scholarly journals 928. Major Decrease in Prevalence of Hepatitis C Viremia in Key Populations following the Second Year of Treatment as Prevention for Hepatitis C (TraP HepC) Program in Iceland

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S30-S30 ◽  
Author(s):  
Magnus Gottfredsson ◽  
Thorarinn Tyrfingsson ◽  
Valgerdur Runarsdottir ◽  
Ingunn Hansdottir ◽  
Ottar M Bergmann ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Addiction Treatment ◽  
Antiviral Agents ◽  
Population Level ◽  
Drop Out ◽  
Treatment As Prevention ◽  
Direct Acting Antiviral ◽  
Before And After ◽  
History Of ◽  
The Impact

Abstract Background Hepatitis C Virus (HCV) commonly affects people who inject drugs (PWID) and/or with history of injection drug use (IDU). They are also disproportionately represented in addiction treatment centers and the penitentiary system. In order to curtail spread of HCV it is therefore important to approach these groups. PWID and prisoners have been prioritized in the TraP HepC program. The impact can thus be assessed by monitoring HCV prevalence at sentinel sites, such as addiction hospitals and prisons. Methods TraP HepC offers direct-acting antiviral agents (DAAs) to all HCV patients in Iceland, starting in January 2016. HCV PCR is performed at the end of treatment and 12 weeks later (SVR12). PWID and prisoners are monitored for reinfection and retreated if needed. We compared the prevalence of HCV viremia among PWID admitted for treatment at Vogur addiction hospital and inmates of the penitentiary system, before and after 2 years of TraP HepC. Results Two years into the program 667 patients had been evaluated of which 632 were initiated on their first course of DAAs and 7 were pending, representing 80% of the estimated total patient population. Of those who completed first treatment according to guidelines the SVR12 is 95.5%. Drop-out from first treatment was 8.2%; nevertheless, the SVR12 was >40% and most of the remaining viremic patients completed or are undergoing retreatment. In 2012–2015, prior to TraP HepC the prevalence of HCV viremia among actively injecting PWID admitted for addiction treatment was 47.9%, dropping to 39.8% in 2016 and 16.2% in 2017 (P < 0.001). Likewise, the prevalence of viremia among patients with history of IDU but not recently injecting fell from 27.4% (2012–2015) to 19.8% in 2016 and 4.1% in 2017 (P < 0.001). The prevalence of viremia among inmates of the penitentiary system was 29% prior to initiation of TraP HepC, dropping to 7% in 2017 (P < 0.01). These results are not explained by declining IDU in the community. Conclusion On a population level the domestic transmission of HCV can be reduced by DAAs when combined with other efforts. Two years into the TraP HepC program the prevalence of viremia among two of the most important drivers of the epidemic has been markedly reduced. The program is ongoing, with further emphasis on increased intensity of screening, retreatment and harm reduction. Disclosures All authors: No reported disclosures.

scholarly journals 2895. Threats to Successful Elimination of Viral Hepatitis: Results from the Nationwide Treatment as Prevention for Hepatitis C (TraP HepC) Program in Iceland

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S81-S82
Author(s):  
Magnus Gottfredsson ◽  
Valgerdur Runarsdottir ◽  
Thorvardur J Love ◽  
Ragnheidur H Fridriksdottir ◽  
Bryndis Sigurdardottir ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Drug Use ◽  
Injection Drug Use ◽  
Addiction Treatment ◽  
Antiviral Agents ◽  
Injection Drug ◽  
Treatment As Prevention ◽  
Direct Acting Antiviral ◽  
Unrestricted Access ◽  
History Of

