeks post treatment (SVR12) in 343 TN/CC patients. The aim of this study is to demonstrate the first US real-world effectiveness of G/P 8-week treatment in genotype 1–6 TN/CC HCV patients. Data from 73 TN/CC patients who initiated 8 weeks of G/P treatment between August 2017 and November 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network and analyzed. Cirrhosis was determined by FIB-4 > 5.2 or was physician reported. The primary outcome was Per Protocol (PP) SVR12. The majority (60%) of patients were male, with (mean values): age 59 years, body mass index (BMI) of 30, aspartate aminotransferase (AST) 105, and alanine aminotransferase (ALT) 101 IU/ml. HCV genotypes (GT) were: GT1 81% (59/73), GT2 10% (7/73), GT3 5% (4/73), GT4 3% (2/73), and GT6 1% (1/73). Eight percent (6/73) of patients had concurrent proton pump inhibitor (PPI) use, and 15% (11/72) had a baseline viral load > 6 MM IU/ml. Zero patients discontinued, two patients were reported as lost to follow-up, and there was one virologic failure. PP sustained virologic response at 12 weeks (SVR12) rate was 99% (70/71), and the intent-to-treat (ITT) SVR12 rate was 96% (70/73). Early real-world experience indicates high effectiveness of the 8-week G/P regimen in a diverse treatment-naïve, compensated cirrhotic US population.

Glecaprevir/Pibrentasvir (G/P) is the only regimen approved by the United States Food and Drug Administriation with 8-week treatment duration for chronic HCV genotype (GT) 1-6 infection in treatment naïve (TN), noncirrhotic (NC) patients. Real world effectiveness data from the US are lacking in these populations and the aim of this study was to address this gap. Data from 560 treatment naïve, noncirrhotic patients who initiated 8 weeks of G/P treatment between August 2017 and April 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network. The primary outcome assessed was Per Protocol (PP) sustained virologic response at 12 weeks post-treatment (SVR12). Seventy one percent (397/560) of patients had HCV genotype 1 infection, and 89% (496/560) had a fibrosis score of F0-2. The majority of patients (85%) received care in community practices. The per protocol (PP) SVR12 rate was 99% (537/540) and intent-to-treat (ITT) SVR12 rate was 96% (537/560). Reasons for not achieving SVR12 were virological failure (0.5%, 3/560), lost-to-follow-up (2%, 13/560) and discontinuation (1%, 7/560). Bivariate analyses including gender, practice type, HCV genotype, eGFR, FIB-4, baseline HCV viral load and insurance type did not reveal significant association with SVR12. Reasons for discontinuations were medical care unrelated to treatment, patient choice, physician choice, insurance denial, positive drug/alcohol screening and side effects. 8-week G/P treatment is highly effective in 560 treatment naïve, noncirrhotic patients from the TRIO network with SVR12 rates similar to those as in registration trials.

Although hepatitis C virus (HCV) infection remains a major clinical, economic, and societal burden, the development of curative antiviral therapy may accelerate the path toward elimination. This analysis assessed the progress of United States (US) states towards achieving the World Health Organization’s (WHO) 2030 HCV elimination targets for incidence, mortality, diagnosis, and treatment. A previously published Markov model was used to simulate HCV progression over time to estimate the path to HCV elimination in each state based on prevalence, annual treatment, and diagnosis inputs from two large US laboratory datasets from January 2013 to December 2017. State-specific fibrosis stage restrictions on treatment in 2017 were included. The model estimated the year individual states would meet the WHO targets for diagnosing 90% of the HCV-infected population, treating 80% of the eligible population, reducing new HCV infections by 80%, and reducing HCV-related deaths by 65%. The minimum number of annual treatments needed between 2020 and 2030 to achieve the WHO treatment target was also calculated. Overall, the USA is projected to achieve HCV elimination by 2037, with individual targets related to mortality, diagnosis, treatment, and incidence being achieved by 2020, 2027, 2033, and 2037, respectively. Three states (Connecticut, South Carolina, and Washington) are on track to meet all four elimination targets by 2030, and 18 states are not expected to meet these targets before 2040. The estimated annual number of treatments required during 2020–2030 nationally to reach the WHO treatment target is 173,514. With the exception of three states, the USA is not on target to meet the WHO 2030 elimination targets and 35% are off track by 10 years or more. Strategies must be implemented to reduce overall prevalence by preventing new infections, increasing rates of screening, improving linkage to care, and implementing unfettered access to curative therapy.

In the original article, there is an error in Fig. 1.

INTRODUCTION: Hepatitis C virus (HCV) infection is a major cause of hepatic and extrahepatic morbidity and mortality. In spite of recommendations for HCV screening, diagnosis, linkage to care and treatment, significant gaps remain in the cascade of care for HCV. As the role of physician specialties for closing these gaps is poorly understood, this study assesses the flow of HCV patients across physician specialties in the US, over the course of the care cascade. METHODS: This retrospective real-world study used two large de-identified national laboratory datasets (2013–2016). Screened patients had a HCV antibody (AB) test and/or HCV RNA viral load test. Diagnosed patients had a positive HCV RNA viral load test, and among this group, fibrosis assessment, genotype test and treatment were evaluated. Treatment was inferred with an algorithm based on changes in viral load. The number/proportion of patients at each step in the care cascade was calculated by physician specialty. Patient flow by physician specialty over the course of care cascade was assessed using Sankey Diagrams. RESULTS: Approximately 17 million patients received HCV screening, and 913,529 were diagnosed. Over the course of the care cascade, there was an increase in the proportion of patients switching to HCV specialists (gastroenterologist, hepatologist, and infectious disease specialist). Generalists (primary care, family practice, internal medicine) ordered 37% of the AB tests, and 15% initiated treatment. HCV specialists ordered 3% of screening tests and 37% initiated treatment. Most of the fibrosis assessment (30%) and genotype tests (29%) were ordered by HCV specialists. Obstetricians/gynecologists ordered 11% of screening tests but only 0.3% initiated treatment. Among 974,277 patients who received a positive AB test, 46% did not receive a confirmatory RNA test. Among diagnosed patients, 57% did not receive fibrosis assessment, 47% did not receive genotype test and 90% did not receive treatment. CONCLUSION: Generalists account for more than one third of all HCV screening tests, however, HCV specialists play a more prominent role in patient assessment (fibrosis status, genotype testing) and treatment. Significant gaps remain in all stages of the cascade of care for HCV, and improved efforts are needed for every physician specialty to address them. Timely screening, monitoring and linkage to care by generalists coupled with early treatment by specialists could effectively reduce the hepatic and extrahepatic burden of HCV.