Estimating regional prevalence of chronic hepatitis C with a capture-recapture analysis.

BACKGROUND: The hepatitis C virus (HCV) infection is a candidate disease for micro-elimination. Accurate baseline HCV prevalence estimation is essential to monitor progress to micro-elimination but can be methodologically challenging in low-endemic regions like the Netherlands due to lack of disaggregated data by age or risk-groups on the number of chronic HCV patients (i.e. HCV RNA positive). This study estimates the number of patients that has had a chronic HCV infection (ever-chronic) in the Utrecht region of the Netherlands. METHODS: In the Utrecht province in the Netherlands, positive HCV tests from the period 2001-2015 from one diagnostic center and four hospital laboratories were collected. A two-source capture-recapture method was used to analyze the overlap between the two registries (with 92% HCV RNA and 8% HCV immunoblot confirmed infections) to obtain the number of ever-chronic HCV infections in the Utrecht region. The Utrecht region was defined as an area with a 25 km radius from the Utrecht city center. The current viremic HCV prevalence was calculated by taking into account the proportion of cured and deceased HCV patients from a local HCV retrieval (REACH) project. RESULTS: The estimated number of ever-chronic HCV patients was 1245 (95% CI 1164-1326) and would indicate a prevalence of 0.10 (95% CI 0.09-0.10) in the Utrecht region. This is 30% (95% CI 21-38%) more than the number of known HCV patients in the records. The ever-chronic HCV prevalence was highest in the 1960-1969 age cohort (0.16; 95% CI 0.14-0.18). Since 50% of the HCV patients were cured or deceased in the REACH-project, the number of current viremic HCV patients was estimated at 623 individuals in the Utrecht region (prevalence 0.05%). CONCLUSION: The results of this study suggest a low ever-chronic and current HCV prevalence in the Utrecht area in the Netherlands, but other studies need to confirm this.

REtrieval And cure of Chronic Hepatitis C (REACH): Results of micro-elimination in the Utrecht province.

BACKGROUND: The Netherlands is one of the six European countries considered on track to eliminate hepatitis C virus by 2030. To achieve this goal, continuous efforts have to be put into designing efficient case-finding strategies, including the retrieval of previously diagnosed hepatitis C virus-infected who are lost to follow-up. AIMS: To trace and treat all lost to follow-up hepatitis C virus patients in the Utrecht region and create an efficient retrieval strategy that can be used in future (national) retrieval initiatives. METHODS: Positive hepatitis C virus diagnostic tests (anti-hepatitis C virus IgG or hepatitis C virus-RNA) from the laboratory of all four hospitals and one central laboratory for primary care diagnostics in the province of Utrecht from 2001 to 2015 were linked to clinical records. Untreated patients with available contact information were deemed eligible for retrieval and invited for reevaluation with (virology) blood tests, fibroscan measurement and possible direct-acting antiviral therapy. MAIN RESULTS: After screening all hepatitis C virus diagnostics, 1913 chronic hepatitis C virus-infected were identified of which 14.1% (n = 269) were invited back into care. Overall, 17.4% was traced with the highest yield (28.3%) in those who lived in the Utrecht province. Through renewed patient assessments, 42 chronic hepatitis C virus infections were re-identified (76% with a history of intravenous drug use, 24% with Metavir F3-F4). Until now, 59% has either scheduled or initiated direct-acting antiviral therapy. CONCLUSION: The retrieval of previously diagnosed hepatitis C virus patients through screening of laboratory diagnostics from the past is feasible and should be pursued for further control and reduction of hepatitis C virus infection. Retrieval is most successful when performed regionally. LAY SUMMARY: To completely eliminate chronic hepatitis C virus (HCV) infection and prevent complications, undiagnosed and also previously diagnosed but lost to follow-up (LFU) HCV patients have to be brought (back) into care for therapy. Retrieval of LFU HCV patients through screening of laboratory diagnostics from the past is feasible and most successful when performed regionally.

