831. Hepatitis C Virus Micro-elimination Within a Human Immunodeficiency Virus Clinic: Challenges in the Home Stretch

Abstract Background Hepatitis c virus (HCV) eradication among persons with HIV (PWH) is alluring since DAAs efficacy is high regardless of HIV status and PWH in care are usually screened for HCV. Despite the potential, barriers to care have prevented many from achieving sustained virologic response (SVR). We performed a pharmacist-led campaign to reduce the proportion of PWH with active HCV and describe the barriers to care. Methods This retrospective review evaluated patients receiving care at a Ryan White-funded clinic from 07/2018 to 12/2020. Patients were eligible if HCV diagnosed ≥1 year and receiving HIV care. The primary endpoint was to compare the prevalence HCV before and after a pharmacy initiative to target the remaining patients at the clinic not treated during first 3 ½ year period of oral DAA therapy availability. Secondary analysis was to identify barriers to care, measure the proportion of patients in each step of the HCV care cascade, and determine predictors of SVR. Among barriers to care, inconsistent engagement was defined as patients with habitual missed appointments. Logistic regression and Chi-square tests were performed. Results 46 of 1,100 PWH had active HCV for ≥1 year. Median age, years since HIV and HCV diagnoses were 58.5 years of age, 17 years, and 11.5 years, respectively. Most patients were male (70%), Black (61%), Latinx (28%), HCV genotype 1 (90%), had an HIV RNA < 200 copies/mL (72%), & had Medicaid (87%). 32/46 patients agreed to therapy, with all getting insurance approval and DAAs delivered. Glecaprevir/pibrentasvir (73%) was the preferred by payors, followed by sofosbuvir/velpatasvir (15%). Eight remained with active HCV and 19 achieved SVR. The prevalence rate dropped from 4.2% to 0.7% (P < 0.0001). Active drug use, inconsistent engagement, mental health disorder and nonadherence were initial barriers to care. After multivariate analysis, patients with inconsistent engagement continued to be less likely achieve SVR compared to those we remained consistently in care (aOR: 0.062, 95 CI: 0.009-0.421). HCV care cascade in PWH within a Ryan White-funded clinic Active HCV includes 46 patients with chronic HCV infection receiving HIV in care at clinic, DAA approval process describes patients agreeing to HCV treatment along a continuum of pending laboratory results or pending prior authorization requests, DAA procurement depicts patients that have received approval and delivery of medications, DAA initiation describes patients who started treatment (27 patients), and SVR documented defines patients with an undetectable HCV RNA 12 weeks after therapy (19 patients). Conclusion Pharmacists can impact the burden of HCV among PWH receiving care. The HCV care cascade remains tied to the HIV continuum of care, with disengagement from care remaining an important rate-limiting step impeding micro-elimination. Disclosures All Authors: No reported disclosures

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Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir Regimen in Haemodialysis Patients With Hepatitis C Virus Infection

Infektološki glasnik ◽

10.37797/ig.39.1.4 ◽

2020 ◽

Vol 39 (1) ◽

pp. 23-27

Author(s):

Antonija Verhaz ◽

Tatjana Roganović ◽

Ljiljana Pašić ◽

Olja Čuković ◽

Tanja Macanović-Kostić

Keyword(s):

