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Background: The introduction of highly effective direct-acting antiviral therapy has changed the hepatitis C virus (HCV) treatment paradigm. However, a recent update on HCV epidemiology in incarcerated settings is necessary to accurately determine the extent of the problem, provide information to policymakers and public healthcare, and meet the World Health Organization's goals by 2030. This systematic review and meta-analysis were performed to determine the prevalence of HCV Ab and RNA in incarcerated settings., Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and Web of Science for papers published between January 2013 and August 2021. We included studies with information on the prevalence of HCV Ab or RNA in incarcerated settings. A random-effects meta-analysis was done to calculate the pooled prevalence and meta-regression to explore heterogeneity., Results: Ninety-two unique sources reporting data for 36 countries were included. The estimated prevalence of HCV Ab ranged from 0.3% to 74.4%. HCV RNA prevalence (available in 46 sources) ranged from 0% to 56.3%. Genotypes (available in 19 sources) 1(a) and 3 were most frequently reported in incarcerated settings. HCV/HIV coinfection (available in 36 sources) was highest in Italy, Estonia, Pakistan, and Spain. Statistical analysis revealed that almost all observed heterogeneity reflects real differences in prevalence between studies, considering I 2 was very high in the meta-analysis., Conclusions: HCV in incarcerated settings is still a significant problem with a higher prevalence than in the general population. It is of utmost importance to start screening for HCV (Ab and RNA) in incarcerated settings to give clear, reliable and recent figures to plan further treatment. This is all in the context of meeting the 2030 WHO targets which are only less than a decade away., Trial Registration: PROSPERO: CRD42020162616., (© 2022. The Author(s).)

