Liver International最新文献

{"title":"MASLD-Brain Aging Study Biases: Distribution Shift and Self-Cancellation","authors":"Shiqin Chen, Hui Li, Qingfeng Wang","doi":"10.1111/liv.70177","DOIUrl":"https://doi.org/10.1111/liv.70177","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Complex Role of Glycine-Conjugated Bile Acids and Gut-Liver Axis in Progressive Alcohol-Related Liver Disease","authors":"Yunyi Yang, Yanming He, Hongjie Yang","doi":"10.1111/liv.70176","DOIUrl":"https://doi.org/10.1111/liv.70176","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Reader—Pregnancy, Thyroid Disease Did Not Alter MASLD-Brain Aging Associations and Mediation of Inflammation","authors":"Jiao Wang, Rongrong Yang, Weili Xu","doi":"10.1111/liv.70180","DOIUrl":"https://doi.org/10.1111/liv.70180","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Liver Serine Protease TMPRSS6 Ameliorates Steatosis and Attenuates Fibrosis in Experimental MASLD","authors":"Mariateresa Pettinato,&nbsp;Valeria Furiosi,&nbsp;Rossana Carleo,&nbsp;Letizia Bavuso Volpe,&nbsp;Shuling Guo,&nbsp;Valeria Mannella,&nbsp;Giovanna Musco,&nbsp;Enrica Gilberti,&nbsp;Giuseppe De Palma,&nbsp;Giorgia Federico,&nbsp;Francesca Carlomagno,&nbsp;Alessandro Cherubini,&nbsp;Serena Pelusi,&nbsp;Anxhela Dano,&nbsp;Antonella Nai,&nbsp;Luca Valenti,&nbsp;Sandro Altamura,&nbsp;Alessia Pagani,&nbsp;Laura Silvestri","doi":"10.1111/liv.70163","DOIUrl":"https://doi.org/10.1111/liv.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common cause of liver disease and a leading contributor to liver-related morbidity and mortality. Currently, no pharmacological approach has demonstrated consistent and long-lasting benefits across all patients. Therefore, identifying new therapeutic targets remains an urgent clinical need. The hepatic serine protease matriptase-2, encoded by <i>TMPRSS6</i>, inhibits the BMP-SMAD pathway. Interestingly, reduced BMP-SMAD signalling in the liver is frequently associated with altered lipid metabolism in patients. Conversely, inactivation of <i>Tmprss6</i> has been linked to reduced high-fat diet-induced obesity. Based on these findings, we hypothesize that TMPRSS6 represents a novel and promising target for the treatment of MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Hepatic <i>TMPRSS6</i> expression was analysed in obese patients with or without MASLD. Adult male mice were fed a MASLD-MASH diet, and once hepatosteatosis was established, they were treated with antisense oligonucleotides targeting <i>Tmprss6</i> while continuing the dietary regimen for an additional 6 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression of the BMP-SMAD inhibitor <i>TMPRSS6</i> was increased in people with MASLD and negatively correlated with PPARα signaling, a key regulator of hepatic lipid metabolism. In experimental MASLD, downregulation of hepatocytic <i>Tmprss6</i> using GalNAc-ASO significantly reduced steatohepatitis and fibrosis and attenuated MASLD-MASH-associated ferroptosis by reshaping hepatic transcription factor activity towards PPARα and SMAD4/SMAD5-driven signalling. Consistently, enhanced BMP-SMAD signalling increased PPARα activity in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings reveal a novel functional crosstalk between TMPRSS6 and PPARα. Pharmacological downregulation of <i>Tmprss6</i> in experimental MASLD mitigates hepatosteatosis, inflammation and fibrosis by enhancing PPARα signalling and attenuating ferroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality and Cancer in Offspring of Mothers With Biopsy-Proven MASLD During Pregnancy: A Nationwide Cohort Study","authors":"Carole A. Marxer,&nbsp;Fahim Ebrahimi,&nbsp;David Bergman,&nbsp;Jiangwei Sun,&nbsp;Hannes Hagström,&nbsp;Marcus Thuresson,&nbsp;Olof Stephansson,&nbsp;Jonas F. Ludvigsson","doi":"10.1111/liv.70174","DOIUrl":"https://doi.org/10.1111/liv.