On-site testing and case management to improve hepatitis C care in drug users: a prospective, longitudinal, multicenter study in the DAA era.

BACKGROUND: Screening and treatment of hepatitis C virus (HCV) infection in people who use drugs (PWUD) remains insufficient. Reducing the burden of HCV infection in PWUD requires interventions focusing on the different steps of the HCV care cascade. METHODS: We performed a prospective, multicenter study, evaluating the impact of an HCV care model on the HCV care cascade among PWUD attending an addiction care center in Belgium between 2015 and 2018. Interventions within the care model consisted of pre-test counseling, on-site HCV screening and case management services. A multiple logistic regression model was performed to identify the independent factors influencing the outcomes. RESULTS: During the study period, 441 PWUD were registered at the addiction care center, 90% (395/441) were contacted, 88% (349/395) were screened for HCV infection. PWUD were more likely to be screened if they had ever injected drugs (p < .001; AOR 6.411 95% CI 3.464-11.864). In 45% (157/349), the HCV antibody (Ab) test was positive, and in 27% (94/349) HCV RNA was positive. Within the Belgian reimbursement criteria (fibrosis stage ≥ F2), 44% (41/94) were treated. Specialist evaluation at the hospital was lower for PWUD receiving decentralized opioid agonist therapy (p = .005; AOR 0.430 95% CI 0.005-0.380), PWUD with unstable housing in the past 6 months before inclusion (p = .015; AOR 0.035 95% CI 0.002-0.517) or if they were recently incarcerated (p = .001; AOR 0.010 95% CI 0.001-0.164). CONCLUSIONS: This HCV care model demonstrated high screening, linkage to care, and treatment initiation among PWUD in Belgium. Using the cascade of care to guide interventions is easy and necessary to monitor results. This population needs guidance, not only for screening and treatment initiation but also for the long-term follow-up since one in six had cirrhosis and could develop hepatocellular carcinoma. Further interventions are necessary to increase linkage to care and treatment initiation. Universal access to direct-acting antiviral therapy from 2019 will contribute to achieving HCV elimination in the PWUD population. TRIAL REGISTRATION: Clinical trial registration details: www.clinicaltrials.gov ( NCT03106194 ).

Early detection of chronic hepatitis B and risk factor assessment in Turkish migrants, Middle Limburg, Belgium.

BACKGROUND: Turkey is an intermediate hepatitis B virus (HBV) endemic country. However, prevalence among Turkish migrants in Belgium is unknown, especially in those born in Belgium with a foreign-born parent, i.e. second-generation migrants (SGM). AIMS: To evaluate the prevalence of HBV infection and associated risk factors in Turkish first-generation migrants (FGM), i.e. foreign-born, and SGM. METHODS: Between September 2017 and May 2019, free outreach testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and antibodies against HBsAg was offered to Turkish migrants in Middle-Limburg, Belgium. Face-to-face questionnaire assessed HBV risk factors. HBsAg positive patients were referred and followed up. Turkish SGM were stratified into birth cohort born before and after 1987, since those born after 1987 should be covered by the universal infant vaccination program. RESULTS: A total of 1,081/1,113 (97.1%) Turkish did go for HBV testing. Twenty-six (2.4%) were HBsAg positive; 11/26 were unaware of their status and 10/11 were successfully referred. HBsAg prevalence was 3.0% in FGM and 1.5% in SGM, p = .070. Only one out of seven HBsAg positive SGM was born after 1987. In the multiple generalized estimating equations model, the most important risk factors for anti-HBc positivity were male gender (p = .021), older age (p < .001), FGM (p < .001), low educational level of the mother (p = .003), HBV infected mother (p = .008), HBV infected siblings (p = .002), HBV infected other family member (p = .004), gynaecological examination in Turkey or unsafe male circumcision (p = .032) and dental treatment in Turkey (p = .049). CONCLUSION: Outreach testing was well-accepted and referral to specialist care was generally successful. National HBV screening should be implemented in the Turkish FGM population and might be considered in SGM not covered by primary prevention strategies.

Hepatitis B virus prevalence and risk factors in hard-to-reach Turkish population living in Belgium: A protocol for screening.

BACKGROUND: Hepatitis B virus (HBV) infection is an important public health problem in the Turkish population, that is, one of the largest migrant populations in Europe. With the introduction of cost-effective antiviral treatments in the past decade, there is a need to identify HBV-infected patients who may benefit from treatment. This study describes the design of a study to assess the HBV prevalence in the Turkish population living in Belgium. Additionally, we will determine the risk factors of HBV infection and the uptake of screening, vaccination, and antiviral treatment in this hard-to-reach Turkish population. METHODS: A longitudinal, epidemiological study will be conducted in the region Middle Limburg Belgium, where the Turkish adult population, 18 years of age and older, will be screened for hepatitis B surface antigen (HBsAg), antibodies against HBsAg (anti-HBs), and antibodies against hepatitis B core antigen (anti-HBc). Educational meetings concerning viral hepatitis B will be organized and there will be 3 ways to be screened for HBV: immediately after the educational meetings, at the Outpatient Hepatology Department of Ziekenhuis Oost-Limburg, and at home visits. Subsequently, participants will be asked to fill in a questionnaire regarding sociodemographic factors, migration history, risk factors for HBV infection (e.g., sharing toothbrushes, HBV-infected family member), and HBV vaccination status. Six months after screening, HBsAg-positive patients will be assessed whether they are under follow-up at the general practitioner or hepatologist. We will also gather information regarding the uptake of vaccination in nonimmunized subjects. DISCUSSION: This study will provide information about the HBV prevalence and distribution of the stages of liver disease in the Turkish population in Belgium. By determining the risk factors for HBV infection, subgroups with an increased prevalence of HBV infection can be identified. CLINICAL TRIAL NUMBER: This clinical trial is registered at clinicaltrials.gov (NCT03396458).