Objective: The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration., Design: We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson., Results: Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I 2 =74.6%) and 5.7 (2.5 to 15.3, I 2 =54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1)., Conclusion: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified., Competing Interests: Competing interests: VS: travel funding from Bayer. FT: DSMB fees from Basilea Pharmaceutica International and ROVI; educational fees from Janssen and Ferrer. PN: consults for AbbVie, AstraZeneca, Bayer, BMS, Eisai, Gilead, Ipsen, Roche. He received grants from AbbVie and BMS. ZM: speaker fees and consultancy for Gilead and AbbVie. RT: personal fees from Merk Sharp & Dorme, Giliad Sciences and AbbVie GK. TM: personal fees from Merk Sharp & Dorme, Giliad Sciences and AbbVie GK. XF: consultancy fees for AbbVie and Gilead Sciences. HT: speaker fees from AbbVie, Gildead, MSD and Bayer. SB: consultancy fees and educational grants from: Gilead Sciences, MSD, Intercept. ED: advisory board from AbbVie; speaking and teaching from Gilead, MSD, AbbVie. M-LY: research grant from Abbott, BMS, Gilead and Merck; consultant of AbbVie, Abbott, BMS, Gilead, Merck and Roche; speaker of AbbVie, Abbott, BMS, Gilead and Merck. YA: donation-funded department funded by Toray Industries Inc., Gilead Sciences, AbbVie GK and Fuji Rebio Inc. AS: has received research funding from AbbVie and Gilead. He has served as a consultant for Wako Diagnostics, Glycotest, Exact Sciences, Roche, GRAIL, Genentech, Bayer, Eisai, Exelixis, AstraZeneca, BMS and TARGET Pharmasolutions. MK: lecture fees from Abott and AstraZeneca. J-FD: advisory committees: AbbVie, Bayer, Bristol-Myers Squibb, Falk, Genfit, Genkyotex, Gilead Sciences, HepaRegenix, Intercept, Lilly, Merck, Novartis. Speaking and teaching: Bayer, Bristol-Myers Squibb, Intercept, Genfit, Gilead Sciences, Novartis, Roche. NM: research founding, lecture fees, advisory committees and travel grants from MSD. Lecture fees, advisory committees and travel grants from AbbVie and Gilead. SP: consulting and lecturing fees from Janssen, Gilead, MSD, AbbVie, Biotest, Shinogui, Viiv and grants from Bristol-Myers Squibb, Gilead, Roche and MSD, without relation to this manuscript. JC: grants and research support from Gilead Sciences, AbbVie, MSD, Shionogi and Intercept Pharmaceuticals (all outside the submitted work). Is a speaker for Gilead Sciences and AbbVie. JLC: reports grant support and/or consultancy and lecture fees from AbbVie, Gilead Sciences, Bristol-Myers Squibb, Janssen and MSD. RV: research grant from AbbVie. GS: consultancy fees and lecture fees from Gilead and AbbVie. FPR: lecture fees AbbVie, Gilead, MSD, Biotest; travel funds AbbVie, Biotest, Kedrion; research funds AbbVie, Gilead, MSD. RB: research grants from MSD, AbbVie and Gilead. JR: educational grants from Amgen, Grüenenthal Pharma, Boehringer Ingelheim España, Janssen-Cilag, Ferrer International, Lilly, Merck Sharp & Dohme and Roche Farma. FT: consultancy fees from AstraZeneca, Bayer, BMS, Eisai and Sirtex. Lecture fees from AlfaSigma and Bayer. Research grants from Bayer. CC: consultancy fees from Bayer, EISAI, MSD, Gilead, ABV. JB: consultancy fees from Arqule, Bayer, Novartis, BMS, BTG-Biocompatibles, Eisai, Kowa, Terumo, Gilead, Bio-Alliance/Onxeo, Roche, AbbVie, Merck, Sirtex, Ipsen, Astra-Medimmune, Incyte, Quirem, Adaptimmune, Lilly, Basilea, Nerviano. Research grants from Bayer and BTG. Educational grants from Bayer and BTG. Lecture fees from Bayer, BTG-Biocompatibles, Eisai, Terumo, Sirtex, Ipsen. GC: consultancy fees from Bayer, Ipsen. MR: consultancy fees from Bayer, BMS, Roche, Ipsen, AstraZeneca and Lilly. Lecture fees from Bayer, BMS, Gilead, Lilly and Roche. Research grants from Bayer and Ipsen., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Study Aims: There is ongoing debate whether antiviral therapy should be initiated in hepatitis B e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels but high HBV DNA levels >2,000 IU/mL. Since the need for antiviral therapy might be different between Asian and Caucasian patients, we studied the long-term disease outcome in Caucasian patients living in Western Europe., Patients and Methods: One hundred sixteen patients with high HBV DNA levels (>2,000 IU/mL) at diagnosis were included in the high viremia group, while those with HBV DNA <2,000 IU/mL were used as controls (n = 327). All patients were Caucasian, HBeAg negative, had normal ALT levels and had no significant liver disease at diagnosis., Results: Median follow-up was 7 + 9.8 years in the high viremia group and this was 10 + 12.5 years in controls. The cumulative probability of a liver-related event over 10 years was 4.8% vs 0.0% in the control group (p=.008). In multivariable analysis, high viremia group was associated with the occurrence of a liver-related event (hazards ratio (HR) 95% confidence interval (CI): 1.20-11.98, p=.023). In this subgroup, older age at diagnosis (HR 95% CI: 1.01-1.16, p=.023) predicted a higher risk of liver-related event. In the high viremia group, liver-related mortality was 0.9% and none of the patients developed hepatocellular carcinoma., Conclusions: HBV DNA >2,000 IU/mL influences the long-term disease outcome in Caucasian HBeAg-negative patients living in Western Europe. Nevertheless, the risk of liver-related events is low., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Background: There is currently no systematic screening for hepatitis C (HCV) reinfection in people who inject drugs (PWID) after treatment in Belgium. However, in a recent meta-analysis, the overall HCV reinfection rate was 5.9/100 person-years (PY) among PWID. Accordingly, this study was undertaken to investigate the reinfection rate in former and active PWID who achieved the end of treatment response after direct-acting antiviral (DAA) treatment in Belgium., Methods: This observational cross-sectional study recruited individuals with a history of injecting drug use who had achieved the end of treatment response to any DAA treatment between 2015 and 2020. Participants were offered a post-treatment HCV RNA test., Results: Eighty-five potential participants were eligible to participate and contacted, of whom 60 participants were enrolled in the study with a median age of 51.0 (IQR 44.3-56.0) years; it was reported that 23.3% continued to inject drugs intravenously after DAA treatment. Liver cirrhosis was present in 12.9%. The majority had genotype 1a (51.7%) or genotype 3 (15.0%) infection. We detected no reinfections in this study population. The total time patients were followed up for reinfection in the study was 78.5 PY (median 1.0 years IQR 0.4-2.0)., Conclusion: Reinfection after successful treatment with DAA initially appears to be very low in Belgian PWID. Therefore, efforts should be made to screen individuals with persistent risk behaviors for reinfection systematically. In addition, a national HCV registry should be established to accurately define the burden of HCV infection and reinfection in Belgium and support the elimination of viral hepatitis C in Europe. Trial registration clinicaltrials.gov NCT04251572, Registered 5 Feb 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04251572 ., (© 2021. The Author(s).)

