JHEP Reports最新文献

{"title":"Pediatric to adult care transfer in rare liver diseases: Recommendations based on insights from a European omnistakeholder event","authors":"Karsten Vanden Wyngaert ,&nbsp;Janne Suykens ,&nbsp;Deirdre Kelly ,&nbsp;Isabel Goncalves ,&nbsp;Ena Lindhart Thomsen ,&nbsp;Jose Willemse ,&nbsp;Zoe Mariño ,&nbsp;João Madaleno ,&nbsp;Jemma Day ,&nbsp;Marianne Samyn ,&nbsp;Mohamed Ali ,&nbsp;Marianne Hørby Jørgensen ,&nbsp;Eva Goossens ,&nbsp;Johan De Munter ,&nbsp;Anneloes Van Staa ,&nbsp;Jo Wray ,&nbsp;Panayiota Protopapa ,&nbsp;Ansgar Lohse ,&nbsp;Ruth De Bruyne","doi":"10.1016/j.jhepr.2025.101403","DOIUrl":"10.1016/j.jhepr.2025.101403","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The transfer journey from pediatric to adult care services of young people with rare liver diseases poses significant challenges and is an underexplored research area. This study examined the critical aspects of, and opportunities for, transfer journey management for these young people in Europe.</div></div><div><h3>Methods</h3><div>In total, 72 individuals, representing 13 countries, participated in an omnistakeholder workshop on 17–18 March 2023. A standardized workshop methodology was used to discuss critical aspects and actions over nine focus sessions. The themes of these sessions were identified by engaging with healthcare providers, young people, and parents. Results (<em>i.e.</em> aspects receiving &gt;25% of the votes) were ranked based on importance and validated by the European Reference Network of Hepatological Diseases (ERN RARE-LIVER) youth panel.</div></div><div><h3>Results</h3><div>Our findings revealed that the critical aspects of transfer journey management predominantly revolved around the transfer itself. Most of the critical aspects and actions were related to improving communication (<em>e.g.</em> allocating sufficient time, 81% of votes; giving consistent information, 43%; and discussing communication preferences, 100%), relational continuity (<em>e.g.</em> appointing a transition person to liaison between stakeholders, 79%), and management continuity (<em>e.g.</em> using a transfer document, 60%). Our results also underscored the importance of peer mentorship programs (100%), informing young people about the transfer process (85%), and implementing joint consultations (93%).</div></div><div><h3>Conclusions</h3><div>Current literature and guidelines on ‘transition’ might not fully address real-world challenges in rare liver diseases, particularly those concerning maintaining continuity of care during the actual transfer process. Future research should examine the effectiveness of strategies aimed at enhancing communication and continuity of care throughout the transfer journey, focusing on stakeholder experience.</div></div><div><h3>Impact and implications</h3><div>This international omnistakeholder workshop explored challenges and opportunities in managing transfer journeys for young people with rare liver diseases. By emphasizing practical implications (leading to actions), it provides a benchmark for improving transfer journeys worldwide, applicable to not only rare liver diseases, but possibly also common liver or other rare diseases. Our findings underscore the fundamental importance of the transfer itself in maintaining continuity of care. The critical aspects identified center around informative, relational, and management continuity of care and have been transformed into minimal criteria.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101403"},"PeriodicalIF":9.