Journal of Viral Hepatitis最新文献

{"title":"Crowdsourcing to increase hepatitis B and C testing and reduce hepatitis stigma among medical students in Bangladesh","authors":"Mohammad Ali,&nbsp;Joseph D. Tucker,&nbsp;Eneyi E. Kpokiri,&nbsp;Dan Wu,&nbsp;M. Anisur Rahman,&nbsp;Titu Mia,&nbsp;Md. Shafiqul Alam Chowdhury,&nbsp;Faroque Ahmed,&nbsp;H. A. Nazmul Hakim,&nbsp;Zunaid Murshed Paiker,&nbsp;Nabila Jashim Nuha","doi":"10.1111/jvh.13945","DOIUrl":"10.1111/jvh.13945","url":null,"abstract":"<p>This study addresses the pervasive challenges of low hepatitis B (HBV) and hepatitis C (HCV) testing rates coupled with the stigma associated with these diseases in low- and middle-income countries (LMICs) with a special focus on Bangladesh. This study aims to introduce an innovative crowdsourcing intervention that involves medical students, a crucial cohort with the potential to shape healthcare attitudes. Through a structured crowdsourcing approach, the study designs and implements a digital intervention to counter stigma and promote testing among medical students in Dhaka, Bangladesh. Participants submitted brief videos or texts aiming to encourage hepatitis testing and reduce stigma. The call, advertised through meetings, emails, and social media, welcomed entries in English or Bengali over 3 weeks. A panel of six judges evaluated each entry based on clarity, impact potential, innovation, feasibility, and sustainability, awarding prizes to students behind the highest-rated submissions. Seventeen videos and four text messages received an average score of 5.5 among 440 surveyed medical students, predominantly 22 years old (16%) and in their fourth year (21%). After viewing, 360 students underwent screening, identifying two previously undiagnosed HBV cases referred for care; no HCV infections were found. Notably, 41% expressed concerns about individuals with HBV working in hospitals or having a doctor living with HBV. In conclusion, this pilot showcases the power of medical students in spearheading campaigns to counter hepatitis stigma and encourage testing. By utilizing crowdsourcing, the study introduces an innovative approach to a persistent issue in LMICs specially in Bangladesh, offering a model that could potentially be adapted by other regions grappling with similar challenges.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 7","pages":"404-408"},"PeriodicalIF":2.5,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140828367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers and enablers to people-centred viral hepatitis care in Vietnam and the Philippines: Results of a patient journey mapping study","authors":"Bethany Holt,&nbsp;Jhaki Mendoza,&nbsp;Hoang Nguyen,&nbsp;Duong Doan,&nbsp;Vy H. Nguyen,&nbsp;Daniel Joy Cabauatan,&nbsp;Lam Dam Duy,&nbsp;Martin Fernandez,&nbsp;Manu Gaspar,&nbsp;Geohari Hamoy,&nbsp;Joseph Michael D. Manlutac,&nbsp;Sinit Mehtsun,&nbsp;Timothy Bill Mercado,&nbsp;Boon-Leong Neo,&nbsp;Bao Ngoc Le,&nbsp;Hoa Nguyen,&nbsp;Huyen Thu Nguyen,&nbsp;Yen Nguyen,&nbsp;Thuy Pham,&nbsp;Todd Pollack,&nbsp;Mary Cris Rombaoa,&nbsp;Pham Thai,&nbsp;Tran Khanh Thu,&nbsp;Pham Xuan Truong,&nbsp;Dung Vu,&nbsp;Janus Ong,&nbsp;David Duong","doi":"10.1111/jvh.13944","DOIUrl":"10.1111/jvh.13944","url":null,"abstract":"<p>In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 7","pages":"391-403"},"PeriodicalIF":2.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13944","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women","authors":"Dee-Dee Shiller,&nbsp;Betty B. Yao,&nbsp;Mong-Jen Chen,&nbsp;Amelia Orejudos,&nbsp;Nael M. Mostafa,&nbsp;John F. Marcinak,&nbsp;Margaret Burroughs,&nbsp;Craig Boyle","doi":"10.1111/jvh.13946","DOIUrl":"10.1111/jvh.13946","url":null,"abstract":"<p>Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (<i>n</i> = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1–2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3–4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (&gt;3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, <i>n</i> = 16; AE [deemed unelated to GLE/PIB], <i>n</i> = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 7","pages":"409-415"},"PeriodicalIF":2.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140670077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An updated assessment of hepatitis delta prevalence among adults in Canada: A meta-analysis","authors":"Robert J. Wong,&nbsp;Grishma Hirode,&nbsp;Jordan Feld,&nbsp;Steven S. Wong,&nbsp;Carol Brosgart,&nbsp;Jeffrey Glenn,&nbsp;Saeed Hamid,&nbsp;Chari Cohen,&nbsp;Beatrice Zovich,&nbsp;John Ward,&nbsp;Heiner Wedemeyer,&nbsp;Cihan Yurdaydin,&nbsp;Robert Gish","doi":"10.1111/jvh.13939","DOIUrl":"10.1111/jvh.13939","url":null,"abstract":"<p>Foreign-born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta-analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488–0.615) persons with CHB; 0.344 M (95% CI 0.288–0.401) were FB and 0.206 M (95% CI: 0.200–0.214) were Canada-born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611–26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada-born persons with HDV, we estimate 35,059 (95% CI: 18,744–52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 6","pages":"324-341"},"PeriodicalIF":2.5,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt","authors":"Saleh A. Alqahtani,&nbsp;Yusuf Yilmaz,&nbsp;Mohamed El-Kassas,&nbsp;Khalid Alswat,&nbsp;Faisal Sanai,&nbsp;May AlZahrani,&nbsp;Faisal Abaalkhail,&nbsp;Manal AlShaikh,&nbsp;Waleed K. Al-Hamoudi,&nbsp;Fatema Nader,&nbsp;Maria Stepanova,&nbsp;Zobair M. Younossi,&nbsp;the Global NASH Council","doi":"10.1111/jvh.13935","DOIUrl":"10.1111/jvh.13935","url":null,"abstract":"<p>Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all <i>p</i> &lt; .