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 )., (© 2021. The Author(s).)

Background: Prevalence data on viral hepatitis B (HBV), hepatitis C (HCV), and HIV infection in prison are often scarce or outdated. There is currently no systematic screening for these blood-borne viral infections (BBV) in Belgian prisons. There is an urgency to assess the prevalence of these BBV to inform policymakers and public healthcare., Methods: This was a multicentre, interventional study to assess the prevalence of BBV using opt-in screening in prisons across Belgium, April 2019 - March 2020. Prisoners were tested using a finger prick and BBV risk factors were assessed using a questionnaire. A generalized linear mixed model was used to investigate the association between the various risk factors and HCV., Results: In total, 886 prisoners from 11 Belgian prisons were screened. Study uptake ranged from 16.9 to 35.4% in long-term facilities. The prevalence of HCV antibodies (Ab), hepatitis B surface antigen (Ag) and HIV Ab/Ag was 5.0% (44/886), 0.8% (7/886), and 0.2% (2/886). The adjusted odds for HCV Ab were highest in prisoners who ever injected (p < 0.001; AOR 24.6 CI 95% (5.5-215.2). The prevalence of detectable HCV RNA in the total cohort was 2.1% (19/886). Thirteen (68.4%) prisoners were redirected for follow-up of their HCV infection., Conclusions: Opt-in testing for viral hepatitis B, C and HIV was relatively well-accepted in prisons. Compared with the general population, prisoners have a higher prevalence of infection with BBV, especially for HCV. Systematic screening for these BBV should be recommended in all prisons, preferably using opt-out to optimize screening uptake., Trial Registration: Retrospectively registered at clinical trials NCT04366492 April 29, 2020., (© 2021. The Author(s).)

Background: Targeted screening for hepatitis C viral (HCV) infection is not yet widely executed in Belgium. When performed in people who use drugs (PWUD), it is mainly focused on those receiving opiate agonist therapy (OAT). We wanted to reach out to a population of difficult to reach PWUD not on centralized OAT, using non-invasive screening as a bridge to re-integration in medical care supported by facilitated referral to a specialist., Methods: This was a prospective, multicenter cohort study in PWUD not enrolled in a centralized OAT program in a community-based facility in Limburg or OAT program in a community-based facility in Antwerp, Belgium, from October 2018 until October 2019. Two study teams recruited participants using an outreach method at 18 different locations. Participants were tested for HCV antibodies (Ab) by finger prick, and risk factors were assessed through a face-to-face questionnaire. Univariate analyses were used to assess the association between HCV Ab and each risk factor separately. A generalized linear mixed model was used to investigate the association between the different risk factors and HCV., Results: In total, 425 PWUD were reached with a mean age of 41.6 ± 10.8, and 78.8% (335/425) were men. HCV Ab prevalence was 14.8% (63/425). Fifty-six (88.9%) PWUD were referred, of whom 37 (66.1%) were linked to care and tested for HCV RNA. Twenty-nine (78.4%) had a chronic HCV infection. Treatment was initiated in 17 (58.6%) patients. The adjusted odds for HCV Ab were highest in those with unstable housing 6 months before inclusion (p < .001, AOR 8.2 CI 95% 3.2-23.3) and in those who had ever shared paraphernalia for intravenous drug use (p < .001, AOR 6.2 CI 95% 2.5-16.0)., Conclusions: An important part tested positive for HCV. Treatment could be started in more than half of the chronically infected referred and tested positive for HCV-RNA. Micro-elimination is necessary to achieve the World Health Organization goals by 2030. However, it remains crucial to screen and link a broader group of PWUD to care than to focus solely on those who inject drugs., Trial Registration: clinicaltrials.gov NCT04363411, Registered 27 April 2020-Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04363411?term=NCT04363411&draw=2&rank=1.

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., (© Acta Gastro-Enterologica Belgica.)