Abstract Background The main driver of the Hepatitis C virus (HCV) epidemic in most western countries is injection drug use (IDU) among people who inject drugs (PWID). Iceland has provided unrestricted access to direct-acting antiviral agents (DAA) to all HCV-infected patients in the country covered by national health insurance, by a program entitled Treatment as Prevention for Hepatitis C (TraP HepC) from 2016 and is on track to become among the first to achieve the WHO goals of eliminating HCV as a public health threat. Methods We analyzed data regarding testing for HCV, incidence of IDU, prevalence of HCV viremia among PWID, drug use in the community and trends in homelessness prior to and during the first 24 months of TraP HepC to monitor outcomes and identify new or persistent challenges. Results Intensity of nationwide testing for HCV increased by 22% in 2016, 60% in 2017, and 81% in 2018 compared with previous years (P < 0.001). During 2016–2018 the incidence of new injection drug use, as surveyed among those admitted for addiction treatment increased by 48%. The total number of PWID admitted annually with HCV viremia however remained relatively stable during the entire period (2010–2018). The prevalence of HCV viremia among people recently injecting drugs admitted for addiction treatment however dropped from 48.7% to 16.2% in 2017, and to 10.2% in 2018 (P < 0.001). Analysis of data regarding stimulant use, as measured by drug levels in wastewater shows an almost threefold increase of amphetamine and an eightfold increase in cocaine levels during 2016–2018 compared with 2015. Concurrently, the number of homeless has doubled. Two years into TraP HepC > 80% of the estimated total HCV-infected population were started on their first course of DAAs. By intention to treat analysis, the cure rate was 92.4% among patients without history of IDU in the past 6 months, compared with 82.9% among active IDU (P = 0.0006); those with history of recent IDU were more likely to discontinue (P < 0.0001). Homelessness carried the highest relative risk (RR) of treatment failure (RR = 2.4, P = 0.008), mostly due to discontinuation. Conclusion Iceland is on track to eliminate HCV, but challenges such as increasing drug use in the community and homelessness need to continuously monitored and addressed; they may jeopardize the success of elimination efforts. Disclosures All Authors: No reported Disclosures.

scholarly journals Virological Factors Associated with Failure to the Latest Generation of Direct Acting Agents (DAA) and Re-Treatment Strategy: A Narrative Review

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 432
Author(s):  
Lorenzo Onorato ◽  
Mariantonietta Pisaturo ◽  
Mario Starace ◽  
Carmine Minichini ◽  
Alessandra Di Fraia ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Clinical Problem ◽  
Narrative Review ◽  
Factors Associated ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

The availability of all oral direct acting antiviral agents (DAAs) has revolutionized the management of HCV infections in recent years, allowing to achieve a sustained virological response (SVR) in more than 95% of cases, irrespective of hepatitis C Virus (HCV) genotype or staging of liver disease. Although rare, the failure to the latest-generation regimens (grazoprevir/elbasvir, sofosbuvir/velpatasvir, pibrentasvir/glecaprevir) represents a serious clinical problem, since the data available in the literature on the virological characteristics and management of these patients are few. The aim of the present narrative review was to provide an overview of the impact of baseline RASs in patients treated with the latest-generation DAAs and to analyze the efficacy of the available retreatment strategies in those who have failed these regimens.

scholarly journals Direct-acting antiviral therapy improves kidney survival in hepatitis C virus–associated cryoglobulinaemia: the RENALCRYOGLOBULINEMIC study

2020 ◽  
Author(s):  
Ana Pérez de José ◽  
Javier Carbayo ◽  
Anna Pocurull ◽  
Teresa Bada-Bosch ◽  
Clara Maria Cases Corona ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Primary Endpoints ◽  
Kidney Involvement ◽  
Before And After ◽  
Mixed Cryoglobulinaemia ◽  
Direct Acting

Abstract Background Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC. Methods The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment. Results Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70–251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04–0.40]; P &lt; 0.001} and improved kidney survival [HR 0.10 ( 95% CI 0.04–0.33); P &lt; 0.001]. Conclusions Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

Changes in serum zinc levels in hepatitis C patients before and after treatment with direct‐acting antiviral agents

2019 ◽  
Vol 49 (11) ◽  
pp. 1353-1356 ◽  
Author(s):  
Toshikuni Suda ◽  
Osamu Okawa ◽  
Ryosaku Shirahashi ◽  
Naohiko Tokutomi ◽  
Masaya Tamano
Keyword(s):  
Hepatitis C ◽  
Antiviral Agents ◽  
Serum Zinc ◽  
Direct Acting Antiviral ◽  
Before And After ◽  
Zinc Levels ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents ◽  
Serum Zinc Levels

