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INTRODUCTION: Hepatitis C virus (HCV) treatment can significantly reduce the risk of liver-related mortality; however, many patients remain unaware of their infection in clinical practice. The aim of this study is to compare the effectiveness of inreach, with and without mailed outreach, to increase HCV screening and follow-up in a large, difficult-to-reach patient population. METHODS: We conducted a pragmatic randomized clinical trial from August 2018 to May 2019 in a large safety-net health system. Patients born between 1945 and 1965 were randomly assigned (1:1) to inreach with an electronic health record reminder to providers (n = 6,195) or inreach plus mailed HCV screening outreach (n = 6,191) to complete HCV antibody screening. Outreach also included processes to promote HCV RNA testing among those with a positive HCV antibody and linkage to care among those with positive HCV RNA. The primary outcome was completion of HCV antibody testing within 3 months of randomization (ClinicalTrials.gov NCT03706742). RESULTS: We included 12,386 eligible patients (median age 60 years; 46.5% Hispanic, 33.0% Black, and 16.0% White). In intent-to-treat analyses, HCV screening completion was significantly higher among inreach-plus-outreach patients than inreach-alone patients at 3 months (14.6% vs 7.4%, P < 0.001) and 6 months (17.4% vs 9.8%, P < 0.001) after randomization. Among those who completed HCV screening within 6 months, a higher proportion of inreach-plus-outreach patients with positive antibody results completed RNA testing within 3 months than inreach-alone patients (81.1% vs 57.1%, respectively, P = 0.02); however, linkage to care within 3 months of HCV infection confirmation did not significantly differ between the 2 groups (48.1% vs 75.0%, respectively, P = 0.24). DISCUSSION: Among difficult-to-reach patients, a combination of inreach and mailed outreach significantly increased HCV screening compared with inreach alone. However, HCV screening completion in both arms remained low, highlighting a need for more intensive interventions.

Achieving practice change can be challenging when guidelines shift from a selective risk-based strategy to a broader population health strategy, as occurred for hepatitis C (HCV) screening (2012-2013). We aimed to evaluate patient and provider barriers that contributed to suboptimal HCV screening and linkage-to-care rates after implementation of an intervention to improve HCV screening and linkage-to-care processes in a large, public integrated healthcare system following the guidelines change. As part of a mixed-methods study, we collected data through patient surveys (n = 159), focus groups (n = 9) and structured observation of providers and staff (n = 9). We used these findings to then inform domains for the second phase, which consisted of semi-structured interviews with patients across the screening-treatment continuum (n = 24) and providers and staff at primary care and hepatology clinics (n = 21). We transcribed and thematically analysed interviews using an integrated inductive and deductive framework. We identified lack of clarity about treatment cost, treatment complications and likelihood of cure as ongoing patient-level barriers to screening and linkage to care. Provider-level barriers included scepticism about establishing HCV screening as a quality metric given competing clinical priorities, particularly for patients with multiple comorbidities. However, most felt positively about adding HCV as a quality metric to enhance HCV screening and linkage to care. Provider engagement yielded suggestions for process improvements that resulted in increased stakeholder buy-in and real-time enhancements to the HCV screening process intervention. Systematic data collection at baseline and during practice change implementation may facilitate adoption and adaptation to improve HCV screening guideline implementation. Findings identified several key opportunities and lessons to enhance the impact of practice change interventions to improve HCV screening and treatment delivery.

BACKGROUND & AIMS: Although serological markers of disease severity improve after hepatitis C virus (HCV) treatment, it is unclear if all patients experience sustained improvement. We aim to evaluate longitudinal changes in aspartate (AST), alanine (ALT) aminotransferase, platelet count (PLT), and fibrosis-4 (FIB-4) after HCV treatment. METHODS: All adult chronic HCV patients who received antiviral therapy from January 2011 to February 2017 at four large urban hospital systems were evaluated to assess changes in AST, ALT, PLT, and FIB-4 from pre-treatment to post-treatment annually up to 4 years after HCV therapy. Comparisons used Student's t-test and analysis of variance, and were stratified by sex, race, ethnicity, age, body mass index (BMI), and diabetes mellitus. RESULTS: Among 2691 patients (62.2% men, 76.9% aged 45–65 years, 56.5% white), all markers of disease severity demonstrated sustained improvements from pre-treatment to 4 years post-treatment (AST 53 U/L to 27.5 U/L, ALT 53 U/L to 29 U/L, PLT 168 × 10(3) to 176 × 10(3), FIB-4 2.51 to 1.68). However, Hispanics and patients with BMI >30 kg/m(2) experienced rebound increases in AST, ALT, and FIB-4 at 4 years post-treatment after experiencing initial improvements in these serological markers in the first-year post-treatment. Sustained improvements in PLT were observed in all groups, including Hispanics and patients with BMI >30 kg/m(2). CONCLUSION: HCV treatment in a large community-based cohort demonstrated sustained improvements in AST, ALT, PLT, and FIB-4. Rebound increases in AST, ALT, and FIB-4 observed in Hispanics and those with BMI >30 kg/m(2) may reflect persisting nonalcoholic fatty liver disease.