Introducing hepatitis C virus healthcare pathways in addiction care in the Netherlands with a Breakthrough project: a mixed method study.

BACKGROUND: People who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. In the Netherlands, active HCV transmission in PWID has practically been halted but uptake of HCV testing and linkage to care remains insufficient in this risk group. A national HCV in Addiction Care (HAC) quality improvement project based on the Breakthrough methodology (i.e. Breakthrough project) aimed to secure proper linkage to care in PWID by introducing local HCV healthcare screening and treatment pathways in addiction care units. AIM: To qualitatively appraise the local HCV healthcare pathways; to evaluate the yield in terms of number of PWID screened, diagnosed, referred, and treated; and to identify best practices and barriers to successful participation in the HAC Breakthrough project. METHODS: Between 2013 and 2016, 12 units of addiction care centers throughout the Netherlands participated in two series of a HAC Breakthrough project. Local multidisciplinary teams created HCV healthcare pathways. Quality assessment of HCV healthcare pathways was performed retrospectively and data on screening results was collected. In-depth interviews were conducted to elucidate best practices and essential elements for successful participation. RESULTS: In total, six HCV healthcare pathways were submitted by ten teams of which 83% was judged to be of "good" or "sufficient" quality. Uptake of HCV-antibody screening was 40% (N = 487/1219) and uptake of HCV-RNA in HCV-antibody positives was 59% (N = 107/181). The project resulted in 76 (6%) newly detected cases of persistent HCV viremia. Of all HCV-RNA positives, 92% was referred to a hepatitis treatment center. In 39% (N = 27/70) of those referred, treatment initiation was documented and 82% (N = 22/27) achieved a sustained virological response. Teams identified several best practices including motivational counseling training, oral swabs for anti-HCV testing, facilitating complementary HCV RNA testing, and supervised hospital visits. CONCLUSION: The HAC Breakthrough project has brought about good quality HCV healthcare pathways in the majority of participating addiction care centers and has successfully linked PWID with ongoing HCV viremia to care. Uptake of HCV screening and treatment after referral were identified as the main gaps to be closed in the HCV cascade of care to achieve final HCV elimination in Dutch PWID (i.e. micro-elimination).

Hepatitis C Elimination in the Netherlands (CELINE): How nationwide retrieval of lost to follow-up hepatitis C patients contributes to micro-elimination.

BACKGROUND & AIMS: The number of chronic hepatitis C virus (HCV)-infected patients who have been lost to follow-up (LTFU) is high and threatens HCV elimination. Micro-elimination focusing on the LTFU population is a promising strategy for low-endemic countries like the Netherlands (HCV prevalence 0.16%). We therefore initiated a nationwide retrieval project in the Netherlands targeting LTFU HCV patients. METHODS: LTFU HCV-infected patients were identified using laboratory and patient records. Subsequently, the Municipal Personal Records database was queried to identify individuals eligible for retrieval, defined as being alive and with a known address in the Netherlands. These individuals were invited for re-evaluation. The primary endpoint was the number of patients successfully re-linked to care. RESULTS: Retrieval was implemented in 45 sites in the Netherlands. Of 20,183 ever-diagnosed patients, 13,198 (65%) were known to be cured or still in care and 1,537 (8%) were LTFU and eligible for retrieval. Contact was established with 888/1,537 (58%) invited individuals; 369 (24%) had received prior successful treatment elsewhere, 131 (9%) refused re-evaluation and 251 (16%) were referred for re-evaluation. Finally, 219 (14%) were re-evaluated, of whom 172 (79%) approved additional data collection. HCV-RNA was positive in 143/172 (83%), of whom 38/143 (27%) had advanced fibrosis or cirrhosis and 123/143 (86%) commenced antiviral treatment. CONCLUSION: Our nationwide micro-elimination strategy accurately mapped the ever-diagnosed HCV population in the Netherlands and indicates that 27% of LTFU HCV-infected patients re-linked to care have advanced fibrosis or cirrhosis. This emphasizes the potential value of systematic retrieval for HCV elimination.

