Era Of Direct-acting Antiviral Therapy Research Articles

Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy.

The present study aimed to clarify the long-term outcomes after curative resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with and without sustained virologic response (SVR) to antiviral therapy. This single-center retrospective cohort study included 216 patients with HCV-related HCC who underwent primary curative resection. Patients were divided into preoperatively achieved SVR, postoperatively achieved SVR through direct-acting antiviral (DAA) therapy and no SVR groups. Associations of SVR and other clinicopathological and surgical variables with overall survival (OS) and recurrence-free survival (RFS) were analyzed. Propensity score (PS) matching was used to reduce selection bias. Patients with pre-SVR (108) and post-SVR (28) had better liver function and less liver fibrosis than those without SVR (80). In multivariate analysis, pre- or post-SVR [hazard ratio (HR), 0.13; 95% confidence interval (CI), 0.03-0.38; P < 0.001] was the only independent predictor of OS. For RFS, pre- or post-SVR (HR, 0.36; 95% CI, 0.18-0.64; P = 0.001) was one of several independent predictors. The study population was divided into the SVR (136 patients) and non-SVR groups. After PS matching, OS and RFS were significantly better in the SVR group (n = 53) than in the non-SVR group (n = 53) (P <0.001 and P = 0.012, respectively). Additionally, OS rates of SVR achieved with DAA were significantly higher than those achieved with interferon (P = 0.019). Achieving SVR by DAA before or after curative resection suppressed recurrence and prevented death in patients with HCV-related HCC.

Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy.

The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.

Timely Hepatitis C RNA Testing and Treatment in the Era of Direct-Acting Antiviral Therapy among People with Hepatitis C in New South Wales, Australia.

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016–2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many.

FRI356 - Incidence and risk factors of hepatitis C liver morbidity and mortality in the era of direct-acting antiviral therapies: a population-based linkage study

FRI356 - Incidence and risk factors of hepatitis C liver morbidity and mortality in the era of direct-acting antiviral therapies: a population-based linkage study

FRI311 - Macroeconomic assessment of overall and per-patient healthcare costs of Hepatitis C-infected patients in an integrated health system in the era of direct-acting antiviral therapy

FRI311 - Macroeconomic assessment of overall and per-patient healthcare costs of Hepatitis C-infected patients in an integrated health system in the era of direct-acting antiviral therapy

Predicting Treatment Failure for Initiators of Hepatitis C Virus Treatment in the era of Direct-Acting Antiviral Therapy.

Introduction: Hepatitis C virus (HCV), the leading cause of advanced liver disease, has enormous economic burden. Identification of patients at risk of treatment failure could lead to interventions that improve cure rates. Objectives: Our goal was to develop and evaluate a prediction model for HCV treatment failure. Methods: We analyzed HCV patients initiating direct-acting antiviral therapy at four United States institutions. Treatment failure was determined by lack of sustained virologic response (SVR) 12 weeks after treatment completion. From 20 patient-level variables collected before treatment initiation, we identified a subset associated with treatment failure in bivariate analyses. In a derivation set, separate predictive models were developed from 100 bootstrap samples using logistic regression. From the 100 models, variables were ranked by frequency of selection as predictors to create four final candidate models, using cutoffs of ≥80%, ≥50%, ≥40%, and all variables. In a validation set, predictive performance was compared across models using area under the receiver operating characteristic curve. Results: In 1,253 HCV patients, overall SVR rate was 86.1% (95% CI = 84.1%, 88.0%). The AUCs of the four final candidate models were: ≥80% = 0.576; ≥50% = 0.605; ≥40% = 0.684; all = 0.681. The best performing model (≥40%) had significantly better predictive ability than the ≥50% (p = 0.03) and ≥80% models (p = 0.02). Strongest predictors of treatment failure were older age, history of hepatocellular carcinoma, and private (vs. government) insurance. Conclusion: This study highlighted baseline factors associated with HCV treatment failure. Treatment failure prediction may facilitate development of data-driven clinical tools to identify patients who would benefit from interventions to improve SVR rates.

