Predictors of engagement in screening for a hepatitis C virus (HCV) treatment trial in a rural Appalachian community.

An HCV treatment trial was initiated in September 2019 to address the opioid/hepatitis C virus (HCV) syndemic in rural Kentucky. The focus of the current analysis is on participation in diagnostic screening for the trial. Initial eligibility (≥18 years of age, county resident) was established by phone followed by in-person HCV viremia testing. 900 rural residents met the inclusion criteria and comprised the analytic sample. Generalized linear models were specified to estimate the relative risk of non-attendance at the in-person visit determining HCV eligibility. Approximately one-quarter (22.1%) of scheduled participants were no-shows. People who inject drugs were no more likely than people not injecting drugs to be a no-show; however, participants ≤35 years of age were significantly less likely to attend. While the median time between phone screening and scheduled in-person screening was only 2 days, each additional day increased the odds of no-show by 3% (95% confidence interval: 2%-3%). Finally, unknown HCV status predicted no-show even after adjustment for age, gender, days between screenings and injection status. We found that drug injection did not predict no-show, further justifying expanded access to HCV treatment among people who inject drugs. Those 35 years and younger were more likely to no-show, suggesting that younger individuals may require targeted strategies for increasing testing and treatment uptake. Finally, streamlining the treatment cascade may also improve outcomes, as participants in the current study were more likely to attend if there were fewer days between phone screening and scheduled in-person screening.

Multiparametric liver assessment in patients successfully treated for hepatitis C: a 4-year follow-up.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. METHODS AND FINDINGS: Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. CONCLUSION: The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies.Clinicaltrials.gov: NCT03434470. ABBREVIATIONS: AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound.

Curtailing infection risks in hepatitis C patients: the effect of antiviral treatment in revision shoulder arthroplasty.

BACKGROUND: Revision shoulder arthroplasty (RevSA) is a complex procedure that can result in various postoperative complications. However, the impact of hepatitis C virus (HCV) on postoperative complications after RevSA remains unclear because of limited and inconsistent evidence. This study aims (1) to investigate the incidence of postoperative complications in patients with HCV undergoing RevSA and (2) to evaluate the impact of HCV treatment on complication rates at different time points after the revision procedure, specifically at 90 days, 1 year, and 2 years. METHODS: We queried a national, all-payer database to investigate recent trends in the use of RevSA among HCV patients to assess postoperative complication rates, including venous thromboembolism (VTE), wound complication, transfusion, and periprosthetic joint infection (PJI). Statistical analyses involved propensity score matching to create balanced cohorts and logistic regression to determine the relative risk of postoperative complications. Data were analyzed with SPSS software (version 24.0 for Windows). The study included patients who underwent partial or total RevSA procedures between January 1, 2010, and December 31, 2020. Patients were identified based on medical claims that included procedural codes for RevSA and associated diagnosis codes for PJI or insertion/removal of an antibiotic spacer. A Bonferroni correction was used because many tests were performed and statistical significance was set at P = .0125. RESULTS: The HCV cohort demonstrated higher PJI rates at 1-year (5.5% vs. 3.9%, P = .006) and 2-year follow-ups (6.7% vs. 4.6%, P = .006). However, no significant differences emerged in VTE and wound complication rates between the HCV and non-HCV cohorts. Comparing untreated and treated HCV patients, the former showed significantly higher PJI rates at 2 years (P = .010), whereas the treated group had significantly lower odds ratios for PJI. When comparing treated HCV patients with the non-HCV cohort, minimal differences were found in postoperative outcomes, indicating no significant difference in the risk of complications between the groups. CONCLUSION: Our study observed an association between HCV patients who received antiviral treatment prior to RevSA and a reduced incidence of PJI compared to untreated HCV patients. When comparing this group to the non-HCV controls, there was no significant difference in the incidence of PJI, suggesting a potential association between antiviral treatment and the observed risk patterns in HCV patients. Proper management of HCV-positive patients during RevSA is crucial for improving outcomes and reducing complications.

Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection.

The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.

Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era.

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS: Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS: With the availability of DAA therapy, racial disparities in post-LT survival have improved.

Public healthcare system utilization for chronic hepatitis C infection in Vietnam.

