Availability Of Direct-acting Antiviral Therapy Research Articles

Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus before and after Availability of Direct-Acting Antiviral Therapy

Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods: Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009–2013 (pre-DAA) and 2016–2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ2 and Fisher’s exact tests. Results: The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, p = 0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) versus pre-DAA (1.3%) (p < 0.0001). Post-DAA there were less MPGN (2% vs. 10%, p = 0.02) and more advanced DGS (85% vs. 61%, p = 0.0002), non-collapsing FSGS (57% vs. 31%, p < 0.0001), IFTA (2.0 vs. 1.6, p = 0.0002), and vascular sclerosis (2.1 vs. 1.6, p < 0.0001). Conclusion: Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.

Management of HCV Positive Patients on Maintenance Dialysis

The prevalence of hepatitis C virus (HCV) is quite high in Pakistan, especially among patients on maintenance hemodialysis (MHD). HCV infection is associated with increased morbidity and mortality among patients on maintenance hemodialysis. The current availability of direct-acting antiviral therapy has changed the picture of HCV prevalence in many countries. Objective: The aim of our study is to assess the prevalence and treatment of HCV infection among patients on maintenance hemodialysis in our setting. Methods: This descriptive cross-sectional study was held in the Medicine department of Mayo Hospital, Lahore for six-months duration from 13th January 2022 to 12th July 2022. The study was conducted on 130 patients to assess HCV seroprevalence among patients on MHD. Data on HCV status, PCR positivity and number of patients receiving active treatment were evaluated. Results: A total of 130 patients on maintenance hemodialysis were included in this study. The incidence of HCV infection was 49 (37.7%). All patients underwent PCR and 32 patients were PCR positive. All except 5 of the 32 PCR positive patients started HCV antiviral treatment. Conclusions: In conclusion, our study helps highlight the high prevalence of HCV among maintenance hemodialysis patients and the need to maintain adequate infection control measures. However, it is encouraging to know that most patients have been treated, and future research will highlight the importance of prompt treatment for MHD patients. It is recommended that all of HCV PCR positive patients were being treated with DAA. Keywords: HCV, Hemodialysis, Antivirals, Seroconversion, Health insurance, Infection.

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

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

Qualitative analysis of the barriers and facilitators influencing uptake of direct-acting antiviral therapy for hepatitis C in a primary healthcare environment.

Historical interferon and ribavirin therapies for hepatitis C virus have been replaced by modern treatments with improved efficacy and tolerability. Despite the availability of direct-acting antiviral therapy, evidence demonstrates poor uptake in Australia. Presently, the barriers and facilitators influencing uptake of direct-acting antiviral therapy are not fully understood, especially in a primary healthcare environment. Our study aimed to discover methods of improving uptake of treatment in the community. We conducted 15 semi-structured, face-to-face interviews in a metropolitan, primary healthcare clinic in Australia. Interviews were recorded, transcribed and subsequently analysed using thematic content analysis. We identified patient-related and healthcare system-related barriers and facilitators to commencing treatment. This included established themes from current literature, and novel themes unique to direct-acting antiviral therapy and primary care. Overall, our study reinforces the importance of public health campaigns to promote community awareness and emphasises the concomitant role of mental health in fostering treatment uptake. Informed by our findings, we suggest further research on an integrated model of care, focused on the domains of disease awareness, patient engagement and treatment adherence. Hence, a community-oriented approach, driven by primary healthcare, ultimately underpins a successful public strategy to improve outcomes for patients affected by hepatitis C.

Estimating the Consensus hepatitis C Cascade of Care among people who inject drugs in Australia: Pre and post availability of direct acting antiviral therapy