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy with murinized tobevibart and elebsiran is efficacious in a liver-chimeric mouse model of HDV infection","authors":"Jiayi Zhou ,&nbsp;Hannah Kaiser ,&nbsp;Evelyn Rocha ,&nbsp;Ashley N. Terrell ,&nbsp;Davide Corti ,&nbsp;Lisa A. Purcell ,&nbsp;Florian A. Lempp ,&nbsp;Andreas S. Puschnik","doi":"10.1016/j.jhepr.2025.101400","DOIUrl":"10.1016/j.jhepr.2025.101400","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Chronic hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis. HDV is a satellite virus of hepatitis B virus (HBV) and depends on the hepatitis B surface antigen (HBsAg) for envelopment and viral entry. Tobevibart (VIR-3434) is an investigational monoclonal antibody targeting the antigenic loop of HBsAg. Elebsiran (VIR-2218) is an investigational RNAi therapeutic targeting a highly conserved region within the HBV genome. The aim of this study was to investigate the antiviral effect of tobevibart and elebsiran on HDV infection in preclinical models.</div></div><div><h3>Methods</h3><div><em>In vitro</em> antiviral activity was determined in an HBV/HDV coinfection model in primary human hepatocytes (PHHs) or Huh7-NTCP cells. The <em>in vivo</em> efficacy of a murinized version of tobevibart alone or in combination with elebsiran was evaluated in HBV/HDV-coinfected liver-chimeric mice.</div></div><div><h3>Results</h3><div>Elebsiran treatment reduced levels of secreted HBsAg and infectious HDV with picomolar potency. Tobevibart exhibited pan-genotypic neutralizing activity against all tested HDV genotypes with EC₅₀ ranging from 1.1 to 4.6 ng/ml. Combination treatment with tobevibart and elebsiran reduced infectious HDV levels in HBV/HDV-coinfected PHHs in an additive manner. <em>In vivo</em>, compared to vehicle, treatment with elebsiran, murinized tobevibart, or their combination significantly decreased HDV RNA serum levels by 0.7 log (<em>p</em> &lt;0.0001), 1.6 log (<em>p</em> = 0.0034) and 2.1 log (<em>p</em> = 0.0002), respectively (measured at day 14 for elebsiran or day 21 for murinized tobevibart and the combination). HBsAg serum levels were reduced by 0.6 log (<em>p</em> &lt;0.0001), 2.0 log (<em>p</em> &lt;0.0001) and 2.8 log (<em>p</em> &lt;0.0001), respectively.</div></div><div><h3>Conclusions</h3><div>Tobevibart and elebsiran exert potent antiviral activity as single agents and in combination. The data support the clinical development of tobevibart and elebsiran for the treatment of patients with chronic HDV infection.</div></div><div><h3>Impact and implications</h3><div>Chronic hepatitis delta is the most severe form of viral hepatitis and is associated with rapid progression of liver-related diseases and a high risk of hepatocellular carcinoma development. To date, there are only limited treatment options available. Tobevibart and elebsiran are currently being evaluated in clinical trials for the treatment of HDV (phase III) and for the treatment of HBV (phase II). The current study demonstrates that tobevibart and elebsiran are efficacious in preclinical models of HBV/HDV coinfection, supporting their clinical development.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101400"},"PeriodicalIF":9.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe alpha-1 antitrypsin deficiency is associated with a higher risk of complications after first decompensation than other aetiologies of cirrhosis","authors":"Lorenz Balcar ,&nbsp;Malin Fromme ,&nbsp;Naomi Kappe ,&nbsp;Benedikt Schaefer ,&nbsp;Soňa Fraňková ,&nbsp;Lukas van Melkebeke ,&nbsp;Jan Stolk ,&nbsp;Mathias Jachs ,&nbsp;Georg Semmler ,&nbsp;Benedikt S. Hofer ,&nbsp;Tammo L. Tergast ,&nbsp;Hannah Rieland ,&nbsp;Anna Sophie Karl ,&nbsp;Jan Sperl ,&nbsp;Martin Wagner ,&nbsp;Mònica Pons ,&nbsp;Harald Hofer ,&nbsp;Markus Peck-Radosavljevic ,&nbsp;Michael Trauner ,&nbsp;Thomas Reiberger ,&nbsp;Mattias Mandorfer","doi":"10.1016/j.jhepr.2025.101398","DOIUrl":"10.1016/j.jhepr.2025.101398","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Alpha-1 antitrypsin deficiency (AATD) causes/predisposes to advanced chronic liver disease. However, the role of the <em>SERPINA1</em> Pi∗ZZ genotype in patients with decompensated cirrhosis is unclear. Thus, we evaluated the impact of the Pi∗ZZ genotype on the disease course after the first hepatic decompensation event.