JHEP Reports最新文献

{"title":"Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes","authors":"Kapish Gupta ,&nbsp;Dongning Chen ,&nbsp;Rebecca G. Wells","doi":"10.1016/j.jhepr.2024.101218","DOIUrl":"10.1016/j.jhepr.2024.101218","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Biliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to result from a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in biliary atresia in Australian livestock, but is found in a limited location and is unlikely to be a significant human toxin. We hypothesized that other unsaturated carbonyl compounds, some with the potential for significant human exposure, might also be biliary toxins.</div></div><div><h3>Methods</h3><div>We focused on the family of microcystins, cyclic peptide toxins from blue-green algae that are found worldwide, particularly during harmful algal blooms. We used primary extrahepatic cholangiocyte spheroids and extrahepatic bile duct explants from both neonatal [a total of 86 postnatal day (P) 2 mouse pups and 18 P2 rat pups (n = 8–10 per condition for both species)] and adult rodents [a total of 31 P15–18 mice (n = 10 or 11 per condition)] to study the biliary toxicity of microcystins and potential mechanisms involved.</div></div><div><h3>Results</h3><div>Results showed that 400 nM microcystin (MC)-RR, but not six other microcystins or the related algal toxin nodularin, caused &gt;80% lumen closure in cell spheroids made from extrahepatic cholangiocytes isolated from 2–3-day-old mice (<em>p</em> &lt;0.0001). By contrast, 400 nM MC-RR resulted in less than an average 5% lumen closure in spheroids derived from neonatal intrahepatic cholangiocytes or cells from adult mice (<em>p</em> = 0.4366). In addition, MC-RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice (<em>p</em> &lt;0.0001), but not 18-day-old mice. MC-RR also caused a 2.3-times increase in reactive oxygen species in neonatal cholangiocytes (<em>p</em> &lt;0.0001), and treatment with <em>N</em>-acetyl cysteine partially prevented microcystin-RR-induced lumen closure (<em>p</em> = 0.0004), suggesting a role for redox homeostasis in its mechanism of action.</div></div><div><h3>Conclusions</h3><div>We identified MC-RR as a selective neonatal extrahepatic cholangiocyte toxin and suggest that it acts by increasing redox stress.</div></div><div><h3>Impact and implications:</h3><div>The plant toxin biliatresone causes a biliary atresia-like disease in livestock and vertebrate animal model systems. We tested the widespread blue-green algal toxin, microcystin-RR, another highly electrophilic unsaturated carbonyl compound that is released during harmful algal blooms, and found that it was also a biliary toxin with specificity for neonatal extrahepatic cholangiocytes. This work should drive further animal studies and, ultimately, studies to determine whether human exposure to microcystin-RR causes biliary atresia.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101218"},"PeriodicalIF":9.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virological markers for clinical trials in chronic viral hepatitis","authors":"Jean-Michel Pawlotsky","doi":"10.1016/j.jhepr.2024.101214","DOIUrl":"10.1016/j.jhepr.2024.101214","url":null,"abstract":"<div><div>Chronic hepatitis virus infections remain a major public health problem, despite significant therapeutic advances over the past two decades. Considerable progress has been made in the treatment of chronic viral hepatitis, but continued efforts are needed to develop and bring to market new drugs to fill the gaps in the current therapeutic armamentarium. Thus, clinical trials to assess the safety and efficacy of these new therapeutic approaches, including the selection of reliable and objective treatment endpoints, are still needed. Virological biomarkers play an important role in the diagnosis, monitoring, and evaluation of antiviral treatment efficacy. They are often used as primary or secondary endpoints in the evaluation of new treatments for chronic viral hepatitis. However, these markers are not all equally informative. The aim of this review article is to provide a comprehensive overview of the available virological tests for chronic viral hepatitis due to hepatitis B, D, C and E viruses, the information they provide and lack, the specific challenges associated with each, and their use in clinical trials of new treatments.