Uptake of hepatitis C virus screening and treatment in persons under opioid substitution therapy between 2008 and 2013 in Belgium.

BACKGROUND: Hepatitis C is a viral infection caused by the hepatitis C virus (HCV) with people who inject drugs as the main group at risk worldwide. AIM: This study investigated the differences in uptake for HCV screening and treatment between persons in opioid substitution therapy (OST) and the other members of the Christian Health Insurance Fund in Belgium. METHODS: Invoice data were retrospectively collected from the Christian Health Insurance Fund, representing 42% of the healthcare users. Information on demographics, screening, diagnostic tests, treatment and disease progression was obtained from 2008 till 2013. All people in this study were aged 20-65 year. Persons in the OST group were identified as having at least one prescription reimbursed for methadone. This group was compared to the other members of the Insurance Fund not on OST (NOST). RESULTS: The Insurance Fund registered 8,409 unique OST and 3,525,190 members in the general group. HCV RNA screening rate was higher in the OST group after correction for age and gender (4.3% vs. 0.2%). Ribavirin reimbursement, did not differ between the OST and NOST group screened for HCV RNA (16.9% vs. 14.4%), though the probability of having ribavirin reimbursed was smaller for females than for males. Procedures concerning disease progression were reimbursed less frequently in the HCV RNA screened OST group compared to the NOST group (0.3% vs. 1.2%). CONCLUSION: People on OST were screened more often for HCV RNA. However, the general uptake for HCV screening and treatment in both populations remained suboptimal.

Mitigating the burden of hepatitis C virus among people who inject drugs in Belgium.

BACKGROUD AND AIMS: In 2010, there were an estimated 10 100 PWID in Belgium and 43% (34%-57%) were HCV infected. Understanding HCV transmission dynamics in high-risk populations and assessing the potential impact of improved HCV treatment strategies requires robust epidemiological data and mathematical modeling. METHODS: CV transmission was modeled using cohorts to track HCV incidence and prevalence among active PWID in the general PWID population, OST and NSP. Model assumptions were derived from published literature and expert consensus. The relative impact of increasing the number of PWID treated with new oral DAAs was considered. RESULTS: If the current transmission paradigm continues, there will be 2645 HCV-infected PWID in 2030. Annually treating 30 (1% of 2015 population) or 120 (4% of 2015 population) HCV-infected PWID with oral DAAs will result in 5% and 25% reductions, respectively, in HCV-infected PWID by 2030. Treating 370 PWID annually (12.5% of 2015 population) will result in a > 90% reduction by 2030. CONCLUSION: Treating a small number of PWID can result in substantial reduction in HCV prevalence in this population ; however, high levels of treatment are necessary to reduce the viral pool and thus the risk of secondary infections. This analysis supports implementation of a screening and treatment strategy among PWID when combined with an expansion of harm reduction programs.

Achieving WHO recommendations for Hepatitis C Virus Elimination in Belgium.

BACKGROUD: The World Health Organization (WHO) released updated guidelines for the screening, care and treatment of patients with chronic hepatitis C virus (HCV) infection. METHODS: A previously described HCV disease burden model was used to develop a "WHO scenario" to achieve the WHO recommendations of a 90% reduction in incidence and 65% reduction in liver-related deaths. After determining the steps necessary to achieve this goal, the impact of realistic constraints was modeled. RESULTS: In 2015, there were 66.200 viremic infections, with 43% diagnosed and 1.350 treated. In order to reduce new infections, treatment must be extended to ≥ F0 patients, including people who inject drugs and other individuals at risk of transmitting HCV. -Additionally, diagnosis and treatment of 3.030 and 4.060 patients, respectively, would be required. The largest attenuation of the WHO scenario would occur if no new cases were diagnosed after 2018 (300% more viremic infections by 2030). Limiting treatment to ≥ F2 patients or treating fewer patients (3.000) would result in 220% or 140% more viremic cases, respectively, compared with the WHO scenario. CONCLUSION: Achieving the WHO guidelines in Belgium requires a coordinated effort to scale up treatment and prevention efforts and to allow treatment access to patients of all fibrosis stages. A scale-up of treatment, however, requires patients to be both diagnosed and linked to care, suggesting a need for increased awareness and expanded screening efforts. Finally, prevention of new HCV infections requires a comprehensive understanding of the population at risk of transmitting HCV.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies.

