Retrospective study of hepatitis C outcomes and treatment in HIV co-infected persons from the Australian HIV Observational Database

Background: The widespread availability of direct-acting antivirals (DAAs) is expected to drastically improve the treatment uptake and cure rate of hepatitis C virus (HCV). In this paper, rates of and factors associated with HCV treatment uptake and cure in the HIV co-infected population in Australia were assessed before access to DAAs. Methods: The medical records of patients in the Australian HIV Observational Database who were reported to be HCV antibody positive from 1999 to 2014 were reviewed for HCV treatment data. Patients with detectable HCV RNA were included in this analysis. Logistic regression models were applied to identify factors associated with treatment uptake and HCV sustained virological response (SVR) 24 weeks’ post treatment. Results: The median follow-up time of those with chronic HCV/HIV co-infection was 103 months (interquartile range 51–166 months). Of 179 HCV viraemic patients, 79 (44.1%) began treatment. In the adjusted model, a higher METAVIR score was the only significant factor associated with treatment uptake (odds ratio (OR) 8.87, 95% confidence interval (CI) 2.00–39.3, P = 0.004). SVR was achieved in 37 (50%) of 74 treated patients. HCV genotypes 2/3 compared with 1/4 remained the only significant factor for SVR in an adjusted multivariable setting (OR 5.44, 95% CI 1.53–19.4, P = 0.009). Conclusions: HCV treatment uptake and SVR have been relatively low in the era of interferon-containing regimens, in Australian HIV/HCV coinfected patients. With new and better tolerated DAAs, treatment of HCV is likely to become more accessible, and identification and treatment of HCV in co-infected patients should become a priority.

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Integrated, Co-located, Telemedicine-based Treatment Approaches for Hepatitis C Virus Management in Opioid Use Disorder Patients on Methadone

Clinical Infectious Diseases ◽

10.1093/cid/ciy899 ◽

2018 ◽

Vol 69 (2) ◽

pp. 323-331 ◽

Cited By ~ 15

Author(s):

Andrew H Talal ◽

Phyllis Andrews ◽

Anthony Mcleod ◽

Yang Chen ◽

Clewert Sylvester ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Multiple Correspondence Analysis ◽

Opioid Use Disorder ◽

Hcv Rna ◽

Directly Observed Therapy ◽

Opioid Use ◽

Hcv Treatment ◽

Opioid Substitution Therapy ◽

Direct Acting

Abstract Background Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. Methods OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. Results Sixty-two HCV RNA–positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. Conclusions HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment.

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Spontaneous Clearance of Chronic HCV: The Key Ending Left in the Dark

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.134 ◽

2019 ◽

Vol 7 (10) ◽

pp. 1657-1659

Author(s):

Nikola Hristov Mumdzhiev ◽

Daniela Valerieva Radicheva ◽

Mariana Penkova Radicheva ◽

Rumen Valchev Tenev ◽

Zlatina Dimitrova Vasileva

Keyword(s):

Hepatitis C ◽

Hcv Rna ◽

Spontaneous Clearance ◽

Hepatitis C Infection ◽

Positive Serology ◽

Mild Disease ◽

Spontaneous Hcv Clearance ◽

Chronic Hcv ◽

Direct Acting ◽

Special Circumstances

BACKGROUND: Hepatitis C is the second leading cause of liver cirrhosis and hepatocellular carcinoma. Although the discovery of direct-acting agents made the disease curable, HCV elimination can be achieved solely by the host’s immunologic arsenal. CASE REPORT: We report the case of a 29-year-old woman with chronic hepatitis C infection - elevated transaminases, positive serology. HCV was detectable on two occasions, and histology showed mild disease - A1F1. Upon follow up and without any treatment, the patient achieved spontaneous clearance confirmed by two consecutive undetectable HCV RNA tests. Spontaneous HCV clearance rarely occurs – 0.5% per person-year. This is sometimes accompanied by special circumstances like additional disease or medical interventions. Host factors like gender and interleukin-28B polymorphisms have been known to contribute to clearance. Viral factors like HCV RNA levels are also a factor. The characteristics of host-viral interplay – age of acquisition and fibrosis stage – cannot be overlooked. CONCLUSION: All of the abovementioned factors contribute to the complex immunological interaction between virus and host and the result, although rarely can be spontaneous clearance.