Objectives: The Belgian population of people living with HIV (PLHIV) has unrestricted access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, since 2017. International literature claims that half of the patients remain untreated in high-income countries with unrestricted access to DAA. This study was initiated to provide an overview of the present situation in Belgium and recommendations for HCV care in PLHIV in other regions., Methods: This was a retrospective, multicenter study of PLHIV in Belgium, from January 1, 2007 to December 31, 2018. The HCV cascade of care was examined., Results: Out of 4607 unique PLHIV, 322 (7.0%) tested positive for HCV antibody and HCV RNA positivity was seen in 289 (6.3%). Of those with a proven HCV infection, 207/289 (71.6%) initiated treatment. Of the 171 (82.6%) persons with a sustained virologic response (SVR), 16 (9.4%) subjects were reinfected., Conclusions: We present a care cascade of 4607 PLHIV in Belgium. Treatment initiation and SVR rates were high compared to other regions. Implementation of a national HCV register to track progress and yearly screening, especially in PLHIV with high-risk behavior, remains crucial. Identifying reasons for not initiating treatment is necessary to achieve elimination of HCV in PLHIV by 2030., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sensitive polymerase chain reaction assays to measure hepatitis B virus (HBV) DNA became only available the last decade. Hence, the long-term outcome of Caucasian patients in Western Europe with hepatitis B e antigen (HBeAg)-negative chronic infection, especially with a baseline HBV DNA level ⩾2000 IU/mL, is still unclear. Out of a cohort of 1936 chronic HBV patients, 413 Caucasian individuals were identified with HBeAg-negative chronic infection, defined as persistently normal alanine aminotransferase (ALT) levels and HBV DNA levels <20 000 IU/mL. During a mean follow-up of 12 years, 366 (88.6%) maintained an HBeAg-negative chronic infection status, whereas 25 (6.1%) developed chronic active hepatitis (CAH). In total, Nine of these 25 CAH cases were related to immunosuppression. In total, 22 (5.3%) individuals had ALT > 2 × upper limit of normal due to non-HBV-related causes. The cumulative probability of spontaneously developing CAH after 10 years was almost exclusively seen in patients with baseline HBV DNA level ⩾2000 IU/mL (11.7% vs 1.2%; P < .001). Advanced liver disease developed significantly more in patients with baseline HBV DNA level ⩾2000 IU/mL (5.2% vs 1.5%; P = .018) and occurred especially in patients with obesity (16.7% vs 4.2%; P = .049). The incidence of hepatocellular carcinoma was 0.0%. Caucasian patients with HBeAg-negative chronic infection and baseline HBV DNA level <2000 IU/mL have an excellent long-term prognosis in the absence of immunosuppressive therapy. However, patients with baseline HBV DNA level ⩾2000 IU/mL are at risk to develop advanced liver disease., (© 2020 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

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., Competing Interests: ÖK received travel grants from Gilead Sciences and his institution received grants from Gilead Sciences, AbbVie, MSD and CyTuVax B.V. NH is holder of the chair in evidence-based vaccinology supported though a gift by Pfizer. All outside the submitted work. RB has received travel grants from AbbVie, Gilead Sciences and MSD to attend scientific congresses and research grants from Gilead and MSD. DB has received travel grants from AbbVie and a research grant from Gilead. PVD acts as chief and principal investigator for vaccine trials conducted on behalf of the University of Antwerp, for which the University obtains research grants from vaccine manufacturers; speakers fees for presentations on vaccines are paid directly to an educational fund held by the University of Antwerp. PVD receives no personal remuneration for this work. GR has received research grants from AbbVie, MSD, Janssen Pharmaceuticals, and has acted as a consultant/advisor for AbbVie, MSD, Gilead Sciences and Bristol-Myers Squibb. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