Background Direct-acting antivirals can cure hepatitis C virus (HCV). Persons with HCV/HIV and living with substance use are disadvantaged in benefiting from advances in HCV treatment. Methods In this randomized controlled trial, participants with HCV/HIV were randomized between February 2016 and January 2017 to either care facilitation or control. Twelve-month follow-up assessments were completed in January 2018. Care facilitation group participants received motivation and strengths-based case management addressing retrieval of HCV viral load results, engagement in HCV/HIV care, and medication adherence. Control group participants received referral to HCV evaluation and an offer of assistance in making care appointments. Primary outcome was number of steps achieved along a series of 8 clinical steps (eg, receiving HCV results, initiating treatment, sustained virologic response [SVR]) of the HCV/HIV care continuum over 12 months postrandomization. Results Three hundred eighty-one individuals were screened and 113 randomized. Median age was 51 years; 58.4% of participants were male and 72.6% were Black/African American. Median HIV-1 viral load was 27 209 copies/mL, with 69% having a detectable viral load. Mean number of steps completed was statistically significantly higher in the intervention group vs controls (2.44 vs 1.68 steps; χ 2 [1] = 7.36, P = .0067). Men in the intervention group completed a statistically significantly higher number of steps than controls. Eleven participants achieved SVR with no difference by treatment group. Conclusions The care facilitation intervention increased progress along the HCV/HIV care continuum, as observed for men and not women. Study findings also highlight continued challenges to achieve individual-patient SVR and population-level HCV elimination. Clinical Trials Registration NCT02641158., In this era of direct-acting antivirals that can cure hepatitis C virus (HCV) infection in 1–3 months, a short-term care facilitation intervention for persons living with HIV and HCV who use drugs is efficacious in making meaningful advances toward HCV cure.

Hepatitis C virus (HCV) testing in persons born from 1945 to 1965 has had limited adoption despite guidelines, particularly among racial/ethnic minorities and socioeconomically disadvantaged patients, who have a higher prevalence of disease burden. We examined the effectiveness of a multifaceted intervention to improve HCV screening in a large safety-net health system. We performed a multifaceted intervention that included provider and patient education, an electronic medical record-enabled best practice alert, and increased HCV treatment capacity. We characterized HCV screening completion before and after the intervention. To identify correlates of HCV screening, we performed logistic regression for the preintervention and postintervention groups and used a generalized linear mixed model for patients observed in both preintervention and postintervention time frames. Before the intervention, 10.1% of 48,755 eligible baby boomer patients were screened. After the intervention, 34.6% of the 34,093 eligible baby boomers were screened (P < 0.0001). Prior to the intervention, HCV screening was lower among older baby boomers and providers with large patient panels and higher in high-risk subgroups including those with signs of liver disease (e.g., elevated transaminases, thrombocytopenia), human immunodeficiency virus-positive patients, and homeless patients. Postintervention, we observed increased screening uptake in older baby boomers, providers with larger patient panel size, and patients with more than one prior primary care appointment. Conclusion: Our multifaceted intervention significantly increased HCV screening, particularly among older patients, those engaged in primary care, and providers with large patient panels.

BACKGROUND: Using data from a randomized trial, we evaluated the cost of HCV care facilitation that supports moving along the continuum of care for HIV/HCV co-infected individuals with substance use disorder. METHODS: Participants were HIV patients residing in the community, initially recruited from eight US hospital sites. They received HCV care facilitation (n=51) or treatment as usual (n=62) for up to six months. We used micro-costing methods to evaluate costs from the healthcare sector and patient perspectives in 2017 USD. We conducted sensitivity analyses varying care facilitator caseloads and examined offsetting savings using participant self-reported healthcare utilization. RESULTS: The average site start-up cost was $6,320 (site range: $4,320–$7,000), primarily consisting of training. The mean weekly cost per participant was $20 (site range: $4–$30) for care facilitation visits and contacts, $360 (site range: $130- $700) for supervision and client outreach, and $70 (site range: $20–$180) for overhead. In sensitivity analyses applying a weekly caseload of 10 participants per care facilitator (versus 1–6 observed in the trial), the total mean weekly care facilitation cost from the healthcare sector perspective decreased to $110. Weekly participant time and travel costs averaged $7. There were no significant differences in other healthcare service costs between participants in the intervention and control arms. CONCLUSION: Weekly HCV care facilitation costs were approximately $450 per participant, but approximately $110 at a real-world setting maximum caseload of 10 participants per week. No healthcare cost offsets were identified during the trial period, although future savings might result from successful HCV treatment.

IntroductionGuidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https://clinicaltrials.gov/ct2/show/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants.MethodsParticipants with HIV-1 RNA ResultsOf 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93-99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non-response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens.ConclusionThis study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/HCV-GT1 co-infected patients.

