Outcomes of liver transplantation for hepatopulmonary syndrome in patients with concomitant respiratory disease.

BACKGROUND & AIMS: Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease. METHODS: This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020. RESULTS: During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463). CONCLUSIONS: The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy.

Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe.

BACKGROUND & AIMS: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. METHODS: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. RESULTS: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p <0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p <0.001). CONCLUSIONS: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. IMPACT AND IMPLICATIONS: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.

Hepatitis C prevalence in incarcerated settings between 2013-2021: a systematic review and meta-analysis.

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 I2 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.

Cascade of care among hepatitis B patients in Maastricht, the Netherlands, 1996 to 2018.

Background & aims: There are approximately 49,000 people (0.34%) in the Netherlands with a chronic hepatitis B virus (HBV) infection. It is unclear how many are linked to care and under follow-up in hepatitis outpatient clinics. This study determined the cascade of care and identified predictors for not being linked to care and loss to follow-up in Maastricht, the Netherlands. Methods: All hepatitis B surface antigen (HBsAg)-positive patients between December 1, 1996 and September 30, 2018 were retrospectively identified. Results: In total, 644 HBsAg-positive patients were identified; of whom 75 had acute HBV infection, 471 chronic HBV infection and 98 unknown. Out of 569 individuals with a chronic/unknown HBV status, 134/569 (23.6%) were not linked to care and 58.7% (195/332 after excluding those who died or achieved HBsAg-seroclearance) were loss to follow-up (LTFU). A predictor for not being linked to care was Caucasian ethnicity (odds ratio (OR) = 2.76 (95% Confidence Interval (CI) = 1.21-6.29); p = .015). Predictors for LTFU were older age (OR = 0.97 (CI = 0.94-0.99); p = .008), HBV DNA >20,000 IU/mL (OR = 0.44 (CI = 0.21 - 0.93); p = .033) and Asian ethnicity (OR = 0.46, (CI = 0.21-1.00); p = .050). Rates of not being linked to care and LTFU decreased over time from 12.7% in 1996 to 4.4% in 2018 and from 79.2% in 1996 to 37.2% in 2018, respectively. Conclusions: A considerable amount of HBsAg-positive individuals were not linked to care or LTFU. This study indicates that ethnicity plays a role in linkage to care and follow-up. Further research is needed to elaborate on those results.

Timing of primary three-dose hepatitis B vaccination and postvaccination serologic testing among a large cohort of healthy adults.

This study evaluated the optimal timing of a primary three-dose hepatitis B vaccination and postvaccination serologic testing (PVST) among a large group of healthy naïve adults in the Netherlands. Data were collected from the Ease Travel Clinic hepatitis B vaccination database. The study population consisted of 22,997 adults who received three hepatitis B vaccinations. Seroprotection was attained in 97.3% individuals. When compared with PVST performed at 1-2 months (98.2%) after the final dose, lower seroprotection rates were observed with <1 (97.3%, p = 0.128), 3-6 (90.6%, p < 0.001), and ≥7 (88.4%, p < 0.001) months after vaccination. Among the subpopulation with a PVST 1-2 months, no statistically significant difference was observed for the various intervals between the first and second vaccination (<1, 1-2, 3-4, or ≥5 months). When compared with 4-5 months between the second and third vaccine dose, lower seroprotection rates were observed with <4 (odds ratio [OR]: 0.29, p = 0.020) and ≥12 (OR: 0.22, p < 0.001) months, although comparable rates were observed with 6-11 months interval (OR: 0.85, p = 0.262). Our data indicate that PVST should be obtained 1-2 months after the last vaccination and a delayed PVST was the major determinant of a lower seroprotection rate after primary three-dose hepatitis B vaccination schedule. Based on our data, the hepatitis B vaccination also leaves room for flexibility for the second dose and the third dose without the necessity of restarting the vaccination series or confirmation of the immune response to the vaccine.

Hepatitis C reinfection in former and active injecting drug users in Belgium.

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 .

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 ).

A multicentre interventional study to assess blood-borne viral infections in Belgian prisons.

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.

Immunogenicity and safety of HBAI20 Hepatitis B vaccine in non-responders: Double-blinded, randomised, controlled phase 2 trial.