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Health-related outcomes through early adulthood among offspring prenatally exposed to maternal metabolic dysfunction-associated steatotic liver disease (MASLD) are insufficiently investigated. We aimed to study the risk of mortality and cancer in such offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This nationwide cohort study included all singleton live born offspring with prenatal exposure to maternal biopsy-proven MASLD (1992–2017; <i>N</i> = 239) in Sweden. MASLD offspring were matched with up to five reference offspring (<i>N</i> = 1131) of mothers without known MASLD by maternal age at delivery, calendar year of delivery, and parity. We used a multivariable Cox proportional hazard model to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for mortality and cancer up until 31 December 2021. For mortality, we stratified by maternal MASLD severity (simple steatosis alone vs. severe MASLD comprising steatohepatitis, liver fibrosis or cirrhosis).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over a median follow-up of 16.9 years, two deaths occurred in offspring prenatally exposed to maternal MASLD (IR 0.5/1000 person-years, 95% CI 0.1–1.8) and seven deaths in reference offspring (IR 0.4/1000 person-years, 95% CI 0.1–0.8), which corresponded to an aHR of 1.78 (95% CI 0.27–11.97). Higher disease severity was not associated with an increased risk of death. We observed few cancer events with similar IR/1000 person-years (0.2 [95% CI 0.0–1.4] vs. 0.3 [0.1–0.6] in reference offspring), which corresponded to an aHR of 0.64 (95% CI 0.07–5.95).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found no evidence that prenatal exposure to maternal MASLD affects the risk of death or cancer through early adulthood but larger studies are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strengthening the Assessment of Antifibrotic Therapy in Compensated Cirrhosis","authors":"Sheng Li,&nbsp;Xiao Wu","doi":"10.1111/liv.70173","DOIUrl":"https://doi.org/10.1111/liv.70173","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Prospective, Blinded Study of Symptom Prevalence and Specificity of Porphyrin Precursors in Carriers of Acute Hepatic Porphyria","authors":"Mohsen Merati,&nbsp;Nanditha Jayakumar,&nbsp;Yuvraaj Kapoor,&nbsp;Hetanshi Naik,&nbsp;Manisha Balwani,&nbsp;Karl E. Anderson,&nbsp;Herbert L. Bonkovsky,&nbsp;Robert J. Desnick,&nbsp;Brendan McGuire,&nbsp;John Phillips,&nbsp;D. Montgomery Bissell,&nbsp;Bruce Wang","doi":"10.1111/liv.70156","DOIUrl":"https://doi.org/10.1111/liv.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>This study aimed to characterise symptoms and assess the prevalence of elevated urine porphyrin precursors in first-degree relatives of acute hepatic porphyria (AHP) patients who have never experienced acute attacks and had no previous AHP genetic or biochemical testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>149 first-degree relatives of confirmed AHP patients, previously unscreened for the family mutation, were recruited. All underwent genetic analysis, with 143 completing a study questionnaire and 118 undergoing urine analysis for delta aminolevulinic acid (ALA) and porphobilinogen (PBG). The questionnaire focused on symptoms, medical and family history, and quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 79 AHP mutation carriers and 70 non-carriers. Carriers had significantly higher ALA (6.98 vs. 2.21 mg/g creatinine) and PBG levels (9.17 vs. 1.31 mg/g creatinine) than non-carriers. Female carriers showed higher ALA (9.29 vs. 3.07 mg/g creatinine) and PBG levels (12.71 vs. 3.16 mg/g creatinine) than male carriers. Porphyria-related symptoms were reported by 27% (21/77) of carriers compared to 15% (10/66) of non-carriers, with carriers more likely to report dark urine and prolonged symptoms. Finally, 30.8% of carriers were asymptomatic high excreters (ASHE) with PBG levels exceeding four times the upper limit of normal (ULN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Significant differences in porphyrin precursor excretion and symptom profiles were found between AHP mutation carriers and controls, as well as between female and male carriers. Female carriers are more likely to excrete porphyrin metabolites above the normal range. A larger than expected number of undiagnosed carriers are ASHE with levels greater than four times the ULN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid Glutamine Synthetase Protects Against Acute Liver Injury in Mice Independent of Its Enzyme Activity","authors":"Jianghong Yu,&nbsp;Menglin Shi,&nbsp;Yumeng Guo,&nbsp;Kaiyi Fu,&nbsp;Jun Zhang,&nbsp;Hao Ding,&nbsp;Mengxiao Ge,&nbsp;Shuangyi Sun,&nbsp;Huilu Zhang,&nbsp;Jie Liu","doi":"10.1111/liv.70105","DOIUrl":"https://doi.org/10.1111/liv.