Hepatitis C elimination in the Netherlands (CELINE): Study protocol for nationwide retrieval of lost to follow-up patients with chronic hepatitis C

Background The Netherlands has a low hepatitis C virus (HCV) prevalence, estimated at 0.16%. Previous studies have shown that up to 30% of the diagnosed HCV population in the Netherlands has been lost to follow-up (LTFU). Retrieval of these patients could halt progression of liver disease in infected patients, reduce the number of infected individuals and limit HCV transmission. Several regional Dutch retrieval projects have already been executed, which demonstrated that retrieval is feasible. Therefore, we initiated a nationwide retrieval project, aiming to achieve microelimination in previously diagnosed but LTFU patients with chronic HCV through retrieval. Methods Laboratory records will be used to identify possible patients with chronic hepatitis C, defined as either a positive most recent HCV RNA or positive HCV antibodies without known RNA result. Reviewing patient records and obtaining current contact information from municipality databases will identify LTFU patients who ar

Socio-economic factors associated with loss to follow-up among individuals with HCV:A Dutch nationwide cross-sectional study

Background and Aims: The path to hepatitis C virus (HCV) elimination is complicated by individuals who become lost to follow-up (LTFU) during care, particularly before receiving effective HCV treatment. We aimed to determine factors contributing to LTFU and whether LTFU is associated with mortality. Methods: In this secondary analysis, we constructed a database including individuals with HCV who were either LTFU (data from the nationwide HCV retrieval project, CELINE) or treated with directly acting antivirals (DAA) (data from Statistics Netherlands) between 2012 and 2019. This database was linked to mortality data from Statistics Netherlands. Determinants associated with being LTFU versus DAA-treated were assessed using logistic regression, and mortality rates were compared between groups using exponential survival models. These analyses were additionally stratified on calendar periods: 2012–2014, 2015–2017 and 2018–2019. Results: About 254 individuals, LTFU and 5547 DAA-treated were included. Being institutionalized (OR = 5.02, 95% confidence interval (CI) = 3.29–7.65), household income below the social minimum (OR = 1.96, 95% CI = 1.25–3.06), receiving benefits (OR = 1.74, 95% CI = 1.20–2.52) and psychiatric comorbidity (OR = 1.51, 95% CI = 1.09–2.10) were associated with LTFU. Mortality rates were significantly higher in individuals LTFU compared to those DAA-treated (2.99 vs. 1.15/100 person-years (PY), p &lt;.0001), while in those DAA-treated, mortality rates slowly increased between 2012–2014 (.22/100PY) and 2018–2019 (2.25/100PY). Conclusion: In the Netherlands, individuals who are incarcerated/institutionalized, with low household income, or with psychiatric comorbidities are prone to being LTFU, which is associated with higher mortality. HCV care needs to be adapted for these vulnerable individuals.</p

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries:A Dutch Nationwide Cohort Study

Background. The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands. Methods. We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation. Results. We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3-infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS. Conclusions. (T)he DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes

Reasons for not commencing direct-acting antiviral treatment despite unrestricted access for individuals with HIV and hepatitis C virus: a multinational, prospective cohort study.

BACKGROUND Individuals with HIV and hepatitis C virus (HCV) who remain untreated with direct-acting antivirals can contribute to HCV transmission and HCV-related mortality. We aimed to compare rates of uptake of direct-acting antivirals following unrestricted access to this treatment in high-income countries and examine factors associated with remaining untreated. METHODS This multinational, prospective cohort study used data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). We analysed data from nine observational cohorts participating in the InCHEHC, including data from six high-income countries (Australia, Canada, France, the Netherlands, Spain, and Switzerland). We included individuals aged 18 years and older, with HIV and HCV (ie, HCV-RNA positive without evidence of spontaneous clearance) during unrestricted access to interferon-free direct-acting antiviral treatment in each country. We calculated the cumulative proportion of participants who remained untreated with direct-acting antivirals, with follow-up starting after the date of unrestricted access or cohort inclusion, whichever occurred most recently. Factors associated with the commencement rate of direct-acting antiviral treatment were assessed using competing-risks regression with the Fine-Gray method. FINDINGS The date of unrestricted access to direct-acting antiviral treatment for people with HIV ranged from Nov 1, 2014, in France to Nov 1, 2017, in Switzerland. We included 4552 individuals with HIV-HCV, mainly men who have sex with men (MSM; n=2156 [47%]) and people who inject or have injected drugs (n=1453 [32%]). 1365 (30%) of 4552 participants remained untreated with direct-acting antivirals. For individuals treated with direct-acting antivirals, median time from start of follow-up to treatment was 5 months (IQR 2-12). For individuals who were not treated with direct-acting antivirals, median follow-up was 22 months (8-30). Being linked to care in Australia, France, or the Netherlands, on antiretroviral therapy, having undetectable HIV RNA, and shorter duration since first positive HCV test were independently associated with higher commencement rate of direct-acting antiviral treatment. Compared with MSM, male heterosexuals and females with unknown or other routes of HIV transmission (ie, neither injection drug use nor heterosexual transmission) had lower rates of commencement. INTERPRETATION Despite unrestricted access, almost a third of individuals with HIV-HCV remained untreated with direct-acting antivirals during follow-up, with variation in commencement rate of HCV treatment between countries and key populations. Increased efforts are required to reach the remaining individuals with HIV who are HCV-viraemic to achieve HIV-HCV micro-elimination. FUNDING None