BACKGROUND: Healthcare utilization is typically adversely affected when the treatment is expensive and requires multiple visits. We examined the determinants of healthcare-seeking for Hepatitis C virus (HCV) infection which is asymptomatic, chronic, and requires costly treatment in an urban tertiary care referral hospital in Vietnam. METHODS: We conducted a secondary analysis of hospital data for patients attending the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam between 2017 and 2020 specifically for HCV infection treatment. Poisson regression was used to determine the effect of personal factors (age, sex, comorbidities) and structural factors (health insurance, proximity to the facility, seasonality, year of visit) on the number of hospital visits. RESULTS: From 2017 to 2020 a total of 22,052 eligible patients sought treatment in the hospital. Among the patients, 50.4% were males and 58.7% were > 50 years of age. The mean number of visits per person was 2.17. In the multivariate analysis compared to 2017, the number of hospital visits increased by 4% in 2018 and then significantly decreased in 2019 and 2020. Visit numbers were significantly lower (6%) among South East region residents compared to those from Central Highlands and for those who lived further away from the hospital. The visit numbers were significantly higher among older age groups (5-11%), those with health insurance (6%), and those with comorbidities (5%) compared to others. Although the number of hospital visits by females was higher (7%) than males in 2017, it significantly decreased in subsequent years. CONCLUSIONS: Our study indicated that there are both structural and individual factors affecting the number of visits for HCV treatment. To meet the global strategy for elimination of HCV, Vietnam Government needs to address the structural and personal barriers to healthcare seeking, with a special focus on women.

Characterizing Persons With HIV/HCV Coinfection Who Remain Untreated for Hepatitis C at Four HIV Clinics in Connecticut (CT): Role of Multiple Overlapping Barriers at the Individual and Clinic System Levels.

Introduction. Direct-acting antiviral medications have made hepatitis C virus (HCV) cure possible for >95% of persons with chronic HCV infection, including those coinfected with HIV. Achieving strategic HCV elimination targets requires an understanding of system, provider, and patient-level barriers to treatment. We explored such barriers among persons with HIV/HCV coinfection who remained untreated for HCV. Methods. Among four primary care HIV clinics in CT with high rates of HCV cure, 25 patients with HIV/HCV coinfection were eligible (no HCV treatment as of March 31, 2021). We conducted retrospective chart reviews of demographics, clinical practice patterns, patient-specific issues such as housing, transportation, food security, and presence of mental health and substance use problems. Results. Among untreated patients, 13 (51%) were female; 17 (68%) were Black; median age was 62 years old. The majority (84%) had injecting drug use (IDU) as HIV transmission risk factor; 14 (56%) were prescribed medication-assisted treatment. Median time since HIV and HCV diagnosis was 25 and 19 years, respectively. Clinic-level barriers were noted in 19 (76%) and included lack of evaluation, treatment not recommended or implemented. Concomitant structural barriers included unstable housing for 11 (44%) and lack of transportation for eight (32%). Most patients had history of illicit substance use (84%) and mental health issues (68%). Many (76%) had multiple potential barriers. Conclusions. Multiple overlapping barriers spanning clinic and patient level domains including social determinants of health were the norm in persons with long-standing HIV/HCV coinfection who have not received HCV treatment. Interventions will require innovative, multi-disciplinary and personalized approaches.

Modeling Combination Hepatitis C Virus Treatment and Prevention Strategies in a Network of People Who Inject Drugs in the United States.

BACKGROUND: Hepatitis C virus (HCV) treatment as prevention (TasP) strategies can contribute to HCV microelimination, yet complimentary interventions such as opioid agonist therapies (OAT) with methadone or buprenorphine and syringe services programs (SSPs) may improve the prevention impact. This modeling study estimates the impact of scaling up the combination of OAT and SSPs with HCV TasP in a network of people who inject drugs (PWID) in the United States. METHODS: Using empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1574 PWID. We used a susceptible-infected model for HCV and human immunodeficiency virus to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years. RESULTS: At the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10% per year and SSP scale up to 40%, the time to achieve microelimination is reduced from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV microelimination within 10 years, with minimal impact from additional OAT scale-up. Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower. CONCLUSIONS: Scale-up of HCV TasP is the most effective strategy for microelimination of HCV. OAT scale-up, however, scale-up may be synergistic toward achieving microelimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.

Clinical treatment for hepatitis C reverses CYP2C19 inhibition.

AIMS: Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV. METHODS: Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Phase 1 was conducted before the treatment with direct-acting antivirals (DAAs) and phase 2 after the sustained virological response. Participants were administered 2 mg of a single oral dose of omeprazole (OME) as probe drug in both phases. Metabolic ratios (MRs) (plasma samples collected at 4 h after OME administration) were calculated by dividing plasma concentrations of 5-hydroxyomeprazole by OME. RESULTS: The MRs for group 1 were 0.45 (0.34-0.60, 90% confidence interval) and 0.69 (0.50-0.96) for phases 1 and 2, respectively, while the MRs for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MRs were different (P < .05) between phases 1 and 2 for both groups, as well as between groups 1 and 2 in phase 1, but not in phase 2 (P > .05). CONCLUSIONS: Both groups presented different MRs before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAA treatment. Groups 1 and 2 were also found to be different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAA treatment.