This study prospectively examined the independent courses of alcohol, drugs, and smoking over 18 months in 154 patients preparing for hepatitis C virus (HCV) treatment in relation to functioning, negative coping, and satisfaction with quality of life in data collected from a randomized controlled trial of multiple-family group psychoeducation for patients preparing for HCV treatment. Patients with HCV who had consistent abstinence, consistent use, or achievement of abstinence after study entry were examined for outcomes pertaining to functioning in the context of HCV, negative coping, and satisfaction with quality of life.Of 309 patients considering treatment for HCV recruited from outpatient clinics at two major university medical centers and a Veterans Affairs medical center for a randomized controlled trial of a psychoeducation intervention, 154 completed baseline, 6-month, and 18-month assessments. The assessments included structured diagnostic interviews; questionnaires examining functioning, coping, and satisfaction with quality of life; medical record review; and urine testing for substances of abuse. For these analyses, substance use patterns were determined as consistent abstinence, consistent use, and achieving abstinence after study entry for alcohol and drug use and smoking.The entire sample generally improved in all of these three outcomes over the course of the study. The course of alcohol, drugs, and smoking predicted HCV-related functioning, negative coping, and satisfaction with quality-of-life outcomes over 18 months. Three specific patterns of use (consistent abstinence, consistent use, and achievement of abstinence after study entry) of these substances diverged in association with outcomes related to functioning, negative coping, and satisfaction with quality of life, not only across trajectories over time within substance types but also among types of substances.This study's finding that different substances were associated with distinct clinical outcomes suggests the need to conceptually unbundle different types of substances in managing HCV. Future research is needed to examine the clinical utility of further unbundling these substances and also to further investigate effects of various amounts of use of these substances.

SummaryBackground Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. Aim To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Methods Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. Results A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P

To elucidate HIV-1 co-infection-induced acceleration of HCV liver disease and identify stage-specific molecular signatures, we applied a new high-resolution molecular screen, the Affymetrix GeneChip Human Transcriptome Array (HTA2.0), to HCV-mono- and HIV/HCV-co-infected liver specimens from subjects with early and advanced disease. Out of 67,528 well-annotated genes, we have analyzed the functional and statistical significance of 75 and 28 genes expressed differentially between early and advanced stages of HCV mono- and HIV/HCV co-infected patient liver samples, respectively. We also evaluated the expression of 25 and 17 genes between early stages of mono- and co-infected liver tissues and between advanced stages of mono- and co-infected patient's samples, respectively. Based on our analysis of fold-change in gene expression as a function of disease stage (i.e., early vs. advanced), coupled with consideration of the known relevant functions of these genes, we focused on four candidate genes, ACSL4, GNMT, IFI27, and miR122, which are expressed stage-specifically in HCV mono- and HIV-1/HCV co-infective liver disease and are known to play a pivotal role in regulating HCV-mediated hepatocellular carcinoma (HCC). Our qRT-PCR analysis of the four genes in patient liver specimens supported the microarray data. Protein products of each gene were detected in the endoplasmic reticulum (ER) where HCV replication takes place, and the genes' expression significantly altered replicability of HCV in the subgenomic replicon harboring regulatory genes of the JFH1 strain of HCV in Huh7.5.1. With respect to three well-known transferrable HIV-1 viral elements-Env, Nef, and Tat-Nef uniquely augmented replicon expression, while Tat, but not the others, substantially modulated expression of the candidate genes in hepatocytic cells. Combinatorial expression of these cellular and viral genes in the replicon cells further altered replicon expression. Taken together, these results showed that HIV-1 viral proteins can exacerbate liver pathology in the co-infected patients by disparate molecular mechanisms-directly or indirectly dysregulating HCV replication, even if lack of association of HCV load and end-stage liver disease in hemophilic patients were reported, and modulating expression of hepatocellular genes critical for disease progression. These findings also provide major insights into development of stage-specific hepatocellular biomarkers for improved diagnosis and prognosis of HCV-mediated liver disease.

Direct-acting antivirals (DAA) for hepatitis C virus (HCV) became available in 2014, but the role of mental health or substance use disorders (MH/SUD) on access to treatment is unknown. The objective of this study was to examine the extent and predictors of HCV treatment in the pre-DAA and post-DAA periods in four large, diverse health care settings in the United States. We conducted a retrospective analysis of 29,544 adults with chronic HCV who did or did not receive treatment from January 1, 2011, to February 28, 2017. Kaplan-Meier curve was used to examine cumulative risk for receiving HCV treatment stratified by MH/SUD. Predictors of HCV treatment in the pre-DAA (January 1, 2011, to December 31, 2013) and post-DAA (January 1, 2014, to February 28, 2017) cohorts were analyzed using multivariate generalized estimating equations and a modified Poisson model. Overall, 21.7% (2,879/13,240) of those with chronic HCV post-DAA were treated compared with 3.5% (574/16,304) in the pre-DAA period. Compared with non-Hispanic whites, Hispanic whites (adjusted odds ratio [AOR] 0.36; 95% confidence interval [CI], 0.25, 0.52) were less likely to be treated in the post-DAA period. Those with concurrent nonalcoholic fatty liver disease (AOR 1.39; 95% CI, 1.05, 1.83), cirrhosis (AOR 2.00; 95% CI, 1.74, 2.31), and liver transplant (AOR 2.72; 95% CI, 1.87, 3.94) were more likely to be treated post-DAA. Those with MH/SUD were less likely to be treated both before (AOR 0.46; 95% CI, 0.36, 0.60) and after (AOR 0.63; 95% CI, 0.55, 0.71) DAA therapy was available. Overall, the cumulative risk for receiving HCV treatment from 2011 to 2017 among those with versus without MH/SUD was 13.6% versus 21.6%, respectively (P < 0.001). Conclusion: The volume of patients treated for HCV has increased in the post-DAA period, especially among those with liver-related comorbidities, but disparities in access to treatment continue among those with MH/SUD.

