Antiviral Era Research Articles

Non-acquired immunodeficiency syndrome defining malignancies in people living with haemophilia and human immunodeficiency virus after direct-acting antiviral era.

Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.

S1710 Evolving Patterns of Cirrhosis Etiology in the Era of Direct-Acting Antivirals on in a Predominately African American Population

S1710 Evolving Patterns of Cirrhosis Etiology in the Era of Direct-Acting Antivirals on in a Predominately African American Population

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.

Rationale for Hepatitis C Virus Treatment During Hematopoietic Stem Cell Transplant in the Era of Novel Direct-Acting Antivirals.

Untreated hepatitis C (HCV) infection in patients undergoing hematopoietic stem cell transplantation (HSCT) can lead to worse outcomes. Traditionally, HSCT patients infected with HCV would wait until after immune reconstitution to receive HCV therapy, as the oncologic urgency of transplant would not allow time for a full preceding treatment course of HCV therapy. However, in the era of newer direct-acting antivirals (DAAs), we propose that concomitant treatment of HCV while undergoing HSCT is safe and feasible, while keeping in mind potential drug-drug interactions. A literature review was performed to summarize the available data on the impact of HCV on patients undergoing HSCT. Drug-drug interactions for DAA's and pertinent HSCT drugs were evaluated using Lexicomp online® and http://hep-druginteractions.org . During HSCT, HCV appears to be a conditional risk factor for sinusoidal obstruction syndrome and a potential risk factor for graft versus host disease, both of which are associated with increased mortality. HCV reactivation and exacerbation may impact the use of chemotherapeutics, but available studies haven't shown impact specifically on HSCT. Limited case reports exist but demonstrate safe and effective use DAAs during HSCT. These, along with a drug-drug interaction review demonstrate agents such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are promising DAAs for use in HSCT. HCV infection may worsen outcomes for patients undergoing HSCT. Concomitant treatment of HCV during HSCT using newer DAAs appears feasible and may improve patient morbidity and mortality, however large-scale studies are needed to further support this practice.

Hepatitis C epidemiology and treatment outcomes in Italy: Impact of the DAA era and the COVID-19 pandemic.

HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID-19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct-acting antiviral (DAA) era, and the COVID-19 period, focusing on treatment outcomes (SVR12, non-SVR12 and patients lost to follow-up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal-Wallis test and chi-square analysis, and were conducted adhering to the intention-to-treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow-up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID-19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high-risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies.

Prevalence of HCV infection in Europe in the DAA era: Review.

In 2016, the Global Health Sector Strategy, ratified by the 69th World Health Assembly, set the ambitious goal of eliminating hepatitis C virus (HCV) and hepatitis B virus infections by 2030, emphasizing the importance of national screening programmes. Achieving this goal depends on each country's ability to identify and treat 80% of chronic hepatitis C cases, a critical threshold set by the World Health Organization. Traditionally, estimates of HCV prevalence have been based on interferon era studies that focused on high-risk subgroups rather than the general population. In addition, the incomplete data available from national registries also limited the understanding of HCV prevalence. The 2016 report from the European Centre for Disease Prevention and Control highlighted that HCV rates varied across European counties, ranging from .1% to 5.9%. However, data were only available for 13 countries, making the overall picture less clear. Additionally, the epidemiological data may have underestimated the true burden of HCV due to lack of awareness among those with chronic infection. The main objective of this review is to provide a comprehensive summary of HCV epidemiology in Europe in the current era of direct-acting antivirals (DAAs). The data included in the analysis range from the end of 2013 to December 2023 and have been categorised according to the United Nations Geoscheme. The resulting synthesis underscores the noteworthy impact of DAA treatment on the epidemiological situation.

Tongue Hyperpigmentation with Peginterferon α-2b Therapy in Hepatitis B: Case Series With Review of Literature

Peginterferon α-2b (Peg IFNα-2b) continues to be used for treating a selected subset of patients with hepatitis B, in the era of direct-acting antivirals for hepatitis C infection. The authors hereby report four cases of tongue pigmentation among 21 patients with hepatitis B, whom they treated in the last 5 years, where at least 48 weeks of Peg IFN were administered. The lesions were mostly self-limiting, having no temporal relation with response to treatment. To the best of the authors’ knowledge, this is the first case series of Peg IFN-induced lingual hyperpigmentation in patients with hepatitis B, which clinicians should be aware of.