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 11","pages":"Article 101214"},"PeriodicalIF":9.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC","authors":"Marta Piqué-Gili ,&nbsp;Carmen Andreu-Oller ,&nbsp;Agavni Mesropian ,&nbsp;Roger Esteban-Fabró ,&nbsp;Marina Bárcena-Varela ,&nbsp;Marina Ruiz de Galarreta ,&nbsp;Carla Montironi ,&nbsp;Iris Martinez-Quetglas ,&nbsp;Sarah Cappuyns ,&nbsp;Judit Peix ,&nbsp;Ieva Keraite ,&nbsp;Albert Gris-Oliver ,&nbsp;Elisa Fernández-Martínez ,&nbsp;Ezequiel Mauro ,&nbsp;Miguel Torres-Martin ,&nbsp;Jordi Abril-Fornaguera ,&nbsp;Katherine E. Lindblad ,&nbsp;Diether Lambrechts ,&nbsp;Jeroen Dekervel ,&nbsp;Swan N. Thung ,&nbsp;Josep M. Llovet","doi":"10.1016/j.jhepr.2024.101212","DOIUrl":"10.1016/j.jhepr.2024.101212","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Transforming growth factor β (TGF-β) plays an oncogenic role in advanced cancer by promoting cell proliferation, metastasis and immunosuppression. &lt;em&gt;PMEPA1&lt;/em&gt; (prostate transmembrane protein androgen induced 1) has been shown to promote TGF-β oncogenic effects in other tumour types. Thus, we aimed to explore the role of &lt;em&gt;PMEPA1&lt;/em&gt; in hepatocellular carcinoma (HCC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We analysed 1,097 tumours from patients with HCC, including discovery (n = 228) and validation (n = 361) cohorts with genomic and clinicopathological data. &lt;em&gt;PMEPA1&lt;/em&gt; levels were assessed by qPCR (n = 228), gene expression data (n = 869) and at the single-cell level (n = 54). Genetically engineered mouse models overexpressing &lt;em&gt;MYC+PMEPA1&lt;/em&gt; compared to &lt;em&gt;MYC&lt;/em&gt; were generated and molecular analyses were performed on the HCCs obtained.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;PMEPA1&lt;/em&gt; was overexpressed in 18% of HCC samples (fold-change &gt;2; n = 201/1,097), a feature associated with TGF-β signalling activation (&lt;em&gt;p &lt;&lt;/em&gt;0.05) and absence of gene body hypomethylation (&lt;em&gt;p &lt;&lt;/em&gt;0.01). HCCs showing both TGF-β signalling and high &lt;em&gt;PMEPA1&lt;/em&gt; levels (12% of cases) were linked to immune exhaustion, late TGF-β activation, aggressiveness and higher recurrence rates after resection, in contrast to HCCs with only TGF-β signalling (8%) or &lt;em&gt;PMEPA1&lt;/em&gt; overexpression (9%). Single-cell RNA sequencing analysis identified &lt;em&gt;PMEPA1&lt;/em&gt; expression in HCC and stromal cells. &lt;em&gt;PMEPA1&lt;/em&gt;-expressing tumoural cells were predicted to interact with CD4&lt;sup&gt;+&lt;/sup&gt; regulatory T cells and CD4&lt;sup&gt;+&lt;/sup&gt; CXCL13&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; exhausted T cells. &lt;em&gt;In vivo&lt;/em&gt;, overexpression of &lt;em&gt;MYC&lt;/em&gt;+&lt;em&gt;PMEPA1&lt;/em&gt; led to HCC development in ∼60% of mice and a decreased survival compared to mice overexpressing &lt;em&gt;MYC&lt;/em&gt; alone (&lt;em&gt;p =&lt;/em&gt; 0.014). &lt;em&gt;MYC&lt;/em&gt;+&lt;em&gt;PMEPA1&lt;/em&gt; tumours were enriched in TGF-β signalling, paralleling our human data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;In human HCC, &lt;em&gt;PMEPA1&lt;/em&gt; upregulation is linked to TGF-β activation, immune exhaustion, and an aggressive phenotype. Overexpression of &lt;em&gt;PMEPA1+MYC&lt;/em&gt; led to tumoural development &lt;em&gt;in vivo&lt;/em&gt;, demonstrating the oncogenic role of &lt;em&gt;PMEPA1&lt;/em&gt; in HCC for the first time.