To achieve the ambitious goals of the WHO to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030, innovative approaches are needed to improve the uptake for screening and treatment in people who inject drugs (PWID). Important barriers to care are difficult venous access and the two-step approach in current point-of-care tests, using an HCV antibody screening test followed by a confirmatory HCV RNA test. In this study, we aimed to validate the new GenXpert instrument to diagnose HCV RNA by finger prick. This prospective study was conducted in a cohort of PWID in 6 alcohol/drug clinic sites and 1 outreach project in Belgium between January 2018 and March 2019. Plasma and capillary whole-blood samples were collected by venepuncture and finger prick, respectively. Sensitivity and specificity of the GenXpert system were compared to the gold standard Artus HCV RNA kit. Of 153 participants enrolled, 147 (96.1%) had results of both the GenXpert system and Artus HCV RNA kit available. HCV RNA was detected in 35 of 147 (23.8%) by the Artus HCV RNA kit and in 36 of 147 (24.8%) by the GenXpert. Median quantitative HCV RNA viral load on finger prick was 28 700 IU/mL (IQR 4070-65 875) vs 1 900 000IU/mL (IQR 416,466-2,265,510) on plasma. The GenXpert instrument had a sensitivity of 100% (95% CI 90%-100%) and a specificity of 99.1% (95.1%-99.9%). The overall diagnostic accuracy was 99.3% (96.3%-99.9%). This study validates the excellent performance of the GenXpert instrument to assess HCV RNA in capillary whole blood by finger prick in a PWID cohort., (© 2020 John Wiley & Sons Ltd.)

Background: Hepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a 'Hepatitis C Plan' since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure., Methods: We examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups., Results: Eleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients., Conclusions: Removing Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium.

Introduction: Patients with haemophilia are one of the subgroups with a high prevalence of hepatitis C virus (HCV) infection. They are a potential target group to eliminate HCV infection thanks to the availability of direct-acting antiviral (DAA) therapy., Aim: To investigate the results of DAA therapy in a cohort of patients with bleeding disorders., Methods: This retrospective study was conducted between July 2018 and April 2019. All patients born before 1990 with haemophilia, von Willebrand factor Disease, factor V deficiency, factor VII deficiency or afibrinogenemia were included in this study., Results: Of 299 patients, 297 (99.3%) were tested for HCV antibody presence and 211 (71.0%) were positive. Of these, 205 (97.1%) were tested for HCV RNA and 153 (72.1%) were chronically infected. In total, 127 (83.0%) received antiviral therapy, and 110 (71.8%) patients were cured by antiviral treatment. The presence of cirrhosis was significantly higher in patients without a cure for HCV infection when compared to patients who achieved sustained virologic response by treatment or never infected (32.6% vs. 12.8% vs. 0%; P < .001). At the end of follow-up in 2019, only 14 (9.1%) patients had a remaining HCV infection. Ten (71.4%) were lost to follow-up, one (7.1%) patient refused, two (14.2%) had comorbidities and one (7.1%) will start treatment soon., Conclusion: In this cohort, the elimination targets for HCV infection in 2030 as proposed by the World Health Organization were already reached. Nevertheless, in order to cure every patient, monitoring tools are necessary., (© 2019 John Wiley & Sons Ltd.)

Background & Aims: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC., Methods: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models., Results: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I 2  = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I 2  = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I 2  = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66)., Conclusion: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates., Lay Summary: There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aim: The hepatitis B virus (HBV) prevalence study performed in 2003 in Belgium is believed to be underestimating HBV prevalence due to underrepresentation of the non-Belgian population. Therefore, we assessed the prevalence and risk factors of HBV infection in a multi-ethnic region situated in Middle-Limburg Belgium, in 2017., Methods: Between May and November 2017, blood samples and questionnaires were taken from patients who presented at the emergency department of a large educational hospital. Blood samples were tested for hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc). A sample size of 1000 persons was required to obtain a representative sample of the general Middle-Limburg population., Results: Of the 1131 patients screened, the overall HBsAg prevalence was 0.97% with differences between Belgians (0.67%) and first-generation-migrants (2.55%), (P = 0.015). Five (45.5%) of 11 HBsAg-positive individuals were not aware of their HBV status. All five (100%) newly diagnosed HBsAg-positive patients had further clinical evaluation and all had a normal level of alanine aminotransferase (ALT). The prevalence of anti-HBc was 8.4%, and was significantly associated with age-gender-ethnicity interaction, presence of HBV-infected household member, hepatitis C virus infection, men who have sex with men, and hemodialysis., Conclusions: In this area with large immigrant populations, we found a higher prevalence of HBV infection compared with the nationwide study of 2003. National HBV screening for first-generation migrants is needed as this high-risk group will go unnoticed due to the possible incorrect interpretation of normal ALT values., (© 2019 Wiley Periodicals, Inc.)

