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Introduction Chronic Hepatitis C infection is considered a systemic disease with extrahepatic manifestations, mainly neuropsychiatric symptoms, which is associated with a chronic low-grade inflammatory state. Hepatitis C virus (HCV) eradication is currently achieved in >98% of cases with oral direct-acting antivirals (DAA). Objectives To study potential clinical neuropsychiatric changes (mood, cognition, sleep, gastrointestinal, sickness, and motion) in HCV-infected patients after HCV eradication with DAA. Methods Design: Cohort study. Subjects: 37 HCV-infected patients, aged

Introduction The WHO would increase diagnosis and treatment of viral hepatitis in the world by 2030, based on the high efficacy of direct-acting-antivirals against HCV, extended vaccination programs in HBC, and epidemiological data. Diagnostic of HCV/HBV infection has been simplified by point-of-care (POC) devices (cheap/easy-to-use/interprete/qick-results), detecting anti-HCV-antibodies or HBV-antigen in capillary blood at the patients´site. The current seroprevalence of viral hepatitis B/C in general population in Spain is 0.5%/1% and would be higher (3-17%) in people with severe-mental-disorder due to risk factors and traditionally less access to health care. Objectives To design a screening protocol for HCV eradication and HBV-detection, and risk factors among severe-mental-disorder patients in a CommunityMentalHealthCenter. To guarantee equal access to viral hepatitis screening and therapy among this population. Methods Outpatients visited along one-year who accepts participate. Using POC-device for qualitative detection of anti-HCV-antibodies (Quickview-of-Lumiquick-Diagnostics®)/HBsAG (Abbott-Rapid-Diagnostics®). Socio-demographic data; mental disorder(ICD-10); HCV/HBV risk-factors; Neurotoxicity-scale (mood/cognition/sleep/gastrointestinal/sickness/motor); SF-12; Patient-satisfaction. Subjects with positive HCV/HBV POC-test will have a on-site venopuncture to assess hemograme/liver tests, and HCV-RNA (Cobas-TaqMan-RocheDiagnostics)/HBsAg-ELISA (Atellica-Siemens). In positive HCV-RNA (active infection) the psychiatric-team will inform the hepatology-team for non-invasive liver fibrosis assessment and DAA prescription. The patient will receive 8-12-weeks on-site treatment, and assessed (Neurotoxicity/SF-12).HCV cure will be confirmed by HCV-RNA in blood. Chronic-cases will be managed at Hepatology-Unit. Results We will present the results of the implementation of the programme and their ability to detect viral-hepatitis-positive cases among patients with severe-mental-disorders and to treat them effectively. Conclusions Our results may support the generalisation of the programme in among CMHC’s. Disclosure No significant relationships.

Introduction Hepatitis C virus (HCV) infection is known to be associated with neuropsychiatric manifestations as part of the disease. Previous neuroimaging studies showed brain connectivity dysfunction among HCV-infected patients Objectives To assess, by MR in resting state, the potential structural and connectivity changes before (BL) and after HCV eradication (FU12) with direct-acting antivirals (DAA), along with clinical parameters. Methods Twenty-one HCV-patients, aged≤55 years, without psychiatric history, nor advanced liver disease, and eligible for DAA, and 25 healthy controls were included. Evaluations were performed at BL and FU12. Brain volume and local gyrification index (LGI) were assessed in MR-T1, and functional connectivity by seed-based analysis (left insula). Depression (MADRS/PHQ9) and neurotoxicity symptomatology (NRS) were assessed. We compared patients between BL/FU12, and controls by means of paired/independent T-test analysis. Results Substained virologycal response was obtained in all patients (100%). Depressive and neurotoxicity symptomatology improved after cure (p

Summary Chronic hepatitis C virus (HCV) infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren’s syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma). In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs) that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications.

Summary Chronic hepatitis C virus (HCV) infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren’s syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma). In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs) that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications.