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Risk Factors Contributing to the Occurrence and Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus Patients Treated with Direct-Acting Antivirals

Biomedicines ◽

10.3390/biomedicines8060175 ◽

2020 ◽

Vol 8 (6) ◽

pp. 175

Author(s):

Sara Kishta ◽

Ashraf Tabll ◽

Tea Omanovic Kolaric ◽

Robert Smolic ◽

Martina Smolic

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Hepatitis C ◽

Dna Ploidy ◽

Hcv Rna ◽

Direct Acting Antivirals ◽

Hepatic Cells ◽

Chronic Hcv ◽

Direct Acting

Although hepatitis C virus (HCV) RNA may be eliminated from blood circulation by direct-acting antivirals (DAA) therapy as assessed by real-time polymerase chain reaction (PCR), HCV RNA can still be present in liver tissue, and this is known as occult HCV. There has been a lot of controversy surrounding the recurrence of hepatocellular carcinoma (HCC) after DAA treatment of hepatic cells infected with chronic HCV. One of the main risk factors that leads to de novo HCC is the chronicity of HCV in hepatic cells. There are many studies regarding the progression of HCV-infected hepatic cells to HCC. However, there is a lack of research on the different molecular mechanisms that lead to the progression of chronic HCV infection to HCC, as well as on the effect of HCV on the alteration of DNA ploidy, which eventually leads to a recurrence of HCC after DAA treatment. In this review article, we will address some risk factors that could lead to the development/recurrence of HCC after treatment of HCV with DAA therapy, such as the role of liver cirrhosis, the alteration of DNA ploidy, the reactivation of hepatitis B virus (HBV), the role of cytokines and the alteration of the immune system, concomitant non- alcoholic fatty liver disease (NAFLD), obesity, alcohol consumption and also occult HCV infection/co-infection. Clinicians should be cautious considering that full eradication of hepatocarcinogenesis cannot be successfully accomplished by anti-HCV treatment alone.

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Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017

10.21203/rs.3.rs-18790/v2 ◽

2020 ◽

Author(s):

Christer F. Aas ◽

Jørn Henrik Vold ◽

Svetlana Skurtveit ◽

Ingvild Odsbu ◽

Fatemeh Chalabianloo ◽

...

Keyword(s):

Hepatitis C ◽

Antiviral Treatment ◽

Prescription Database ◽

Agonist Therapy ◽

Hcv Treatment ◽

Opioid Agonist ◽

Direct Acting Antiviral ◽

Opioid Agonist Therapy ◽

Treatment Uptake ◽

Direct Acting

Abstract Background: Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries.Methods: This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. Results: In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0).Conclusions: An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients.

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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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Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017

10.21203/rs.2.21198/v1 ◽

2020 ◽

Author(s):

Christer frode Aas ◽

Jørn Henrik Vold ◽

Svetlana Skurtveit ◽

Ingvild Odsbu ◽

Fatemeh Chalabianloo ◽

...

Keyword(s):

Hepatitis C ◽

Prescription Database ◽

Cumulative Frequency ◽

Agonist Therapy ◽

Hcv Treatment ◽

Opioid Agonist ◽

Direct Acting Antiviral ◽

Opioid Agonist Therapy ◽

Treatment Uptake ◽

Direct Acting

Abstract Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate cumulative frequency of HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were adjusted for age, gender, and OAT medications and studied in a logistic regression model. Results In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV treatment uptake increased in both countries, giving a cumulative frequency of around one-third in both countries at the end of the study period. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients during the introduction period of new direct-acting treatment regimens. However, a further scale-up is crucial to be able to control and eliminate the HCV endemic among OAT patients.

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Hepatitis C core antigen: a simple predictive marker for treatment response to the new direct-acting antiviral drugs in chronic HCV Egyptian patients

Egyptian Liver Journal ◽

10.1186/s43066-021-00092-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Asmaa M. Elbrolosy ◽

Moamena S. Elhamouly ◽

Emad M. Eed ◽

Gamalat A. El Gedawy ◽

Mai Abozeid ◽

...

Keyword(s):

Hepatitis C ◽

Treatment Response ◽

Antiviral Drugs ◽

Core Antigen ◽

Hcv Rna ◽

Promising Alternative ◽

Direct Acting Antiviral ◽

Significant Difference ◽

Chronic Hcv ◽

Direct Acting

Abstract Background Successful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new direct-acting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays. Our main objectives were to correlate between serum levels of HCVcAg and HCV RNA loads in chronic HCV patients as well as to explore the potential value of HCVcAg assay in predicting treatment response to the new DAAs. The study enrolled a total of 280 chronic HCV-infected patients scheduled to start the new regimen for treatment of chronic HCV by all-oral, interferon-free DAAs. According to the viral load, the studied individuals were arranged into three groups corresponding to mild, moderate, and sever viremia. Serum level of HCVcAg was determined by ELISA technique and HCV RNA viral loads were quantified using the real-time PCR system. The assays were performed three times for all participants: prior to initiation of treatment, at the end of treatment (week 12), and 3 months post-treatment cessation (week 24). Results A statistically significant difference between HCV RNA and HCVcAg baseline levels among different viremia groups was detected (P < 0.001). There was a significant positive correlation between HCV RNA and HCVcAg baseline values among all the studied cases (P < 0.05) with a correlation coefficient of 0.752, 0.976, and 1.00 respectively for mild, moderate, and severe viremia groups. 92.9% (260/280) of the studied patients achieved sustained virologic response, 3.6% (10/280) were non-responders, and 3.6% (10/280) had recurrent viremia/relapse as regards RT-PCR results. Conclusion HCVcAg is a promising alternative to HCV RNA assay. The ELISAs for HCVcAg proved excellent correlations with HCV RNA levels. Moreover, HCVcAg can be introduced as a simple and highly specific tool for monitoring the new DAA regimens particularly in low-resource settings.