BACKGROUND & AIMS: Approximately 5%-10% of the general population respond inadequately to licensed recombinant hepatitis B vaccines. We assessed the immunogenicity and safety of a new HBAI20 vaccine, consisting of a new AI20 adjuvant (20-µg recombinant human IL-2 attached to 20-µg aluminium hydroxide) in combination with HBVaxPro®-10 µg. METHODS: In a double-blinded, randomised, controlled phase 2 trial, 18- to 59-year-old healthy non-responders (titre <10 mIU/ml after three or more doses of hepatitis B vaccine) were assigned (3:1 ratio) to receive either HBAI20 vaccine or HBVaxPro®-10 µg in a 0, 1 and 2-month schedule. The primary outcome was seroprotection (titre ≥ 10 mIU/ml) measured 1-3 months following the third vaccination. RESULTS: A total of 133 participants were randomised to receive either HBAI20 vaccine (n = 101) or HBVaxPro®-10 µg (n = 32). In the modified intention-to-treat analysis, the seroprotection rate after the third vaccination was 92.0% (80/87) in the HBAI20 group and 79.3% (23/29) in the HBVaxPro®-10-µg group, P = .068. Using a generalised linear mixed model to adjust for stratification factors, a higher odds of seroprotection with HBAI20 vaccine was shown (adjusted odds ratio = 3.48, P = .028). Frequency of mild and moderate local adverse events was greater in the HBAI20 group than in the HBVaxPro®-10 µg. Rates of severe local adverse events and systemic adverse events were low and similar in both groups. CONCLUSIONS: In this group of hepatitis B vaccine non-responders, the HBAI20 vaccine demonstrated a higher seroprotection rate when adjusting for stratification factors and a similar safety profile compared to the licensed recombinant HBVaxPro®-10 µg.

Hepatitis B virus prevalence in first-time blood donors in Flanders, Belgium: Impact of universal vaccination and migration.

BACKGROUND: Transfusion-transmissible infections such as hepatitis B virus (HBV) remain a major concern for the safety of blood transfusion. This cross-sectional study aimed to assess the trend of HBV prevalence and associated risk factors among a first-time donor population in a low endemic country. STUDY DESIGN AND METHODS: Between 2010 and 2018, blood samples were collected from first-time donors presented at donor collection sites of Belgian Red Cross-Flanders. They were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and HBV DNA, HIV and hepatitis virus C (HCV) antibodies and RNA, and syphilis antibodies. RESULTS: A total of 211,331 first-time blood donors (43.7% males, median age 25 years) were analyzed. HBsAg prevalence decreased from 0.06% in 2010 to 0.05% in 2018 (p = .004) and this declining trend was accompanied by an increased number of donors in the HBV vaccinated birth cohort (p < .001). HBsAg prevalence was 0.33% in foreign-born donors and 0.02% in Belgian natives (p < .001). Multivariate risk profiling showed that anti-HBc positivity was significantly associated with mainly foreign-born donors (odds ratio [OR] = 9.24) but also with older age (OR = 1.06), male gender (OR = 1.32), year of blood donation (OR = 0.94), and co-infections with HCV (OR = 4.31) or syphilis (OR = 4.91). DISCUSSION: The decreasing trend in HBV prevalence could mainly be explained by the introduction of the universal HBV vaccination. Being born in endemic areas was the most important predictor for HBV infection while the co-infections with syphilis suggest unreported sexual risk contacts.

The hepatitis C cascade of care in the Belgian HIV population: One step closer to elimination.

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.

The effect of universal infant vaccination on the prevalence of hepatitis B immunity in adult solid organ transplant candidates.