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Concomitant Medication ◽

Demographic Data ◽

Virologic Response ◽

Hcv Infection ◽

Hcv Rna ◽

Stage Renal Disease

Background: Hepatitis C virus (HCV) infection is common among patients on haemodialysis (HD) therapy and is an important cause of morbidity and mortality. In patients with chronic kidney disease (CKD), the risks for negative outcomes are significantly higher in HCV-infected patients than in those without HCV infection, including progression to cirrhosis, hepatocellular carcinoma and liver-related mortality. Ombitasvir (OBV), paritaprevir (PTV), ritonavir (r), and dasabuvir (DSV) are all hepatically metabolized and, therefore, require no dose adjustment in patients with any degree of renal impairment. Aims: We studied the safety and efficacy of OBV/PTV/r + DSV in a small group of HCV infected patients on haemodialysis therapy. Methods: Treatment course with ombitasvir/paritaprevir/ritonavir and dasabuvir; (3-DAA regimen of OBV/PTV/r+DSV±RBV) was analysed. Pre-treatment evaluation of HCV infection included HCV RNA, genotype, and liver fibrosis assed by transient fibroelastography (FibroScan). The stage 5 CKD was defined as an eGFR of <15 mL/min/1.73 m2, respectively; those on haemodialysis were considered to have stage 5 CKD or end-stage renal disease (ESRD). Demographic data and concomitant medication were retrieved from patients’ records. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Among 7 treated patients, 6 were male and 1 female, all were infected with genotype 1 (5 GT1b, 2 GT1a). Patient had compensated liver cirrhosis and six patients did not have liver cirrhosis, none were liver transplant recipients. All of seven patients completed 12 weeks of treatment and achieved SVR12. Concomitant medication had to be modified with the treatment initiation in 5 out of 7 patients. One of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, diarrhoea. Adverse events were primarily mild, and no patient discontinued treatment due to an AE. Conclusions: Treatment with OBV/PTV/r +DSV ± RBV was well-tolerated and resulted in high rates of SVR12 (100%) for patients with HCV GT1b/1a on haemodialysis.

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Clinical Implications of Detectable Baseline Hepatitis C Virus-Genotype 1 NS3/4A-Protease Variants on the Efficacy of Boceprevir Combined With Peginterferon/Ribavirin

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu078 ◽

2014 ◽

Vol 1 (2) ◽

Cited By ~ 10

Author(s):

John A. Howe ◽

Jianmin Long ◽

Stuart Black ◽

Robert Chase ◽

Patricia McMonagle ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virologic Response ◽

Virologic Failure ◽

Virologic Response ◽

Phase Iii ◽

Hcv Rna ◽

Genotype 1 ◽

Virus Genotype ◽

The Impact

Abstract Background. We analyzed the impact of pretreatment variants conferring boceprevir-resistance on sustained virologic response (SVR) rates achieved with boceprevir plus peginterferon-α/ribavirin (P/R) for hepatitis C virus (HCV)-genotype-1 infection. Methods. NS3-protease-polymorphisms emerging coincident with virologic failure on boceprevir/P/R regimens were identified as resistance-associated variants (RAVs). Baseline samples pooled from 6 phase II or phase III clinical trials were analyzed for RAVs by population sequencing. Interferon (IFN)-responsiveness was predefined as >1 log reduction in HCV-RNA level during the initial 4-week lead-in treatment with P/R before boceprevir was added. The effective boceprevir-concentration inhibiting RAV growth by 50% (EC50) was determined using a replicon assay relative to the wild-type referent. Results. Sequencing was performed in 2241 of 2353 patients (95.2%) treated with boceprevir. At baseline, RAVs were detected in 178 patients (7.9%), including 153 of 1498 genotype-1a infections (10.2%) and 25 of 742 genotype-1b infections (3.4%) (relative risk, 3.03; 95% confidence interval [CI], [2.01, 4.58]). For IFN-responders, SVR24 (SVR assessed 24 weeks after discontinuation of all study medications) rates were 78% and 76% with or without RAVs detected at baseline, respectively. For the 510 poor IFN-responders, SVR24 rates were 8 of 36 subjects (22.2% [11.7%, 38.1%]) when baseline RAVs were detected vs 174 of 474 subjects (36.7% [32.5%, 41.1%]) when baseline RAVs were not detected (relative likelihood of SVR24 [95% CI], 0.61 [0.32, 1.05]). Sustained virologic response was achieved in 7 of 8 (87.5%) IFN-nonresponders with baseline variants exhibiting ≤2-fold increased EC50 for boceprevir in a replicon assay, whereas only 1 of 15 (7%) IFN-nonresponders with baseline RAVs associated with ≥3-fold increased EC50 achieved SVR. Conclusions. Baseline protease-variants appear to negatively impact SVR rates for boceprevir/P/R regimens only when associated with decreased boceprevir susceptibility in vitro after a poor IFN-response during the lead-in period.

