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.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

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, I2=74.6%) and 5.7 (2.5 to 15.3, I2=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.

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.

Identification and treatment of viral hepatitis C in persons who use drugs: a prospective, multicenter outreach study in Flanders, Belgium.

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.

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.

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.

Elimination of hepatitis C virus infection in patients with haemophilia in Belgium: A single-centre experience.

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.

Acute hepatitis B notification rates in Flanders, Belgium, 2009 to 2017.

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.

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).

Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis.

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%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 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 (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ±â€¯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.

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.

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.

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

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

Personalized subcutaneous administration of hepatitis B surface antibodies without nucleos(t)ide analogs for patients at risk of renal failure after liver transplantation: a prospective single center cohort study.

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.