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications:&lt;/h3&gt;&lt;div&gt;&lt;em&gt;PMEPA1&lt;/em&gt; can enhance the tumour-promoting effects of TGF-β in cancer. In this study, we demonstrate that &lt;em&gt;PMEPA1&lt;/em&gt; is highly expressed in ∼18% of patients with hepatocellular carcinoma (HCC), a feature associated with poor prognosis, TGF-β activation and exhaustion of immune cells. Similarly, in mouse models, &lt;em&gt;PMEPA1&lt;/em&gt; overexpression promotes HCC development, which demonstrates its oncogenic role. The identification of &lt;em&gt;PMEPA1&lt;/em&gt; as oncogenic driver in HCC and its role in immune exhaustion and poor clinical outcomes enhances our under","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 11","pages":"Article 101212"},"PeriodicalIF":9.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver stiffness measurement predicts clinical outcomes in autoimmune hepatitis","authors":"Ignasi Olivas ,&nbsp;Pinelopi Arvaniti ,&nbsp;Stella Gabeta ,&nbsp;Sonia Torres ,&nbsp;Maria Del Barrio ,&nbsp;Alvaro Díaz-González ,&nbsp;Paula Esteban ,&nbsp;Mar Riveiro-Barciela ,&nbsp;Ezequiel Mauro ,&nbsp;Sergio Rodríguez-Tajes ,&nbsp;Kalliopi Zachou ,&nbsp;George N. Dalekos ,&nbsp;María-Carlota Londoño","doi":"10.1016/j.jhepr.2024.101213","DOIUrl":"10.1016/j.jhepr.2024.101213","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Liver stiffness measurement (LSM) has been shown to adequately predict outcomes in patients with liver disease. However, the value of LSM as a predictor of disease progression in autoimmune hepatitis (AIH) remains to be determined. This study aimed to evaluate the role of LSM as a predictor of disease progression and decompensation of cirrhosis in patients with AIH.</div></div><div><h3>Methods</h3><div>This multicentre cohort study included 439 patients with histologically confirmed AIH and at least one LSM during follow-up. The association between the first LSM performed at least 6 months after treatment initiation (baseline LSM [BLSM]) and cirrhosis development and poor outcomes (decompensation, liver transplantation, and/or liver-related death) was assessed using Cox regression and its discriminating capacity with a receiver-operating characteristic curve.</div></div><div><h3>Results</h3><div>Most patients were female (n = 301, 70%), with a median age of 52 years. BLSM performed after a median of 2.18 (1.19-4.68) years had a median value of 6 kPa (4.5-8.5). At the time of BLSM, 332 (76%) patients had achieved a biochemical response and 57 (13%) had cirrhosis. During follow-up, eight patients (2%) presented with poor outcomes and 26 (7%) developed cirrhosis. BLSM was higher among patients with poor outcomes (13.5 kPa <em>vs.</em> 6 kPa; <em>p &lt;</em>0.001) and was independently associated with cirrhosis development (hazard ratio 1.300; <em>p &lt;</em>0.001), irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes, with AUCs of 0.859 (95% CI 0.789-0.929) and 0.900 (95% CI 0.847-0.954), respectively.</div></div><div><h3>Conclusion</h3><div>BLSM could play a significant role in predicting AIH outcomes, potentially identifying a subgroup of patients at a high risk of progressing to cirrhosis and experiencing decompensation.</div></div><div><h3>Impact and implications:</h3><div>The value of liver stiffness measurement as a predictor of outcomes in patients with autoimmune hepatitis (AIH) remains to be determined. In this large multicentre study, liver stiffness measurement was found to be an independent predictive factor of adverse clinical outcomes and cirrhosis development in AIH, irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes in AIH.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 11","pages":"Article 101213"},"PeriodicalIF":9.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A home-based exercise programme attenuates fatigue in primary biliary cholangitis: Results from the EXCITED clinical trial","authors":"Alice Freer ,&nbsp;Felicity R. Williams ,&nbsp;Simon Durman ,&nbsp;Jennifer Hayden ,&nbsp;Matthew J. Armstrong ,&nbsp;Palak J. Trivedi","doi":"10.1016/j.jhepr.2024.101210","DOIUrl":"10.1016/j.jhepr.2024.101210","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Fatigue is a commonly reported symptom of primary biliary cholangitis (PBC). We conducted a single-arm, open-label clinical trial to assess the efficacy of a physiotherapist-led home-based exercise programme (HBEP) in patients with PBC and moderate-to-severe fatigue (NCT04265235).