</div></div><div><h3>Methods</h3><div>We retrospectively included 59 adults with decompensated cirrhosis and severe AATD (Pi∗ZZ) from 12 European tertiary care centres. First decompensation was considered as baseline. To compare the course of AATD to other cirrhosis aetiologies, we applied propensity score matching for Child-Turcotte-Pugh (CTP) score as well as age/sex. Patients were followed until further decompensation, liver transplantation or liver-related death.</div></div><div><h3>Results</h3><div>Most patients were male (74.6%), with a mean age of 55 years. The most common type of first decompensation was ascites (n = 40; 67.8%), followed by variceal bleeding (n = 13; 22.0%) and overt hepatic encephalopathy (n = 6; 10.2%). Median CTP and MELD (model for end-stage liver disease) scores at first decompensation were 8 and 14, respectively. Median MELD scores were 16 and 20 points at listing and liver transplantation (median time on list: 2.9 [IQR 1.1-7.2] months), respectively. Patients with other aetiologies (subdistribution hazard ratio: steatotic liver disease: 0.62, 95% CI 0.44-0.88, <em>p =</em> 0.007; abstinent alcohol-associated liver disease: 0.50, 95% CI 0.35-0.71, <em>p</em> &lt;0.001; hepatitis C virus-associated cirrhosis: 0.56, 95% CI 0.37-0.83, <em>p =</em> 0.004) had a significantly lower risk of further hepatic decompensation, liver transplantation, or liver-related death, compared to those with Pi∗ZZ. Exchanging further decompensation with acute-on-chronic liver failure yielded similar results.</div></div><div><h3>Conclusion</h3><div>Our study defines the course of decompensated cirrhosis in patients with severe AATD (Pi∗ZZ), who are particularly prone to complications of cirrhosis and exhibit a more progressive disease course than those with cirrhosis of other aetiologies.</div></div><div><h3>Impact and implications</h3><div>Alpha-1 antitrypsin deficiency is an inherited disease that affects the lung and the liver. Carrying two severely dysfunctional copies of the alpha-1 antitrypsin gene may cause advanced chronic liver disease/cirrhosis. Affected individuals with a first complication of cirrhosis are more prone to developing further liver-related events (including multiorgan dysfunction) and requiring liver transplantation (which cures the inherited liver disease) compared to patients who have similarly advanced liver disease. These findings should prompt the development of disease-modifying treatments and early listing for liver transplantation.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101398"},"PeriodicalIF":9.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53 and TIGAR promote redox control to protect against metabolic dysfunction-associated steatohepatitis","authors":"Celine I. Wittke ,&nbsp;Eric C. Cheung ,&nbsp;Dimitris Athineos ,&nbsp;Nicola Clements ,&nbsp;Liam Butler ,&nbsp;Mark Hughes ,&nbsp;Vivienne Morrison ,&nbsp;Dale M. Watt ,&nbsp;Karen Blyth ,&nbsp;Karen H. Vousden ,&nbsp;Timothy J. Humpton","doi":"10.1016/j.jhepr.2025.101397","DOIUrl":"10.1016/j.jhepr.2025.101397","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div><em>TP53</em> is a potent tumour suppressor that coordinates diverse stress response programmes, ranging from pro-survival activities to cell death. p53 is also engaged during tissue damage and repair, including within the liver. Metabolic dysfunction-associated steatohepatitis (MASH) is a major driver of hepatocellular carcinoma, but our understanding of the molecular determinants of MASH remains incomplete. Here, we investigate p53 activity throughout MASH development, with implications for disease prevention.</div></div><div><h3>Methods</h3><div>This study utilises non-invasive imaging of p53 activity and liver-specific p53 deletion within the context of mouse models of diet and genetically induced MASH. Histopathological analyses are employed to monitor differential disease progression. Molecular mechanisms are assessed within an <em>in vitro</em> obesogenic system utilising western blotting and flow cytometry. Human relevance is examined through transcriptomic analyses of patients with MASH.