Early Outcomes of Multivisceral Transplant Using Hepatitis C–Positive Donors

In the era of direct-acting antiviral therapies, hepatitis C-positive organs offer a strategy to expand the donor pool. Heart failure patients with concomitant renal insufficiency benefit from combined heart/kidney transplant. In 2017, we began utilizing organs from hepatitis C donors for heart/kidney transplants. Characteristics and outcomes of heart/kidney transplants were collected at our institution from 2012 through 2019. We determined patient cohorts by donor hepatitis C antibody status, antibody positive (HCV+) vs antibody negative (HCV-). Outcomes of interest include survival, postoperative allograft function, and waitlist time. Summary and descriptive statistics, as well as survival analyses, were performed. Thirty-nine patients underwent heart/kidney transplantation from 2012-2019. Twelve patients received HCV+ organs, and 27 patients received HCV- organs with minimal differences in donor and recipient cohort characteristics. Recipients who consented to receive HCV+ organs had a shorter median waitlist time. HCV+ and HCV- groups had similar perioperative and early postoperative cardiac function and similar rates of delayed renal graft function. HCV+ recipients demonstrated higher creatinine levels at 3 months posttransplant compared with HCV- recipients, but by 1-year post-transplant, creatinine levels in both groups were similar. The groups had similar 30-day and 1-year survival. This study is a single-center series of heart/kidney transplant using HCV+ donors. When the potential increased risk of early postoperative renal dysfunction is balanced against similar survival and decreased waitlist time, the results suggest that HCV+ donors are an important source of transplantable organs for heart/kidney transplantation.

Should We Continue Wasting Hearts? Outcomes of Heart Transplantation From Hepatitis C Donors: A Systematic Literature Review

Background The number of patients dying awaiting heart transplantation (HT) can be reduced through HT from Hepatitis C nucleic acid test positive donors (HCV+D) to negative recipients (HCV-R). This strategy remains underused. Objective Analyze the outcomes of HT from HCV+D to HCV-R, of several transplant centers in the era of direct-acting antiviral therapy (DAA). Methods We searched for literature published from January 2015 to April 2020 with “Hepatitis C Virus” & “Heart Transplantation” as keywords. Results We identified 195 HT from HCV+D to HCV-R, done in 12 centers, reported as part of clinical studies, case reports, or case series. There were no deaths reported due to HCV infection in recipients of HCV+D and their survivals at 1, 6, and 12 months were 96.2, 93.2, and 89.3 percent, respectively (table 1). Sustained virologic response at 12 weeks (SVR-12) was achieved in all cases where the data were available. HCV was transmitted via HT to 97.6% of the reported subjects, and all with viremia received DAA. DAA was started after identifying viremia (delayed strategy) in 10 centers, and in 2 of them preemptively (immediately after HT). DAA duration was intended for 12 weeks in the delayed regimen, and 4 in the preemptive, with no difference in SVR-12. Within the preemptive regimen, no changes or extension of DAA were reported, while 5 subjects in the delayed regimen required either changes or extensions (to 24 weeks) of the initial DAA. Conclusions HCV is highly contagious via HT. Current DAA provides an excellent cure rate, with all cases reported to date achieving SVR-12. For those under a preemptive regimen, no changes or extension in DAA were required. Recipients of hearts from HCV+D had an excellent survival, and no deaths related to HCV were reported.

Changing Population of Liver Transplant Recipients in the Era of Direct-acting Antiviral Therapy.

Background and Aims: With the availability of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection and changing liver disease etiology for liver transplantation (LT), data on the changes in LT recipient population in the DAA era are scanty.Methods: The United Network for Organ Sharing (UNOS) registry (01/2007 to 06/2018) was used to develop a retrospective cohort of LT recipients for HCV, alcohol-associated liver disease (ALD), and non-alcoholic steatohepatitis (NASH). LT recipients in the DAA era (2013-2018) were compared with those in the pre-DAA era (2007-2012) era for recipient characteristics. Chi-square and analysis of variance were the statistical tests used for categorical and continuous variables, respectively.Results: Of 40,309 LT recipients (21,110 HCV, 7586 NASH, and 11,713 ALD), the 21,790 in the DAA era (9432 HCV, 7240 ALD, and 5118 NASH) were more likely to be older, female, obese, diabetic, have acute-on-chronic liver failure with a higher model for end-stage liver disease score, receive grafts with a lower donor risk index, and have waited on the LT list for a shorter period compared with their pre-DAA era counterparts. Specific to ALD, LT recipients with alcohol hepatitis were more likely to be younger at the time of LT. Of 9895 LT recipients with hepatocellular carcinoma, recipients in the DAA era were observed to have a higher proportion of HCV (43% vs. 32%, p<0.001), a lower proportion of ALD (9% vs. 12%, p<0.001), and no change for NASH (13% vs. 13%, p=0.9) compared with the pre-DAA era. Within the hepatocellular carcinoma population, LT recipients in the DAA era were older, diabetic, and waited on the LT list longer compared with their pre-DAA counterparts.Conclusions: Along with changing liver disease etiology in the DAA era, the LT recipient population demographics, comorbidities, liver disease severity, and graft quality are changing. These changes are relevant for future studies, immunosuppression, and post-transplant follow-up.

