Direct-acting Antiviral Treatment Research Articles

Treatment uptake among notified cases of hepatitis C virus infection in Norway, 1990 to 2022: a registry-based study to monitor progress towards elimination.

BackgroundHepatitis C virus (HCV) infection is targeted for elimination as a public health threat by 2030. The World Health Organization goal for treatment uptake is ≥ 80% among cases diagnosed with an active HCV infection (RNA- or core antigen-positive), maintained for 2 years.AimTo calculate treatment uptake, time from diagnosis to treatment start and complete treatment dispensation among notified cases of HCV infection in Norway.MethodWe linked national data on notified cases diagnosed from 1990-2022 to dispensed prescriptions for HCV treatment from January 2004-February 2023 and data on residence status at the end of 2022. We described treatment uptake by demographic and epidemiological characteristics. We calculated the median number of months from diagnosis to treatment start by year. For direct-acting antiviral treatment periods, complete dispensation was based on the treatment and number of defined daily doses.ResultsAmong 12,178 notified cases that had an active infection at diagnosis and were still resident, 10,091 (83%) had received treatment. Uptake among resident cases was > 80% in 2021 and 2022. The median number of months from diagnosis to treatment decreased over time to 3 (interquartile range: 1-5) among cases diagnosed in 2021 and 2022. From 2015-22, 89-93% of direct-acting antiviral treatment periods annually had complete treatment dispensed.ConclusionNorway has achieved the elimination goal for treatment uptake among notified cases diagnosed with an active HCV infection. This highlights the benefit of a strategy that includes unrestricted, simplified and integrated treatment options.

Rate of hepatitis C reinfection after successful direct-acting antivirals treatment among people who inject drugs in Spain: the LIVERate study.

Hepatitis C virus (HCV) reinfection following successful treatment threatens the achievement of HCV elimination. The primary aim of this study is to assess reinfection rate three years after sustained virologic response (SVR) in people who inject drugs (PWID) that are on opioid agonist treatment (OAT) who underwent anti-HCV treatment with interferon-free regimens. Observational, non-interventional, prospective, descriptive study carried out in Spanish tertiary public hospitals between 2017 and 2022. Participants comprised 186 adult HCV infected individuals, 85.5% males with a mean age (Standard Deviation, SD) of 50.1 (5.9). All were enrolled in an OAT program at baseline and had attained SVR 12 weeks after therapy completion with an interferon-free treatment. Baseline data were abstracted from medical chart information collected through the routine clinical practice. The overall rate of HCV reinfection three years after SVR12 among PWID was 1.2 new cases per 100 person-years of follow-up at a median of 15.9 months. In the subgroup analyses, those with injection drug practice and without a stable housing had higher reinfection rates. Although PWID in OAT present a low rate of reinfection by HCV after successful treatment, a closer monitoring in the first year and strengthening inter-consultations with services responsible for monitoring addiction in these patients will be crucial to reduce risky behaviors avoiding HCV reinfection.

Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.

Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%. Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure. HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.

The effect of cognitive emotion regulation on direct-acting antivirals adherence in patients with hepatitis C