BackgroundBelgium is a low-endemic country for hepatitis B. Universal hepatitis B vaccination in infants with catch-up in the age cohort of 10-13 year-olds began in 1999.AimsOur objective was to evaluate the effect of prevention and control strategies on acute hepatitis B notification rates in Flanders (Belgium) from 2009 to 2017.MethodsThis observational study collected demographic data and risk factors for acute hepatitis B from mandatory notifications to the Agency for Care and Health.ResultsIn Flanders, acute hepatitis B notification rates per 100,000 population decreased from 1.6 in 2009 to 0.7 in 2017. These rates declined in all age groups: 0-4-year-olds: 0.6 to 0.0, 5-14-year-olds: 0.2 to 0.0, 15-24-year-olds: 0.8 to 0.7, 25-34-year-olds: 3.4 to 1.1 and ≥ 35-year-olds: 1.59 to 0.7. There was also a downward trend in acute hepatitis B notification rates in native Belgians and first-generation migrants. Among 15-24-year-olds and 25-34-year-olds, a possible reversal of the decreasing trend was observed in 2016 and 2015, respectively. Among 548 acute hepatitis B cases, the main route of transmission was sexual activity (30.7%), and the pattern of transmission routes over time showed an increasing proportion of sexual transmission in men who have sex with men (MSM) after 2014. During the period from 2009 to 2017, five mother-to-child transmissions were reported.ConclusionsPrevention and control strategies were effective in reducing the acute hepatitis B notification rate. However, stronger prevention and control measures are needed in adult risk groups, particularly MSM.

Objectives: Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) have a major impact on mortality worldwide. Although effective treatments are available for both HBV and HCV infection, <50% of the patients are even diagnosed in Belgium. This study assessed the real-life testing-and diagnosis rate by general practitioners (GPs) in Flanders, Belgium., Setting: We assessed the testing rate for HBV and HCV in 48 primary care practices with electronic medical records linked into one central registry in Flanders, Belgium., Participants: The registry contains data of 440 140 patients over 20 years, which corresponds to 2.2% of the total Flemish population yearly. The primary care practices are distributed across Flanders and the patient population is representative for the distribution of age, gender and socioeconomic status at the community level., Results: Of 440 140 patients included in the registry, 7892 (1.8%) patients were screened for hepatitis B surface antigen (HBsAg) and 7206 (1.6%) for hepatitis C antibody (HCV Ab) of whom 369 (4.7%) and 163 (2.3%) tested positive, respectively. Of 14 059 patients with chronic liver enzyme elevation, 1112 (7.9%) and 1395 (9.9%) were tested for HBsAg and HCV Ab, respectively. There was no improvement in testing rates over time., Conclusions: This study demonstrates that real-life testing uptake for viral hepatitis B and C is suboptimal in the general practices in Flanders, even in patients with chronically elevated liver enzymes. As GPs play a crucial role in prevention, diagnosis and linkage to care, efforts and strategies to increase the testing uptake for HBV and HCV are urgently needed., Competing Interests: Competing interests: RB has received travel grants from Abbvie, MSD and Gilead to attend scientific congresses. OMK has received travel grants from Gilead to attend scientific congresses. DB has received a travel grant from Abbvie. FN has received research grants, consultancy agreements and travel grants from UCB, Ipsen, Roche, Astellas, Ferring, Novartis, Janssen-Cilag, Abbvie, Gilead, CAF, Intercept, Gore, BMS, MSD, Promethera Biosciences, Ono Pharma and Durect. GR has received research grants from MSD, AbbVie, Janssen Pharmaceuticals, and has acted as a consultant/advisor and for Gilead Sciences, Abbvie, MSD and BMS. BA, BV, PM, CM and GG report no conflict of interest., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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).