Changes in hepatitis C virus prevalence and incidence among people who inject drugs in the direct acting antiviral era

BackgroundThe World Health Organization (WHO) has set a goal to eliminate hepatitis C virus (HCV) infection by 2030, including a 90% reduction of HCV incidence. With the introduction of a needle syringe program (NSP) in Stockholm, Sweden, and unrestricted availability of direct acting antiviral (DAA) treatment, we investigate the change of prevalence and incidence of HCV infection among people who inject drugs (PWID) over time. MethodsAll persons attending the Stockholm NSP 2013-2021 (n=4,138) were included. The prevalence of viremic HCV infection was investigated yearly. For incidence analysis, PWID at risk with at least one follow-up test were included. Participants were divided into naive defined as anti-HCV negative (n=791), and exposed, defined as anti-HCV positive with a negative HCV RNA (n=1,030). Risk factors for HCV infection were analyzed using parametric exponential proportional hazards regression models. ResultsThe prevalence of viremic HCV infection decreased from 62% to 30% year 2013-2021 while the prevalence of cured after treatment increased from 0 to 22%, corresponding to 42% cured after treatment out of eligible in 2021. The overall incidence rate in naive was 16.9 (95% CI 15.0-19.0) and in exposed 12.8 (95% CI 11.6-14.2) per 100 person years (PY) and was not significantly reduced years 2013-2015 to 2020-2021 in either group. Risk factors for incident HCV infection in multivariable analysis were sharing needles/syringes, younger age, custody/prison past year, and homelessness, whereas opioid agonist treatment was protective. ConclusionThe prevalence of HCV was halved in PWID as unrestricted DAA treatment became available and NSP was established in Stockholm. However, overall incidence was not reduced. To meet the WHO incidence goal, targeting PWID with high injection risk behaviors for testing and treatment is essential, along with engagement in harm reduction services.

Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication.

Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

Risk of HBV reactivation in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors in the antiviral era

BackgroundAlthough routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade‐based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals.MethodsWe included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr.ResultsHBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010–21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246–10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946–148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581–0.831, P = 0.006).ConclusionHBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.

Ongoing Gaps in the Hepatitis C Care Cascade during the Direct-Acting Antiviral Era in a Large Retrospective Cohort in Canada: A Population-Based Study.

To achieve hepatitis C virus (HCV) elimination, high uptake along the care cascade steps for all will be necessary. We mapped engagement with the care cascade overall and among priority groups in the post-direct-acting antivirals (DAAs) period and assessed if this changed relative to pre-DAAs. We created a population-based cohort of all reported HCV diagnoses in Quebec (1990-2018) and constructed the care cascade [antibody diagnosed, RNA tested, RNA positive, genotyped, treated, sustained virologic response (SVR)] in 2013 and 2018. Characteristics associated with RNA testing and treatment initiation were investigated using marginal logistic models via generalized estimating equations. Of the 31,439 individuals HCV-diagnosed in Quebec since 1990 and alive as of 2018, there was significant progress in engagement with the care cascade post- vs. pre-DAAs; 86% vs. 77% were RNA-tested, and 64% vs. 40% initiated treatment. As of 2018, a higher risk of not being RNA-tested or treated was observed among individuals born <1945 vs. >1965 [hazard ratio (HR); 95% CI; 1.35 (1.16-1.57)], those with material and social deprivation [1.21 (1.06-1.38)], and those with alcohol use disorder [1.21 (1.08-1.360]. Overall, non-immigrants had lower rates of RNA testing [0.76 (0.67-0.85)] and treatment initiation [0.63 (0.57-0.70)] than immigrants. As of 2018, PWID had a lower risk of not being RNA tested [0.67 (0.61-0.85)] but a similar risk of not being treated, compared to non-PWID. Engagement in the HCV care cascade have improved in the post-DAA era, but inequities remain. Vulnerable subgroups, including certain older immigrants, were less likely to have received RNA testing or treatment as of 2018 and would benefit from focused interventions to strengthen these steps.