Association between recent herpes zoster but not herpes simplex infection and subsequent risk of malignancy in women: a retrospective cohort study.

The association between herpes zoster and subsequent cancer risk is still unclear. Consequently, doubts remain regarding the need for investigation of herpes patients for co-existing or subsequent malignancy. This is a retrospective cohort study comparing cancer risk in patients after herpes zoster and age-/sex-matched non-herpes zoster patients, in a primary care-based continuous morbidity database. We tested for interaction by gender, age, diabetes, HRT use or antiviral therapy. Analyses were repeated for patients with and without herpes simplex. The hazard ratio (HR) comparing cancer risk in herpes zoster vs. control patients was significant in all women, women aged > 65 years and subgroups of breast and colorectal cancer (HRs 1·60, 1·82, 2·14, 2·19, respectively). For men, a significant association was found for haematological cancers (HR 2·92). No associations were found with herpes simplex. No interaction was identified with antiviral therapy, diabetes or HRT treatment. We concluded that there was a moderate significant association between herpes zoster and subsequent cancer risk in women aged > 65 years, without any influence of antiviral therapy. No association was found with herpes simplex. There is insufficient reason for extensively testing older patients with herpes zoster or herpes simplex for the presence of occult cancer.

The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons.

The main consequence of the loss of MM and muscle strength is limitations of physical performance and disability in older people. It is unclear whether a decline in functional capacity results from the loss of MM and/or the qualitative impairment of the muscle tissue. The aim of our research was to investigate the relationship between physical performance and grip strength, inflammatory markers and MM in a population of community-dwelling very old persons. This study is a cross-sectional analysis within the BELFRAIL-study, a cohort study of subjects aged 80 years and older (n=567). MM was assessed by bioelectrical impedance. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined on fasting blood samples. Logistic regression analysis was build using a low physical performance level evaluated according to Short Physical Performance Battery (SPPB) (dependent variable) and grip strength, pro-inflammatory status and MM (independent variables) adjusted for age and for the total number of chronic diseases. Low SPPB scores were associated with grip strength scores for women (OR 0.86 (95% CI 0.77-0.96)), and for men (OR 0.89 (95% CI 0.81-0.96)). The relationships between low SPPB and MM or inflammatory profile were not significant. Our results show that low physical performance remains associated with low grip strength even after considering other risk factors for sarcopenia in the oldest old and support the hypothesis that low muscle strength is a better indicator than low MM. The role of an inflammatory component in the age-related loss of muscle strength and function could not be confirmed.

The influence of renal function on vitamin D metabolism in the very elderly.

OBJECTIVES: Hypovitaminosis D and chronic kidney disease (CKD) are highly prevalent in older adults. The factors correlating with 25-OH-vitamin D and PTH levels were analyzed in older adults with and without CKD. DESIGN: We performed a cross-sectional analysis embedded within the BELFRAIL study. SETTING: A population-based prospective cohort study of the very elderly in Belgium. PARTICIPANTS: 325 participants, all aged 80 or older. MEASURMENTS: Time of year and LAPAQ score were used as proxies for sunshine exposure. Vitamin D3 supplementation, gender, institutionalisation, age, level of education, and serum calcium and phosphorus level were examined as possible confounders in the analyses. RESULTS: There was no correlation between the presence of CKD and low 25-OH-vitamin D levels, but there was a significant (p<0.01) correlation between CKD and high PTH levels. Among the participants with a normal eGFR, the LAPACQ score, vitamin D supplementation, season, log PTH value and eGFR were correlated with log 25-OH-vitamin D levels. Among the participants with CKD, only vitamin D supplementation, log PTH levels and serum calcium levels were correlated with log 25-OH-vitamin D levels. Gender, log 25-OH-vitamin D values, serum calcium and phosphorus levels and eGFR were correlated with log PTH values in the patients with normal eGFR. Log 25-OH-vitamin D values, serum phosphorus levels, vitamin D supplementation (p=0.07), season (p=0.10) and eGFR were correlated with log PTH values in the patients with CKD. CONCLUSION: Exposure to sunshine and an active lifestyle were correlated with higher 25-OH-vitamin D levels in older adults without CKD. The PTH level in patients with CKD may be influenced by the season.