Despite availability of highly effective direct acting antivirals (DAA), barriers in access to these therapies limit our ability to achieve HCV eradication. We aim to evaluate overall rates and predictors of HCV treatment across four community-based health-care systems focusing on race/ethnicity and insurance-specific disparities. We retrospectively evaluated all adults with chronic HCV at four health care systems from 1 January 2011 to 28 February 2017, which included a large proportion of ethnic minorities, two safety-net systems, and a broad payer mix across four states. Overall and stratified HCV treatment rates were calculated using Kaplan–Meier methods. Multivariate logistic regression models evaluated for predictors of receiving treatment. Among 29,544 chronic HCV patients (60.5% male, 38.4% black, 8.8% Hispanic, 18.7% Medicaid, 25.9% Medicare, 22.5% private/commercial), overall annual treatment rates were stable from 2011 (0.5%) to 2013 (2.0%), but increased from 2014 (4.8%) to 2017 (16.9%) after availability of DAAs. While similar treatment rates were observed by sex, significantly lower odds of treatment were observed in Hispanics (OR 0.48, 95% CI 0.39–0.60, p

Background Direct-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort. Methods This retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up. Results DAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16–0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up. Conclusions Effective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0969-3) contains supplementary material, which is available to authorized users.

Appointment-keeping behavior is an important requisite for HCV linkage and treatment initiation. In this study we examine what impact hepatitis C (HCV) knowledge and attitudes has on appointment-keeping behavior among a cohort of HCV and HCV/HIV patients. Knowledge scores and attitude scales, obtained from a cross-sectional survey, were correlated with proportion of appointments kept 1 year prior to taking the survey. Independent risk factors for missing appointments were examined by multiple regression analysis. 292 HCV patients completed the survey, and 149 (51%) were co-infected with HIV. HCV patients kept 67.5 ± 17.4% of their total appointments and a similar proportion (67 ± 38.2) of Liver Clinic appointments, but they attended a higher proportion (73 ± 24.4) of Primary Care Clinic appointments. However, certain health beliefs, psychiatric illness, and HIV co-infection were independently associated with lower levels of appointment-keeping behavior. HCV knowledge was not associated with appointment-keeping behavior. Health beliefs, psychiatric illness, and HIV co-infection are associated with missing appointments, but no link between knowledge and appointment keeping behavior is apparent. In order to increase engagement into HCV care, HCV care coordination programs need to focus on addressing health beliefs and providing resources to those at highest risk for missing appointments.

A successful psychoeducation program for serious mental illness, PsychoEducation Responsive to Families (PERF), was modified for hepatitis C virus (HCV). An effectiveness study was carried out comparing HCV-PERF with didactic education.A sample of 309 adult HCV patients was recruited from three outpatient settings and randomized (60% HCV-PERF, 40% didactic control). Groups met for 90 min bimonthly for 6 months following separate structured protocols. HCV-PERF sessions included a didactic curriculum developed uniquely for groups by member choice, with group problem-solving and support interactions. Patients were assessed at baseline, after the intervention, and 1 year later. Demographic and HCV-related variables and structured diagnostic interview data were obtained.Both groups improved significantly on major depression and alcohol and drug use, quality of life, risk behaviors, and treatment satisfaction, and worsened on disability and perceived HCV-related problems. Intervention groups did not differ on outcomes.Even though the active intervention did not achieve a significant improvement relative to the control condition, the observable improvements in both conditions warrant further exploration of the contributions of education and support as potentially important elements of HCV behavioral intervention. Further study is needed to identify elements common to education interventions that may be contributory to the improved outcomes over time.