</div></div><div><h3>Methods</h3><div>A 12-week individualised HBEP (aerobic + resistance based) was delivered to patients with a PBC-40 fatigue domain score ≥33. The primary efficacy outcome measure was a reduction in fatigue severity by ≥5 points. Secondary outcome measures included other domains of PBC-40, the FIS (fatigue impact scale), ESS (Epworth sleepiness score), HADS (hospital anxiety and depression scale), aerobic capacity (ISWT [incremental shuttle walk test], Duke activity status index (predicted VO₂ peak) and physical function (short physical performance battery [SPPB]).</div></div><div><h3>Results</h3><div>A total of 31 patients were recruited, of whom 30 completed the 12-week HBEP (29 women; median age 53 years, median alkaline phosphatase value: 1.5x the upper limit of normal, median bilirubin: 12 μmol/L, and median baseline PBC-40 fatigue score 42). The primary outcome was met by 26 patients, with a median reduction in PBC-40 fatigue score of -10.5 points (IQR -9 to -13; <em>p &lt;</em>0.001). Reductions were also observed in the symptom, cognition, and emotion domains of PBC-40, and in the FIS, ESS and HADS (<em>p &lt;</em>0.01 for all measures). This was alongside increases in the median ISWT (+90 m; IQR 57.5-110), predicted VO₂ peak (+2.41 ml/kg/min; IQR 0.01-4.05), and SPPB (+1 point; IQR 0-1.4) (all <em>p &lt;</em>0.001). 28 participants achieved the maximum SPPB score of 12/12 (<em>vs.</em> 13 patients at baseline; <em>p &lt;</em>0.001). No significant adverse events were reported.</div></div><div><h3>Conclusion</h3><div>This proof-of-concept study shows that a HBEP is safe, feasible, and has the potential to attenuate fatigue. Controlled trials are needed to validate the efficacy of exercise interventions in PBC.</div></div><div><h3>Impact and implications:</h3><div>Fatigue is a common symptom in primary biliary cholangitis (PBC), and is linked to cognitive dysfunction, somnolence, and reduced activity. The pathogenesis is multifactorial, and muscle bioenergetic abnormalities have been proposed to contribute. In this study, we show that a home-based exercise programme, consisting of aerobic and resistance-based sets, can be safely delivered to people living with PBC. In addition, the programme led to a reduction in fatigue severity, less daytime sleepiness and improved cognitive function.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 12","pages":"Article 101210"},"PeriodicalIF":9.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of artificial intelligence for liver diseases: A survey from the EASL congress 2024","authors":"Laura Žigutytė ,&nbsp;Thomas Sorz-Nechay ,&nbsp;Jan Clusmann ,&nbsp;Jakob Nikolas Kather","doi":"10.1016/j.jhepr.2024.101209","DOIUrl":"10.1016/j.jhepr.2024.101209","url":null,"abstract":"<div><div>Artificial intelligence (AI) methods enable humans to analyse large amounts of data, which would otherwise not be feasibly quantifiable. This is especially true for unstructured visual and textual data, which can contain invaluable insights into disease. The hepatology research landscape is complex and has generated large amounts of data to be mined. Many open questions can potentially be addressed with existing data through AI methods. However, the field of AI is sometimes obscured by hype cycles and imprecise terminologies. This can conceal the fact that numerous hepatology research groups already use AI methods in their scientific studies. In this review article, we aim to assess the contemporaneous use of AI methods in hepatology in Europe. To achieve this, we systematically surveyed all scientific contributions presented at the EASL Congress 2024. Out of 1,857 accepted abstracts (1,712 posters and 145 oral presentations), 6 presentations (∼4%) and 69 posters (∼4%) utilised AI methods. Of these, 55 posters were included in this review, while the others were excluded due to missing posters or incomplete methodologies. Finally, we summarise current academic trends in the use of AI methods and outline future directions, providing guidance for scientific stakeholders in the field of hepatology.