Hepatitis C prevalence in injecting drug users in Europe, 1990-2007: impact of study recruitment setting.

Monitoring injecting drug users' (IDUs) health is challenging because IDUs form a difficult to reach population. We examined the impact of recruitment setting on hepatitis C prevalence. Individual datasets from 12 studies were merged. Predictors of HCV positivity were sought through a multilevel analysis using a mixed-effects logistic model, with study identifier as random intercept. HCV prevalence ranged from 21% to 86% across the studies. Overall, HCV prevalence was higher in IDUs recruited in drug treatment centres compared to those recruited in low-threshold settings (74% and 42%, respectively, P < 0·001). Recruitment setting remained significantly associated with HCV prevalence after adjustment for duration of injecting and recent injection (adjusted odds ratio 0·7, 95% confidence interval 0·6-0·8, P = 0·05). Recruitment setting may have an impact on HCV prevalence estimates of IDUs in Europe. Assessing the impact of mixed recruitment strategies, including respondent-driven sampling, on HCV prevalence estimates, would be valuable.

A comparison between the force of infection estimates for blood-borne viruses in injecting drug user populations across the European Union: a modelling study.

A number of studies have been conducted in injecting drug user (IDU) populations in Europe, in which the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was measured together with demographic and epidemiological information such as age and the age at first injection. A measure of the risk of becoming infected is the force of infection (FOI), defined as the per capita rate at which susceptible individuals acquire infection. The objective of this study was to estimate the FOI and its heterogeneity for HBV, HCV and HIV (where available) for IDU populations in a number of countries in Europe. Data were obtained from five countries: Belgium, the United Kingdom, Spain and Italy, and the Czech Republic, which provided two data sets. The model describes the prevalence of infection as a function of the FOI that may vary over time or duration of IDU. In addition to this, if two or more infections were being considered then a parameter describing the potential heterogeneity of the FOI within the IDU population was also estimated. The results here add to the growing evidence that new initiates to injecting are at an increased risk of blood-borne viral infection compared with more experienced IDUs. In addition, there is evidence of individual heterogeneity of FOI estimates within the overall IDU populations. This suggests that different proportions of individuals in each population are at increased risk of infection compared with the rest of the population. Future interventions should identify and target these individuals. Moreover, changes over time in individual heterogeneity estimates of IDU populations may provide an indicator for measuring intervention impacts.

The epidemic history of hepatitis C among injecting drug users in Flanders, Belgium.

We employed recently developed statistical methods to explore the epidemic behaviour of hepatitis C subtype 1a and subtype 3a among injecting drug users (IDUs) in Flanders, Belgium, using new gene sequence data sampled among two geographically distinct populations of IDUs. First the extent of hepatitis C transmission across regions/countries was studied through calculation of association indices. It was shown that viral exchange had occurred between both populations in Flanders as well as across international borders. Furthermore, evidence was found suggestive of subtypes 1a and 3a predominantly circulating in subpopulations of Flemish IDUs, exhibiting different degrees of travelling/migration behaviour. Secondly, through coalescent-based analysis the viral epidemic history of the hepatitis C subtype 1a and 3a epidemics was inferred. Evidence was found for different dynamic forces driving both epidemics. Moreover, results suggested that the hepatitis C subtype 3a epidemic has reached a steady state, while the hepatitis C 1a epidemic has not, which therefore might become the predominant subtype among IDUs.