Successful Transplantation of 96 Hepatitis C-positive Donor Hearts in the Era of Direct-Acting Antiviral Therapies

For patients awaiting heart transplantation (HT), hepatitis C virus (HCV)-positive donors offer to expand the donor pool, shorten wait times and decrease wait list mortality. While early reported outcomes have been promising, knowledge of 1-year outcomes in larger cohorts of patients remains unclear. Between September 2016 and September 2019, 96 patients underwent HT from HCV-positive donors, 83 of whom were viremic at time of organ recovery. All patients were treated with standard immunosuppression and, for those who developed donor-derived HCV (dd-HCV), with a course of direct-acting antiviral (DAA) therapy. Data collection and analysis were performed after obtaining IRB approval and informed patient consent. Baseline characteristics: Mean age of recipients at time of HT was 52 ± 12 years (72% male, 68% Caucasian, 44% on left ventricular assist device support). Mean age of donors was 32 ± 7 years. Among donors, results of HCV antibody (Ab) and nucleic acid testing (NAT) were: 80 Ab+/NAT+, 13 Ab+/NAT-, 3 Ab-/NAT+. Time to transplant: Among all patients, median active waitlist time from consent to acceptance of HCV-positive donors was 4 days (IQR 1, 17). Hepatitis C testing and treatment: No recipients of NAT- donor hearts developed HCV infection. Of 83 patients who received NAT+ donor hearts, 80 (96.4%) developed dd-HCV. Treatment with DAA therapy was well tolerated and yielded sustained virologic responses in 100% of treated patients (n=52, to date). Survival: Among 80 patients with dd-HCV, survival at 30-days and 1-year post-HT was 91.2% and 88.3%, respectively, not significantly different when compared to patients transplanted with HCV-negative donors during the same time frame (30-day survival 96%, p=0.10; 1-year survival 91.6%, p=0.27). In the era of direct-acting antiviral therapies, hepatitis C-positive donors are a viable strategy to expand the donor pool, potentially reducing waitlist duration and mortality.

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy.

The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.

Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C

For patients awaiting heart transplant, hepatitis C-positive donors offer an opportunity to expand the donor pool, shorten wait times, and decrease wait-list mortality. While early reported outcomes among few heart transplant recipients have been promising, knowledge of 1-year outcomes in larger cohorts of patients is critical to shared decision-making with patients about this option. To better define the association of hepatitis C-positive donors with heart transplant volumes, wait-list duration, the transmission and cure of donor-derived hepatitis C, and morbidity and mortality at 1 year. This was a prospective, single-center observational study of 80 adult (age 18 years or older) patients who underwent heart transplant using hearts from hepatitis C-positive donors between September 2016 and April 2019 at a large academic medical center. Among donors, who were considered hepatitis C-positive if results from hepatitis C antibody and/or nucleic acid testing were positive, 70 had viremia and 10 were seropositive but did not have viremia. Follow-up was available through May 15, 2019. Comparisons were drawn with patients who underwent transplant with hearts from hepatitis C-negative donors during the same period. In addition to standard posttransplant management, transplant recipients who developed donor-derived hepatitis C infection were treated with direct-acting antivirals. The main outcomes included wait-list duration and 1-year survival in all patients, and for those who developed donor-derived hepatitis C, the response to direct-acting antiviral treatment. Of 80 patients, 57 (71.3%) were men, 55 (68.7%) were white, and 17 (26.3%) were black; the median age at transplant was 54.5 years (interquartile range, 46-62 years). Following consent to accept hearts from hepatitis C-exposed donors, the median days to heart transplant was 4 (interquartile range, 1-18). No recipients of donors with negative nucleic acid testing results (10 [12.5%]) developed donor-derived hepatitis C. Of 70 patients who were recipients of donors with positive nucleic acid testing results, 67 (95.7%) developed donor-derived hepatitis C over a median follow-up of 301 days (interquartile range, 142-617). Treatment with direct-acting antivirals was well tolerated and yielded sustained virologic responses in all treated patients. Within the cohort with infection, 1-year patient survival was 90.4%, which was not significantly different compared with the cohort without infection or with patients who received transplants from hepatitis C-negative donors during the same period. In the era of direct-acting antivirals, hepatitis C-positive donors are a viable option to expand the donor pool, potentially reducing wait-list duration and mortality. In heart transplant recipients with donor-derived hepatitis C, infection is well-tolerated and curable, and 1-year survival is equivalent to that in recipients of hepatitis C-negative donors.