Progress and Barriers Towards Elimination of Chronic Hepatitis C in Children

2020 ◽  
Author(s):  
Magdalena Pluta ◽  
Maria Pokorska-Śpiewak ◽  
Małgorzata Aniszewska ◽  
Barbara Kowalik-Mikołajewska ◽  
Magdalena Marczyńska
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Antiviral Agents ◽  
Population Level ◽  
Direct Acting Antiviral ◽  
Current State ◽  
Direct Acting ◽  
Mother To Child ◽  
Direct Acting Antiviral Agents

AbstractChronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.

scholarly journals Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Fabián Aldunate ◽  
Natalia Echeverría ◽  
Daniela Chiodi ◽  
Pablo López ◽  
Adriana Sánchez-Cicerón ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
South American ◽  
Genotype 1 ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Before And After ◽  
Treatment Naïve ◽  
Direct Acting

Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

scholarly journals Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhanyi Li ◽  
Ying Liu ◽  
Ying Zhang ◽  
Xiaoqiong Shao ◽  
Qiumin Luo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Ns5a Region ◽  
Treatment Naïve ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

Background and Objective. The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4). Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

Autoimmune liver serology before and after successful treatment of chronic hepatitis C by direct acting antiviral agents

2019 ◽  
Vol 102 ◽  
pp. 89-95 ◽  
Author(s):  
Benedetta Terziroli Beretta-Piccoli ◽  
Claudia Di Bartolomeo ◽  
Gaia Deleonardi ◽  
Ana Gabriela Grondona ◽  
Tania Silvestri ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Successful Treatment ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Before And After ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Risk factors for remaining liver injury in patients with virological elimination of chronic hepatitis C

2019 ◽  
Vol 57 (02) ◽  
pp. 139-147 ◽  
Author(s):  
Stefan Mauss ◽  
Lukas Buendgens ◽  
Stefan Christensen ◽  
Patrick Ingiliz ◽  
Florian Berger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Cirrhosis ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Hcv Genotype ◽  
Direct Acting Antiviral ◽  
Genotype 2 ◽  
Before And After ◽  
Male Sex ◽  
Normal Alt

Abstract Background and aims Disease activity, but also demographics, lifestyle, and comorbidities, may influence alanine aminotransferase (ALT) levels in hepatitis C virus (HCV)-infected patients. Direct-acting antiviral agents (DAA) achieve virological cure in > 90 % of patients, regardless of HCV genotype and fibrosis stage. This allows assessing determinants for ALT levels before and after elimination of HCV. Methods Our prospective cohort included HCV- and HIV/HCV-infected patients treated with DAA at 9 German centers (GECCO cohort). We analyzed all consecutive patients with sustained virological response (SVR) at week 12 (SVR12) and/or 24. Normal ALT was defined as ≤ 35 U/L, regardless of sex. Results At baseline, 1477 out of 1774 patients (83 %) had ALT > 35 U/L, and 297 (17 %) had ALT ≤ 35 U/L. Baseline ALT > 35 U/L was independently associated with male sex, higher body mass index (BMI), liver cirrhosis, and not being on opioid substitution. After SVR, > 80 % of patients normalized ALT, and even patients with low baseline ALT further reduced ALT levels. However, ALT remained > 35 U/L in 15 % (221/1477) after SVR12. By multivariate analysis, ALT > 35 U/L at SVR12 was associated with male sex, higher BMI, liver cirrhosis, baseline ALT, HCV genotype 2, and younger age. Obesity, cirrhosis, and ALT were also independent factors associated with ALT > 15 U/L at SVR12 in patients with normal ALT at baseline. Conclusions Male sex, advanced liver fibrosis, and obesity are main risk factors for the lack of ALT normalization and/or ALT decline after SVR, indicative of fatty liver disease as a relevant comorbidity in hepatitis C.

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