Hepatology Communications最新文献

{"title":"Integrated hepatic ferroptosis gene signature dictates pathogenic features of ferroptosis.","authors":"Takashi Matsumoto, Akihiro Nita, Yohei Kanamori, Ayato Maeda, Tomomi Nita, Noriko Yasuda-Yoshihara, Kosuke Mima, Hirohisa Okabe, Katsunori Imai, Hiromitsu Hayashi, Yuta Matsuoka, Katsuya Nagaoka, Keiichi I Nakayama, Yuki Sugiura, Yasuhito Tanaka, Hideo Baba, Toshiro Moroishi","doi":"10.1097/HC9.0000000000000721","DOIUrl":"10.1097/HC9.0000000000000721","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, a distinctive form of cell death induced by iron-dependent lipid peroxidation, is implicated in various biological processes, including liver diseases. Establishing an iron overload-induced ferroptosis model and identifying hepatic gene signatures associated with ferroptosis are crucial for understanding its role in liver pathogenesis.</p><p><strong>Methods: </strong>F-box and leucine-rich repeat protein 5 (FBXL5) is a substrate-recognition component of the SCF E3 ligase complex that restricts intracellular iron levels. In this study, we used liver-specific Fbxl5-null mice to establish an iron overload-induced ferroptosis model. Transcriptome analysis identified genes involved in hepatic ferroptosis. Integrating these gene signatures with another ferroptosis model enabled the assessment of ferroptosis-related pathology in murine liver injury models and in 174 patients undergoing liver resection surgery.</p><p><strong>Results: </strong>Iron overload induced severe liver damage in liver-specific Fbxl5-null mice, characterized by elevated liver enzymes, histopathological changes, and lipid peroxidation. Transcriptome analysis revealed a distinct set of genes associated with hepatic ferroptosis response. Generating a gene signature for evaluating ferroptosis enhanced the understanding of ferroptosis-related pathologies in liver diseases. Iron overload exacerbated liver damage in murine ischemia-reperfusion injury models via ferroptosis induction. In human patients, elevated serum iron levels correlated with sustained postoperative liver damage, indicating heightened susceptibility to ferroptosis.</p><p><strong>Conclusions: </strong>Here, a murine model of iron overload-induced hepatic ferroptosis was established, and a gene signature indicative of hepatic ferroptosis response in both mice and humans was identified. These findings underscore the role of ferroptosis in liver injury progression and suggest potential therapeutic targets for liver disease intervention.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158244","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":"Meaningful differences in patient-reported outcome measurement scores in liver disease.","authors":"Archita P Desai, Eric S Orman, Tarek G Aridi, Timothy Stump, Lauren Nephew, Marwan S Ghabril, Michael Fallon, Naga Chalasani, Patrick Monahan","doi":"10.1097/HC9.0000000000000727","DOIUrl":"10.1097/HC9.0000000000000727","url":null,"abstract":"<p><strong>Background: </strong>Patient-reported outcome measures (PROMs) are being used more often in chronic liver disease (CLD) clinical care and research. Their interpretability can be greatly enhanced by establishing the smallest meaningful score difference (MSD). We report scores of commonly used PROMs and their MSDs in patients at different stages of liver disease.</p><p><strong>Methods: </strong>Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile, Chronic Liver Disease Questionnaire (CLDQ), and Short Form-36 (SF-36) v1.0 scores were aggregated from 2442 adults with CLD at 4 different stages: inpatients with decompensated cirrhosis (n=1146) and outpatients with cirrhosis (n=677) or CLD (n=128) or recipients of liver transplant (LT, n=490) between June 2014 and April 2023 from 3 academic centers. MSDs were estimated using distribution and anchor-based methods.</p><p><strong>Results: </strong>The study sample's median age was 60.0 (IQR: 51.0-66.0); 55% were male, 17% Hispanic, 84% White, and 49% college educated. The etiology of CLD was alcohol in 36%, metabolic dysfunction-associated steatohepatitis (MASH) in 31%, and viral hepatitis B/C in 26%. Median PROMIS domain scores were generally lowest in inpatients and highest after transplant. For PROMIS, distribution-based and anchor-based MSDs ranged from 3 to 4 for individual domains and 4 to 6 for summary scores. Distribution-based MSDs were 1 for CLDQ and ranged from 7 to 11 for individual SF-36 domains, except role limitations domains, which ranged from 15 to 18, and component scores, which were 3. When compared across stages of liver disease, PROMIS MSDs were generally similar, although they tended to be 0.5-1.0 points smaller in the decompensated population compared to the stable populations.