Alcohol accelerates the course of hepatitis C (HCV) infection and liver damage. Little is known about recency of alcohol use among patients with HCV.Alcohol consumption recency was compared among HCV patients with and without alcohol use disorders and current and lifetime alcohol use histories.Patients considering antiviral treatment for HCV (n = 309) recruited from university-affiliated and VA liver and infectious disease clinics were assessed for lifetime and current-year psychiatric disorders and alcohol-use patterns. Full diagnostic interviews, self-report surveys, medical record review, and urine screening for recent alcohol and drug use were conducted.60% used alcohol in the last year. Besides alcohol history, those who stopped using alcohol in the past year differed from those with no lifetime use only in gender (60% vs. 22%); however, patients no longer using alcohol in the last year were less likely than those still using to have a current drug use disorder (16% vs. 3%) or last-month drug use (52% vs. 30%), and had fewer current risky behaviors (1.3 vs. 0.6). Among patients with last-year alcohol use, those with past alcohol use disorders differed from those without only by higher prevalence of drug use disorder (84% vs. 47%) and drug use after HCV diagnosis (67% vs. 43%).Patients who had stopped using alcohol for at least a year were much like those who never used alcohol in regard to other drug use, psychiatric history, smoking, and risky behaviors. These findings indicate that HCV patients with at least a year of abstinence from alcohol, including those with a history of alcohol use disorder, should be considered HCV treatment candidates.

Much of the research to date on barriers to treatment for patients with hepatitis C has approached the problem from either the perspective of the medical provider or the healthcare system.To better understand these barriers from the patients' perspectives, nine exploratory focus groups of patients with hepatitis C (N=48) were conducted in 2008 and 2009, using a hybrid qualitative analysis.Eight content categories emerged. Treatment-related issues, including barriers to care, were most emphasized, representing nearly one-half of the entire content. Need for accurate disease-related information was also extensively discussed. Social factors were important, including considerable focus on stigma. Participants described coping abilities including faith and perseverance.Areas of concern expressed in these focus groups represent underexplored areas that may warrant additional attention or areas for intervention and investigation, such as exploring differences between perceptions of patients and providers regarding the hepatitis C treatment process and addressing barriers to care.

Background HCV treatment has increased since direct-acting antivirals became available. HIV clinics are scaling-up treatment to eradicate HCV. Little is known about HIV patients and access to HCV treatment. Methods We retrospectively analyzed all HIV/HCV co-infected patients within our safety-net hospital system who received outpatient care in our HIV clinics from November 1, 2015 to October 31, 2017. Data were abstracted on demographics, insurance, HIV RNA, drug use, homelessness, and number of visits. No visits for >1 year was lost to care and missed visits was missing >1 primary care visit. We examined the association of these variables to risk of having a detectable HCV RNA (surrogate marker for HCV treatment) through multivariate logistic regression. Results We identified 914 with HIV/HCV (72% male, 55% Black, 35% Medicaid, 29% Medicare, 16% Ryan White, 13% homeless) of which 47% were heterosexual, 36% MSM, and 14% IDU. HIV was undetectable in 74%, 69% were between age 46 and 65, 17% had active alcohol use and 33% had drug use. HCV RNA was available for 868 and was detected in (57%). Whites and Hispanics compared with Blacks were less likely to have detectable HCV RNA. Detectable HCV RNA was more likely in those >50 years of age compared with 1 missed visit, and lost to care. Conclusion We found that those at risk for not being treated for HCV were Blacks, older patients and those not engaged in HIV care or not suppressed on HIV treatment. To achieve HCV eradication will require efforts to engage older patients, Blacks, those noncompliant with ART, and not engaged in HIV care. HCV Virus Detected (n = 497) HCV Virus Undetected (n = 371) AOR (95% CI) Race/ethnicity Black 311 (63) 171 (46) Reference White 126 (25) 116 (31) 0.54 (0.38, 0.77)*** Hispanic 56 (11) 70 (19) 0.55 (0.35, 0.86** Other 4 (0.8) 14 (4) 0.25 (0.08, 0.81)** Age group < 40 56 (11) 63 (17) Reference 40–49 84 (17) 78 (21) 1.35 (0.80, 2.25) 50–59 229 (46) 146 (39) 1.83 (1.14, 2.91)* > = 60 128 (60) 84 (23) 2.29 (1.35, 3.89)* HIV detected no 341 (69) 310 (84) Reference yes 156 (31) 61 (28) 1.92 (1.33, 2.76) *** Lost to care no 395 (79) 336 (91) Reference yes 102 (21) 35 (9) 2.17(1.39, 3.39)*** Missed >1 visit No 214 (43.1) 229(61.7) reference Yes 283 (56.9) 142 (38.3) 1.77 (1.31, 2.39)*** *** P < 0.001 P < 0.01 P < 0.05. Disclosures M. K. Jain, Gilead Sciences: Grant Investigator, Grant recipient and Research support. Janssen: Investigator, Research support. GSK/ViiV: Investigator, Consulting fee and Research support. Merck: Investigator, Research support.