Barriers to hepatitis C direct-acting antiviral therapy among HIV/hepatitis C virus-coinfected persons.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States. METHODS: The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription. RESULTS: Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA. CONCLUSIONS: In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.

Engaging the Community in Designing a Hepatitis C Virus Treatment Program for Adults Experiencing Homelessness.

Despite the availability of cure for hepatitis C virus (HCV), people experiencing homelessness (PEH) are challenged with initiating and completing HCV treatment. The design of culturally sensitive HCV treatment programs is lacking. The objective was to employ community-based participatory research methods to understand perceptions of HCV-positive PEH, and providers, on the design and delivery of a culturally sensitive, nurse-led community health worker (RN/CHW) HCV initiation and completion program. Four focus group sessions were conducted with HCV-positive PEH (n = 30) as well as homeless service providers (HSP; n = 7) in Skid Row, Los Angeles. An iterative, thematic approach provided the themes of essentials of successful participant engagement and retention: Role of nurse-Led CHW in promoting: (a) tangible and emotional support; (b) cognitive and behavioral support; and (c) financial and structural resources. The goal of this study is to provide the groundwork for future research of HCV program design to support HCV cure among homeless populations.

Longitudinal evolution of vertically HIV/HCV-co-infected vs HCV-mono-infected children.

HIV co-infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV-infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co-infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV-co-infected patients and age- and sex-matched vertically HCV-mono-infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty-seven co-infected patients were compared with 67 matched HCV-mono-infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co-infected vs 20% mono-infected had progressed to advanced fibrosis (P = .617). Peg-IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P-value < .001). At treatment initiation, co-infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard-to-treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV-co-infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg-IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct-acting antivirals against HCV for vertically co-infected patients.

Response to direct-acting antivirals for hepatitis C treatment in vertically HIV/HCV co-infected patients.

Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.

Continuum of hepatitis C care cascade in prison and following release in the direct-acting antivirals era.

BACKGROUND: People with criminal justice involvement contribute remarkably to the rising hepatitis C virus (HCV) burden; however, the continuum of care is a major barrier to prison-based programs. We aimed to evaluate a comprehensive HCV care model in an Iranian provincial prison. METHODS: Between 2017-2018, in the Karaj Central Prison, newly admitted male inmates received HCV antibody testing and venipuncture for RNA testing (antibody-positive only). Participants with positive RNA underwent direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir). Sustained virological response was evaluated at 12 weeks post-treatment (SVR12). RESULTS: Overall, from 3485 participants, 182 (5.2%) and 117 (3.4%) tested positive for HCV antibody and RNA, respectively. Among 116 patients who were eligible for treatment, 24% (n = 28) were released before treatment and 72% (n = 83) initiated DAA therapy, of whom 81% (n = 67/83) completed treatment in prison, and the rest were released. Of total released patients, 68% (n = 30/44) were linked to care in community, and 70% (n = 21/30) completed treatment, including 60% (n = 12/20) and 90% (n = 9/10) among those who were released before and during treatment, respectively. The overall HCV treatment uptake and completion were 89% (n = 103/116) and 85% (n = 88/103), respectively. From people who completed treatment, 43% (n = 38/88) attended for response assessment and all were cured (SVR12 = 100%). CONCLUSIONS: Integrated HCV care models are highly effective and can be significantly strengthened by post-release interventions. The close collaboration of community and prison healthcare systems is crucial to promote high levels of treatment adherence. Future studies should investigate the predictors of engagement with HCV care following release.

Trends in Treatment Uptake and Provider Specialty for Hepatitis C Virus (HCV) Infection in the Veterans Affairs Healthcare System: Results From the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES).

Between 2001 and 2017, 108133 persons (45.7% of diagnosed cases) were initiated on anti-hepatitis C virus treatment in the Veterans Affairs healthcare system. In 2017, nonphysician clinicians accounted for 22.2% of prescriptions, infectious diseases specialists for 14.9%, and gastroenterologists/hepatologists for 10.3%. In the pre-direct-acting antiviral era, they accounted for 7.2%, 26.7%, and 11.6%, respectively.

Integrated, Co-located, Telemedicine-based Treatment Approaches for Hepatitis C Virus Management in Opioid Use Disorder Patients on Methadone.

BACKGROUND: Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. METHODS: OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. RESULTS: Sixty-two HCV RNA-positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. CONCLUSIONS: HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment.

Scaling Up Hepatitis C Prevention and Treatment Interventions for Achieving Elimination in the United States: A Rural and Urban Comparison.