Extrahepatic Malignancies Are the Leading Cause of Death in Patients with Chronic Hepatitis B without Cirrhosis: A Large Population-Based Cohort Study.

(1) Background: Accurate statistics on the causes of death in patients with chronic hepatitis B (CHB) are lacking. We investigated mortality rates and causes of death over time. (2) Methods: Data on patients newly diagnosed with CHB from 2007 to 2010 (cohort 1, n = 223,424) and 2012 to 2015 (cohort 2, n = 177,966) were retrieved from the Korean National Health Insurance Service. Mortality data were obtained from Statistics Korea. The causes of death were classified as liver-related (hepatic decompensation or hepatocellular carcinoma [HCC]) or extrahepatic (cardiovascular-related, cerebrovascular-related, or extrahepatic malignancy-related). (3) Results: Over a 10-year follow-up period of 223,424 patients (cohort 1) with CHB, the overall mortality was 1.54 per 100 person-years. The mortality associated with HCC was the highest (0.65 per 100 person-years), followed by mortality related to extrahepatic malignancies (0.26 per 100 person-years), and cardio/cerebrovascular diseases (0.18 per 100 person-years). In the non-cirrhotic CHB (87.4%), 70% (11,198/15,996) of patients died due to non-liver-related causes over ten years. The 10-year overall mortality was 0.86 per 100 person-years. Among these, mortality due to extrahepatic malignancies had the highest rate (0.23 per 100 person-years), followed by mortality related to HCC (0.20 per 100 person-years), and cardio/cerebrovascular diseases (0.16 per 100 person-years). The 5-year mortality associated with extrahepatic malignancies increased from 0.36 per 100 person-years (cohort 1) to 0.40 per 100 person-years (cohort 2). (4) Conclusions: Mortality related to HCC decreased, whereas mortality related to extrahepatic malignancies increased in the antiviral era. Extrahepatic malignancies were the leading cause of death among patients with CHB without cirrhosis.

Success of the US Veterans Health Administration's Hepatitis C Virus Care Continuum in the Direct-acting Antiviral Era.

Estimated hepatitis C prevalence within the Veterans Health Administration is higher than the general population and is a risk factor for advanced liver disease and subsequent complications. We describe the hepatitis C care continuum within the Veterans Health Administration 1 January 2014 to 31 December 2022. We included individuals in Veterans Health Administration care 2021-2022 who were eligible for direct-acting antiviral treatment 1 January 2014 to 31 December 2022. We evaluated the proportion of Veterans who progressed through each step of the hepatitis C care continuum, and identified factors associated with initiating direct-acting antivirals, achieving sustained virologic response, and repeat hepatitis C viremia. We identified 133 732 Veterans with hepatitis C viremia. Hepatitis C treatment was initiated in 107 134 (80.1%), with sustained virologic response achieved in 98 136 (91.6%). In those who achieved sustained virologic response, 1097 (1.1%) had repeat viremia and 579 (52.8%) were retreated for hepatitis C. Veterans of younger ages were less likely to initiate treatment and achieve sustained virologic response, and more likely to have repeat viremia. Stimulant use and unstable housing were negatively associated with each step of the hepatitis C care continuum. The Veterans Health Administration has treated 80% of Veterans with hepatitis C in care 2021-2022 and achieved sustained virologic response in more than 90% of those treated. Repeat viremia is rare and is associated with younger age, unstable housing, opioid use, and stimulant use. Ongoing efforts are needed to reach younger Veterans, and Veterans with unstable housing or substance use disorders.