Evidence for a substantial role of sharing of injecting paraphernalia other than syringes/needles to the spread of hepatitis C among injecting drug users.

In industrialized countries, transmission of hepatitis C occurs primarily through injecting drug use. Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of other injecting paraphernalia is increasing. In this paper, the independent effects of sharing paraphernalia other than syringes/needles have been estimated. The prevalence and force of infection were modelled using three serological data sets from drug users in three centres in Belgium as a function of the sharing behaviour. It was found that sharing of materials other than syringes/needles indeed seemed to contribute substantially to the spread of hepatitis C among injecting drug users.

Molecular epidemiology of hepatitis C among drug users in Flanders, Belgium: association of genotype with clinical parameters and with sex- and drug-related risk behaviours.

The aim of this study was to determine the genotypic variation of hepatitis C among drug users in Flanders and to relate the distribution of genotypes to the characteristics of the population. Hepatitis C virus RNA (HCV-RNA) quantification and genotyping was performed on stored samples from 161 anti-HCV-positive injecting and non-injecting drug users. Information on sociodemographic status, drug-related risk behaviour and sexual risk behaviour was available for each drug user. HCV-RNA was present in 152 of 161 samples (94.4%). Genotype 1 was predominant (48.7%), followed by genotype 3 (41.2%), genotype 4 (8.8%) and genotype 2 (1.4%). In the multivariate analysis, lack of a history of injecting drug use was confirmed as a statistically significant predictor for infection with genotype 1. Predictors for infection with genotype 3 were the presence of anti-HBc antibodies and a history of injecting drug use. Being tattooed emerged as a statistically significant predictor for infection with genotype 4. The 94.4% prevalence of HCV-RNA among anti-HCV-positive drug users was considerably higher than the 54-86% chronicity rate found globally among HCV-infected patients. The results of this study suggest the existence of separate transmission networks for injecting drug users and non-injecting drug users. Finally, the results suggest that tattooing practices play a role in the spread of HCV among drug users.

The epidemiology of hepatitis C among injecting drug users in Belgium.

In industrialised countries, injecting drug use is currently the most important risk factor for infection with hepatitis C, resulting in high prevalence rates of hepatitis C among injecting drug users. To contain the hepatitis C epidemic major efforts should be done to prevent new infection among injecting drug users. Monitoring infection rates are crucial as it may provide feedback on the effectiveness of interventions. In this article the epidemiology of hepatitis C among injecting drug users in Belgium is briefly reviewed. More specifically the prevalence of anti-HCV antibodies, the prevalence of co-infections, the proportion of chronic HCV carriers, the distribution of genotypes and preventive measures among injecting drug users in Belgium are discussed and compared to the situation elsewhere in Western Europe.

Substance use in Belgium : prevalence and management.

Substance use is emerging in Belgium. The 'typical user' starts at a young age. Polydrug use has become very common. Cannabis and alcohol are the most frequently used substances among the school population. Heroin and cocaine are the most frequently injected drugs. Sharing of injecting material and paraphernalia is reported to happen in half of the subjects injecting drugs. Substance use causes a lot of adverse organic, social and psychiatric events. Management of substance use consists of information, drug-free treatment and harm reduction, including substitution and maintenance programs. The management of care in Belgium differs between the regions.

Methadone and buprenorphine maintenance therapies for patients with hepatitis C virus infected after intravenous drug use.