Summary Hepatitis C virus (HCV) treatment is rapidly changing but little is known about patients' attitudes and knowledge about HCV. This study used a cross-sectional survey to examine the relationship between HCV knowledge and attitudes towards HCV in patients with HCV mono-infection and HIV/HCV co-infection. Subsequently, an education intervention was developed with an abridged version of the cross-sectional survey administered before and after the education session to assess changes in knowledge and attitudes. 292 people participated in the cross-sectional survey, and 87 people participated in the education intervention. In the cross-sectional survey, the mean knowledge score regarding HCV was low (

Despite recent advances in hepatitis C virus (HCV) therapeutics, the combination of pegylated interferon and ribavirin (PEGIFN/RBV) remains the cornerstone of treatment. Optimization and individualization of PEGIFN dosing could improve outcomes. Week one PEGIFN serum concentrations in 42 HCV genotype 1-infected patients treated with conventional PEGIFN/RBV were analyzed using multicompartmental pharmacokinetic models. For each patient, pharmacokinetic parameter estimates, weight, age, interleukin-28B (IL-28B) single-nucleotide polymorphism, CD4 count, baseline HCV RNA, gender, race, and HIV status were examined using classification and regression tree analysis to identify factors predictive of sustained viral response (SVR). Survival analysis was performed to compare the time to undetectable viral load in patients with and without the highest scoring predictor. PEGIFN concentrations varied at least 87-fold. Pharmacokinetics were best described by a two-compartment model with an 8.4-h absorption lag. Patient weight correlated with PEGIFN systemic clearance based on fractal geometry relationships. SVR was achieved in 36% of patients; a PEGIFN cumulative 1-week area under the curve (AUC) of ≤0.79 mg · h/liter scored highest in predicting poor response, followed by a weight of ≥93.7 kg. Patients with a PEGIFN AUC of >0.79 mg · h/liter achieved undetectable viral load more rapidly than those with a lower AUC (hazard ratio, 1.63; 95% confidence interval, 1.21 to 2.04). PEGIFN exhibits wide pharmacokinetic variability, mainly driven by patient weight, so that the standard dose may not reach levels needed to achieve SVR. Optimizing dose to patient weight and PEGIFN AUC in the first week offers a solution to improve SVR and to potentially shorten duration of therapy.

Liver-related complications such as hepatocellular carcinoma (HCC) are a major cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), particularly among those also infected with hepatitis B or hepatitis C viruses. There is a lack of consensus regarding the clinical presentation, treatment options, and outcomes in HIV-infected patients with HCC. We compared the clinical presentation, treatment, and survival of patients with HCC, with and without HIV infection.We conducted a retrospective cohort study of cirrhotic patients diagnosed with HCC at a large safety-net hospital between January 2005 and December 2010. Patients without known HIV serologic status were excluded. Demographic features, tumor characteristics, treatment regimens, and survival were compared between patients (n = 26) with and without HIV infection (n = 164). Survival curves were generated by using Kaplan-Meier plots and compared by using the log-rank test.A higher percentage of HIV-infected patients presented with compensated liver disease (Child-Turcotte-Pugh stage A) than those without HIV infection (62% vs 32%, respectively; P = .01), as well as those with early-stage tumors (Barcelona Clinic Liver Cancer stage A, 39% vs 17%, respectively; P = .04 and Okuda stage I, 50% vs 21%, respectively; P.01). HIV-infected patients were more likely to be cured of HCC than uninfected patients (27% vs 4%, respectively; P = .01), but median overall survival times were similar between groups (9.6 vs 5.2 months, respectively; P = .85). The 1-year rates of survival for HIV-infected and uninfected patients were 40% and 38%, respectively.HIV-infected patients present with earlier-stage HCC and more preserved liver function than uninfected patients, resulting in more curative treatment options. Despite this difference, overall survival was similar between patients with HCC with and without HIV infection.

The purpose of this study was to assess the one-year prevalence of drug use and of concurrent alcohol use among hepatitis C (HCV) patients seeking treatment from specialty HCV clinics.Patients with confirmed HCV RNA considering HCV treatment (N = 309) were recruited from university-affiliated and Veterans Affairs medical centers.The prevalence of current drug use in the last year was 65% (201/309) among patients considering HCV treatment. More than one-fourth of the sample used drugs at some time in their lives but none in the last year. Only 7% (22/309) of patients reported no lifetime drug use. The prevalence of concurrent drug and alcohol use in the last year was 72% (145/201) and 52% (105/201) in the last month.More than half of current drug users were still consuming alcohol in the last month despite the fact that they had all been informed of the potential for accelerated liver damage from continued alcohol use. This finding suggests that achieving abstinence from drug use does not necessarily imply that abstinence from alcohol has been obtained. Integration of substance treatment and HCV treatment into a unified disease management approach might increase treatment eligibility and compliance and improve disease outcomes.

Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.

Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation.Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted.To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials.Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.