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glutamine synthetase (GS, encoded by <i>Glul</i>) is a well-known ammonia-detoxifying enzyme, but its function in acute liver injury (ALI) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Lipopolysaccharide (LPS) and D-galactosamine (D-GalN) were utilised to construct the murine ALI model. <i>C57BL/6J-Glul</i>^{<i>em1(flox)Smoc</i>} mice (<i>Glul</i>^<i>f/f</i>) and <i>B6.129-Lyz2</i>^{<i>tm1(cre)smoc</i>} (<i>Lyz2-Cre</i>) transgenic mice were crossed to generate <i>Lyz2</i>⁺<i>Glul</i>^<i>f/f</i> (<i>Glul</i>^{<i>∆Lyz2</i>}) mice with a selectively knockout of <i>Glul</i> in myeloid cells. Histological staining experiments were performed to evaluate liver injury. Flow cytometry and RNA sequencing analyses were conducted to investigate the effects of <i>Glul</i> deficiency on liver immunity. Additionally, several strategies were applied to intervene ALI in mice, including administration of CCL2 neutralising antibody or GS inhibitor L-methionine sulfoximine (MSO), as well as adeno-associated virus (AAV)-mediated enhancement of GS expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression of <i>Glul</i> in myeloid cells was downregulated in wild-type mice after ALI modelling by LPS/D-GalN. Moreover, <i>Glul</i>^{<i>∆Lyz2</i>} mice demonstrated aggravated ALI and higher mortality upon LPS/D-GalN challenge, compared to the control <i>Glul</i>^<i>f/f</i> littermates. Notably, <i>Glul</i> deficiency significantly contributed to the activation of monocyte-derived macrophages (MoMFs), secretion of C-C chemokine ligand 2 (CCL2) and the recruitment of C-C chemokine receptor 2-positive monocytes. Treatment with CCL2 neutralising antibody significantly alleviated ALI by inhibiting MoMF activation. Interestingly, although MSO treatment effectively blocked the enzyme activity of GS, it exerted both preventive and therapeutic effects against ALI, which could be attributed to the elevation of GS protein level. Therefore, in vivo global or myeloid GS was overexpressed via AAV delivery system, which demonstrated potent protective efficacy against ALI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provided an updated look at the protective role of GS independent of its enzyme activity in ALI and shed light on the potential therapeutical strategies for ALI intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning Reveals Liver MRI Features Associated With PNPLA3 I148M in Steatotic Liver Disease","authors":"Yazhou Chen,&nbsp;Benjamin P. M. Laevens,&nbsp;Teresa Lemainque,&nbsp;Gustav Anton Müller-Franzes,&nbsp;Tobias Seibel,&nbsp;Carola Dlugosch,&nbsp;Jan Clusmann,&nbsp;Paul-Henry Koop,&nbsp;Rongpeng Gong,&nbsp;Yuanyuan Liu,&nbsp;Niharika Jakhar,&nbsp;Feng Cao,&nbsp;Simon Schophaus,&nbsp;Thriveni Basavanapura Raju,&nbsp;Anastasia Artemis Raptis,&nbsp;Felix van Haag,&nbsp;Joel Joy,&nbsp;Rohit Loomba,&nbsp;Luca Valenti,&nbsp;Jakob Nikolas Kather,&nbsp;Titus J. Brinker,&nbsp;Moritz Herzog,&nbsp;Ivan G. Costa,&nbsp;Diego Hernando,&nbsp;Kai Markus Schneider,&nbsp;Daniel Truhn,&nbsp;Carolin V. Schneider","doi":"10.1111/liv.70164","DOIUrl":"https://doi.org/10.1111/liv.70164","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Steatotic liver disease (SLD) is the most common liver disease worldwide, affecting 30% of the global population. It is strongly associated with the interplay of genetic and lifestyle-related risk factors. The genetic variant accounting for the largest fraction of SLD heritability is &lt;i&gt;PNPLA3&lt;/i&gt; I148M, which is carried by 23% of the western population and increases the risk of SLD two to three-fold. However, identification of variant carriers is not part of routine clinical care and prevents patients from receiving personalised care.