</p><p><strong>Conclusions: </strong>This study provides data-driven recommendations for MSDs, enhancing the interpretability of commonly used PROMs in liver disease and facilitating the integration of PROMs in various clinical and research settings.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158306","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":"A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework.","authors":"Aaron Hakim, Kung-Hung Lin, Tae-Hwi Schwantes-An, Marco Abreu, Jingyi Tan, Xiuqing Guo, Katherine P Yates, Luca Lotta, Niek Verweij, Rohit Loomba, David E Kleiner, Jeffrey B Schwimmer, Jerome I Rotter, Naga P Chalasani","doi":"10.1097/HC9.0000000000000728","DOIUrl":"10.1097/HC9.0000000000000728","url":null,"abstract":"<p><strong>Background: </strong>There is a substantial heritable component to metabolic dysfunction-associated steatotic liver disease (MASLD), and several genetic variants that promote MASLD development or associate with its severity have been reported. These associations vary in terms of their effect size and degree of replication.</p><p><strong>Methods: </strong>We developed a framework to classify previously identified MASLD genetic polymorphisms into 4 tiers based on effect size and extent of replication in the literature. We tested the association between \"tier 1\" single-nucleotide polymorphisms (OR ≥1.5, replicated in >2 independent studies) and biopsy measures of MASLD severity in a large, well-characterized histologic cohort of MASLD patients (n=3094).</p><p><strong>Results: </strong>Across 19 \"tier 1\" variants reflecting 11 genetic loci, only those in the PNPLA3-SAMM50-PARVB locus showed significant associations with biopsy-proven fibrosis severity and NAFLD activity score; the highest risk was for the rs738409 p.I148M variant in PNPLA3. A genetic risk score based on \"tier 1\" variants, as well as a previously developed genetic risk score based on variants in PNPLA3, TM6SF2, and HSD17B13, were both associated with fibrosis and NAFLD activity score, but these results were driven entirely by PNPLA3 rs738409.</p><p><strong>Conclusions: </strong>Our study provides a framework to prioritize evaluation of genetic polymorphisms for future replication efforts and demonstrates that in a large case-only cohort, histologic severity of MASLD is only robustly associated with the presence of variation in PNPLA3 among known candidate genes. These findings may have implications for patient risk stratification based on the presence of PNPLA3 rs738409.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158221","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":"Comparing the performance of 3 sarcopenia definitions for predicting adverse events prior to liver transplant.","authors":"Heidi E Johnston, Hannah L Mayr, Melita Andelkovic, Tahnie G Takefala, Yanyan Chen, Aaron P Thrift, Graeme A Macdonald, Ingrid J Hickman","doi":"10.1097/HC9.0000000000000701","DOIUrl":"10.1097/HC9.0000000000000701","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is a syndrome of severe muscle wasting, associated with adverse outcomes related to liver transplantation (LT). There are several approaches used to identify sarcopenia. We aimed to investigate the prevalence of sarcopenia using 3 different criteria and determine how these performed in relation to clinical outcomes.</p><p><strong>Methods: </strong>The cohort study included 237 adults with cirrhosis referred for LT. Sarcopenia was identified using (1) CT-defined; and the (2) original and (3) updated European Working Group on Sarcopenia in Older People criteria (EWGSOP1 and 2). Logistic regression was used to estimate OR and 95% CI for the relationships between sarcopenia and receiving an LT, unplanned admissions pre-LT, surgical complications, and length of stay for the LT admission. Fine-Gray competing risk analysis explored the impact of sarcopenia on receiving an LT and unplanned admissions. The AUC determined the predictive utility of the criteria.</p><p><strong>Results: </strong>The prevalence of CT-defined sarcopenia (52%) was more than twice and 4-fold that of EWGSOP1-defined (22%) and EWGSOP2-defined (11%) sarcopenia, respectively. No criteria demonstrated a significant association with time to LT nor the time to unplanned admissions pre-LT. Similarly, none of the 3 criteria had superior predictive utility for the clinical outcomes for unplanned hospital admissions pre-LT of receiving an LT, with all 3 criteria having identical moderate AUCs for unplanned admissions (0.70) and similar weak AUCs (≤0.55) for the likelihood of receiving an LT.