The combination of ribavirin and pegylated interferon is used to treat hepatitis C, but it achieves viral clearance in 19%–52% of patients infected with hepatitis C virus (HCV) genotype 1 and in 76%–80% of patients infected with HCV genotypes 2 and 3 [1–3]. Such host factors as race and infection with human immunodeficiency virus (HIV) have been associated with a poor response to treatment [3–5]. The optimal clinical outcome—a sustained virologic response (SVR)—is closely associated with an early response (ER) at week 4 of treatment [6]. Thus, early changes in the HCV level can give insights as to why some groups have a poor response to anti-HCV treatment. Viral kinetics studies [7–11] have shown a lower effectiveness of interferon in black Americans, compared with white Americans [8], and this lower effectiveness is a possible explanation for the lower SVR encountered among blacks [3]. Similarly, treatment trials involving HIV/HCV-infected patients have also demonstrated a lower SVR [4, 5]. However, whether the presence of HIV alters the early viral kinetics of HCV during interferon therapy remains unclear. Viral genotype is another important determinant of responsiveness: HCV genotype 1 is less responsive than HCV genotypes 2 and 3, which demonstrate first- and second-phase decreases faster than those observed for genotype 1 [9, 11]. The different viral clones observed within an individual have different pharmacodynamic responses to exogenous interferon. Nonstructural 5A (NS5A) is a viral protein that has been most associated with interferon responsiveness, especially the interferon sensitivity–determining region. NS5A binds and inhibits the protein kinase R–binding domain (PKRbd), attenuating the kinase action in interferon-mediated antiviral responses in a manner that varies among viral quasispecies [9, 11–14]. It has been suggested that variation from an interferon-resistant prototype viral sequence for genotype 1b (ie, HCV-J) is associated with greater likelihood of a response to therapy; however, this suggestion remains controversial [15–22]. We undertook a thorough reexamination of NS5A to determine how variations in this region might contribute to an ER to anti-HCV therapy. We hypothesized that viral factors, such as the composition of NS5A quasispecies and the dynamic changes in NS5A quasispecies during the first week of therapy, may be associated with the virologic response at week 4 (ie, an ER) and an eventual SVR.

Hepatitis C virus (HCV) monoinfection has been linked to type 2 diabetes mellitus (DM). We evaluated the effect of HCV on risk of DM in relation to traditional risk factors such as age, body mass index (BMI) and family history of DM in an HIV-infected population.This was a retrospective, cross-sectional study of 1529 HIV-infected out-patients. An adjusted multivariate logistic regression was performed to assess the effect of HCV seropositivity on DM stratified by low and high propensity for DM based on age, BMI and family history.Race, age, BMI, family history and HCV were associated with DM. Use of protease inhibitors (PIs) was not associated with DM, but HIV/HCV-coinfected patients were less likely to be on PIs than those with HIV infection alone. In a multivariate analysis controlled for race, the association between HCV and DM was stronger in lean, young patients without a family history of DM; the low-risk group. No association between HCV and type 2 DM was seen in patients who were older or overweight or had a family history of DM; the high-risk group. PI use did not affect the association between HCV and DM.Hepatitis C is an independent risk factor for type 2 diabetes in young, lean, HIV-infected patients. HIV-infected patients with HCV infection, regardless of whether they are on PIs, should be carefully screened for DM even if traditional risk factors for DM are not present.

Background Those in safety-net hospitals are especially vulnerable to lack of access to specialty care and curative treatment (Tx) for hepatitis C (HCV). We examined predictors of receiving HCV Tx in safety-net hospitals. Methods We retrospectively examined all adults who received care 1/1/11–2/28/17 in our two safety-net hospitals in California and Texas and had a diagnosis of HCV. We examined age, race/ethnicity, gender, insurance status, body mass index, liver-related complications (heptocelluar cancer (HCC), cirrhosis, ascites, non-alcoholic fatty liver disease, (NAFLD) hepatic encephalopathy, variceal bleeding) non-liver related co-morbidities [HIV, non-HCC cancers, mental health, cardiovascular disease (CVD), hypertension (HTN), diabetes (DM)] alcohol use, and drug use. We evaluated the predictors of receiving HCV Tx using multivariate logistic regression models. Results Among 14,776 HCV patients in the study, most of the HCV patients (61% male, 43% Black, and 16% Hispanic) had Indigent care (42%), Medicare (14%), and Medicaid (27%). Co-morbidities in this population included mental health (71%), CVD (60%), HTN (51%), DM (21%), and HIV (9%). Indigent care, mental health and CVD co-morbidities were associated with lower rates of HCV Tx but Other race and NAFLD were associated with higher rates of Tx (see Table 1). Table 1: Logistic regression results predicting HCV TX in Safety Net Hospitals in Texas and California Total (n = 14,776) N (%) HCV TX (n = 646) N (%) OR 95% Confidence Interval White (ref) Black 6339 (42.9) 245 (37.9) 0.98 0.80–1.19 Other 152 (1.0) 34 (5.3) 1.52 1.10–2.09 Hispanic 2330 (15.8) 120 (18.6) 1.07 0.84-1.35 Commercial (ref) Medicare 2032 (13.8) 87 (13.5) 0.70 0.47-1.04 Medicaid 3927 (26.6) 162 (25.1) 0.78 0.55-1.10 Indigent 6217 (42.1) 244 (37.8) 0.63 0.44-0.88 HIV 1380 (9.3) 71 (11) 1.29 0.98-1.68 Mental Health 10,507 (71.1) 403 (62.4) 0.82 0.67-0.99 NAFLD 443 (3) 26 (4) 1.65 1.04-2.61 Cirrhosis 2631 (17.8) 122 (18.9) 0.96 0.76-1.22 CAD 8820 (59.7) 297 (46) 0.56 0.47-0.68 Conclusion In our safety-net hospitals only 4.4% received HCV Tx. Those with indigent funding, mental illness or cardiac disease were significantly less likely to receive HCV Tx. These data indicate that certain populations are less likely to have access to HCV care. The reasons for this remains unknown. If we are to move towards HCV elimination, we must find strategies to increase access. Disclosures M. K. Jain, Gilead: Grant Investigator, Research grant and Research support. Merck: Grant Investigator, Research grant. R. Wong, Gilead Sciences: Grant Investigator, Research grant