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 12","pages":"Article 101209"},"PeriodicalIF":9.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic profiles differentiate between porto-sinusoidal vascular disorder, cirrhosis, and healthy individuals","authors":"Georg Semmler ,&nbsp;Oleksandr Petrenko ,&nbsp;Juanjo Jose Lozano ,&nbsp;Sarah Shalaby ,&nbsp;Juan I. Sánchez-Avila ,&nbsp;Nara Marella ,&nbsp;Thomas Hannich ,&nbsp;Katharina Wöran ,&nbsp;Lorenz Balcar ,&nbsp;Benedikt Simbrunner ,&nbsp;Katharina Lampichler ,&nbsp;Behrang Mozayani ,&nbsp;Michael Trauner ,&nbsp;Mattias Mandorfer ,&nbsp;Thomas Reiberger ,&nbsp;Juan-Carlos García-Pagán ,&nbsp;Bernhard Scheiner","doi":"10.1016/j.jhepr.2024.101208","DOIUrl":"10.1016/j.jhepr.2024.101208","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Porto-sinusoidal vascular disorder (PSVD) is a rare and diagnostically challenging vascular liver disease. This study aimed to identify distinct metabolomic signatures in patients with PSVD or cirrhosis to facilitate non-invasive diagnosis and elucidate perturbed metabolic pathways.</div></div><div><h3>Methods</h3><div>Serum samples from 20 healthy volunteers (HVs), 20 patients with histologically confirmed PSVD or 20 patients with cirrhosis were analyzed. Metabolites were measured using liquid chromatography-mass spectrometry. Differential abundance was evaluated with Limma’s moderated t-statistics. Artificial neural network and support vector machine models were developed to classify PSVD against cirrhosis or HV metabolomic profiles. An independent cohort was used for validation.</div></div><div><h3>Results</h3><div>A total of 283 metabolites were included for downstream analysis. Clustering effectively separated PSVD from HV metabolomes, although a subset of patients with PSVD (n = 5, 25%) overlapped with those with cirrhosis. Differential testing revealed significant PSVD-linked metabolic perturbations, including pertubations in taurocholic and adipic acids, distinguishing patients with PSVD from both HVs and those with cirrhosis. Alterations in pyrimidine, glycine, serine, and threonine pathways were exclusively associated with PSVD. Machine learning models utilizing selected metabolic signatures reliably differentiated the PSVD group from HVs or patients with cirrhosis using only 4 to 6 metabolites. Validation in an independent cohort demonstrated the high discriminative ability of taurocholic acid (AUROC 0.899) for patients with PSVD <em>vs.</em> HVs and the taurocholic acid/aspartic acid ratio (AUROC 0.720) for PSVD <em>vs.</em> cirrhosis.</div></div><div><h3>Conclusions</h3><div>High-throughput metabolomics enabled the identification of distinct metabolic profiles that differentiate between PSVD, cirrhosis, and healthy individuals. Unique alterations in the glycine, serine, and threonine pathways suggest their potential involvement in PSVD pathogenesis.</div></div><div><h3>Impact and implications:</h3><div>Porto-sinusoidal vascular disorder (PSVD) is a vascular liver disease that can lead to pre-sinusoidal portal hypertension in the absence of cirrhosis, with poorly understood pathophysiology and no established treatment. Our study demonstrates that analyzing the serum metabolome could reveal distinct metabolic signatures in patients with PSVD, including alterations in the pyrimidine, glycine, serine and threonine pathways, potentially shedding light on the disease's underlying pathways. These findings could enable earlier and non-invasive diagnosis of PSVD, potentially reducing reliance on invasive procedures like liver biopsy and guiding diagnostic pathways.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 12","pages":"Article 101208"},"PeriodicalIF":9.