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We analysed MRI images and common genetic variants in &lt;i&gt;PNPLA3, TM6SF2, MTARC1, HSD17B13&lt;/i&gt; and &lt;i&gt;GCKR&lt;/i&gt; from a cohort of 45 603 individuals from the UK Biobank. Proton density fat fraction (PDFF) maps were generated using a water-fat separation toolbox, applied to the magnitude and phase MRI data. The liver region was segmented using a U-Net model trained on 600 manually segmented ground truth images. The resulting liver masks and PDFF maps were subsequently used to calculate liver PDFF values. Individuals with (PDFF ≥ 5%) and without SLD (PDFF &lt; 5%) were selected as the study cohort and used to train and test a Vision Transformer classification model with five-fold cross validation. We aimed to differentiate individuals who are homozygous for the &lt;i&gt;PNPLA3&lt;/i&gt; I148M variant from non-carriers, as evaluated by the area under the receiver operating characteristic curve (AUROC). To ensure a clear genetic contrast, all heterozygous individuals were excluded. To interpret our model, we generated attention maps that highlight the regions that are most predictive of the outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Homozygosity for the &lt;i&gt;PNPLA3&lt;/i&gt; I148M variant demonstrated the best predictive performance among five variants with AUROC of 0.68 (95% CI: 0.64–0.73) in SLD patients and 0.57 (95% CI: 0.52–0.61) in non-SLD patients. The AUROCs for the other SNPs ranged from 0.54 to 0.57 in SLD patients and from 0.52 to 0.54 in non-SLD patients. The predictive performance was generally higher in SLD patients compared to non-SLD patients. Attention maps for &lt;i&gt;PNPLA3&lt;/i&gt; I148M carriers showed that fat deposition in regions adjacent to the hepatic vessels, near the liver hilum, plays an important role in predicting the presence of the I148M variant.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our study marks novel progress in the non-invasive detection of homozygosity for &lt;i&gt;PNPLA3&lt;/i&gt; I148M through the application of dee","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of Non-Invasive Tests for Liver Fibrosis in People Living With Alpha-1 Antitrypsin Deficiency","authors":"Joost Boeckmans,&nbsp;Jörn M. Schattenberg,&nbsp;Malin Fromme,&nbsp;Pavel Strnad,&nbsp;Hannes Hagström","doi":"10.1111/liv.70165","DOIUrl":"https://doi.org/10.1111/liv.70165","url":null,"abstract":"<p>Severe alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition characterised by low systemic levels of alpha-1 antitrypsin due to its retention in the liver. Consequently, it predisposes individuals to the development of chronic obstructive pulmonary disease and liver cirrhosis. Much progress has been made to non-invasively monitor liver fibrosis and cirrhosis in individuals with other liver diseases, but it remains unclear how to assess liver disease in people with AATD. This narrative review examined the available evidence on non-invasive tests (NITs) to stage liver fibrosis and predict incident major adverse liver outcomes in people with AATD. Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE), blood-based NITs, and serum liver enzymes are generally normal or mildly elevated in individuals with AATD. Further, VCTE-LSM and blood-based NITs, including the AST to platelet ratio index and fibrosis-4 score, have diagnostic utility for predicting F2 and F3 fibrosis and hold excellent (AUROC ≥ 0.90) prognostic value for incident major adverse liver outcomes. Gamma-glutamyl transferase also exhibits diagnostic and prognostic utility but is subject to multiple non-AATD-related fluctuations. A potential strategy to non-invasively assess liver disease stage and estimate the risk of major adverse liver outcomes in people with AATD could consist of a combination of VCTE-LSM with blood-based biomarker panels. Future studies should explore if liver stiffness naturally fluctuates over time in people with AATD, assess the ideal frequency of follow-up, and evaluate if NITs can guide the treatment of AATD-related liver disease.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}