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, <i>p</i> &lt; .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all <i>p</i> &lt; .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 6","pages":"300-308"},"PeriodicalIF":2.5,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevation of S2-bound α1-acid glycoprotein is associated with chronic hepatitis C virus infection and hepatocellular carcinoma","authors":"Carlos Oltmanns,&nbsp;Birgit Bremer,&nbsp;Laura Kusche,&nbsp;Per Stål,&nbsp;Robin Zenlander,&nbsp;Jan Tauwaldt,&nbsp;Ingvar Rydén,&nbsp;Peter Påhlsson,&nbsp;Markus Cornberg,&nbsp;Heiner Wedemeyer","doi":"10.1111/jvh.13943","DOIUrl":"10.1111/jvh.13943","url":null,"abstract":"<p>There is an urgent need for new high-quality markers for the early detection of hepatocellular carcinoma (HCC). Åström et al. suggested that S2-bound α1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated the predictive advantage of S2-bound AGP in the early detection of HCC. In a retrospective case–control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (<i>n</i> = 93), we measured S2-bound AGP using the HepaCheC® ELISA kit (Glycobond AB, Linköping, SE) at the start of treatment, end of treatment and follow-up (maximum: 78 months). Patients were retrospectively propensity score matched (1:2). Thirty-one patients chronically infected with HCV developed HCC after a sustained virological response, while 62 did not. In addition, samples of patients with chronic hepatitis B virus infection, metabolic dysfunction-associated steatotic liver disease and HCC of different etiologies were analysed. S2-bound AGP elevation in HCC patients was confirmed. However, we did not observe a predictive advantage of S2-bound AGP for the early detection of HCC during treatment and follow-up. Interestingly, S2-bound AGP levels correlated with aspartate aminotransferase (ρ = .56, <i>p</i> = 9.5×10⁻¹⁵) and liver elastography (ρ = .67, <i>p</i> = 2.2×10⁻¹⁶). Of note, S2-bound AGP decreased in patients chronically infected with HCV after treatment-induced HCV clearance. Fucosylated S2-bound AGP levels were elevated in patients with chronic HCV and HCC. The potential role of S2-bound AGP as a novel tumour marker requires further investigation.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 7","pages":"383-390"},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13943","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which patients should be considered for gene therapy","authors":"Wolfgang Miesbach","doi":"10.1111/jvh.13900","DOIUrl":"https://doi.org/10.1111/jvh.13900","url":null,"abstract":"<p>Gene therapy for haemophilia, utilizing adeno-associated viral vectors (AAVs) and coagulation factor genes, have demonstrated promising results, leading to recent approvals and introduction of the first gene therapy products into clinical practice. For successful and safe use, there are predefined inclusion and exclusion criteria, and the treatment process and associated risks should be thoroughly understood and long-term safety and efficacy carefully evaluated during follow up. As gene therapy becomes more accessible outside of clinical study centers, continuous evaluation of patient eligibility for subsequent AAV-based treatments becomes essential. Thorough evaluation of factors such as liver condition, anti-AAV status, and medical history ensures that gene therapy maximizing benefits while minimizing risks. Apart from fulfilling the established inclusion and exclusion criteria, the success of gene therapy is greatly influenced by the motivation and willingness of patients to accept temporary constraints, such as regular laboratory monitoring, potential use of immunosuppressants, and thorough documentation. Furthermore, various patient-related factors play a significant role in the management and outcomes of gene therapy, making a comprehensive evaluation essential. With the accumulation of more data, there is potential for the expansion of certain inclusion criteria, which may allow for a larger number of eligible patients to benefit from gene therapy. Empowering patients through shared decision-making enables them to thoroughly consider the therapy's potential benefits and risks.