IntroductionAdherence to direct-acting antivirals (DAAs) could be a predictor of chronic viral hepatitis C (HCV) therapeutic failure. We examined the perceptions of patients receiving DAAs to determine how cognitive factors influence their decision to maintain adherence. Also, we explored the threshold of DAAs adherence for obtaining sustained virologic response (SVR) among patients with HCV, in order to better implement a strategy that improves the DAAs adherence in the future clinical practice.MethodsA single-arm prospective study was performed. Patients with HCV that started and completed DAAs treatment in the County Hospital of Craiova, Dolj, Romania, were enrolled. Patients’ medication adherence was assessed using the HCV-AD10 questionnaire, and the cognitive emotion regulation was measured with CERQ questionnaire (five positive/adaptive cognitive emotion-regulation domains and four negative/maladaptive domains). Spearman correlation analysis was conducted to explore the relationships between adherence and different factors. ROC-curves were used to evaluate the adherence threshold to achieve SVR. A linear regression model was performed to analyze the primary outcome (DAAs adherence) to be the target variable based on given independent variables (age, treatment duration, severity of HCV, the nine adaptive and maladaptive strategies).Results368 patients (mean age: 61 years) with HCV diagnosed 4.05 ± 6.38 (average) years ago were enrolled. Mean (±SD) adherence via HCV-AD10 was 91.51 ± 8.34, and the proportion of the participants achieving SVR was 96%. Patients with an adherence less than 84% (5 patients, 1.36%) was considered nonadherent and they have a high probability of not achieving response (sensitivity and specificity of 83% and 80%, respectively). We obtained significantly higher values of three adaptive strategies between adherent and nonadherent patients following DAAs treatment: in positive refocusing (p-value = 0.044), refocus on planning (p-value = 0.037), and positive reappraisal (p-value = 0.047).DiscussionThe interplay between the three adaptive strategies of the cognitive emotion regulation and the enhancement of DAAs adherence contributes to a more holistic comprehension of patient behavior in the context of HCV treatment. Increasing refocusing and planning using goal setting and assisting patients in establishing specific, achievable goals can be crucial strategies for clinicians aiming to improve adherence among their patients.

English

Objectives: Direct-acting antivirals (DAAs) share pharmacokinetic pathways with many comedications commonly administered to patients living with chronic hepatitis C virus (HCV) infection (PLWHCV). International guidelines recommend a thorough drug-drug interaction (DDI) risk assessment prior to starting DAA therapy and before starting comedications. This study aims to evaluate the impact of potential multiple DDIs in the real-life adverse event (AE) profile of PLWHCV treated with DAAs. Material and method: This is a retrospective, observational study using electronic medical records. Patients included were PLWHCV and were treated with either the protease inhibitor (PI) free DAA sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) between 2017 and 2020. Potential (single and multiple) DDIs were identified using the Liverpool HEP Interaction Checker. AEs potentially associated to DDIs were identified during DAA treatment period. Results: 1620 patients with DAA prescriptions (SOF/VEL or GLE/PIB) were included. Of these, 123 were predicted to have multiple DDIs (multi-DDI). About 10% (123/1256) of the patients receiving ≥2 comedications were at risk of multi-DDI with DAA. Most comedication-associated AEs were recorded in this multi-DDI population (88.9%, 16/18), meaning that 13% (16/123) of the multi-DDI population suffered AEs. According to DAA regimen, more comedication-associated AEs were reported in GLE/PIB-treated as compared with SOF/VEL-treated patients (18.3% [13/71] vs 5.8% [3/52] p<0.05). These AEs were mainly reported by primary care physicians (62.5%). Discussion: PLWHCV predicted to have multiple DDIs are at high risk of AEs. Moreover, fewer comedication-associated AEs were identified with the PI-free DAA SOF/VEL as compared with GLE/PIB.

Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC.

The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.

Cost-effectiveness analysis of emergency department-based hepatitis C screening and linkage-to-care program

BackgroundIn the United States (US), hepatitis C virus (HCV) screening is not covered by payers in settings outside of primary care. A non-traditional, emergency department (ED)-based HCV screening program can be cost-effective and identify infection in vulnerable populations with a high HCV risk. This study examined the long-term cost-effectiveness of routine HCV screening and linkage-to-care for high-risk patients in the ED from the payer’s perspective.MethodsThe University of Illinois Hospital and Health Sciences System (UIH) implemented Project HEAL (HIV & HCV Screening, Education, Awareness, Linkage-to-Care). Under this initiative, patients who presented to the ED received opt-out HCV screening if they were at high risk for HCV infection (birth cohort between 1945 and 1964, persons who inject drugs, and HIV infection) with subsequent linkage-to-care if infected. Using the summary data from Project HEAL, a hybrid decision-analytic Markov model was developed based on the HCV screening procedure in the ED and the natural history of HCV. A 30-year time horizon and 1-year cycle length were used. All patients who received the ED-based HCV screening were referred for treatment with direct-acting antiviral (DAA) regardless of their fibrosis stage.ResultsWhen unscreened/untreated patients received DAA treatment at F1, F2, F3, and compensated cirrhosis stages, the incremental cost-effectiveness ratio (ICER) ranged from $6,084 to $77,063 per quality-adjusted life year (QALY) gained. When unscreened/untreated patients received DAA treatment at the decompensated cirrhosis stage, no HCV screening was dominated.ConclusionED-based HCV screening and linkage-to-care was cost-effective at the willingness-to-pay (WTP) threshold of $100,000/QALY in all scenarios. A reduction in infected persons in the community may provide additional benefits not evaluated in this study.

