Establishing the cascade of care for hepatitis C in England—benchmarking to monitor impact of direct acting antivirals

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case finding, referral, treatment uptake and retention in care. Using data from the sentinel surveillance of blood‐borne virus (SSBBV) testing between 2005 and 2014, we investigate the continuum of care of those tested for HCV in England. Persons ≥1 year old with an anti‐HCV test and subsequent RNA tests between 2005 and 2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment and patient outcomes. Between 2005 and 2014, 2 390 507 samples were tested for anti‐HCV, corresponding to 1 766 515 persons. A total of 53 038 persons (35 190 men and 17 165 women) with anti‐HCV positive were newly reported to SSBBV. An RNA test was conducted on 77.0% persons who were anti‐HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models, confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat.     

Barriers to treatment of chronic hepatitis C with direct acting antivirals in an urban clinic

Introduction and aimDirect-acting antiviral (DAA) agents are highly effective for treatment of chronic hepatitis C virus (HCV) yet access to treatment remains a serious challenge. The aim of this study was to identify barriers to treatment initiation with DAA-containing regimens in an urban clinic setting.Materials and methodsA retrospective cohort of all chronic HCV patients seen in an urban academic practice in Jacksonville, FL, USA from 1/2014 to 1/2017 was analyzed. Baseline characteristics were recorded and a review of medical records was performed to identify barriers to treatment initiation and overall success rates.ResultsTwo-hundred and forty patients with chronic HCV were analyzed. Fifty-six percent of patients were African-American and 63% were insured through Medicaid/county programs or uninsured. Sixty-nine percent had barriers to initiating antiviral therapy categorized as psychosocial (n = 112), provider (n = 26), medical (n = 20), and insurance-related factors (n = 7). The most commonly encountered psychosocial barriers included failure to keep appointments (79/240, 33%), active substance abuse (18/240, 8%), and failure to obtain laboratory testing (11/240, 5%). Overall, only 27% of patients evaluated were initiated on DAA-containing regimens with 18% reaching SVR12 within the 36-month study period.ConclusionIn conclusion, only 27% of patients who presented to an urban academic practice with chronic HCV received DAA-containing regimens over a 36-month period. Psychosocial issues were the major barriers to antiviral therapy. These findings illustrate the need for an integrated approach that addresses psychosocial factors as well as comorbidities and adherence to care in order to increase rates of HCV treatment in at risk patients.     

Hepatitis C care cascade before and during the direct-acting antiviral eras in New South Wales,Australia: A population-based linkage study

The hepatitis C virus (HCV) care cascade characterization is important for monitoring progress towards HCV elimination. This study evaluated HCV care cascade and factors associated with treatment during pre-DAA (2011–2012 and 2013–2015) and DAA (2016–2018) eras in New South Wales (NSW), Australia. We conducted a cohort study of people with an HCV notification (1993 to 2017) through end 2018, linked to administrative datasets, including HCV treatment and non-hospital services. Those aged <18 years, died within first 6 months of study period or notification, and who had successful HCV treatment in period before were excluded. Sex-specific spontaneous viral clearance was incorporated to estimate treatment-eligible population. The study population in each period were cumulative and brought forward from one period to the next. Among 115,667 people with HCV notification, 87,063 fulfilled eligibility criteria. During 2011 to 2012, 2013 to 2015, and 2016 to 2018, cumulative HCV notifications were 71,677, 77,969, and 80,017; 52,016, 56,793, and 57,467 were eligible for treatment; 29%, 48%, and 64% confirmed HCV RNA positive; and 0.6%, 5%, and 38% initiated HCV treatment, respectively. Birth cohort 1945 to 1964 (vs. ≥1965), males, non-Aboriginal ethnicity, regional/rural area of residence, and HCV/HIV co-infection were associated with higher treatment uptake. Incarceration and drug dependence were associated with higher treatment uptake during the DAA era. In Australia, many marginalized populations including those incarcerated and those with drug dependence have equitable treatment uptake in the DAA era. Targeted strategies are required to enhance treatment uptake for females and Aboriginal populations.     