Background Monitoring the hepatitis C virus (HCV) cascade of care (CoC) among people who inject drugs (PWID) is an essential component of the response to World Health Organisation's (WHO) hepatitis elimination goals. This study aimed to estimate the Consensus hepatitis C CoC among PWID using data collected in Australia prior to and after the introduction of unrestricted direct-acting antiviral (DAA) therapy in March 2016.Methods The Australian Needle Syringe Program Survey is a cross-sectional bio-behavioural surveillance system that recruits >2000 PWID annually. Using data from 2015 and 2019, HCV antibody and ribonucleic acid (RNA) test results from dried blood spots were combined with self-reported data on HCV diagnostic testing and treatment to project HCV Consensus CoC indicators at a population-level among Australian PWID.Results Among an estimated 75,000 people who inject drugs on a regular basis in Australia, the number with active HCV infection declined from 32,619 (44%) in October 2015 to 12,679 (17%) in October 2019. The majority (78% in 2015 and 2019) of PWID reported HCV diagnosis, while the proportion of those diagnosed who were treated increased from 3% in 2015 to 47% in 2019. Among those treated, the proportion who were HCV RNA negative and assumed to have been successfully treated (cured), increased from 27% in 2015 to 88% in 2019.Conclusion This study demonstrates remarkable HCV CoC progress among PWID in Australia following availability of DAA therapy. There was a substantial increase in the proportion of HCV diagnosed PWID who initiated treatment and were cured, while the number of PWID with active HCV infection more than halved over a 3.5 year period. Estimates of the Consensus hepatitis C CoC among PWID is required to monitor progress toward WHO HCV elimination goals.

Regional Variation in Utilization of Hepatitis C-Positive Organs for Heart Transplantation in the United States

Purpose With increasing organs available in light of the national opioid epidemic and the availability of direct acting-antiviral (DAA) therapy for Hepatitis C virus (HCV), HCV antibody (Ab)+ organs serve as an important potential supply to the donor pool. We sought to examine trends over time in the utilization of HCV Ab+ organs both nationally and regionally. Methods We queried the United Network for Organ Sharing registry data in the DAA era between January 2012 and March 2018 for adults ≥18 years who had undergone heart transplantation with a HCV Ab+ donor as well as donor recovery data. Results The incidence of HCV Ab+ deceased donors have increased from 4.6% in 2012 to 8.7 in 2018 (p Conclusion Over the last two years, with the availability of DAA therapy, there has been increased nationwide recovery and utilization of HCV Ab+ donor hearts that is accompanied by significant regional variability. Adopting standardized protocols across UNOS regions and transplant centers may increase utilization of these donors more effectively and potentially lead to better outcomes.

Moving Towards HCV Elimination Among People Living with HIV in Australia: Analysis of the CEASE Prospective Cohort Study

Background: HCV elimination among people living with HIV may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy (from March 2016). Our aim was to evaluate HCV treatment uptake, outcome, and HCV RNA prevalence among HIV/HCV co-infected adults in Australia following the availability of DAA therapy. Methods: The Control and Elimination of HCV from HIV-infected individuals within Australia (CEASE) prospective cohort study enrolled adults with HIV and current (HCV RNA positive) or past (anti-HCV antibody positive, HCV RNA negative) HCV infection from 14 primary and tertiary clinics. Cumulative and annual HCV treatment uptake, outcome, and HCV RNA prevalence was evaluated, with follow up through May 2018 (median follow-up: 2.63 years, IQR 1.96, 3.20). Factors associated with DAA uptake were analysed using Cox regression. Findings: Between July 2014 and March 2017, 402 HIV/HCV antibody-positive participants were enrolled (95% male [80% gay and bisexual men], 13% cirrhosis, 79% history of injecting drug use [39% current injecting]). Cumulative HCV treatment uptake among those ever eligible was 91% (336/371). Annual HCV treatment uptake increased from 7% and 11% per year in 2014 and 2015, to 80% and 35% per year in 2016 and 2017, respectively. HCV viraemic prevalence declined from 82% in 2014 to 8% in 2018. Interpretation: High uptake and effectiveness of unrestricted government-subsidised DAA therapy has permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden among people living with HIV in Australia, suggesting that elimination within this population is feasible. Clinical Trial Number: The study was registered with ClinicalTrials.gov (NCT02102451). Funding Statement: The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Research reported in this publication was supported by Gilead Sciences Inc as an investigator-initiated study. The content is solely the responsibility of the authors. Declaration of Interests: None of the authors had commercial relationships that might pose a conflict of interest in connection with this manuscript. Ethics Approval Statement: All study participants provided written informed consent before study procedures. The study protocol was approved by St Vincent’s Hospital, Sydney Human Research Ethics Committee (primary study committee) and was conducted according to the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice (ICH/GCP) guidelines and local regulatory requirements.