Long-term Effect of the HCV Elimination With Direct-acting Antivirals on the Progression of Gastroesophageal Varices.

Gastroesophageal varices (GEV) hemorrhage is a serious complication that can lead to unfavorable outcomes in cirrhotic patients. However, the clinical impact of HCV elimination [sustained viral response (SVR)] by direct-acting antivirals (DAAs), particularly on the long-term effects on the endoscopic findings of GEV have not been sufficiently evaluated. This study aimed to investigate whether HCV elimination with DAA treatment suppresses the progression of GEV. The clinical courses of the endoscopic findings of GEV were retrospectively compared between patients without an SVR (non-SVR group: n=71) and those who achieved an SVR with DAAs (DAA-SVR group: n=38). At 1, 3, 5, and 7 years, the cumulative GEV progression rates were 8.7%, 32.8%, 45.6%, and 66.2%, respectively. At 3 years, the cumulative GEV progression rate in the DAA-SVR group was similar to that in the non-SVR group. Beyond 3 years, cases with GEV progression were found in the non-SVR group, but not in the DAA-SVR group. At 7 years, the cumulative GEV progression rate in the DAA-SVR group was significantly lower than that in the non-SVR group (p<0.05, log-rank test). Variceal hemorrhage occurred in eight patients in the non-SVR group, while no bleeding events were observed in the DAA-SVR group during the observational period [8/71 (11.3%) vs. 0/38 (0.0%), p<0.05]. DAA treatment suppresses the progression of GEV over the long term.

Epidemiology of hepatitis C from 2015 to 2022 in a central Italian region: the OPT-HepaC project

Abstract Background Chronic hepatitis C virus (HCV) infection is a major global public health problem. This study investigated the evolving landscape of HCV in Tuscany (Italy) from 2015 to 2022, considering demographic shifts, clinical profiles, treatment regimens, and outcomes. Methods The study was conducted in order to characterize HCV-positive patients who started treatment between 2015 and 2022 in Tuscan prescribing centers. The study was part of OPT-HepaC, a project funded by Regional Health Service. Data on demographics, clinical history and outcomes were collected. Three different temporal eras were analysed: the period before andfter the universal availability of direct-acting antivirals (DAA) and the COVID-19 era. Treatment’s effectiveness was evaluated by the Sustained Virological Response (SVR12), assessed 12 weeks after the end of treatment. Outcomes included SVR12, non-SVR12 and lost to follow-up (LTFU). ANOVA, Kruskal-Wallis test and multinomial logistic regression were used for statistical analysis. Results 6882 HCV patients (age: 58.88±14.21) were treated by the centres participating at the study. Males (56.4%) and Italian (91.8%) were predominant. Sociodemographic and variable characteristics vary across the time. While the overall SVR12 remained stable over time (χ2(2)=0.357, p = 0.837), the LTFU rate significantly increased during the COVID-19 era. Facilitating factors for the non-SVR12 and LTFU outcomes were male gender (Odds Ratio (OR)=2.134, p = 0.006)/cirrhosis (OR = 1.713, p = 0.040)/HIV co-infection (OR = 3.251, p = 0.005) and DAA treatment of third generation (OR = 4.187, p = 0.006), respectively. Conclusions The study provides a comprehensive view of the HCV landscape, highlighting demographic changes, treatment regimens and outcomes. The COVID-19 pandemic affected service delivery, delaying HCV diagnosis/treatment and influencing the LTFU rate. Despite challenges, the region maintained high SVR12 rates, emphasizing the importance of sustained efforts in HCV care. Key messages • The study highlights the dynamic nature of HCV management in Tuscany. • The study emphasises the need for continuous adaptation to public health challenges, providing insights for future public health strategies.