2938. Hepatitis C Virus Care Continuum in the Direct-acting Antiviral Era within the US Veterans Health Administration

Abstract Background Estimated hepatitis C prevalence within the Veterans Health Administration is higher than the general population and is a risk factor for advanced liver disease and its associated complications. We describe the hepatitis C care continuum within the Veterans Health Administration between January 1, 2014 and December 31, 2022. Methods Individuals in Veterans Health Administration care 2021-2022 who were eligible for direct-acting antiviral treatment between January 1, 2014 and December 31, 2022 comprised our cohort. We evaluated the proportion of Veterans who progressed through each step of the hepatitis C care continuum, and identified factors associated with initiating direct-acting antivirals, achieving sustained virologic response, and repeat hepatitis C viremia after achieving sustained virologic response. Results We identified 133,732 Veterans with hepatitis C viremia during our study timeframe. Hepatitis C treatment was initiated in 107,134 (80.1%), with sustained virologic response achieved in 98,136 (91.6%). In those who achieved sustained virologic response, 1,097 (1.1%) had subsequent repeat viremia and 579 (52.8%) were retreated for hepatitis C. Veterans of younger ages were less likely to initiate treatment and achieve sustained virologic response, and more likely to have repeat viremia. Stimulant use and unstable housing were negatively associated with each step of the hepatitis C care continuum.Table 1:Characteristics of Veterans with HCV ViremiaTable 2:Factors Associated with DAA Treatment Initiation in those with HCV ViremiaFigure 1:Overview of the VHA Hepatitis C Care Continuum as of December 31, 2022 Conclusion The Veterans Health Administration has treated 80% of Veterans with hepatitis C with direct-acting antiviral therapy since its approval in 2014 and achieved sustained virologic response in more than 90% of those treated. Repeat viremia is rare and is associated with younger age, unstable housing, opioid use, and stimulant use. Ongoing efforts are needed to reach younger Veterans, and Veterans with unstable housing or substance use disorders. Disclosures All Authors: No reported disclosures

2496. Hepatitis C Virus Among Inpatients in the Direct-acting Antiviral Era: Prevalence, Linkage to Care, Treatment Disparities, and Comorbidity Burden

Abstract Background The advent of direct-acting antivirals (DAAs) calls for optimized hepatitis C virus (HCV) screening, linkage to care (LTC), access to cure, and mitigation of disease burden among health systems. We assessed HCV burden and care gaps among inpatients in a large volume, tertiary care setting during the DAA era. Methods This is a retrospective cohort analysis of inpatients admitted at least once to medicine services from 2014 to 2021. We used analytic software to query electronic health records. We assessed demographics, comorbidities, HCV diagnosis, LTC, and treatment occurring at any point during the study period. Odds ratios (OR) were utilized to assess differences in key comparator groups. Results Over the sampling period, 79793 unique patients were evaluated. The care cascade flowchart is displayed in Figure 1. Overall, 44136 were screened for HCV (55%). Of those screened, 3475 (8%) had a positive viral load. Viremic patients were more likely males (OR 2.04; CI 1.89-1.92), patients with mental health disorders (OR 1.29; CI 1.02-1.38), or opioid use disorder (OR 7.3; CI 5.81-9.21). These same groups were also more likely to be screened. Among viremic patients 1641 (47%) attended treatment clinics. Those with mental health disorders (OR 1.28; CI 1.12-1.46) and alcohol use disorder (OR 3.02; CI 2.5-3.65) were more likely to attend clinics. Those less likely to establish care were Millennials (OR 0.22; CI 0.18-0.27), Generation-X (OR 0.44; CI 0.37-0.52), and patients with opioid use disorder (OR 0.60; CI 0.41-0.87). A total of 950 (58%) patients were prescribed DAAs. Millennials (OR 0.44; CI 0.32-0.61), Generation-X (OR 0.61; CI 0.48-0.78), and those from rural areas (OR 0.62; CI 0.41-0.94) were less likely begin DAA. Those with HIV co-infection (OR 1.83; CI 1.23-2.74) and cirrhosis (OR 1.63; 1.27-2.09) were more likely to start DAA. Flow chart examining HCV care cascade of inpatients admitted to at least once to medicine services at the University of Alabama at Birmingham hospital from January 1 2014 to December 31 2021. T flow chart depicts number of inpatients who underwent HCV screening, confirmation of viremia, clinic attendance, and treatment initiation at any point during the study period.Table 1:Baseline characteristics of inpatients admitted to medicine services from 2014 to 2021 and status of testing for Hepatitis C virus infection. Mean age is 62 with standard deviation of 17.8 years. *Diagnosis based on ICD-10 diagnosis codes in electronic medical records. Conclusion In this large longitudinal analysis of inpatients cared for at a tertiary safety net hospital, a high proportion of individuals underwent HCV screening, and infection was highly prevalent. Care disparities remain and further optimization of HCV screening, LTC, and treatment will need to target younger populations, those with opioid use disorder, and living in rural areas. Disclosures Ricardo A. Franco, MD, Abbvie: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Grant/Research Support|Theratechnologies: Advisor/Consultant

Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug-drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era

BackgroundTransplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre–direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test–positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. Methods and ResultsWe performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT– donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT– cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT– hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. ConclusionsThese findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Countering 'the moral science of biopolitics': Understanding hepatitis C treatment 'non-compliance' in the antiviral era.

Although new hepatitis C treatments are a vast improvement on older, interferon-based regimens, there are those who have not taken up treatment, as well as those who have begun but not completed treatment. In this article, we analyse 50 interviews conducted for an Australian research project on treatment uptake. We draw on Berlant's (2007, Critical Inquiry, 33) work on 'slow death' to analyse so-called 'non-compliant' cases, that is, those who begin but do not complete treatment or who do not take antiviral treatment as directed. Approached from a biomedical perspective, such activity does not align with the neoliberal values of progress, self-improvement and rational accumulation that pervade health discourses. However, we argue that it is more illuminating to understand them as cases in which sovereignty and agency are neither simplistically individualised nor denied, and where 'modes of incoherence, distractedness, and habituation' are understood to co-exist alongside 'deliberate and deliberative activity […] in the reproduction of predictable life' (Berlant, 2007, p. 754). The analysed accounts highlight multiple direct and indirect forces of attrition and powerfully demonstrate the socially produced character of agency, a capacity that takes shape through the constraining and exhausting dynamics of life in conditions of significant disadvantage.

Incidence of Hepatocellular Carcinoma in Hepatitis C Patients Treated with Direct-Acting Antivirals and Its Relation to Hepatic Fibrosis Stage

Abstract Introduction Significant advances in understanding of the molecular virology, life cycle, and pathogenesis of Hepatitis C Virus (HCV) led to the Direct-Acting Anti-viral (DAA) era of HCV therapy in 2011 (Hezode et al.,2015). It can be expected that rates of HCV-associated hepatocellular carcinoma (HCC) will decrease significantly after the widespread adoption of DAAs, However Hepatitis C patients with cirrhosis who were treated with direct-acting antivirals had increased likelihood of developing HCC (Tayyab et al., 2020) (Kozbial et al., 2016). HCC was also associated with greater liver stiffness according to transient elastography and lower platelet counts (Conti et al., 2016). The aim of this study is to investigate incidence of HCC in Egyptian HCV patients in whom other predominant HCV genotypes are prevalent and different treatment protocols followed. Methods This was a retrospective study including 400 chronic HCV patients who were following up their medical condition at Kobri El-Koba Military Hospital hepatology outpatient clinic from January 2018 to September 2019. Patients were divided into two main equal groups regarding either received HCV direct acting antivirals or not. Incidence of HCC after 18 months of follow up were compared between two groups. Its relation to hepatic fibrosis stage was calculated in both groups. Results DAA receiving group had significantly lower incidence of HCC than non DAA receiving group (control group). Eleven patients in DAA receiving group developed HCC (5.5%) compared to twenty-two patients in control group (11%) with P- value 0.04. Although there was no significant difference between two groups regarding pre-treatment prevalence of ascites, splenomegaly, or esophageal varices, DAA receiving group had statistically significant advanced hepatic fibrosis when compared to control group. Before starting treatment, DAA Receiving group shows (4.5% F0, 14% F1, 7% F2, 11.5% F3 and 63% F4) versus (20.5% F0, 14% F1, 18.5% F2, 6.5% F3 and 40.5% F4) in control group with highly significant P value 0.00. Conclusion Incidence of HCC decreased significantly after DAA in chronic HCV patients. Decreased incidence occurred despite advanced hepatic fibrosis in this group of patients.

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study

ObjectivesTo quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population.DesignPopulation based...