Characteristics of Hepatitis C+ vs Hepatitis C- Donors

Purpose With the advent of direct acting antiviral therapies (DAAs) for Hepatitis C (HCV), the use of HCV donors in adult heart transplantation is increasing. We sought to characterize HCV+ vs. HCV- donors to assess whether significant differences in donor quality and rates of organ acceptance and transplantation exist. Methods Between January 1, 2018 and August 15, 2018 we evaluated 427 heart transplant donors offered to the adult heart transplant program at Vanderbilt University Medical Center. We compared age, sex, BMI, cause of donor death, and rates of organ acceptance transplantation. We examined any heart donor during this time frame that was HCV antibody and/or HCV NAT positive. Results The Table demonstrates the characteristics of all 427 donors comparing HCV + vs HCV- donors. HCV+ donor hearts come predominantly from male donors among whom the overwhelming cause of death is drug overdose. These hearts have a higher likelihood of being accepted for transplant and being transplanted, relative to hearts from HCV- donors. Conclusion In the era of DAAs, utilization of HCV+ hearts is a viable strategy to help expand the donor pool.

Successful Transplantation of 58 Hepatitis C-Exposed Donor Hearts in the Era of Direct-Acting Antiviral Therapies

Purpose The shortage of suitable donors for heart transplantation (HT) contributes to wait-list mortality and increased reliance on mechanical circulatory support. Since the advent of direct-acting antivirals (DAA) for treatment of hepatitis C (HCV), utilization of hepatitis C-exposed donors is now a viable strategy to expand the donor pool and potentially reduce waitlist time. Methods Between September 2016 and October 2018, 58 patients underwent HT from HCV-exposed donors. All patients were treated with standard immunosuppression and, for those who developed HCV infection, with a course of DAA. Data collection and analysis were performed after obtaining informed patient consent and IRB approval. Results Baseline characteristics: Mean age of recipients at time of HT was 52 ± 13 years (72% male, 69% Caucasian, 41% on left ventricular assist device support). Mean age of donors was 30 ± 7 years. Among donors, results of HCV antibody (Ab) and nucleic acid testing (NAT) were: 47 Ab+/NAT+, 9 Ab+/NAT-, 2 Ab-/NAT+. Time to transplant: Among all patients, active waitlist time from time of consent to accept HCV-exposed donors was median 4 days (IQR 1, 17). Hepatitis C testing and treatment: No recipients of NAT- donor hearts developed HCV infection. Of the 49 patients who received NAT+ donor hearts, 46 (94%) developed HCV infection, including 27 patients who completed DAA therapy with cure demonstrated by absence of viremia at 12 weeks post-treatment (SVR12), 7 patients in whom treatment is ongoing or recently completed, and 7 patients who have yet to initiate treatment. By the time of ISHLT 2019, we expect to have SVR12 data for all infected patients who have completed treatment, 30 of whom will be at least one year post-HT. To date, there has been no suggestion of increased rates of rejection, graft dysfunction or vasculopathy among infected patients, nor has there been a suggestion of liver injury. Conclusion In the era of highly effective HCV pharmacotherapy, the use of HCV-exposed donors safely allows for expansion of the donor pool.