</p><p><strong>Conclusions: </strong>Sarcopenia in patients undergoing LT evaluation is prevalent. EWGSOP criteria appear to offer no advantage over CT-only criteria in identifying patients at increased risk of adverse LT outcomes. Bedside measures of muscle function may be of benefit in tracking the effectiveness of interventions targeting sarcopenia.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158242","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":"Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease.","authors":"Clavia Ruth Wooton-Kee, Hari K Yalamanchili, Islam Mohamed, Manal Hassan, Kenneth D R Setchell, Monica Narvaez Rivas, Ayse K Coskun, Vasanta Putluri, Nagireddy Putluri, Prasun Jalal, Michael L Schilsky, David D Moore","doi":"10.1097/HC9.0000000000000707","DOIUrl":"10.1097/HC9.0000000000000707","url":null,"abstract":"<p><strong>Background: </strong>Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many farnesoid X receptor (FXR) metabolic target genes in WD, including the bile salt exporter pump, the major determinant of bile flow.</p><p><strong>Methods: </strong>We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis.</p><p><strong>Results: </strong>FXR binding within Atp7b-/- mouse livers displayed surprising complexity: FXR binding was increased in distal intergenic regions but decreased in promoter regions in Atp7b-/- versus wild-type mice. Decreased FXR occupancy in Atp7b-/- versus wild-type mice was observed in hepatocyte metabolic and bile acid homeostasis pathways, while enrichment of FXR binding was observed in pathways associated with cellular damage outside of hepatocytes. Indeed, disparate FXR occupancy was identified in parenchymal and non-parenchymal marker genes in a manner that suggests decreased FXR activity in parenchymal cells, as expected, and increased FXR activity in non-parenchymal cells. Consistent with altered FXR function, serum and liver bile acid concentrations were higher in Atp7b-/- mice than in wild-type mice. Comparison of bile acid profiles in the serum of WD patients with \"liver,\" \"neurological,\" or \"mixed\" disease versus healthy controls also revealed increases in specific bile acids in WD-liver versus healthy controls.</p><p><strong>Conclusions: </strong>We identified novel FXR-occupancy across the genome that varied in parenchymal and non-parenchymal cells, demonstrating complex FXR regulation of metabolic and hepatocellular stress pathways in Atp7b-/- mice. Dynamic changes in FXR activity support our novel finding of altered bile acid metabolism in Atp7b-/- mice and WD patients.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132262","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":"Critical commentary on the study comparing TIPS, tunneled peritoneal catheter, and ascites pump in refractory ascites.","authors":"Ibrahim Nagmeldin Hassan","doi":"10.1097/HC9.0000000000000725","DOIUrl":"10.1097/HC9.0000000000000725","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132310","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":"VLDL lipidomics reveals hepatocellular lipidome changes in metabolic dysfunction-associated steatotic liver disease.","authors":"David Guardamino Ojeda, Yusuf Yalcin, Yered Pita-Juarez, Aaron Hakim, Susmita Bhattarai, Zsu-Zsu Chen, John M Asara, Margery A Connelly, Melissa R Miller, Michelle Lai, Z Gordon Jiang","doi":"10.1097/HC9.0000000000000716","DOIUrl":"10.1097/HC9.0000000000000716","url":null,"abstract":"<p><strong>Background: </strong>The production of VLDL is one of the primary mechanisms through which liver cells regulate intracellular lipid homeostasis. We hypothesize that the disease characteristics of metabolic dysfunction-associated steatotic liver disease (MASLD) differentially impact VLDL lipid composition. This study comprehensively examines the relationship between VLDL-lipidome and MASLD histology and disease-associated genetics, aiming to define MASLD-related VLDL changes.</p><p><strong>Methods: </strong>We performed untargeted lipidomics on serum VLDL particles in a cohort of biopsy-proven MASLD patients to examine the relationship between VLDL-lipidome and MASLD disease features as well as MASLD-related genetic variants.