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An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTime HCV RNA Assay

Journal of Clinical Microbiology ◽

10.1128/jcm.03030-14 ◽

2015 ◽

Vol 53 (4) ◽

pp. 1264-1269 ◽

Cited By ~ 12

Author(s):

Christoph Sarrazin ◽

Inge Dierynck ◽

Gavin Cloherty ◽

Anne Ghys ◽

Katrien Janssen ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virologic Response ◽

Pegylated Interferon ◽

Virologic Response ◽

Similar Proportion ◽

Hcv Rna ◽

Pure System ◽

Treatment Naïve ◽

Total Therapy

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.)

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Scaling up the in-hospital hepatitis C virus care cascade in Taiwan

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0150 ◽

2021 ◽

Vol 27 (1) ◽

pp. 136-143

Author(s):

Chung-Feng Huang ◽

Pey-Fang Wu ◽

Ming-Lun Yeh ◽

Ching-I Huang ◽

Po-Cheng Liang ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Rna ◽

Treatment Rate ◽

Hcv Treatment ◽

Testing Rate ◽

Treatment Uptake ◽

Care Cascade ◽

Reflex Testing ◽

Set Up

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without.Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation.Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001).Conclusions: The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.

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Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents

QJM ◽

10.1093/qjmed/hcab100.038 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Tarek Mohamed Yousef ◽

Maha Mohsen Mohamed Kamal El Din ◽

Tari Magdy Aziz George ◽

Amr Adel Elzohary Mohamed

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Agents ◽

Virologic Response ◽

Hcv Rna ◽

Occult Hepatitis ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Occult Hepatitis C ◽

Direct Acting Antiviral Agents

Abstract Background Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. Objectives The aim of the study to detect the prevalence of occult hepatitis C Virus infection in patients who achieved a sustained virologic response (SVR) to direct-acting antiviral agents and to outline predictors of OCI. Patients and Methods This study included 100 patients with chronic HCV infection without liver cirrhosis attending to hepatitis C clinics at Ain Shams University Hospital, Ahmed Maher Teaching hospital and Elgomhorya Teaching Hospital.who received sofosbuvir (400mg) plus daclatasvir (60mg) daily for 12 weeks with or without ribavirin according to National committee to combat viral hepatitis (NCCVH) protocol. Results We tested peripheral blood for HCV RNA in PBMCs to detect OCI. Occult HCV was found positive in 12% of the studied cases. Occult HCV was positive more in male cases. Positive cases had significantly lower age, and higher total bilirubin, direct bilirubin, AST and ALT levels. Age had significant moderate diagnostic performance in predicting occult HCV, while direct bilirubin has significant low diagnostic performance in predicting occult HCV. Conclusion OCI following direct antiviral therapy may be present in some cases, and this may require further testing of patients with SVR particularly in younger male patients with persistantly high liver enzymes.

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SILEN-C3, a Phase 2 Randomized Trial with Faldaprevir plus Pegylated Interferon α-2a and Ribavirin in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02497-13 ◽

2014 ◽

Vol 58 (6) ◽

pp. 3429-3436 ◽

Cited By ~ 12

Author(s):

Douglas Dieterich ◽

Tarik Asselah ◽

Dominique Guyader ◽

Thomas Berg ◽

Marcus Schuchmann ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Pegylated Interferon ◽

Virologic Response ◽

Interferon Α ◽

Hcv Rna ◽

Genotype 1 ◽

Once Daily ◽

Treatment Naïve

ABSTRACTFaldaprevir is an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor which, when administered for 24 weeks in combination with pegylated interferon α-2a and ribavirin (PegIFN/RBV) in treatment-naive patients in a prior study (SILEN-C1; M. S. Sulkowski et al., Hepatology 57:2143–2154, 2013, doi:10.1002/hep.26276), achieved sustained virologic response (SVR) rates of 72 to 84%. The current randomized, open-label, parallel-group study compared the efficacy and safety of 12 versus 24 weeks of 120 mg faldaprevir administered once daily, combined with 24 or 48 weeks of PegIFN/RBV, in 160 treatment-naive HCV genotype 1 patients. Patients with maintained rapid virologic response (HCV RNA of <25 IU/ml at week 4 and undetectable at weeks 8 and 12) stopped all treatment at week 24, otherwise they continued PegIFN/RBV to week 48. SVR was achieved by 67% and 74% of patients in the 12-week and 24-week groups, respectively. Virologic response rates were lower in the 12-week group from weeks 2 to 12, during which both groups received identical treatment. SVR rates were similar in both groups for patients achieving undetectable HCV RNA. Most adverse events were mild or moderate, and 6% of patients in each treatment group discontinued treatment due to adverse events. Once-daily faldaprevir at 120 mg for 12 or 24 weeks with PegIFN/RBV resulted in high SVR rates, and the regimen was well tolerated. Differences in the overall SVR rates between the 12-week and 24-week groups were not statistically significant and possibly were due toIL28Bgenotype imbalances;IL28Bgenotype was not tested, as its significance was not known at the time of the study. These results supported phase 3 evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT00984620).