Interleukin-28B (IL28B) polymorphisms are associated with viral response to peginterferon and ribavirin (RBV) in chronic hepatitis C (HCV). Their recognition represents a breakthrough in the understanding of the role of the host in viral eradication. How these polymorphisms determine viral eradication is unknown. The IL-28B variants are hypothesized to have a differential impact on HCV quasispecies evolution during treatment with pegylated interferon (PEG-IFN) and RBV. In this study, HCV RNA levels were measured at early time points in 33 naive genotype 1 hepatitis C patients and clonal analysis of the entire NS5A region was performed on sera from baseline and Day 7. Site rs12979860 polymorphisms were determined by direct sequencing of PCR products and classified into CC, CT, and TT and were identified in 13, 11, and 9 patients, respectively. The CC polymorphism more commonly was seen in Whites versus Blacks [12/21 (57%) vs. 1/12 (8%), P = 0.009] and HIV-infected versus mono-infected [13/25 (52%) vs. 0/8 (0%), P = 0.009]. Patients with CC and non-CC had similar baseline viral loads. More patients with the CC polymorphism had amino acid substitutions in NS5A compared to non-CC patients. Despite similar baseline viral diversity, by Day 7, significantly more patients with CC had higher non-synonymous substitution values compared to non-CC (P = 0.02). Chronic hepatitis C patients with the CC IL28B polymorphism have a higher number of amino acid substitutions in the NS5A region and early viral evolution due to greater interferon induced selective pressure during this critical period of treatment. J. Med. Virol. 84:1913–1919, 2012. © 2012 Wiley Periodicals, Inc.

Objective Despite the remarkable improvements in pharmacologic treatment efficacy for hepatitis C (HCV) reported in published clinical trials, published research suggests that, in "real-world" patient care, these medical outcomes may be difficult to achieve. This review was undertaken to summarize recent experience in the treatment of HCV in clinical settings, examining the course of patients through the stages of treatment and barriers to treatment encountered. Method A comprehensive and representative review of the relevant literature was undertaken to examine HCV treatment experience outside of clinical trials in the last decade. This review found 25 unique studies with data on course of treatment and/or barriers to treatment in samples of patients with HCV not preselected for inclusion in clinical trials. Results Results were examined separately for samples selected for HCV infection versus HCV/HIV coinfection. Only 19% of HCV-selected and 16% of HCV/HIV-coinfection selected patients were considered treatment eligible and advanced to treatment; even fewer completed treatment (13% and 11%, respectively) or achieved sustained virologic response (3% and 6%, respectively). Psychiatric and medical ineligibilities were the primary treatment barriers. Conclusion Only by systematically observing and addressing potentially solvable medical and psychosocial barriers to treatment will more patients be enrolled in and complete HCV therapy.

Summary. Investigating the evolution of the hepatitis C viral (HCV) genome in the small number of patients that experience viral breakthrough might shed light on the problem of resistance to interferon therapy. Within the HCV genome, sequence diversity of the viral nonstructural 5A protein-coding region (NS5A) has been linked to interferon responsiveness. We analysed the temporal sequence changes within NS5A in genotype 1a patients: 6 breakthrough (BT), 12 sustained virologic responders (SVR) and 12 non-responders (NR), all of whom had received full dose peg-interferon and ribavirin therapy. The entire NS5A region was amplified by reverse transcription (RT)-PCR followed by direct sequencing of serum samples from baseline and three on-treatment time points for each group. Comparing baseline sequences with week 12 and later time points, BT patients resembled SVR patients in having a higher number of amino acid substitutions at week 12 than NR patients; however, the number of amino acid substitutions in this group decreased at and after BT. Substitutions were focused in the V3 and flanking regions in BT patients but not in SVR patients. The high number of substitutions in NS5A in both BT and SVR groups suggests that selective pressure is associated with viral response to therapy. Our results provide evidence that amino acid substitutions within the NS5A coding region may reflect a host response that drives selective pressure for viral adaptation.