The Hepatitis C virus treatment cascade at an urban postincarceration transitions clinic

Transitions clinics, which provide medical care to individuals who have been released from incarceration, reach a population at high risk for hepatitis C Virus (HCV) infection. We used the HCV treatment cascade to describe HCV care at an urban postincarceration transitions clinic, identifying gaps in care and determining reasons for lapses in care. In this retrospective cohort study, we reviewed electronic health records for all formerly incarcerated individuals receiving care at the Bronx Transitions Clinic. HCV treatment cascade measures included the following: detection of HCV antibodies, confirmation of chronic infection, specialist referral, specialist evaluation, initiation of treatment, completion of treatment and achievement of SVR. We recorded reasons for lapses in care. Of 451 patients accessing care, 317 (70%) were screened for HCV antibodies, and 106 (33%) tested positive. Of the 106 antibody‐positive patients, 93 (88%) were evaluated for HCV viremia and 84 (79%) were confirmed to have chronic HCV infection; 19% of the total sample had chronic HCV infection. Of these 84 with chronic HCV, 48 (57%) received specialist referral, 30 (36%) were evaluated, 8 (10%) initiated treatment, and 5 (6%) completed treatment and achieved SVR. Some treatment lapses occurred because patients were deemed unstable for treatment (12%) or were re‐incarcerated (5%). Chronic HCV infection was common among transitions clinic patients. Few were treated and cured. Patients lost contact with providers before consideration for antiviral therapy. Referral to specialty providers was a gap in care. Increasing HCV treatment in this population will likely require intensive delivery models.     

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens

ABSTRACT

Background: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres.

Methods: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report.

Results: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results.

Conclusions: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.     

Gaps in the hepatitis C continuum of care among sex workers in Vancouver,British Columbia: Implications for voluntary hepatitis C virus testing,treatment and care

BACKGROUND:

Hepatitis C virus (HCV) eradication leads to reduced morbidity, mortality and transmission. Despite the disproportionate burden of HCV among sex workers, data regarding the HCV care continuum in this population remain negligible.

METHODS:

Using baseline data from an ongoing cohort of women sex workers in Vancouver (An Evaluation of Sex Workers’ Health Access, January 2010 to August 2013), the authors assessed HCV prevalence and engagement in the HCV care continuum within the past year. Multivariable logistic regression analyses were used to evaluate associations with recent (ie, in the past year) HCV testing.

RESULTS:

Among 705 sex workers, 302 (42.8%) were HCV seropositive. Of these, 22.5% were previously unaware of their HCV status, 41.7% had accessed HCV-related care, 13.9% were offered treatment and only 1.0% received treatment. Among 552 HCV-seronegative sex workers, only one-half (52.9%) reported a recent HCV test. In multivariable analysis, women who self-identified as a sexual/gender minority (adjusted OR [aOR] 1.89 [95% CI 1.11 to 3.24]), resided in the inner city drug use epicentre (aOR 3.19 [95%CI 1.78 to 5.73]) and used injection (aOR 2.00 [95% CI 1.19 to 3.34]) or noninjection drugs (aOR 1.95 [95% CI 1.00 to 3.78]) had increased odds of undergoing a recent HCV test, while immigrant participants (aOR 0.24 [95% CI 0.12 to 0.48]) had decreased odds.

CONCLUSIONS:

Despite a high burden of HCV among sex workers, large gaps in the HCV care continuum remain. Particularly concerning are the low access to HCV testing, with one-fifth of women living with HCV being previously unaware of their status, and the exceptionally low prevalence of HCV treatment. There is a critical need for further research to better understand and address barriers to engage in the HCV continuum for sex workers.     