Background & Aims: Patients are not screened adequately for hepatitis C virus infection in Belgium. In the USA, the Center for Disease Control recommends screening for patients born in the babyboom period (1945-1965). In Europe, the babyboom cohort was born between 1955 and 1974, but no screening policy has been targeted to this group. We aimed to study the prevalence of hepatitis C virus in an emergency department population in Belgium and the risk factors associated with hepatitis C virus infection., Method: We performed a monocentric, cross-sectional seroprevalence study between January and November 2017 in a large Belgian non-university hospital. Patients aged 18-70 years presenting at the emergency department were eligible. Patients completed a risk assessment questionnaire and were screened for hepatitis C virus antibodies (Ab) with reflex hepatitis C virus ribonucleic acid testing., Results: Of 2970 patients, 2366 (79.7%) agreed to participate. hepatitis C virus Ab prevalence was 1.31%. Twenty-one (67.7%) hepatitis C virus Ab-positive patients were born between 1955 and 1974. With a previous treatment uptake of 54.5%, the prevalence of viremia was 0.9% in retrospect; 0.2% were newly diagnosed. The weighted multiple logistic regression model identified males born in the 1955-1974 cohort, intravenous drug use and high endemic birth country as significant risk factors for hepatitis C virus infection (P < 0.05)., Conclusion: Although the prevalence of hepatitis C virus Ab at the emergency department was higher than previously estimated for the general population in Belgium, the number of newly diagnosed patients with viremia was low. To optimize screening strategies, screening should be offered to males born in the 1955-1974 cohort, but especially in drug users, the prison population and immigrants from high endemic countries., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Currently, nucleos(t)ide analogs (NAs) in monotherapy are favored as prophylaxis against hepatitis B recurrence after liver transplantation. However, in patients at risk of renal failure, renal safety of NAs is of concern. We investigated the safety and efficacy of subcutaneous (SC) hepatitis B immunoglobulins (HBIG) in monotherapy. This is a single-arm prospective trial in patients transplanted >1 year. We included 43 Caucasian patients. The majority was treated with calcineurin inhibitors, and several patients had other risk factors for renal impairment as well: diabetes mellitus (n = 10/43), arterial hypertension (n = 11/43), and hyperlipidemia (=10/43). At inclusion, 42% (n = 18) had chronic kidney disease ≥ grade 3a. All patients were switched from IV HBIG with or without NAs to SC HBIG without NAs. After one year, the targeted titer was lowered to ≥150 IU/l in patients with low risk of recurrence. Mean follow-up time was 36 ± 5 months. None of the patients had a relapse of HBsAg or HBV DNA. The treatment was well tolerated, safe and the renal function remained unchanged both in patients with (n = 18) or without (n = 25) renal impairment at baseline. The mean HBsAb titer could be decreased from 343 ± 163 to 199 ± 81 IU/l in the low-risk group (n = 17) and 218 ± 71 IU/l in the high-risk group (n = 26). In 86% (n = 37) doses, reductions were possible, which significantly lowered the cost of treatment. SC HBIG without NAs had a 100% success rate in the long-term prevention of HBsAg and HBV DNA reappearance, without deterioration of renal function., (© 2018 Steunstichting ESOT.)