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of alcohol intake in patients with steatotic liver disease and excessive alcohol intake","authors":"Emil Deleuran Hansen ,&nbsp;Nikolaj Torp ,&nbsp;Stine Johansen ,&nbsp;Johanne Kragh Hansen ,&nbsp;Marianne Lerbæk Bergmann ,&nbsp;Camilla Dalby Hansen ,&nbsp;Sönke Detlefsen ,&nbsp;Peter Andersen ,&nbsp;Ida Villesen ,&nbsp;Katrine Bech ,&nbsp;Katrine Thorhauge ,&nbsp;Gitte Hedegaard Jensen ,&nbsp;Katrine Prier Lindvig ,&nbsp;Torben Hansen ,&nbsp;Emmanuel A. Tsochatzis ,&nbsp;Jonel Trebicka ,&nbsp;Maja Thiele ,&nbsp;Aleksander Krag ,&nbsp;Mads Israelsen ,&nbsp;the GALAXY and MicrobLiver consortia","doi":"10.1016/j.jhepr.2024.101200","DOIUrl":"10.1016/j.jhepr.2024.101200","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Quantifying alcohol intake is crucial for subclassifying participants with steatotic liver disease (SLD) and interpreting clinical trials of alcohol-related liver disease (ALD) and metabolic and alcohol-related liver disease (MetALD). However, the accuracy of self-reported alcohol intake is considered imprecise. We compared the diagnostic and prognostic utility of self-reported alcohol intake with blood-based biomarkers of alcohol intake: phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT).</div></div><div><h3>Methods</h3><div>We studied 192 participants from two randomized controlled trials on MetALD and ALD, all with current or former excessive alcohol intake (≥24/36 [♀/♂] grams daily for at least 1 year) and biopsy-proven liver disease. We assessed self-reported alcohol intake, PEth, and CDT at four time points. We collected follow-up data on hepatic decompensation and death manually through electronic medical records.</div></div><div><h3>Results</h3><div>Most participants were male (n = 161, 84%) with a mean age of 59 (SD 9) years and 73 participants reported 1-week abstinence before inclusion; the remaining reported a median alcohol intake of 43 g/day. Median PEth was 0.5 μmol/L (IQR: 0.0–1.3) and %CDT = 1.9 (IQR: 1.6–2.3). Of 32 patients reporting at least 6 months of abstinence; 27 (84%) was confirmed by PEth &lt;0.05 μmol/L. Self-reported alcohol intake correlated well with PEth (r = 0.617) and moderately with CDT (r = 0.316). Self-reported alcohol intake, PEth, and CDT all predicted hepatic decompensation and death. However, PEth showed the highest prediction, surpassing self-reported alcohol intake (Harrel’s C, PEth = 0.80 <em>vs.</em> self-reported = 0.68, <em>p</em> = 0.026).</div></div><div><h3>Conclusions</h3><div>Self-reported abstinence can be considered reliable in clinical trials. However, PEth is superior in predicting hepatic decompensation and death in patients with MetALD and ALD.</div></div><div><h3>Impact and implications</h3><div>An accurate quantification of alcohol intake is crucial in the clinical phenotyping of patients with steatotic liver disease and when designing clinical trials. This study found self-reported abstinence to be reliable but phosphatidylethanol was a more accurate prognostic biomarker of hepatic decompensation and death in a clinical trial setting. Findings may inform the design of future trials in patients with steatotic liver disease.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101200"},"PeriodicalIF":9.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(24)00207-6","DOIUrl":"10.1016/S2589-5559(24)00207-6","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 9","pages":"Article 101203"},"PeriodicalIF":9.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924002076/pdfft?md5=e4a27c989694a622d4c22d6a3640d55d&pid=1-s2.0-S2589555924002076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(24)00210-6","DOIUrl":"10.1016/S2589-5559(24)00210-6","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 9","pages":"Article 101206"},"PeriodicalIF":9.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924002106/pdfft?md5=36611aac042aa5927b580993b9e51763&pid=1-s2.0-S2589555924002106-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}