</div></div><div><h3>Results</h3><div>Using a p53 reporter mouse, we report early and sustained activation of hepatic p53 in response to a high-fat and high-sugar diet (<em>p &lt;</em>0.05 at 100 days in males, <em>p &lt;</em>0.001 at 200 days in females). Liver-specific loss of p53 accelerates progression of benign fatty liver disease to MASH, which is characterised by high levels of reactive oxygen species, extensive fibrosis, and chronic inflammation (all <em>p &lt;</em>0.0001, n = 13 per high-fat high-sugar group). Our findings indicate that p53 induces the antioxidant gene TP53-induced glycolysis and apoptosis regulator (TIGAR) <em>in vivo</em> and <em>in vitro</em>. We show that loss of TIGAR exacerbates lipid peroxidation during MASH development <em>in vivo</em> (<em>p &lt;</em>0.001) and that TIGAR is engaged in human MASH (<em>p &lt;</em>0.001).</div></div><div><h3>Conclusions</h3><div>Our work demonstrates an important role for the p53-TIGAR axis in protecting against MASH and implicates redox control as a barrier against disease progression that is therapeutically targetable.</div></div><div><h3>Impact and implications</h3><div>p53 is of intense interest as a potent tumour suppressor and compounds targeting the pathway have been developed and trialled as anti-cancer therapies. Our findings suggest that early activation of p53 is similarly protective against metabolic dysfunction-associated steatohepatitis and that redox control is an important mediator of this protection. Further studies evaluating the efficacy of proactive activation of p53 in the liver to prevent metabolic dysfunction-associated steatohepatitis, or administration of targeted antioxidants to augment p53 redox protection, could provide new treatment approaches for a condition with few approved therapies.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101397"},"PeriodicalIF":9.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing epidemiology of hepatocellular carcinoma in the Mediterranean area: A challenge for surveillance?","authors":"Andrea Pasta ,&nbsp;Giulia Pieri ,&nbsp;Edoardo G. Giannini ,&nbsp;for the Italian Liver Cancer (ITA.LI.CA) Group","doi":"10.1016/j.jhepr.2025.101396","DOIUrl":"10.1016/j.jhepr.2025.101396","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101396"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemia-free liver transplantation improves long-term outcomes in a 5-year follow-up study","authors":"Zehua Jia ,&nbsp;Jiaxing Zhu ,&nbsp;Jiayi Zhang ,&nbsp;Jian Zhang ,&nbsp;Changjun Huang ,&nbsp;Niancun Zhang ,&nbsp;Songming Li ,&nbsp;Yuqi Dong ,&nbsp;Yao Liu ,&nbsp;Ping Zeng ,&nbsp;Tielong Wang ,&nbsp;Zhitao Chen ,&nbsp;Yunhua Tang ,&nbsp;Qiang Zhao ,&nbsp;Maogen Chen ,&nbsp;Yinghua Chen ,&nbsp;Anbin Hu ,&nbsp;Weiqiang Ju ,&nbsp;Yi Ma ,&nbsp;Dongping Wang ,&nbsp;Zhiyong Guo","doi":"10.1016/j.jhepr.2025.101393","DOIUrl":"10.1016/j.jhepr.2025.101393","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Ischemia-free liver transplantation (IFLT) is a novel technique designed to avoid ischemia–reperfusion injury (IRI). Here, we report the first detailed 5-year follow-up outcomes.</div></div><div><h3>Methods</h3><div>We conducted a cohort study comparing long-term outcomes between IFLT and conventional liver transplantation (CLT) recipients of livers donated after brain death (DBD). The primary objective was to evaluate 5-year patient and graft survival. Additional endpoints included graft loss, biliary complications, rejection, infections, and liver-related laboratory tests. Subgroup analysis was performed to validate the generalizability of the results in patients with pre-transplant hepatocellular carcinoma (HCC).</div></div><div><h3>Results</h3><div>A total of 168 patients were enrolled, with 38 patients in the IFLT group and 130 patients in the CLT group. Five-year patient survival (86.84% <em>vs</em>. 56.92%; hazard ratio [HR] 0.246, 95% confidence interval [CI] 0.098–0.620; <em>p</em> &lt;0.01) and graft survival (84.61% <em>vs</em>. 