Integrating hepatitis C and addiction care for people who inject drugs in the era of direct-acting antiviral therapy

As new, more tolerable and effective hepatitis C virus (HCV) treatments are available, there is a global need to consider how to maximize treatment access for groups who are most affected by HCV. A substantial number of people who inject drugs (PWID) are living with HCV, yet only a minority have received treatment. HCV treatment programs that are integrated into community-based addiction care may be a successful way to overcome barriers and increase access and uptake of HCV treatment for this population. Examples of successful HCV and addiction care integration in the community have been documented. However, potential challenges to integration exist and include changing healthcare provider roles, lack of stimulant use research and restrictive drug policies. Successful engagement of PWID in HCV care is critical step towards the elimination of HCV infection. Further research and efforts are needed in order to reach this goal.

Management of acute HCV infection in the era of direct-acting antiviral therapy.

The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) guidelines supported "the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety", whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir-ledipasvir, sofosbuvir-velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD-IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.

Hepatitis C care continuum and associated barriers among people who inject drugs in Chennai, India

BackgroundLittle is known regarding barriers to hepatitis C virus (HCV) treatment among people who inject drugs (PWID) in low-resource settings, particularly in the era of direct-acting antiviral therapies. MethodsBetween March, 2015–August, 2016, a cross-sectional survey was administered to community-based PWID in Chennai, India to examine the HCV care continuum and associated barriers. Adjusted prevalence ratios (APR) were estimated by multivariable Poisson regression with robust variance. ResultsAll participants were male (n = 541); 152 participants had HCV mono-infection and 61 participants had HIV/HCV co-infection. Only one HCV mono-infected and one HIV/HCV co-infected participant was linked to HCV care. Overall, there was moderate knowledge of HCV disease but poor knowledge of HCV treatment. Higher total knowledge scores were negatively associated with HIV/HCV co-infection (vs. HCV mono-infection), though this was not statistically significant in adjusted analysis (APR = 0.71 [95%CI = 0.47–1.06]). Participants ≥45 years (APR = 0.73 [95%CI = 0.58–0.92]) and participants with HIV/HCV co-infection (APR = 0.64 [95%CI = 0.47–0.87]) were less willing to take weekly interferon injections for 12 weeks. Willingness to undergo HCV treatment improved with decreasing duration of therapy, higher perceived efficacy, and use of pills vs. interferon, though willingness to use interferon improved with decreasing duration of therapy. Most participants preferred daily visits to a clinic for HCV treatment versus receiving a month’s supply. Participants ≥45 years (vs. <45 years; APR = 0.70 [95%CI = 0.56–0.88]) and participants with HIV/HCV co-infection (APR = 0.75 [95%CI = 0.57–0.98]) were less likely to intend on seeking HCV care. Common reasons for not having already seen a provider for HCV treatment differed by HIV status, and included low perceived need for treatment (HCV-mono-infected), competing money/health priorities and costs/fears about treatment (HIV/HCV-co-infected). ConclusionResidual gaps in HCV knowledge and continuing negative perceptions related to interferon-based therapy highlight the need to scale-up educational initiatives. Readiness for HCV treatment was particularly low among HIV/HCV co-infected and older PWID, emphasizing the importance of tailored treatment strategies.

Management of hepatitis C infection in the era of direct-acting antiviral therapy

Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

Hepatitis C Treatment in HIV Coinfection: Approaches, Challenges, and Future Opportunities

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection is a significant cause of morbidity and mortality in people living with HIV/AIDS. Indeed, HCV is more likely to progress to end-organ dysfunction in HIV-infected people, and fibrosis progresses more quickly in this population than in the general population. While historical treatments combining interferon and ribavirin were less efficacious in HIV/HCV coinfection, modern direct-acting antiviral (DAA) therapies have shown similar clinical efficacy in HIV/HCV coinfection as in HCV monoinfection. In light of these findings, HIV/HCV-coinfected patients may benefit even more from new HCV treatment approaches. The choice of DAA therapy for HCV in HIV-infected patients should be based on the patient’s disease stage, prior treatment history, and viral characteristics such as genotype and/or resistance mutations, just as it is in patients with HCV monoinfection. Potential drug-drug interactions between HIV antiretroviral therapy (ART) and HCV DAA therapy must be considered when prescribing HCV treatment and may impact the choice of treatment. Caution is advised when considering DAA regimens that have not been studied in HIV/HCV populations due to lack of data regarding efficacy, the potential for drug-drug interactions, or both. In the era of DAA therapy and with many therapeutic options available to tailor appropriate regimens in order to avoid drug-drug interactions, HCV should be treated aggressively in HIV-infected persons to reduce morbidity and mortality.