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Background & Aims: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes.Methods: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using stand-ardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies.Results: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected in-dividuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hos-pitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). Conclusions: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors.Clinical Trial Registration: The protocol was submitted to clinicaltrials.gov (NCT04670419).(c) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. This study is a retrospective analysis of routinely collected data, within the Belgian National Reference Centre (NRC) programme funded by the National Institute for Health and Disability Insurance (RIZIV-INAMI, Belgium). TV is supported by a senior clinical investigator grant of the Research Foundation Flanders (FWO) (number 18B2821N, Belgium). JS and NH acknowledge funding from the European Research Council (ERC) Horizon 2020 research and innovation program (grant agreement 682540 — TransMID, European Union). The funding sources did not have any role in study design, in the collection, analysis, and interpretation of data, in the manuscript writing, or in the decision to submit the paper for publication. We thank Harry Dalton for helpful discussions on the national data collection and clinical outcome analysis and Christophe Conrad for his help in collecting patients data. The authors also especially thank all physicians from the following centres who participated in the study: Algemeen Ziekenhuis Alma, Eeklo; Algemeen Medisch Laboratorium, Antwerpen; Algemeen Stedelijk Ziekenhuis, Aalst; Algemeen Ziekenhuis Delta, Roeselare; Algemeen Ziekenhuis Delta, Torhout; Algemeen Ziekenhuis Nikolaas, Sint-Niklaas; Algemeen Ziekenhuis Sint-Elisabeth, Zottegem; Algemeen Ziekenhuis, Turnhout; Centre Hospitalier Universitaire Brugmann, Brussels; Centre Hospitalier de l’Ardenne, Libramont; Hôpital de Braine-l’Alleud-Waterloo, Braine-l’Alleud; Hôpital Delta, Brussels; Centre Hospitalier de Mouscron, Mouscron; Centre Hospitalier Régional Haute Senne, Soignies; Centre Hospitalier Epicura, Hornu; Centre Hospitalier Universitaire de Liège, Liège; Centre Hospitalier de la Wallonie Picarde, Tournai; Clinique CHC, Waremme; Grand Hôpital de Charleroi, Charleroi; Gasthuiszusters Antwerpen, Antwerpen; Hôpital Princesse Paola, Marche-en-Famenne; Hôpital Iris Sud, Brussels; Instituut voor Tropische Geneeskunde, Antwerpen; Hôpital de Jolimont, La Louvière; Centre Hospitalier de Jolimont, Lobbes; Centre Hospitalier de Jolimont, Nivelles; Centre Hospitalier de Jolimont, Tubize; Eurofins Labo Van Poucke, Kortrijk; Medisch Labo Medina, Dendermonde; Algemeen Ziekenhuis Maria Middelares, Gent; Ziekenhuis Netwerk Antwerpen Middelheim, Antwerpen; Cliniques Universitaires Saint-Luc, Brussels; Centre Hospitalier Universitaire UCL, Dinant; Centre Hospitalier Universitaire UCL, Namur; Centre Hospitalier Universitaire de MontGodinne, Yvoir; Clinique Saint-Luc, Bouge; Clinique Notre-Dame de Grâce, Gosselies; Sint-Andriesziekenhuis, Tielt; Algemeen Ziekenhuis West, Veurne; Algemeen Ziekenhuis Sint Blasius, Dendermonde; Algemeen Ziekenhuis SintJan, Brugge; Klinik Sankt-Joseph, Sankt-Vith; Algemeen Ziekenhuis SintLucas, Gent; Algemeen Ziekenhuis Sint-Maarten, Mechelen; Centre Hospitalier Universitaire Saint-Pierre, Brussels; Sint-Trudo Ziekenhuis, Sint-Truiden; Centre Hospitalier Universitaire Tivoli, La Louvière; Hôpital Erasme – Cliniques Universitaires de Bruxelles, Brussels; Universitair Ziekenhuis Antwerpen, Antwerpen; Universitair Ziekenhuis Gent, Gent; Cassiman David, Laleman Wim, Van Malenstein Hannah, Verslype Chris and Van der Merwe Schalk from Universitair Ziekenhuis Leuven, Leuven; Virga Jesse Ziekenhuis, Hasselt; Universitair Ziekenhuis Brussel, Brussels; Jan Yperman Ziekenhuis, Ieper.

Background: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. Methods: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. Results: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Foundation Against Cancer Belgium, Grant/Award Number: 2014-087

Isabelle Colle - Consulting: Promethera; Grant/Research Support: abbvie; Patent Held/Filed: Trombogenics; Speaking and Teaching: BMS Christophe Moreno - Consulting: Abbvie, Janssen, Gilead, BMS, MSD; Grant/Research Support: Janssen, Gilead, Roche, Astellas, Abbvie Frederik Nevens - Consulting: MSD, CAF, Intercept, Gore, BMS, Abbvie, Novartis, Durect, Janssens-Cilag, Ono Pharma, Promethera Biosciences, Gilead; Grant/Research Support: Ferring, Roche, Astellas, Novartis, Janssen-Cilag, Abbvie, Gilead

Introduction Hepatitis C viral infection (HCV) remains one of the main causes of chronic liver disease worldwide. It has now become a curable disease due to the development of direct acting antivirals (DAA). Therefore, the WHO has set a target to eliminate HCV completely. To reach this target, people who inject drugs (PWID) need to be treated as they are the largest risk group for HCV in the western world. Furthermore, treatment of HCV in PWID is recommended by the treatment guidelines. The aim was to study the uptake and outcome of treatment for HCV in PWID and the general population. Method We performed a Belgian, nation-wide, retrospective cohort study in 12 hospitals. All patients who were treated in these hospitals with simeprevir-sofosbuvir, daclatasvir-sofosbuvir, or ombitasvir/paritaprevir ritonavir – dasabuvir between December 2013 and November 2015 were included. These regimens were chosen based on the Belgian reimbursement criteria. All centers were experienced in treating HCV infected PWID. In case antiviral treatment was started, data were collected in a central database. PWID were subdivided in active users, defined by drug use during therapy with DAA, and former PWID. A PWID was defined by someone who used intravenous drugs at least once. Results The study population consisted of 419 patients: 111 PWID, subdivided in 23 active users and 88 former PWID, and 308 non-PWID treated with one of the above DAA regimens ± ribavirin. PWID (active and former) were younger (p=0.000), predominantly male (p=0.000), had a lower BMI (p=0.006), abused more alcohol (p=0.000), used more benzodiazepines (p=0.000) and were more infected with genotype 1a, 3 and 4 (p=0.000). Active PWID were less treatment experienced (p=0.05) and used less other medications (p=0.043). There were no differences in fibrosis score (F3, F4) (p=0.454) between all groups. PWID had a similar rate of side-effects (p=0.961). There was a trend towards more psychological complaints in PWID (p=0.051). Similar rates of treatment completion (p=0.095) and SVR (p=0.372) were achieved irrespective of active substance abuse. Conclusion Although DAA are safe and effective also in (active) drug users, PWID are still highly underrepresented in a Belgian treatment cohort, also in the era of new DAA therapy. As this risk-group is at the heart of the HCV epidemic, more efforts are necessary to reach this group.