56.92%; HR 0.307, 95% CI 0.131–0.719; <em>p</em> &lt;0.01) rates were significantly improved in the IFLT group compared with the CLT group. In the multivariate analysis, IFLT emerged as an independent protective factor for 5-year patient survival (HR 0.246, 95% CI 0.098–0.620; <em>p</em> &lt;0.01). Conversely, HCC before transplantation (HR 2.039, 95% CI 1.159–3.590; <em>p</em> &lt;0.05), donor age (HR 1.022, 95% CI 1.001–1.040; <em>p</em> &lt;0.05), and extended criteria donor (HR 2.088, 95% CI 1.215–3.590; <em>p</em> &lt;0.01) were identified as independent risk factors for impaired 5-year patient survival. In patients with pre-transplant HCC, the 5-year overall survival rate of the IFLT group was also significantly higher than that of the CLT group after adjustment for HCC risk factors (82.35% <em>vs</em>. 42.03%; HR 0.249, 95% CI 0.074–0.831; <em>p</em> &lt;0.05).</div></div><div><h3>Conclusions</h3><div>Long-term (5-year) follow-up data demonstrate that the use of IFLT potentially improves both patient and graft survival, when compared with CLT, in transplantation of brain-dead donor livers.</div></div><div><h3>Impact and implications</h3><div>Ischemia-free liver transplantation (IFLT) has emerged as a new approach designed to avoid IRI throughout all episodes of the transplant procedure. It has been confirmed that the use of IFLT can substantially reduce early-onset graft IRI-related complications. In this first 5-year follow-up study on the IFLT technique, we demonstrate that, compared with conventional liver transplantation, IFLT can potentially improve long-term patient and graft survival by reducing cancer recurrence. This new technique has the potential to change current clinical practice, particularly in the use of marginal grafts and in patients with HCC.</div></div><div><h3>Clinical Trials registration</h3><div>chictr.org (ChiCTR-OPN-17012090).</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101393"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and mortality of alcohol-related hepatitis in Denmark – an update, 2016–2023","authors":"Khaibar Ghulam Hazrat ,&nbsp;Sidsel Hyldgaard Støy ,&nbsp;Thomas Damgaard Sandahl ,&nbsp;Peter Jepsen","doi":"10.1016/j.jhepr.2025.101390","DOIUrl":"10.1016/j.jhepr.2025.101390","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Alcohol-related hepatitis (AH) is a severe liver disease associated with high mortality. This study provides data on the incidence and mortality of AH in Denmark from 2016 to 2023.</div></div><div><h3>Methods</h3><div>We identified all patients with a first-time hospital discharge diagnosis of AH and a serum bilirubin level &gt;3 mg/dl in 2016–2023. We computed the standardized incidence rate of AH in the Danish population and mortality from admission with AH. We compared the results to our previously published findings for the 1999-2008 period.</div></div><div><h3>Results</h3><div>We included 1,016 patients with a median age of 54.7 years (66% men). The standardized incidence rate was 21.7 per million per year, which remained stable during the study period for both men and women. Mortality was high: 18% at 28 days, 26% at 84 days, and 40% at 365 days. Although 28-day and 84-day mortality risks were lower in 2023 compared to earlier years, no overall trend of improvement was observed. The median MELD score at admission, available for 846 patients, was consistently high at 26, and 75% had severe AH (MELD &gt;21). Compared to an incidence rate of approximately 45 per million per year in 2009, the incidence of AH has since decreased dramatically, mirroring Danish alcohol sales.</div></div><div><h3>Conclusions</h3><div>The incidence of AH in Denmark markedly declined from 2009 but stabilized between 2016 and 2023. Mortality remains high, emphasizing the need for better treatment strategies.