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 S1","pages":"9-13"},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring for liver cancer post-gene therapy—How much and how often?","authors":"Ype P. de Jong,&nbsp;Ira M. Jacobson","doi":"10.1111/jvh.13898","DOIUrl":"https://doi.org/10.1111/jvh.13898","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) has long been recognized as a complication in people with chronic liver disease, particularly those with cirrhosis. Two gene therapies for haemophilia A and B recently approved in Europe and the US utilize adeno-associated virus (AAV) vectors designed to target hepatocytes. A number of other AAV gene therapies are undergoing clinical investigation for both liver and extrahepatic diseases, many of which likely transduce hepatocytes as well. Although AAV vectors predominantly persist in episomal forms, concerns about insertional mutagenesis have arisen due to findings in pre-clinical models and in a small subset of human HCC cases featuring wild-type AAV integrations in proximity to potential oncogenes. Despite the absence of any causative link between AAV vector therapy and HCC in approved extrahepatic gene therapies or haemophilia gene therapy trials, the package inserts for the recently approved haemophilia gene therapies advise HCC screening in subsets of individuals with additional risk factors. In this review, we discuss HCC risk factors, compare various screening modalities, discuss optimal screening intervals, and consider when to initiate and possibly discontinue screening. At this early point in the evolution of gene therapy, we lack sufficient data to make evidence-based recommendations on HCC screening. While AAV vectors may eventually be shown to be unassociated with risk of HCC, we presently favour a cautious approach that entails regular surveillance until such time as it is hopefully proven to be unnecessary.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 S1","pages":"35-40"},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The benefits of gene therapy in people with haemophilia","authors":"Courtney D. Thornburg","doi":"10.1111/jvh.13882","DOIUrl":"https://doi.org/10.1111/jvh.13882","url":null,"abstract":"<p>Haemophilia is an inherited bleeding disorder which causes significant morbidity and mortality, especially in the severe form. Prophylaxis with factor replacement has high efficacy in reducing bleeding but is limited by the need for frequent intravenous infusion and fluctuations in haemostasis between doses. Additional prophylaxis therapies are being developed which may overcome some of the current treatment barriers. Gene therapy (GT) is being developed to provide a functional cure such that there is sustained factor expression and minimal to no need for additional haemostatic therapy. There are now two approved gene therapies for haemophilia which may be transformative for many individuals. Benefits of GT should go beyond increasing factor activity and reducing bleeding as persons with haemophilia aim to achieve a ‘haemophilia-free mind’ and health equity with optimal health and well-being.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 S1","pages":"4-8"},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis after gene therapy, what are the possible causes?","authors":"Ann Maina,&nbsp;Graham R. Foster","doi":"10.1111/jvh.13919","DOIUrl":"https://doi.org/10.1111/jvh.13919","url":null,"abstract":"<p>Hepatitis is a common adverse event following gene therapy for haemophilia, often associated with a loss of transgene expression. Investigating the potential causes and implications of this is crucial for the overall success of treatment. Gene therapy trials using adeno-associated virus (AAV) vectors have demonstrated promising results marked by increases in factor FVIII and FIX levels and reductions in episodes of bleeding. However, hepatocellular injury characterised by elevations in alanine aminotransferases (ALT) has been noted. This liver injury is typically transient and asymptomatic, posing challenges in determining its clinical significance. Proposed causes encompass immune-mediated responses, notably T cell cytotoxicity in response to the AAV vector, direct liver injury from the viral capsid or transcribed protein via the unfolded protein response and pre-existing liver conditions. Liver biopsy data conducted years post-gene therapy infusion has shown sinusoidal infiltration without significant inflammation. The overall safety profile of gene therapy remains favourable with no evidence drug-induced liver injury (DILI) based on Hy's Law criteria. Essential pre-therapy monitoring and identifying patients at high risk of liver injury should involve liver function tests and non-invasive fibroscans, while novel blood-based biomarkers are under exploration. Further research is required to comprehend the mechanisms underlying transaminitis, loss of transgene expression and long-term effects on the liver, providing insights for optimising gene therapy for haemophilia.</p>","PeriodicalId":17762,"journal":{"name":"Journal of Viral Hepatitis","volume":"31 S1","pages":"14-20"},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.13919","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}