Changes in hepatic steatosis before and after direct acting antiviral treatment in people living with HIV and Hepatitis C coinfection.

Both HIV and hepatitis C virus (HCV) infection increase the risk of hepatic steatosis (HS), which in turn contributes to the severity and progression of liver disease. Direct acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear. HS was assessed using the controlled attenuation parameter (CAP) and the hepatic steatosis index (HSI) in participants coinfected with HIV-HCV from the Canadian Coinfection Cohort. Changes in HS, before, during and after successful DAA treatment, were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides and hazardous drinking). 431 participants with at least one measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval (CrI) 1.6, 4.9) before, and 3.9 dB/m (95% CrI: 1.9, 5.9) after DAA treatment, irrespective of pre-treatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI: -0.1, 0.5) before and 0.2 (95% CrI -0.1, 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI -5.9, -3.1). When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.

Serum collagen IV as a predictor for response to direct-acting antivirals hepatitis C therapy

ABSTRACT Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher (P < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4–25.2) vs.9.7 (7.2–12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated (p < 0.05) with decreased albumin (r=-0.266), elevated APRI (r = 0.288), and elevated FIB-4 (r = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control.

DAA treatment for HCV reduce risk of hepatocellular carcinoma: a 10-years follow-up study based on Chinese patients with hepatitis C

The long-term benefits of direct-acting antiviral (DAA) therapy after achieving sustained virological response (SVR) remain uncertain in the Chinese population. This study evaluates the incidence of hepatocellular carcinoma (HCC), hepatic decompensation, and all-cause mortality among Chinese hepatitis C patients treated with DAAs. We included patients diagnosed since 2011 and followed them until November 1, 2022. The primary outcomes were HCC, hepatic decompensation, and mortality. Multivariable proportional hazards model was used to assess the impact of SVR and cirrhosis status. The cohort consisted of 1272 patients with SVR (92.1%) and 109 without SVR (7.9%), with a median follow-up of 61 months. The incidence of HCC was significantly lower in the SVR group (5.1 per 1000 person-years) compared to the no-SVR group (15.0 per 1000 person-years). Achieving SVR was associated with a significantly reduced risk of HCC (adjusted hazard ratio: 0.32; 95% CI 0.16–0.67). Cirrhosis was linked to an increased risk of developing HCC and hepatic decompensation. These findings highlight the importance of early DAA treatment, particularly for patients with cirrhosis.

Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

Single-center retrospective review of standard versus minimal monitoring for hepatitis C direct-acting antiviral therapy