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Hepatitis C Virus (HCV) diagnosis, epidemiology and access to treatment in a UK cohort

10.1101/216937 ◽

2017 ◽

Author(s):

Emily Adland ◽

Gerald Jesuthasan ◽

Louise Downs ◽

Victoria Wharton ◽

Gemma Wilde ◽

...

Keyword(s):

Hepatitis C Virus ◽

Viral Load ◽

Hepatitis C ◽

Positive Predictive Value ◽

Predictive Value ◽

Clinical Care ◽

Virologic Response ◽

Hcv Infection ◽

Hcv Rna ◽

Direct Acting Antiviral

ABSTRACTBackgroundAs direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment.MethodsWe performed a retrospective study of HCV infection in a UK teaching hospital to evaluate the performance of different diagnostic laboratory tests, to describe the population with active HCV infection, and to determine the proportion of these individuals who access clinical care.ResultsOver a total time period of 33 months between 2013 and 2016, we tested 38,510 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag+ and/or HCV RNA+) in 359 (positive rate 0.9%). Our in-house HCV-Ab test had a positive predictive value of 87% when compared to repeat HCV-Ab testing in a regional reference laboratory, highlighting the potential for false positives to arise based on a single round of antibody-based screening. Of those confirmed Ab-positive, 70% were HCV RNA positive. HCV-Ag screening performed well, with 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p<0.0001). Among the 359 cases of infection, the median age was 37 years, 85% were male, and 36% were in prison. Among 250 infections for which genotype was available, HCV genotype-1 (n=110) and genotype-3 (n=111) accounted for the majority. 117/359 (33%) attended a clinic appointment and 48 (13%) had curative treatment defined as sustained virologic response at 12 weeks (SVR12).ConclusionsHCV-Ab tests should be interpreted with caution as an indicator of population prevalence of HCV infection, both as a result of the detection of individuals who have cleared infection and due to false positive test results. We demonstrate that active HCV infection is over-represented among men and in the prison population. A minority of patients with a diagnosis of HCV infection access clinical care and therapy; enhanced efforts are required to target diagnosis and providing linkage to clinical care within high risk populations.ABBREVIATIONSDAADirect Acting AntiviralELISAEnzyme linked immunosorbent assayHCVHepatitis C VirusHCV-AbIgG antibody to Hepatitis C virusHCV-AgHepatitis C virus core antigenHCV RNAHepatitis C ribonucleic acid (viral load)MSMmen who have sex with menNATnucleic acid testingPCRpolymerase chain reaction (test for viral load)PPVpositive predictive valuePWIDpeople who inject drugsSDGSustainable Development GoalsSVRsustained virologic responseWHOWorld Health Organisation

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Efficacy and safety of ledipasvir/sofosbuvir in 5,028 Mongolian patients infected with genotype 1 hepatitis C virus: A multicenter study

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0023 ◽

2021 ◽

Vol 27 (1) ◽

pp. 125-135

Author(s):

Oidov Baatarkhuu ◽

Jae Seung Lee ◽

Jazag Amarsanaa ◽

Do Young Kim ◽

Sang Hoon Ahn ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Real World ◽

Virologic Response ◽

Hcv Rna ◽

Efficacy And Safety ◽

Genotype 1 ◽

High Efficacy ◽

Genotype 1A ◽

End Of Treatment

Background/Aims: Ledipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients.Methods: Between 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12).Results: Most patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA >6×10<sup>6</sup> IU/mL (n=866; 17.2%), or liver stiffness >9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%).Conclusions: LDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.

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