Hepatitis C virus in hemophilia:Health-related quality of life after successful treatment in the sixth Hemophilia in the Netherlands study

INTRODUCTION: Persons with hemophilia and hepatitis C virus (HCV) infection have a lower health‐related quality of life (HRQoL) than those never HCV infected. However, it is unknown whether HRQoL after HCV eradication is comparable to individuals never HCV infected. We aimed to compare HRQoL between HCV‐cured and never chronically HCV‐infected persons with hemophilia. METHODS: All persons with hemophilia in the Netherlands were invited for a nationwide study conducted in 2018–2019. For the current analysis, participants born before 1992 with data on HRQoL and HCV status were included. HCV status was collected from medical records. HRQoL was measured by RAND‐36 questionnaire, with a minimally important difference set at 4.0 points. Multivariable linear regression was used to adjust for age, hemophilia severity, HIV status, and self‐reported joint impairment. RESULTS: In total, 486 persons were eligible; 180 were HCV cured and 306 never chronically HCV infected. Compared with those never HCV infected, HCV‐cured individuals were older (57 vs. 53 years), more often had severe hemophilia (67% vs. 21%), and reported more impaired joints (median 3 vs. 0). Compared with those never HCV infected, adjusted RAND‐36 domain scores of HCV‐cured individuals cured were lower on all RAND‐36 domains except Pain, ranging from a difference of 4.5 (95% CI, −8.8 to −0.3) for Physical functioning to 11.3 (95% CI, −19.4 to −3.1) for Role limitations due to physical problems. CONCLUSION: Despite effective HCV treatment, HRQoL of HCV‐cured persons with hemophilia is still lower than HRQoL of those never chronically HCV‐infected on all RAND‐36 domains. This implies that careful psychosocial follow‐up and support are indicated

Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection?

Hepatocellular carcinoma (HCC) and variceal bleeding are among the most common causes of liver-related mortality in patients with hepatitis C virus (HCV)-induced cirrhosis. Current guidelines recommend HCC and gastroesophageal varices (GEV) surveillance in patients with HCV infection and cirrhosis. However, since the recent introduction of direct-acting antivirals, most patients with cirrhosis are now cured of their chronic HCV infection. As virological cure is considered to substantially reduce the risk of cirrhosis-related complications, this review discusses the current literature concerning the surveillance of HCC and GEV in patients with HCV-induced cirrhosis with a focus on the setting following sustained virological response

Viral hepatitis in haemophilia: historical perspective and current management

The introduction of clotting factor concentrates has substantially improved the lives of people with clotting factor deficiencies. Unfortunately, the transmission of blood-borne viral infections through these plasma-derived products led to a huge epidemic of human immunodeficiency virus and viral hepatitis in people with haemophilia (PWH). In a significant proportion of PWH exposed to these viruses, the ensuing decades-long chronic infection resulted in excess morbidity and mortality. Fortunately, developments in the safety of blood products, as well as vaccination and highly effective antiviral treatments have improved the prospects of PWH. The present article reviews the background of the viral hepatitis epidemic in PWH, the natural history of hepatitis B and C infections and their long-term management

Loss to follow-up in the hepatitis C care cascade: A substantial problem but opportunity for micro-elimination

Since the advent of direct-acting antivirals, elimination of hepatitis C viral (HCV) infections seems within reach. However, studies on the HCV cascade of care show suboptimal progression through each step for all patient groups. Loss to follow-up (LTFU) is a major issue and is a barrier to HCV elimination. This review summarizes the scale of the LTFU problem and proposes a micro-elimination approach. Retrieving LTFU patients and re-engaging them with care again has shown to be feasible in the Netherlands. Micro-elimination through retrieval can contribute to reaching the World Health Organization's viral hepatitis elimination targets by 2030