</div></div><div><h3>Impact and implications</h3><div>This study investigated the incidence and mortality of alcohol-related hepatitis (AH) in Denmark from 2016 to 2023, providing updated data in the context of declining alcohol consumption. While AH incidence has decreased since 2009, mirroring reduced alcohol intake, it has stabilized in recent years, and mortality remains high. These findings highlight the ongoing burden of AH for healthcare providers, researchers, and policymakers. Our results can support early interventional strategies, guide clinical management, and reinforce public health efforts to reduce alcohol consumption. Limitations, such as the lack of detailed treatment data, should be considered to avoid overgeneralization.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101390"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of long-term HBsAg seroclearance in patients with HBeAg-negative chronic hepatitis B","authors":"Hae Lim Lee ,&nbsp;Soon Kyu Lee ,&nbsp;Ji Won Han ,&nbsp;Hyun Yang ,&nbsp;Heechul Nam ,&nbsp;Pil Soo Sung ,&nbsp;Hee Yeon Kim ,&nbsp;Sung Won Lee ,&nbsp;Do Seon Song ,&nbsp;Jung Hyun Kwon ,&nbsp;Chang Wook Kim ,&nbsp;Si Hyun Bae ,&nbsp;Jong Young Choi ,&nbsp;Seung Kew Yoon ,&nbsp;Jeong Won Jang","doi":"10.1016/j.jhepr.2025.101391","DOIUrl":"10.1016/j.jhepr.2025.101391","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Predicting the long-term HBsAg seroclearance, an ideal endpoint, is relevant for decision-making regarding antiviral therapy for patients with chronic hepatitis B (CHB). This study aimed to identify predictors and develop a prediction model for HBsAg seroclearance in patients with HBeAg-negative CHB.</div></div><div><h3>Methods</h3><div>A total of 2,032 untreated HBeAg-negative patients who underwent a 2-year baseline observation period were enrolled. Prediction models were developed using independent predictors of seroclearance, and their performance was evaluated through internal and external validation using an independent cohort of 753 patients, along with sensitivity analyses.</div></div><div><h3>Results</h3><div>The estimated annual incidence of HBsAg seroclearance was 2.22% (15,508 person-years). <strong>Hep</strong>atitis <strong>B</strong> virus DNA <strong>L</strong>evel (Low-to-intermittently high-level viremia), <strong>O</strong>ld age, male <strong>S</strong>ex, and hepatitis B <strong>S</strong>urface antigen level &lt;250 IU/ml independently predicted seroclearance. Subsequently, two prediction models were developed: HepBLOSS-1 and a simplified version, HepBLOSS-2. These models demonstrated excellent performance in predicting seroclearance at 5, 10, and 15 years, with C-indices and time-dependent area under the receiver operating characteristics curve (AUROC) values of 0.81–0.89. The 10-year cumulative incidence rate in patients with scores of ≥13 in HepBLOSS-1 and those with scores of 8 in HepBLOSS-2 was over 50%. Both models underwent rigorous internal and external validation, demonstrating good predictability with time-dependent AUROCs exceeding 0.80. The predicted seroclearance rate closely aligned with the observed rate in both models.</div></div><div><h3>Conclusions</h3><div>The HepBLOSS models for HBsAg seroclearance exhibited an outstanding ability to stratify the probability of seroclearance over a 15-year period. These models hold promising potential to guide treatment decisions, aiming to achieve a functional cure in patients with CHB.</div></div><div><h3>Impact and implications</h3><div>Achieving a functional cure for chronic hepatitis B, defined as HBsAg seroclearance, is a realistic treatment endpoint, especially given the virus’s lifelong persistence in hepatocytes and its significant association with improved prognosis. This study identified independent predictors of seroclearance, including HBV DNA levels, age, sex, and HBsAg levels, and developed a robust prediction model based on these factors. The models demonstrated strong predictive accuracy over a 15-year period, offering valuable guidance for clinicians in establishing treatment strategies and predicting patient prognosis.