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Standard Versus Extended Duration Direct-Acting Antiviral Therapy in Hepatitis C Patients With Slow Response to Treatment

Annals of Pharmacotherapy ◽

10.1177/1060028020921166 ◽

2020 ◽

Vol 54 (11) ◽

pp. 1057-1064

Author(s):

Ashley H. McKnight ◽

Mary L. Townsend ◽

Mohamed G. Hashem ◽

Susanna Naggie ◽

Lawrence P. Park ◽

...

Keyword(s):

Hepatitis C ◽

Primary Objective ◽

Response To Treatment ◽

Patient Specific ◽

Hcv Rna ◽

Viral Kinetics ◽

Factors Associated ◽

Direct Acting Antiviral ◽

Extended Duration ◽

Direct Acting

Background: Response-guided hepatitis C therapy was standard with interferon-based regimens but is not used for direct-acting antivirals (DAAs). Week 4 viral kinetics may predict sustained virological response (SVR) with DAAs, but it is unclear whether extending therapy in slow responders affects outcomes. Objectives: The primary objective was to compare SVR rates between traditional and extended duration groups. Secondary objectives were to compare SVR rates among subgroups and to determine factors associated with SVR. Methods: This institutional review board–approved, retrospective, single-center study identified patients with chronic hepatitis C virus (HCV) infection with detectable week 4 HCV RNA who were treated with DAAs. Patients were excluded for early discontinuation, treatment regimen not recommended first-line, or missing HCV RNA labs. Patients were stratified into traditional and extended duration groups. The primary end point was SVR. Secondary end points included factors associated with SVR and rationale for extension of therapy duration. Results: A total of 363 patients were included; 58 (16%) received extended therapy. Patients were primarily genotype 1a (70%) and treatment naïve (80%). More than half had advanced fibrosis or cirrhosis. SVR12 rates were 100% in the extended duration group and 96.7% in the traditional duration group ( P = 0.37). There were no associations with SVR and prespecified patient-specific factors. Sample size was limited. Conclusion and Relevance: Based on these findings, a recommendation for extension of therapy cannot be made for patients with detectable HCV RNA at week 4 of treatment at this time. Cost analyses may help guide recommendations to re-treat rare failures versus extend therapy in all slow responders.

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Moving Towards Hepatitis C Microelimination Among People Living With Human Immunodeficiency Virus in Australia: The CEASE Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz985 ◽

2019 ◽

Vol 71 (6) ◽

pp. 1502-1510 ◽

Cited By ~ 9

Author(s):

Marianne Martinello ◽

Jasmine Yee ◽

Sofia R Bartlett ◽

Phillip Read ◽

David Baker ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis C ◽

Scale Up ◽

Hcv Rna ◽

People Living With Hiv ◽

Bisexual Men ◽

Hcv Treatment ◽

Treatment Uptake ◽

Immunodeficiency Virus

Abstract Background Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. Methods The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Results Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94). Conclusions High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. Clinical Trials Registration NCT02102451.

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Progress Towards Elimination of Hepatitis C Infection Among People Who Inject Drugs in Australia: The ETHOS Engage Study

Clinical Infectious Diseases ◽

10.1093/cid/ciaa571 ◽

2020 ◽

Cited By ~ 1

Author(s):

Heather Valerio ◽

Maryam Alavi ◽

David Silk ◽

Carla Treloar ◽

Marianne Martinello ◽

...

Keyword(s):

Hepatitis C ◽

Drug Treatment ◽

People Who Inject Drugs ◽

Hcv Infection ◽

Hcv Rna ◽

Spontaneous Clearance ◽

Hepatitis C Infection ◽

Hcv Treatment ◽

Opioid Agonist ◽

Treatment Uptake

Abstract Background Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. Methods The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). Results Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00–2.16), incarcerated in the previous year (2.04; 1.38–3.02), and those injecting drugs daily or more (2.26; 1.43–2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68; .48–.95), participants who were homeless (.59; .38–.96), and those injecting daily or more (.51; .31–.89). People aged ≥45 years (1.46; 1.06–2.01) and people receiving OAT (2.62; 1.52–4.51) were more likely to report HCV treatment. Conclusions Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment.

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