Long‐term outcomes of direct acting antivirals in post‐transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis

Long‐term functional outcomes of sofosbuvir‐based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post‐transplant hepatitis C virus (HCV) recurrence. Seventy‐three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24‐week sofosbuvir with ribavirin±pegylated interferon or interferon‐free sofosbuvir‐based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82‐112) weeks. Twelve of 73 (16.4%) died (10 non‐FCH, 2 FCH) and two underwent re‐LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non‐FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow‐up, MELD and Child‐Turcotte‐Pugh scores improved both in non‐FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short‐treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long‐term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child‐Turcotte‐Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals‐based treatments for severe post‐transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long‐term survival. The setting of severe HCV recurrence may require the identification of “too‐sick‐to‐treat patients” to avoid futile treatments.     

Hepatitis C virus testing,liver disease assessment and treatment uptake among people who inject drugs pre‐ and post‐universal access to direct‐acting antiviral treatment in Australia: The LiveRLife study

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct‐acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole‐blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre‐DAA era to 38% in the DAA era. Significant liver fibrosis (F2‐F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18‐7.04) and attending a clinical follow‐up with nurse (aOR, 3.19; 95% CI, 1.61‐6.32) or physician (aOR, 11.83; 95% CI, 4.89‐28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.     

Examining hepatitis C virus testing practices in primary care clinics

Prior studies found that hepatitis C virus (HCV) risk assessment and testing in primary care clinics were suboptimal. We aimed to determine the actual HCV testing rate among patients with HCV risk factors and to identify variables predictive of testing. In order to do so, we performed a prospective cohort study among patients seen in four urban primary care clinics. At the initial visit, patients were given a questionnaire that listed HCV risk factors and they were instructed to check 'yes' or 'no' if they did or did not have a risk factor, respectively. Patients then handed this questionnaire to their physician during their initial visit. Among those who acknowledged having a HCV risk factor via the questionnaire, we determined the subsequent HCV testing rate and calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) to identify variables predictive of testing. Of the 578 individuals who acknowledged having a HCV risk factor via the questionnaire, only 8% (46/578) were tested for HCV within 2 months of their initial visit. Among those tested, 11% (5/46) had a positive HCV antibody test result. The only variable predictive of HCV testing after adjusting for confounders was having a specific HCV risk factor identified and documented in the chart by physicians [16% (26/159) vs 5% (20/419); aOR 4.5, 95% CI 2.1-9.5]. In summary, 92% of patients with a HCV risk factor were not tested for HCV in the primary care setting, and efforts to improve such rates are clearly warranted.     

Enhancing the hepatitis B care cascade in Australia: A cost‐effectiveness model

If Australia is to successfully eliminate hepatitis B as a public health threat, it will need to enhance the chronic hepatitis B (CHB) care cascade. This study used a Markov model to assess the impact, cost and cost‐effectiveness of scaling up CHB diagnosis, linkage to care and treatment to reach national and international elimination targets for hepatitis B in Australia. Compared to continued current trends, the model calculated the difference in care cascade projection, disability‐adjusted life years (DALYs), costs and the incremental cost‐effectiveness ratio (ICER), of scaling up CHB diagnosis, linkage to care and treatment to reach: (a) Australia's 2022 national targets and (b) the WHO’s 2030 global targets. Achieving the national and WHO targets had ICERs of A$13 435 (A$10 236‐A$21 165) and A$14 482 (A$13 031‐A$25 641) per DALY averted between 2016 and 2030 in Australia, respectively. However, this excluded implementation and demand generation costs. The ICER for the National Strategy and WHO Strategy remained under A$50 000 per DALY averted if Australia spent up to A$328 or A$538 million, respectively, per annum (for 2016‐2030) on implementation and demand generation activities. Sensitivity analysis showed that cost‐effectiveness was predominately driven by the cost of CHB treatment and influenced by disease progression rates. Hence for Australia to reach the National Hepatitis B Strategy 2022 targets and WHO Strategy 2030 targets, it requires an improvement in the CHB care cascade. We estimated it is cost‐effective to spend up to A$328 million or A$538 million per year to reach the National and WHO Strategy targets, respectively.     

