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.

Prediction of Hepatocellular Carcinoma and Liver-related Events in Anti-hepatitis D Virus-positive Individuals.

BACKGROUND & AIMS: Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis, with a high risk of developing hepatocellular carcinoma (HCC) and liver-related mortality. Risk stratification is needed to guide HCC surveillance strategies and to prioritize treatment with antiviral agents. METHODS: We conducted a multicenter retrospective cohort of anti-hepatitis D virus (HDV)-positive individuals managed at sites in the Netherlands and the United Kingdom. We studied the 5-year cumulative incidences of HCC and liver-related events (first of HCC, liver transplantation, and liver-related mortality), in the overall cohort and among relevant subgroups. RESULTS: We analyzed 269 anti-HDV-positive individuals with a median follow-up of 4.3 years in which 47 first events occurred. The 5-year cumulative incidences of HCC and liver-related events were 3.8% and 15.6% in the overall cohort. The 5-year cumulative incidence of HCC and liver-related events for individuals without cirrhosis was 0% and 0.9% compared with 12% and 41.3% for individuals with cirrhosis (P < .001). The 5-year cumulative incidence of HCC and liver-related events was 0% and 2.1% among individuals with low PAGE-B scores, compared to 3.2% and 21.1% with intermediate and 25.4% and 45.5% with high-risk scores (P < .001). We found comparable results for the Fibrosis-4 score. Findings were consistent regardless of cirrhosis or detectable HDV RNA (P < .001). CONCLUSION: Anti-HDV-positive individuals are at high risk of adverse liver-related outcomes. The incidence of HCC was negligible among individuals without cirrhosis and among individuals with low baseline PAGE-B and/or Fibrosis-4 scores. Therefore, these scores can be used to guide HCC surveillance strategies and potentially also for treatment prioritization.

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.

Clinical audit of quality of care among patients with viral hepatitis in primary care in a low endemic region.

BACKGROUND: The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma. OBJECTIVES: This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level. METHODS: This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021. RESULTS: A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively. CONCLUSION: In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels.

Infections with the hepatitis B virus (HBV) and hepatitis C virus (HCV) are a leading cause of death worldwide. Over the last decade, several new therapeutic agents have been developed and can now prevent hepatitis-related deaths. Awareness and increasing testing rates for viral hepatitis in primary care could therefore contribute to control these diseases. The findings of our clinical audit among primary health care practices in Flanders, Belgium demonstrate that screening for HBV and HCV infection can be improved in primary health care in a low endemic region, especially in high-risk groups (e.g. migrants who originate from an endemic country) and patients with abnormal ALT level. The observed suboptimal testing rate in primary health care may be due to a lack of information on risk groups. Future research should focus on interventions to enhance testing, linkage to care, and treatment initiation for HBV and HCV infection among well-defined risk groups in primary health care.

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 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.

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.

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.

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.

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.

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 ).

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 .

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.

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.

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.

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.

The influence of ethnicity on disease outcome in patients with chronic hepatitis B infection.

Since the cultural diversity in Western Europe is growing, this study assessed whether foreign-born chronic hepatitis B (CHB) patients have more cirrhosis than Dutch- or Belgian-born patients, with a main focus on the Turkish population. Baseline characteristics (eg, socioeconomic status [SES]), biological characteristics, and disease outcome (eg, cirrhosis) were collected for all patients. Between December 2009 and January 2015, 269 CHB patients participated from the outpatient departments of three hospitals in the Netherlands, Belgium, and Turkey. Out of the 269 CHB patients, 210 were foreign-born and 59 were Dutch- or Belgian-born. Compared with Dutch- or Belgian-born patients, foreign-born patients had a higher prevalence of low SES (58% vs 31%; P = 0.001) and cirrhosis (27% vs 10%; P = 0.007). Among the Turkish population, there were no significant differences regarding the prevalence of low SES (73% vs 61%; P = 0.170), alcohol abuse (1% vs 5%; P = 0.120), anti-hepatitis C virus positivity (4% vs 0%; P = 0.344), anti-hepatitis D virus positivity (1% vs 6%; P = 0.297), and cirrhosis (37% vs 27%; P = 0.262) between patients (n = 102) living in Turkey (local) and Turkish CHB (n = 38) patients living in the Netherlands or Belgium (immigrant). In multivariate analysis, low SES (odds ratio, 5.7; 95% confidence interval, 2.3-14.5; P < 0.001) was associated with cirrhosis. In this study, foreign-born CHB patients were associated with more advanced HBV-related liver disease with 27% having cirrhosis. However, ethnicity was not associated with cirrhosis when SES was included in the multivariate analysis. The similar prevalence of cirrhosis in local Turkish compared to immigrant Turkish CHB patients is novel and warrants further investigation.

Prevalence and risk factors of hepatitis B virus infection in Middle-Limburg Belgium, year 2017: Importance of migration.

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.

Screening for hepatitis C at the emergency department: Should babyboomers also be screened in Belgium?

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.