Background and Aim: Hepatitis C viral infection (HCV) has become a curable disease due to the development of direct acting antivirals (DAA). The WHO has set a target to eliminate HCV completely. Therefore, people who inject drugs (PWID) also need to be treated. In this study, we compared the real-life uptake and outcome of DAA treatment for HCV in PWID and non-PWID., Methods: We performed a nation-wide, retrospective cohort study in 15 hospitals. All patients who were treated with simeprevir-sofosbuvir, daclatasvir-sofosbuvir, or ombitasvir/paritaprevir ritonavir-dasabuvir between December 2013 and November 2015 were included., Results: The study population consisted of 579 patients: 115 PWID (19.9%) and 464 non-PWID (80.1%). Of the PWID 18 were active PWID (15.6%), 35 still received opiate substitution therapy (OST) (30.4%) and 62 were former PWID without OST (53.9%). PWID were more infected with genotype 1a and 3 (p=0.001). There were equal rates of side-effects (44.7% vs. 46.6%; p=0.847), similar rates of treatment completion (95.7% vs 98.1%; p=0.244) and SVR (93.0% vs 94.8%; p=0.430) between PWID and non-PWID, respectively., Conclusion: PWID, especially active users, are underserved for DAA treatment in real life in Belgium. Reimbursement criteria based on fibrosis stage make it difficult to treat PWID. Treatment adherence is similar in PWID and the general population, even in patients with active abuse. DAA were safe and effective in PWID despite the higher prevalence of difficult-to-treat genotypes. Based on these data more efforts to treat PWID are needed and policy changes are necessary to reach the WHO targets., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background & Aims: Hepatitis C viral infection (HCV) after injection drug use is very prevalent. The kind of genotype determines the response to treatment. However, no systematic review update on the global genotype distribution of HCV in people who inject drugs (PWID) is currently available., Methods: A systematic review was performed by using the keywords: Genotype, Hepatitis C, Injection drug user/Intravenous drug user/Substance user/ PWID, Name of countries in Pubmed, Embase and PsycINFO. The results were compared with the review of Gower et al. in 2014, concerning the distribution of HCV genotypes in the general HCV population., Results: Using these keywords, 132 studies in 48 countries (from 1995 to 2015) were collected. After grading these results, the data of 48 studies were used to determine the distribution of genotypes in PWID. Genotype 1 is the most prevalent genotype all over the world in PWID. In Europe, genotypes 1, 3 and 4 are highly prevalent. In North and South America and in Australia genotype 1 and 3 are most prevalent. In Asia genotype 2 and 6, and Africa genotype 1a and 4 are mostly observed. Overall, the most important differences comparing with the general population are a lower prevalence of genotype 1b in the PWID population and higher prevalence of genotype 1a and 3., Conclusions: There is a different prevalence of genotype distribution in PWID than in the general population. Genotype 3 is especially highly prevalent in the Western countries., Lay Summary: Hepatitis C viral infection after injection drug use is very prevalent. The most important genotype causing HCV infection in PWID globally is genotype 1, as is the case in the general population, but also genotype 3 is highly prevalent in PWID. Genotype 4 is most prevalent in Africa, spreading into Europe, whereas genotype 2 and 6 are more located in Asia. The most important difference comparing to the general population are generally lower prevalence of genotype 1b, and higher prevalence of genotype 1a and 3 in PWID. As the genotype nowadays still determines the treatment, and as there is a different genotype distribution than in the general population, it is important to identify the genotype also in PWID., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: Heavily calcified atherosclerotic plaques can be prepared for stenting by rotational atherectomy (RA). Clinical outcomes with drug-eluting stents (DES) versus bare-metal stents (BMS) after RA have not been investigated sufficiently. We present a single-centre study comparing the efficacy and long-term outcome of DES versus BMS after RA., Methods and Results: We performed a retrospective cohort study of all patients who were treated with RA at our institution between January 2004 and March 2012. Clinical follow-up was obtained at 1 year. Procedural success (defined as a residual stenosis < 30%) was recorded, as was the 1-year incidence of myocardial infarction (MI), stent thrombosis (ST) and major adverse cardiac events (MACE), a composite end point of cardiac death, MI or target lesion revascularization (TLR). Eighty-five patients underwent RA followed by stenting, 30 receiving a BMS and 55 a DES, and completed 1-year clinical follow-up. Baseline clinical and angiographic characteristics were similar, and procedural success was achieved in 99% of the patients. At 1 year the overall incidence of MACE was 19%, and no significant differences in clinical outcome between DES and BMS were seen (MACE: 9 (16%) vs 7 (23%), P = 0.44; cardiac death: 3 (5%) vs 0 (0%); MI: 4 (7%) vs 5 (17%), P = 0.2; TLR: 2 (4%) vs 3 (10%), P = 0.25; ST: 2 (4%) vs 2 (7%), P = 0.52, respectively)., Conclusions: In this study, no significant differences in medium-term clinical outcomes between DES and BMS after RA were observed, although there was a definite trend to improved outcomes with DES.

We have tested for large BRCA1 gene rearrangements in German high-risk breast and ovarian cancer families previously screened negative for point mutations by dHPLC and sequencing. Using the novel MLPA method, two deletions of exons 1A, 1B and 2 and exon 17, respectively, were detected in four out of 75 families investigated in Southern Germany. An identical exon 17 deletion with the same breakpoints and a deletion of exons 1A, 1B and 2 were found by fluorescent multiplex PCR in two out of 30 families investigated in Northern Germany. Combining both populations, genomic rearrangements were found in 6% of the mutation-negative families and 3% of all high-risk families and account for 8% of all BRCA1 mutations. Our data indicate that the exon 17 deletion may be a founder mutation in the German population. The prevalence of BRCA1 gene deletions or duplications in our patients is similar to previous reports from Germany and France. Genomic quantification by MLPA is a useful method for molecular diagnostics in high-risk breast cancer families., (Copyright 2004 Wiley-Liss, Inc.)

Deficiency of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, the only disorder exclusively affecting hepatic ketogenesis, is a cause of hypoglycemic coma. We report that the diagnosis can be made by typical laboratory findings (hypoketosis, elevated free fatty acids, normal acylcarnitines, specific urinary organic acids) during acute episodes.