Defer or treat? Reasons for treatment decisions in patients with chronic hepatitis C genotype 1 in the early era of directly acting antiviral agents

BackgroundIn chronic genotype 1 hepatitis C, telaprevir or boceprevir plus peginterferon and ribavirin have become the new standard of care. Aim of this study was to identify factors contributing to the decision whether to defer or treat with the current triple regimens.MethodsProspective assessment of eight parameters on 0-4-point scales by the attending physician at a German tertiary referral centre between 1st September 2011 and 31st December 2012.Results307 patients were evaluated at least once by one of the 11 hepatologists involved; 267 patients were considered, but only 163 were recommended to receive triple therapy. Multivariate regression analysis revealed that a higher degree of fibrosis was most strongly associated with a recommendation for treatment (OR 2.69), followed by the patients’ demand (OR 2.27), presumed efficacy (OR 1.62), and tolerability (OR 1.58). A high risk of decompensation was associated with the decision to defer (OR 0.39). Speed of progression, compliance, extrahepatic manifestation, gender and age were not significantly related to the recommendation. Treatment was finally started in 101 patients (32.9%).ConclusionIn chronic genotype 1 hepatitis C, advanced fibrosis and patients’ preference are the main rationales to choose treatment rather than deferral in a real-life setting.     

Estimating the treatment cascade of chronic hepatitis B and C in Greece using a telephone survey

Accurate diagnosis and treatment rates for chronic hepatitis B (HBV) and C virus (HCV) infections are usually missing. Aim of this study was to estimate the HBV and HCV treatment cascade (proportion and absolute numbers of tested, aware/unaware, infected and treated) in Greek adults. A telephone survey was conducted in a sample representative of the Greek adult general population. Prevalence rates were age‐standardized for the Greek adult population and corrected for high‐risk individuals not included in the survey. Of the 9974 participants, 5255 (52.7%) had been tested for HBV and 2062 (20.7%) for HCV with the proportion varying according to age and being higher in middle‐age groups (P < 0.001). HBsAg was reported positive in 111/5255 (2.11%) and anti‐HCV in 26/2062 (1.26%) tested cases. The age‐adjusted prevalence was estimated to be 2.39% for HBV and 1.79% for HCV. Taking into account individuals at high risk for viral hepatitis not included in the survey, the ‘true’ prevalence was estimated to be 2.58% for HBV and 1.87% for HCV. Anti‐HBV and anti‐HCV treatment had been taken by 36/111 (32.4%) chronic HBV and 15/26 (57.7%) chronic HCV patients. In conclusion, almost 50% of chronic HBV and 80% of chronic HCV patients in Greece may be unaware of their infection, while only 32% or 58% of diagnosed chronic HBV or HCV patients, respectively, have been ever treated. Therefore, intensive efforts are required to improve the efficacy of screening for HBV and particularly for HCV as well as to reduce the barriers to treatment among diagnosed patients.     

Find the Missing Millions: Malaysia’s experience with nationwide hepatitis C screening campaign in the general population

Approximately 2.5% of the Malaysian population is currently living with hepatitis C virus (HCV) infection. Yet, the public awareness of the disease is limited and under‐screening remains a major challenge. With the support of international non‐for‐profit organizations, the Ministry of Health in Malaysia recently launched a one‐week nationwide hepatitis C screening campaign in conjunction with the World Hepatitis Day. For the first time, the rapid diagnostic test (RDT) for HCV screening was introduced in public health institutions. This campaign involved 49 hospitals and 38 health clinics across the country, targeting the adult general population with unknown HCV infection status. Of the 11 382 participants undergoing the RDT, 1.9% were found to be positive for hepatitis C antibody (anti‐HCV) and were referred to on‐site medical departments or nearby hospitals for confirmatory testing and treatment. Men, the Malay ethnic group, intranasal and injection drug users and ex‐prisoners were shown to have higher odds of being positive for anti‐HCV. In addition to serving as a model to educate the general population about the disease, this campaign demonstrates the feasibility of decentralizing HCV screening, particularly by promoting the use of RDT, and linking the HCV‐infected patients to care in Malaysia.     

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.