In the United States, hepatitis C virus (HCV) transmission is rising among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modeling, we investigated the impact of scaling up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky, and San Francisco, California, where HCV seroprevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service programs (SSP) in urban San Francisco (established community) than in rural Perry County (young, expanding community). We modeled the proportion of HCV-infected PWID needing HCV treatment annually to reduce HCV incidence by 90% by 2030, with and without MAT scale-up (50% coverage, both settings) and SSP scale-up (Perry County only) from 2017. With current MAT and SSP coverage during 2017-2030, HCV incidence would increase in Perry County (from 21.3 to 22.6 per 100 person-years) and decrease in San Francisco (from 12.9 to 11.9 per 100 person-years). With concurrent MAT and SSP scale-up, 5% per year of HCV-infected PWID would need HCV treatment in Perry County to achieve incidence targets-13% per year without MAT and SSP scale-up. In San Francisco, a similar proportion would need HCV treatment (10% per year) irrespective of MAT scale-up. Reaching the same impact by 2025 would require increases in treatment rates of 45%-82%. Achievable provision of HCV treatment, alongside MAT and SSP scale-up (Perry County) and MAT scale-up (San Francisco), could reduce HCV incidence.

Safety and efficacy of elbasvir/grazoprevir in Asian participants with hepatitis C virus genotypes 1 and 4 infection.

BACKGROUND AND AIM: Estimates suggest that in Asia, more than 31 million individuals have hepatitis C virus infection. The present analysis was conducted to assess the efficacy and safety of elbasvir/grazoprevir in Asian participants enrolled in the elbasvir/grazoprevir phase 2/3 clinical trials. METHODS: This is an integrated analysis of data from 12 international phase 2/3 clinical trials. Asian participants with chronic hepatitis C virus genotype 1 or 4 infection who received elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks or elbasvir/grazoprevir plus ribavirin for 16 weeks were included in this analysis. The primary end point was sustained virologic response at 12 weeks after completion of therapy (SVR12). RESULTS: Seven hundred eighty Asian participants from 15 countries were included in this analysis. SVR12 was achieved by 756/780 (96.9%) of all participants, including 748/772 (96.9%) of those who received elbasvir/grazoprevir for 12 weeks and 8/8 (100%) of those who received elbasvir/grazoprevir plus ribavirin for 16 weeks. In the genotype 1b-infected population, the SVR12 rate was 691/709 (97.5%), and there was no impact of age, high baseline viral load, or presence of cirrhosis. The most frequently reported adverse events were nasopharyngitis (8.0%), upper respiratory tract infection (5.4%), and diarrhea (5.2%). Twenty participants receiving elbasvir/grazoprevir for 12 weeks reported a total of 25 serious adverse events, and 7 (0.9%) discontinued treatment because of an adverse event. CONCLUSION: Elbasvir/grazoprevir administered for 12 weeks is an effective and generally well-tolerated treatment option for Asian individuals with hepatitis C virus genotype 1b infection.

Liver stiffness measurements in chronic hepatitis C: Treatment evaluation and risk assessment.

BACKGROUND AND AIM: Liver stiffness (LS), measured by transient elastography, has been validated as a non-invasive surrogate for liver fibrosis. METHODS: We investigated the long-term predictive ability of LS for hepatocellular carcinoma (HCC) development and overall survival in 1146 patients with chronic hepatitis C by using LS value at enrollment. We also investigated chronological changes in LS based on antiviral therapy and its outcome in 752 patients. RESULTS: During the mean follow-up period of 6.6 years, 190 patients developed HCC. Cumulative HCC incidence rates at 5 years were clearly stratified as 1.7% in the ≤ 5 kPa, 3.3% in 5.1-10 kPa, 16.7% in 10.1-15 kPa, 24.4% in 15.1-20 kPa, 36.3% in 20.1-25 kPa, and 43.7% in > 25 kPa subgroups (P < 0.001). Overall survival was also stratified: 10-year survival rates were 99.3% in the ≤ 5 kPa, 95.4% in 5.1-10 kPa, 81.4% in 10.1-15 kPa, 79.5% in 15.1-20 kPa, 66.1% in 20.1-25 kPa, and 49.1% in > 25 kPa subgroups (P < 0.001). LS decreased at a rate of 8.1% per year in those who achieved sustained virological responses, but increased at 0.1% per year in those who could not achieve sustained virological response instead of antiviral therapy, and increased at 3.7% per year in those who did not undergo antiviral therapy. CONCLUSIONS: Liver stiffness measurements can be useful in the prediction of HCC development and overall survival and in the evaluation of chronological changes in liver fibrosis grade during and after antiviral therapy.

Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study.

BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.