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101391"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: “Surveillance for hepatocellular carcinoma in patients with primary biliary cholangitis: For all or just for some?”","authors":"Jihye Lim ,&nbsp;Jonggi Choi","doi":"10.1016/j.jhepr.2025.101395","DOIUrl":"10.1016/j.jhepr.2025.101395","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101395"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning empowered gadolinium-free contrast-enhanced abbreviated MRI for diagnosing hepatocellular carcinoma","authors":"Yunfei Zhang ,&nbsp;Ruofan Sheng ,&nbsp;Xianling Qian ,&nbsp;Heqing Wang ,&nbsp;Fei Wu ,&nbsp;Haoran Dai ,&nbsp;Mingyue Song ,&nbsp;Chun Yang ,&nbsp;Jianjun Zhou ,&nbsp;Weiguo Zhang ,&nbsp;Mengsu Zeng","doi":"10.1016/j.jhepr.2025.101392","DOIUrl":"10.1016/j.jhepr.2025.101392","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;By reducing some magnetic resonance imaging (MRI) sequences, abbreviated MRI (aMRI) has shown extensive promise for detecting hepatocellular carcinoma (HCC). We aim to develop deep learning (DL)-based gadolinium-free contrast-enhanced (CE) aMRI protocols (DL-aMRI) for detecting HCC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In total, 1,769 patients (913 with HCC) were retrospectively included from three institutions for training, testing, and external validation. Stable diffusion-based DL models were trained to generate CE-MRI, including T1-weighted arterial, portal venous, transitional, and hepatobiliary phase images (AP-syn, VP-syn, TP-syn, and HBP-syn, respectively). Non-contrast-MRI (NC-MRI), including T2-weighted, diffusion-weighted, and pre-contrast T1-weighted (Pre) sequences, along with either actual or DL-synthesized CE-MRI (AP, VP, TP, and HBP or AP-syn, VP-syn, TP-syn, and HBP-syn), were used to create conventional complete MRI (cMRI) and DL-aMRI protocols. An inter-method comparison of image quality between DL-aMRI and cMRI was conducted using a non-inferiority test. The sensitivity and specificity of DL-aMRI and cMRI for detecting HCC were statistically compared using the non-inferiority test and generalized estimating equations models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;DL-aMRI showed a remarkable reduction in acquisition time compared with cMRI (4.1 &lt;em&gt;vs.&lt;/em&gt; 28.1 min). The image quality of DL-synthesized CE-MRI was not inferior to that of actual CE-MRI (&lt;em&gt;p&lt;/em&gt; &lt;0.001). There was an excellent inter-method agreement between the HCC sizes measured by the two protocols (R&lt;sup&gt;2&lt;/sup&gt; = 0.9436–0.9683). The pooled sensitivity and specificity of cMRI and DL-aMRI were 0.899 and 0.925 and 0.866 and 0.922, respectively. No significant differences were found between the sensitivity and specificity of the two protocols.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The proposed DL-aMRI could facilitate precise HCC diagnosis with no need for contrast agents, a substantial reduction in acquisition time, and preservation of both NC-MRI and CE-MRI data. DL-aMRI may serve as a valuable tool for HCC diagnosing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;In this multi-center study involving 1,769 participants, we developed a generative deep learning-based abbreviated MRI (DL-aMRI) strategy that provides an efficient, contrast-agent-free alternative for detecting HCC with accuracy comparable to that of conventional complete MRI, significantly reducing acquisition time from 28.1 min to just 4.1 min. This strategy is valuable for clinicians who face significant workloads resulting from long MRI scanning times and the potential adverse effects of contrast agents, as well as for researchers focused on developing cost-effective and accessible diagnostic tools for HCC detection. The proposed DL-aMRI protocol has practical implications for clinical settings, enhancing diagnostic efficiency while maintainin","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101392"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}