BackgroundHighly effective direct-acting antiviral (DAA) therapies have transformed the landscape of hepatitis C virus (HCV) treatment. However, there continues to be limited data regarding the efficacy and safety of required in-person clinic visits (standard monitoring) versus completely telehealth clinic visits (minimal monitoring) during HCV therapy, which could delay practice adoption. ObjectivesThis study aimed to assess the rates of undetectable HCV ribonucleic acid (RNA) in sustained viral load 12 weeks after therapy (SVR12) in standard versus minimal monitoring approaches during DAA. MethodsA 12-month, single-center retrospective cohort study was conducted in treatment-naïve HCV-infected adults who received DAA therapy between May 1, 2020, and April 30, 2021. The standard monitoring group had ≥1 in-person clinic visit with HCV RNA laboratory monitoring during DAA treatment. The minimal monitoring group had entirely telehealth visits without HCV RNA laboratory monitoring during treatment. Both groups received telephonic touchpoints throughout DAA treatment from a clinical pharmacist practitioner and a nurse care coordinator. The primary outcome was SVR12. ResultsFrom May 2020 to April 2021, 133 patients with HCV met inclusion criteria and were treated with DAA (standard, n = 56; minimal, n = 77), with no differences in baseline demographics. Overall, total encounters during DAA treatment remained significantly higher in the standard than minimal monitoring group (standard, 2.1 ± 0.8, vs. minimal, 1.7 ± 0.9; P < .01). Although minimal monitoring had higher loss to follow-up rates (standard, 7.1%, vs. minimal, 18.2%; P = 0.06), the modified intention-to-treat analysis showed no differences in sustained virologic response (SVR) between standard and minimal monitoring approaches (standard, 98.1%, n = 51, vs. minimal, 95.3%, n = 60; P = 0.41). ConclusionsThis single-center retrospective cohort study demonstrated that minimal monitoring during HCV treatment was as effective in achieving SVR cure rates as standard monitoring. Eliminating required in-person clinic visits during DAA therapy alongside a collaborative approach may play a major role in overcoming barriers to HCV care in select patients.

An evolutionary concept analysis: stigma among women living with hepatitis C

BackgroundStigma is a complex social phenomenon that leads to marginalization and influences the course of illness. In the context of hepatitis C virus (HCV), stigma is a well-documented barrier to accessing care, treatment, and cure. In recent years, HCV rates among women have increased, resulting in an urgent need to address stigma and its harmful effects. The purpose of this concept analysis was to investigate stigma in the context of women living with HCV using Rodgers’ evolutionary method.MethodsPubMed, CINAHL, Scopus, Medline, PsycINFO, and Nursing and Allied Health were used to identify articles describing HCV stigma among women. Articles from peer-reviewed journals and geographic locations, published between 2002–2023, were included in the analysis. As specified in Rodgers’ evolutionary method, articles were analyzed with a focus on the concept’s context, surrogate and related terms, antecedents, attributes, examples, and consequences.ResultsFollowing screening, 33 articles were selected for inclusion in the analysis. Discrimination and marginalization were identified as surrogate and related terms to stigma; and antecedents of stigma were identified as limited knowledge, fear of diagnosis, and disclosure. Prevalent attributes of stigma in the literature were described as feelings of decreased self-worth, negative stereotyping, and fear of transmission. Importantly, HCV stigma among women is unique in comparison to other forms of infectious disease-related stigma, primarily due its impact on women’s identity as mothers and caregivers. Stigmatization of women living with HCV resulted in negative consequences to personal relationships and healthcare access due to decreased health-seeking behaviours. Although access to HCV treatment has changed considerably over time, a temporal analysis could not be completed due to the limited number of articles.ConclusionsStigma in the context of women living with HCV has its own unique antecedents, attributes, and consequences. This enhanced understanding of stigma among women living with HCV has the potential to inform improved and more effective approaches to care, which will be required to reach HCV elimination. Furthermore, this analysis identifies stigma layering and stigma in the direct-acting antiviral treatment era as areas for more in-depth future inquiry.

Hepatocellular Carcinoma Incidences and Risk Factors in Hepatitis C Patients: Interferon versus Direct-Acting Agents.

Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens. A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan-Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences. DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. <3 years from the end of treatment: DAA: 1.43% vs. 1.00% per year; IFN: 0.47% vs. 0.36% per year, both p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC. DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up.

Socioeconomic Deprivation Weighs Heavily on Liver Fibrosis and Mortality After Hepatitis C Cure (ANRS CO22Hepather).