The balancing perspective of hard-to-reach hepatitis C patients who were lost to follow-up: A qualitative study.

BACKGROUND: In the foreseeable future, patients with hepatitis C virus (HCV) with good healthcare access will all have been cured and the lost to follow-up (LFU) HCV-population will increasingly exist of hard-to-reach patients. Efforts to retrieve these individuals with HCV have been moderately successful so far. A deeper understanding of the reasons for loss to follow-up and the underlying processes is lacking. AIMS: To explore reasons for previous loss to follow-up in patients with HCV who have been brought back into care. METHODS: In 2017, fifteen patients with HCV who were evaluated at the University Medical Center Utrecht (UMCU) Infectious diseases outpatient clinic as part of the "REtrieval And cure of Chronic Hepatitis C" (REACH)-project were included in this study through convenience sampling. Face-to-face semi-structured in-depth interviews were conducted and a qualitative analysis based on the grounded theory was applied. RESULTS: A basic socio- psychological process named "maintaining the achieved balance" was uncovered in patients with HCV who were LFU. This "achieved balance" is the result of a transformative process following the initial HCV diagnosis. It is a steadfast stance in which participants keep HCV out of sight and in the margin of their lives in order to reestablish an optimal state of well-being. The balancing perspective is subsequently defended by repeated evasive behavioral patterns to avoid confrontation with the disease. CONCLUSION: The balancing perspective gives insight into why individuals with HCV were not retained in care but also why they remained LFU thereafter. Physicians should realize that this mindset can be persistent and repeated efforts may be needed to finally trace and retrieve these patients.

The Impact of Hepatitis C Virus Direct-Acting Antivirals on Patient-Reported Outcomes: A Dutch Prospective Cohort Study.

INTRODUCTION: Pegylated interferon-based therapy for hepatitis C virus (HCV) negatively impacts nutritional state and patient-reported outcomes (PROs) such as health-related quality of life (HRQL). Clinical trials with direct-acting antivirals (DAAs) report significant PRO improvement but real-world data are still scarce. METHODS: Prospective cohort study recruiting HCV patients treated with DAAs in 2015-2016. Data at baseline, end of treatment (EOT) and 12 weeks thereafter (FU12) included: patient-reported medication adherence; SF-36; Karnofsky Performance Status; paid labour productivity; physical exercise level; nutritional state [by body mass index (BMI) and Jamar hand grip strength (HGS)] and Beliefs about Medicines Questionnaire. Potential factors predicting these PROs were evaluated with multiple regression analysis. RESULTS: A total of 68 patients were enrolled: 85% male, median age 57 years, 80% genotype 1, 40% cirrhotics, 46% haemophilia. Both cure rate and patient-reported adherence were 97%. SF-36 Physical Component Summary did not change (43.2 ± 11.9, 44.9 ± 10.3 and 44.7 ± 10.9 at baseline, EOT and FU12, p = 0.71). In contrast, SF-36 mental component summary (MCS) decreased transiently during therapy (49.2 ± 11.9, 44.6 ± 10.3 and 49.9 ± 12.6 at baseline, EOT and FU12, p < 0.01). Concomitant ribavirin-use was the only independent predictor of decreased SF-36 MCS. BMI (25.7 ± 4.5 and 25.6 ± 4.4 at baseline and EOT, p = 0.8) and Jamar HGS (39.7 ± 13.0, 37.4 ± 11.9 and 37.9 ± 13.8 at baseline, EOT and FU12, p = 0.56) did not change. CONCLUSION: Our study reveals concomitant ribavirin as the only independent predictor of transient decrease in SF-36 mental HRQL during DAA therapy. In contrast to interferon-based therapy, DAAs do not affect BMI or Jamar HGS.