BACKGROUND: Hepatitis B virus (HBV) immunity is recommended to optimize outcomes after solid organ transplantation (SOT). This study assessed the prevalence and predictors of HBV immunity at the time patients were placed on transplant waiting list over a period from 1997 to 2019 in a low HBV endemic region. METHODS: Data were obtained from the University Hospitals Leuven transplant database. Minors and patients with past/current HBV infection were excluded. From 1986, Belgian patients are covered by the universal infant vaccination; therefore, birth cohort was stratified in those born ≥1986 vs <1986. RESULTS: The study population consisted of 3297 SOT candidates. HBV immunity rate was superior in renal transplant candidates (55.3%), and this number was 21.5%, 15.4% and 16.8% for liver, cardiac and pulmonary transplant candidates, respectively, P < .001. Among liver transplant candidates, HBV immunity rate was 14.8% in decompensated cirrhotic patients and 27.9% in those without advanced cirrhosis (P < .001). The overall immunity rate increased from 19.3% in period 1997-2008 to 32.8% in 2009-2019, P < .001. In multivariable analyses, younger age (odds ratio (OR) 95% confidence interval (CI): 0.97-0.98, P < .001) and birth cohort ≥ 1986 (OR 95% CI: 1.18-2.66, P = .006) were associated with increased HBV immunity. CONCLUSION: An increase in HBV immunity was observed over a 20-year period related to the introduction of universal infant HBV vaccination. Nevertheless, this study highlights the low overall HBV immunity at the time of listing for organ transplantation and points out the need of an increased awareness and vaccination strategy at an early disease stage.

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.

Outcome in Caucasian patients with hepatitis B e antigen negative chronic infection: A long-term observational cohort study.

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.

Validation of hepatitis C virus RNA detection using capillary blood by finger prick (GenXpert system)-Hepatitis C fingerprick study.

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.

Eliminating viral hepatitis C in Belgium: the micro-elimination approach.

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.

Ethnicity and response to primary three-dose hepatitis B vaccination in employees in the Netherlands, 1983 through 2017.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination is recommended to all employees who have an occupational risk in the Netherlands. This study assessed the determinants of the immune response to primary standard three-dose HBV vaccination (0, 1, 6 months), with the main focus on ethnicity. METHODS: Out of 76 239 individuals who received HBV vaccination between April 1983 and December 2017, 11 567 persons with a known country of birth and complete vaccination schedule were included in this study. Weighted multiple logistic regression with Firth's bias adjustment was used to assess the determinants of nonresponse (anti-HBs < 10 mIU/mL) and low response (anti-HBs 10-99 mIU/mL). RESULTS: Baseline characteristics of the study population (n = 11 567) were as follows: mean age 27.5 years (95% confidence interval [CI], 27.23-27.72), 99.4% born in the Netherlands and 93.5% of Western European origin. Of all identified subjects, 180 (1.6%) were HBV vaccine nonresponders and 549 (4.8%) were low responders. When compared with individuals aged <40 years, the rate of nonresponse (4.3% vs 0.8%; P < .001) and low response (11.9% vs 2.9%; P < .001) was higher in those aged 40 years or older. The height of anti-HBs levels were lower in those subjects aged >40 years in comparison with those younger than 40 years, P < .001. All nonresponders were born in the Netherlands. Although no significant association was found between nonresponse and individuals of Western European origin (adjusted odds ratio [aOR] = 1.20; 95% CI, 0.66-2.44; P = .163), low response to HBV vaccination was significantly associated with Western European origin (aOR = 2.21; 95% CI, 1.41-3.86; P = .001). Significant determinants for nonresponse were older age at vaccination (aOR = 1.06; 95% CI, 1.06-1.07; P < .001) and male gender (aOR = 2.51; 95% CI, 1.97-3.22; P < .001). CONCLUSIONS: The nonresponse rate was low in our study population. Our findings suggest that the vaccines being used for the primary vaccination are probably less immunogenic for older individuals, males, and persons of Western European origin.

Case report of delayed seroprotection rather than non-response after primary three-dose hepatitis B vaccination.

We describe a delayed hepatitis B seroprotection 12 weeks after the primary vaccination schedule in a 57-year-old male with smoldering multiple myeloma. Based on undetectable anti-HBs antibodies 6 weeks after the third vaccination, the index person was previously considered to be a hepatitis B vaccine non-responder. Because hepatitis B vaccination started in the 1980s, many hepatitis B vaccine non-responders have received a revaccination regimen. If more cases of genuine delayed hepatitis B seroprotection surface in patients with hematologic malignancies, delayed seroprotection should be considered before the commencement of hepatitis B revaccination.

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).

Assessing testing rates for viral hepatitis B and C by general practitioners in Flanders, Belgium: a registry-based study.

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.