Although Hepatitis C virus (HCV) infection can be cured with direct-acting antivirals (DAA), some cured patients face a serious risk of advanced liver damage and early mortality. In order to avoid these two negative health outcomes, it is important to identify and assess related risk factors. Little is currently known about socioeconomic and behavioural factors in this context. Using data from the ANRS CO22 Hepather cohort, we tested for associations between socioeconomic and behavioural factors and (i) advanced liver fibrosis (defined as an FIB-4 > 3.25) assessed longitudinally using a mixed-effects logistic regression model (both the whole population and stratified on advanced liver fibrosis status at the time of HCV cure) and (ii) all-cause mortality (Cox proportional hazards model), during post-HCV cure follow-up. Among 5833 participants cured of HCV, living in poverty was associated with postcure advanced liver fibrosis in participants without this diagnosis at the time of HCV cure (population attributable fraction-PAF-of 8.6%) and with mortality in the whole study population (PAF of 10.6%). The detrimental effects of unhealthy alcohol use and heavy tobacco smoking, as well as the beneficial effect of living with a stable partner were also highlighted. We highlighted the major role of poverty and behavioural factors in advanced liver fibrosis and all-cause mortality in patients cured of HCV. Encouraging linkage to social support services and healthy behaviours after successful DAA treatment could limit morbidity and increase survival in this population. Clinical Trial Registration: ClinicalTrials.gov: NCT01953458.

The Real-World Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C in Patients Active Malignancies.

Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.

Hazardous Alcohol Use and Its Effect on Direct-Acting Antiviral Therapy Initiation among People with Active Injection Drug Use and Current Hepatitis C Infection.

Hepatitis C virus (HCV) infection and hazardous alcohol use are both preventable causes of morbidity and mortality among people who inject drugs (PWID). In the general population, hazardous alcohol is associated with a reduced likelihood of HCV treatment initiation. Less is known about the prevalence and impact of hazardous alcohol use on direct-acting antiviral (DAA) therapy initiation among PWID with active injection drug use. PWID were recruited via street outreach in Baltimore, Maryland, between 2018 and 2019 and were enrolled in a study cohort. Participants completed a study survey and underwent HCV testing. Self-reported DAA therapy initiation was evaluated at follow-up visits every six months. Hazardous alcohol use was determined based on an AUDIT-C score of ≥4 for men or ≥3 for women. Data were analyzed using multivariable logistic regression with generalized estimating equations. Of the 720 PWID recruited, 291 had detectable HCV RNA, and only 134 were aware of their HCV infection. The mean (±standard deviation) age of those that were aware of their infection was 48.7 (±10.3) years, with a slight majority (53.0%) being male and predominantly African American (64.9%). The majority (80/134, 59.7%) met criteria for hazardous alcohol use. Only 16 (11.9%) PWID reported DAA therapy initiation within six months, and 20 (14.9%) reported it within 12 months of follow-up. Hazardous alcohol use (aOR = 1.23, 95% CI = 0.43-3.53) was not associated with DAA treatment initiation. There was a high prevalence of hazardous alcohol use, low rates of oral DAA therapy initiation, and no association between self-reported hazardous alcohol use and initiation of oral DAA therapy in our sample of PWID that were aware of their chronic HCV infection. Strategies to increase HCV treatment uptake in PWID with active drug use are urgently needed and should integrate alcohol and drug use evaluation and care.

Effect of direct-acting antivirals on the titers of human pegivirus 1 during treatment of chronic hepatitis C patients.

Human pegivirus 1 coinfections are common in hepatitis C virus (HCV) patients, persisting for years. However, little is known about how pegivirus coinfections are affected by treatment with pangenotypic direct-acting antivirals (DAAs) against HCV. We identified human pegivirus by metagenomic analysis of chronic HCV patients undergoing protease, NS5A, and polymerase inhibitor treatment, in some patients with the addition of pegylated interferon, and followed viral kinetics of both viruses to investigate treatment effects. Only during HCV DAA treatment regimens that included the more broad-spectrum drug sofosbuvir could we detect a consistent decline in pegivirus titers that, however, rebounded to pretreatment levels after treatment cessation. The addition of pegylated interferon gave the highest effect with pegivirus titers decreasing to below the assay detection limit, but without clearance. These results reveal the limited effect of frontline HCV drugs on the closest related human virus, but sofosbuvir appeared to have the potential to be repurposed for other viral diseases.