Background and Aim: Serum HBV RNA and HBcrAg levels have been proposed as useful biomarkers in the management of HBV patients, however their role in chronic hepatitis Delta (CHD) is currently unknown., Methods: Consecutive untreated CHD patients were enrolled in a cross-sectional study in three EU centers. Clinical and virological characteristics were collected. Serum HBV RNA and HBcrAg levels were quantified by an automated real-time investigational assay (Cobas® 6800, Roche Diagnostics, Pleasanton, Ca, USA) and by LUMIPULSE® G HBcrAg assay (Fujirebio Europe), respectively. In 18 patients with available liver biopsies, intrahepatic analyses were performed., Results: Overall, 240 HDV patients were enrolled: median age 46 years, 62% males, 53% cirrhotics, 57% NUC-treated, median ALT 70 U/L, HBsAg 3.8 log 10 IU/mL, 88% HBeAg-negative, median HDV RNA 4.9 log 10 IU/mL. HBV RNA tested positive (>10 cp/mL) in only 8% of the patients [median 40 (13-82,000) cp/mL], whereas HBcrAg was ≥3 log 10 U/mL in 77% [median 4.2 (3.0-8.0) log 10 U/mL]. By combining these biomarkers, 3 categories were identified: 23% double negative (HBV RNA neg/HBcrAg neg), 9% double positive (HBV RNA pos/HBcrAg pos) and 68% HBV RNA negative/HBcrAg positive. HBV RNA levels positively correlated with male sex and detectable HBV DNA, while positive HBcrAg correlated with higher HBsAg levels. Double positive patients were younger, non-European, with elevated ALT and HDV RNA levels and detectable HBV DNA. Intrahepatic HDV RNA and HBV RNA were positive in most samples, while intrahepatic levels of covalently closed circular (ccc)DNA were low., Conclusions: In untreated CHD, most patients had undetectable HBV RNA but quantifiable HBcrAg ("divergent pattern") in the absence of HBeAg. Additional studies aimed to unravel the molecular mechanisms underlying these findings are warranted., Competing Interests: Declaration of Competing Interest Elisabetta Degasperi: Advisory Board: AbbVie, Roche; Speaking and teaching: Gilead, AbbVie; Travel support: Gilead, Advanz Pharma Sabela Lens: Lecture fees from Gilead and Abbvie. Maria Francesca Cortese: Advisor for Roche Xavier Forns: Advisor for Gilead and Abbvie Caroline Scholtès: Lecture fees from Gilead and Abbvie; Travel support: Gilead Caroline Charre: Lecture fees from Gilead, MSD, ViiV Healthcare; travel support: Gilead, ViiV Healthcare Massimo Levrero: Lecture fees from Gilead, Abbvie, MSD, Roche, CLS Behring; Advisor for Roche Pietro Lampertico: Advisory Board/Speaker Bureau for: Roche Pharma/Diagnostics, Gilead Sciences, Gsk, Abbvie, Janssen, Myr, Eiger, Antios, Aligos, Vir, Grifols, Altona, Roboscreen Other authors report no potential conflict of interest., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Direct-acting antivirals have greatly simplified the treatment of hepatitis C virus (HCV), yet circuits that bring diagnosis and treatment closer to people who inject drugs (PWID) are needed to achieve the elimination targets of the WHO. With this purpose we have established an externalized nurse-driven circuit among former and active PWID in an addiction centre (AC) and a harm reduction centre (HRC)., Methods and Settings: The nursing staff offered HCV screening, diagnosis and treatment to the AC and HRC users, administered medication after the hepatologist's remote prescription to those with an active infection who accepted being treated, and implemented educational and harm reduction interventions., Participants and Results: Between October 2018 and March 2021, 566 users accepted screening. 134 (24%) had an active infection, with a higher prevalence among HRC users (42% vs 17%; p<0.001), who were more frequently foreigners, homeless and reported active drug use and syringe sharing. Treatment initiation was similar between groups. Overall sustained viral response (SVR) for intention-to-treat (ITT) and per protocol (PP) was 70% and 88% respectively. Overall adherence was good in both groups; however, SVR was higher in AC users compared to HRC users (ITT-SVR 81% vs 55%). All reinfections (6% by ITT) occurred in the HRC group. Overall loss to follow-up rate was 21%., Conclusions: This patient-centred nurse-driven circuit demonstrates that HCV treatment can be successfully delivered to PWID even with active drug use and socio-economic complexity. User-specific characteristics need to be considered when setting up these interventions to maximize success., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background and Aim: Determining suitable copper parameters for monitoring Wilson disease remains a topic of ongoing discussion. International recommendations currently rely on the combination of urinary copper excretion and nonspecific liver markers when considering therapy and time elapsed since diagnosis. The emergence of exchangeable copper (CuEX) as a novel measurement reflecting the "free copper pool" held promise as a valuable target to ensure metabolic stability during follow-up, although the validation of target ranges remains unknown. We aimed to evaluate CuEX quantification in repeated samples from 92 real-world patients with Wilson disease during a 2-year period., Approach: Patients were classified as "stable" if a diagnosis had been made more than 1 year before and were compliant with stable anti-copper drug and dose. Otherwise, patients were classified as "nonstable.", Results: Two hundred and thirteen CuEX samples were obtained per clinical practice. Overall, 57% of CuEX measurements fell below the reference "range of normality," whereas only 34% were within and 9% were above normal levels. There was no association of CuEX levels with therapy, elapsed time from diagnosis, or clinical stability, although most of the samples above normality corresponded to nonstable patients. Only 23.4% of the CuEX samples were aligned with data obtained from concomitant urinary copper excretion., Conclusions: Our findings suggest that CuEX is a suboptimal tool for assessing copper homeostasis when used alone and should be used with caution if no additional information is available. Normal reference intervals for Wilson disease-treated patients should be redefined, as most CuEX quantifications fell in the lower range, with no sign of overtreatment in these patients., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background and Objectives: Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls., Methods: This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios., Results: The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27-2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66-2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02-2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26-6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90-8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51-2.44)., Conclusions: Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients., (© 2024. The Author(s).)

Introduction: Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation., Methods: Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN., Results: Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months., Discussion: Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year., (Copyright © 2024 by The American College of Gastroenterology.)