Harm reduction and viral hepatitis C in European prisons: a cross-sectional survey of 25 countries.

BACKGROUND: Current estimates suggest that 15% of all prisoners worldwide are chronically infected with the hepatitis C virus (HCV), and this number is even higher in regions with high rates of injecting drug use. Although harm reduction services such as opioid substitution therapy (OST) and needle and syringe programs (NSPs) are effective in preventing the further spread of HCV and HIV, the extent to which these are available in prisons varies significantly across countries. METHODS: The Hep-CORE study surveyed liver patient groups from 25 European countries in 2016 and mid-2017 on national policies related to harm reduction, testing/screening, and treatment for HCV in prison settings. Results from the cross-sectional survey were compared to the data from available reports and the peer-reviewed literature to determine the overall degree to which European countries implement evidence-based HCV recommendations in prison settings. RESULTS: Patient groups in nine countries (36%) identified prisoners as a high-risk population target for HCV testing/screening. Twenty-one countries (84%) provide HCV treatment in prisons. However, the extent of coverage of these treatment programs varies widely. Two countries (8%) have NSPs officially available in prisons in all parts of the country. Eleven countries (44%) provide OST in prisons in all parts of the country without additional requirements. CONCLUSION: Despite the existence of evidence-based recommendations, infectious disease prevention measures such as harm reduction programs are inadequate in European prison settings. Harm reduction, HCV testing/screening, and treatment should be scaled up in prison settings in order to progress towards eliminating HCV as a public health threat.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs.

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection.

Eligibility of persons who inject drugs for treatment of hepatitis C virus infection.

In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus (HCV) infection. Although people who inject drugs (PWID) are the major source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these patients, and substitution therapy and active substance use are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning HCV infection and treatment strategies in PWID.

Resource use and cost of hepatitis C-related care.

BACKGROUND: Chronic hepatitis because of the hepatitis C virus (CHC) is a major health problem that can lead to decompensated cirrhosis, hepatocellular carcinoma, and eventually death, all of which are associated with significant healthcare costs. AIM: To update the cost of care of CHC according to the different severity stages of the disease in a west European country (Belgium). METHODS: Medical records of 157 patients, who were referred to the medical specialist at different stages of disease, were reviewed to identify the medical costs over a follow-up period of 3 years or 2 years in the case of liver transplantation (LT). Six disease stages were defined on the basis of histology (Metavir classification) and/or clinical data. RESULTS: In comparison with mild disease, the cost increased 1.6 times in the case of decompensated cirrhosis, 1.9 times in the case of hepatocellular carcinoma, and 3.4 in the case of LT. The costs for medication, hospitalization, and ambulatory care were, respectively, on the one hand, 81, 8, and 11% for mild disease and, on the other, 18, 79, and 3% for LT. In the case of a sustained viral response, the cost of follow-up within 3 years decreased by 45% for patients with mild and moderate disease. CONCLUSION: Antiviral treatment is the most important factor governing cost in mild and moderate disease, but once complications of CHC occur, hospitalization costs far exceed the cost of antiviral therapy. Already during the first 3 years of follow-up, sustained viral response decreased the cost significantly. Treatment of patients with CHC in an early stage has the potential to be cost-effective.

Early prediction of major depression in chronic hepatitis C patients during peg-interferon alpha-2b treatment by assessment of vegetative-depressive symptoms after four weeks.

AIM: To study the predictive value of the vegetative-depressive symptoms of the Zung Depression Rating Scale for the occurrence of depression during treatment with peg-interferon alpha-2b of chronic hepatitis C (CHC) patients. METHODS: The predictive value of vegetative-depressive symptoms at 4 wk of treatment for the occurrence of a subsequent diagnosis of major depressive disorder (MDD) was studied in CHC patients infected after substance use in a prospective, multi-center treatment trial in Belgium. The presence of vegetative-depressive symptoms was assessed using the Zung Scale before and 4 wk after the start of antiviral treatment. RESULTS: Out of 49 eligible patients, 19 (39%) developed MDD. The area under the ROC curve of the vegetative Zung subscale was 0.73, P = 0.004. The sensitivity at a cut-point of > 15/35 was 95% (95% CI: 74-100). The positive predictive value equalled 44% (95% CI: 29-60). CONCLUSION: In this group of Belgian CHC patients infected after substance use, antiviral treatment caused a considerable risk of depression. Seven vegetative-depressive symptoms of the Zung scale at wk 4 of treatment predicted 95% of all emerging depressions, at a price of 56% false positive test results.