Community Strategy for Hepatitis B, C, and D Screening and Linkage to Care in Mongolians Living in Spain

Mongolian community; Community program; Viral hepatitis screeningComunidad mongola; Programa comunitario; Cribado de hepatitis viralComunitat mongol; Programa comunitari; Cribatge de hepatitis viralMongolia has one of the highest viral hepatitis infection (B, C, and D) rates in the world. The aims of this study were to increase awareness of this disease and promote viral hepatitis screening in the Mongolian community living in Spain. Through a native community worker, Mongolian adults were invited to a community program consisting of an educational activity, an epidemiological questionnaire, and rapid point-of-care testing for hepatitis B and C. In those testing positive, blood extraction was performed to determine serological and virological parameters. In total, 280 Mongolians were invited to the program and 222 (79%) attended the event: 139 were women (63%), mean age was 42 years, and 78 (35%) had viral hepatitis risk factors. Testing found 13 (5.8%) anti-HCV-positive individuals, 1 with detectable HCV RNA (0.5%), 8 HBsAg-positive (3.6%), and 7 with detectable HBV DNA (3.1%). One additional individual had HBV/HCV co-infection with detectable HBV DNA and HCV RNA. Two subjects had hepatitis B/D co-infection (0.9%). The knowledge questionnaire showed a 1.64/8-point (20.5%) increase in correct answers after the educational activity. In summary, a viral hepatitis community program was feasible and widely accepted. It increased awareness of this condition in the Mongolian community in Spain and led to linkage to care in 22 participants, 50% of whom were unaware of their infection.This project was funded by GILEAD SCIENCES (GLD21/00139)

Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D

Chronic hepatitis D; Anti-HDV screening; HDV diagnosisHepatitis crònica D; Cribatge anti-HDV; Diagnòstic de HDVHepatitis crónica D; Cribado anti-HDV; Diagnóstico de HDVBackground & Aims Although EASL guidelines recommend anti-HDV testing in all HBsAg-positive individuals, HDV infection remains an underdiagnosed condition. We describe the impact of an HDV screening program by reflex anti-HDV testing in all HBsAg-positive samples and compare the results before and after its implementation. Methods In total, 2,236 HBsAg-positive determinations were included from January 2018 to December 2021. Only the first sample from each participant was evaluated: 1,492 samples before reflex anti-HDV testing (2018–2020) and 744 samples after (2021). Demographic and clinical characteristics of anti-HDV-positive patients were collected. Results Before reflex testing, anti-HDV had been tested in 7.6% (114/1492) of HBsAg-positive individuals: 23% (91/390) attended in an academic hospital and only 2% (23/1,102) in primary care centres. After reflex testing was established, 93% (691/744) of HBsAg-positive cases were evaluated for anti-HDV: 91% (533/586) in the academic hospital and 100% (158/158) in primary care. The anti-HDV-positive prevalence was similar before and after reflex testing: 9.6% (11/114) and 8.1% (56/691), respectively. However, the absolute number of anti-HDV-positive patients increased. Most anti-HDV-positive patients were young, HBeAg-negative, Caucasian males. HDV-RNA was detectable in 35 (65%) of 54 tested, HBV-DNA was undetectable in 64%, and alanine aminotransferase levels were normal in 48%. Conclusions Anti-HDV reflex testing quintupled the absolute number of diagnoses of chronic hepatitis D infection. Before the reflex test, a large percentage of HBsAg-positive individuals had not undergone any anti-HDV determination. Implementation of reflex testing increases the diagnosis of patients with chronic hepatitis D.This study received support in part from the Instituto de Salud Carlos III (PI20/01692)

LINK-B: study protocol of a retrospective and prospective project for identification and linkage to care of people living with hepatitis B in a large health area of Barcelona

Hepatology; Telemedicine; VirologiaHepatologia; Telemedicina; VirologiaHepatología; Telemedicina; VirologíaIntroduction An estimated 290 million people are living with hepatitis B virus (HBV) worldwide; in Spain, the prevalence of hepatitis B virus surface antigen (HBsAg) is 0.4%. In our setting, many HBsAg-positive individuals are not linked to care, which implies a barrier to receiving treatment and controlling the infection. The main objective of this project is to evaluate the performance of a programme designed to achieve appropriate linkage to specialist care of HBsAg-positive individuals, newly tested or previously tested and lost to follow-up. Methods and analysis This is a retrospective and prospective study in which all HBsAg-positive cases recorded in the microbiology database will be identified. The retrospective phase will include cases detected between 2018 and 2020, and the prospective phase will run from January 2021 to June 2022. The project will be carried out in a tertiary university hospital covering the northern health area of Barcelona with a catchment population of 450 000 inhabitants and 16 affiliated primary care centres. The central laboratory detects approximately 1200 HBsAg-positive individuals every year; therefore, we expect to identify around 4000 patients over the duration of the project. The medical records of HBsAg-positive individuals will be consulted to identify and retrieve those who have not been appropriately linked to care. Candidates will be contacted to offer specialist disease assessment and follow-up. A website will be created to provide HBV-related information to primary care physicians, and a mobile phone application will be available to patients to improve the linkage circuits and ensure follow-up continuity. Ethics and dissemination The Vall d’Hebrón Hospital Ethics Committee (PR(AG)201/2021) and the Spanish Agency of Medicines and Medical Devices approved this study. The findings will be disseminated through peer-reviewed publications and conference presentations. This programme could increase the number of HBsAg-positive individuals properly linked to care and achieve better HBV monitoring, which will have a positive impact on WHO’s viral hepatitis elimination goals.This project is supported by Gilead Sciences through the competitive research 'HBV Treat' (protocol number IN-ES-320-6107)

In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments

Deep sequencing; Mutagens; QuasispeciesSeqüenciació profunda; Mutàgens; QuasiespècieSecuenciación profunda; Mutágenos; CuasiespecieHere, we report the in-host hepatitis E virus (HEV) quasispecies evolution in a chronically infected patient who was treated with three different regimens of ribavirin (RBV) for nearly 6 years. Sequential plasma samples were collected at different time points and subjected to RNA extraction and deep sequencing using the MiSeq Illumina platforms. Specifically, we RT-PCR amplified a single amplicon from the core region located in the open-reading frame 2 (ORF2). At the nucleotide level (genotype), our analysis showed an increase in the number of rare haplotypes and a drastic reduction in the frequency of the master (most represented) sequence during the period when the virus was found to be insensitive to RBV treatment. Contrarily, at the amino acid level (phenotype), our study revealed conservation of the amino acids, which is represented by a high prevalence of the master sequence. Our findings suggest that using mutagenic antivirals concomitant with high viral loads can lead to the selection and proliferation of a rich set of synonymous haplotypes that express the same phenotype. This can also lead to the selection and proliferation of conservative substitutions that express fitness-enhanced phenotypes. These results have important clinical implications, as they suggest that using mutagenic agents as a monotherapy treatment regimen in the absence of sufficiently effective viral inhibitors can result in diversification and proliferation of a highly diverse quasispecies resistant to further treatment. Therefore, such approaches should be avoided whenever possible.This study was partially supported by Plan Estratègic de Recerca i Innovació en Salut (PERIS)—Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297, Grant PID2021-126447OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe; Projects PI19/00301 and PI22/00258 funded by Instituto de Salud Carlos III (ISCIII) and cofounded by the European Union; and Gilead’s biomedical research project GLD21/00006. S.C.-C has received support from Spanish Ministry of Education, grant FPU21/04150. M.I.-L. received the support of a fellowship from the “la Caixa” Foundation (ID 100010434), whose code is “LCF/BQ/DR23/12000020”