Heroin addiction is a chronic relapsing disease that is difficult to cure, but stabilisation and harm reduction can importantly increase the life time expectancy and the quality of life of the patient, his immediate vicinity and society in general. Currently, no proven effective pharmacological interventions are available for cocaine addiction, and treatment has to rely on existing cognitive behaviour therapies combined with contingency management strategies. Substitution therapy, however, is effective in caring for heroin addicts. Methadone is a synthetic opioid that counteracts withdrawal symptoms of heroin. Buprenorphine is a derivative of the morphine alkaloid, thebaine, and is a partial opioid agonist at the micro opioid receptor in the nervous system. A substitution treatment program effectively reduces and often eliminates heroin injection behaviour, rendering patients more socially stabilised. Reduction in the number of viral co-infections can be observed. Methadone undergoes oxidative biotransformation in the liver, but is also stored in the liver and released into the blood in unchanged form. The usual dose can be continued in patients with stable chronic liver disease, including advanced cirrhosis. In acute liver disease or acute decompensation of chronic liver disease, close clinical observation for signs of narcotic overdose or withdrawal is necessary. A modest alteration in methadone dose may be appropriate for some patients. Buprenorphine can cause liver dysfunction after sublingual and even more after intravenous administration. It is advised to follow the liver function during buprenorphine treatment and to warn the clients for intravenous use of buprenorphine. Neither methadone nor buprenorphine do influence the effect of interferon and ribavirin during the treatment of chronic hepatitis C patients. It may be necessary to increase the dosage of methadone during interferon treatment.

Prevalence of hepatitis C in drug users in Flanders: determinants and geographic differences.

The prevalence of hepatitis C and related risk factors in drug users were compared in two geographic regions in Belgium, the city of Antwerp and the mixed urban-rural area of Limburg. All 310 participants were surveyed and screened for hepatitis B, hepatitis C and HIV. Prevalence rates of anti-HCV, anti-HBc and anti-HIV were 71, 62 and 4% in Antwerp and 46, 21 and 0% in Limburg respectively. Injecting drug use, duration of injecting drug use, work as a commercial sex-worker, originating from Turkey or Northern Africa, marginalization and anti-HBc positivity were identified as independent predictors for hepatitis C infection. In this study an important difference in HCV seroprevalence among drug users in a methadone maintenance programme across two geographic regions in Belgium was demonstrated. This was explained not only by variations in drug-related risk behaviour, but also by differences in sexual risk behaviour and socio-economic status.

Management of hepatitis C virus infections in intravenous drug users.

Intravenous drug use is a major route of hepatitis C virus (HCV) transmission. In Belgium, more than 70% of the intravenous drug users (IVDUs) are HCV seropositive. In the past, medical treatment of HCV-positive IVDUs has been controversial. However, current studies support that the anti-HCV therapy of IVDUs should be the same as in other HCV-infected patients. In prison populations, HCV screening and therapy has to be performed. Patients should be counseled about the benefits of alcohol abstinence, should be educated about safer injection techniques to avoid reinfection, and should be vaccinated to avoid hepatitis A or B co-infections. Treatment of HCV infections should not be withheld from patient populations with complicated social problems. Physicians should rather develop individual treatment and follow-up plans in order to optimize compliance in IVDUs.

Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system.

A formulation of recombinant hepatitis B surface antigen (HBsAg) combined with a novel adjuvant system, SBAS4--a combination of aluminium salt and monophosphoryl lipid A (MPL), was assessed in 27 healthy adult volunteers with a commercial vaccine (Engerix-B) as control. After three doses (0, 1, 6 months schedule), reactogenicity profiles were similar. Local reactions were essentially mild, the most frequent being soreness at the injection site. Seroprotection was achieved after two doses in all subjects given the candidate vaccine, all Engerix-B vaccines being seroprotected after the third dose. After the second and third doses, higher anti-HBs Geometric Mean Titres (GMTs) were observed in the group which received the formulation with the novel adjuvant system, and cellular immunity, measured as HBsAg-specific lymphoproliferation was stronger than with Engerix-B. These results indicate that the new formulation is safe, well-tolerated and immunogenic and may promote more rapid protection against hepatitis B infection.