</p><p><strong>Results: </strong>Among 1514 detected lipid species in VLDL, triglyceride (TG), phosphatidylcholine (PC), and ceramide (Cer) were the top classes. Moderate to severe hepatic steatosis was associated an increase in VLDL-TG, especially those with palmitic acid (C16:0). A unified acyl chain distribution analysis revealed that steatosis was associated with increases in TGs with saturated and monounsaturated fatty acyl chains, but decreases in polyunsaturated fatty acyl chains, a pattern that was not mirrored in acyl chains from VLDL-PC or VLDL-Cer. Lobular inflammation was associated with reductions in lipids with polyunsaturated acyl chains, particularly docosahexaenoic acid (C22:6). Meanwhile, patients with advanced liver fibrosis (stages 3-4) had reductions in VLDL-TGs with both saturated and polyunsaturated acyl chains and overall enrichment in Cer species. Furthermore, MASLD-associated genetic variants in PNPLA3, TM6SF2, GPAM, HSD17B13, and MTARC1 demonstrated distinct VLDL-lipidomic signatures in keeping with their biology in lipoprotein metabolism.</p><p><strong>Conclusions: </strong>Hepatic steatosis and liver fibrosis in MASLD are associated with distinct VLDL-lipidomic signatures, respectively. This relationship is further modified by MASLD-genetics, suggesting a differential impact of pathogenic features on hepatocellular lipid homeostasis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132326","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":"Specialists and primary care physicians feel discomfort managing pain in cirrhosis and desire nonpharmacologic options.","authors":"Oluomachukwu Anaenugwu, Elliot B Tapper, Marina Serper","doi":"10.1097/HC9.0000000000000720","DOIUrl":"10.1097/HC9.0000000000000720","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132325","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":"Skeletal muscle and MASLD: Mechanistic and clinical insights.","authors":"Thomas Marjot, Matthew J Armstrong, Jonathan G Stine","doi":"10.1097/HC9.0000000000000711","DOIUrl":"10.1097/HC9.0000000000000711","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is intrinsically linked with widespread metabolic perturbations, including within skeletal muscle. Indeed, MASLD is associated with a range of skeletal muscle abnormalities, including insulin resistance, myosteatosis, and sarcopenia, which all converge on the liver to drive disease progression and adverse patient outcomes. This review explores the mechanistic links between skeletal muscle and MASLD, including the role of abnormal glycemic control, systemic inflammation, and disordered myokine signaling. In turn, we discuss how intrinsic liver pathology can feed back to further exacerbate poor skeletal muscle health. Given the central importance of skeletal muscle in MASLD pathogenesis, it offers clinicians an opportunity to intervene for therapeutic benefit. We, therefore, summarize the role of nutrition and physical activity on skeletal muscle mass, quality, and metabolic function and discuss the knock-on effect this has on the liver. An awareness of these treatment strategies is particularly important in the era of effective pharmacological and surgical weight loss interventions, which can be associated with the development of sarcopenia. Finally, we highlight a number of promising drug agents in the clinical trial pipeline that specifically target skeletal muscle in an attempt to improve metabolic and physical functioning.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132323","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":"Parental liver disease mortality is associated with unfavorable outcomes in patients with alcohol-associated hepatitis.","authors":"Wanzhu Tu, Samer Gawrieh, Lauren Nephew, Craig McClain, Qing Tang, Srinivasan Dasarathy, Vatsalya Vatsalya, Douglas A Simonetto, Carla Kettler, Gyongyi Szabo, Bruce Barton, Yunpeng Yu, Patrick S Kamath, Arun J Sanyal, Laura Nagy, Mack C Mitchell, Suthat Liangpunsakul, Vijay H Shah, Naga Chalasani, Ramon Bataller","doi":"10.1097/HC9.0000000000000666","DOIUrl":"10.1097/HC9.0000000000000666","url":null,"abstract":"<p><strong>Background: </strong>How parental alcohol use disorder and liver disease-related mortality influence the risk and the outcomes of alcohol-associated hepatitis (AH) in the offspring is unknown.</p><p><strong>Methods: </strong>We analyzed data from 2 prospective observational studies of AH cases and heavy drinking controls (HDCs). Family history of parental alcohol use disorder and liver disease mortality was assessed at the study entry. Logistic regression and Cox proportional hazard models were used to assess the influences of family history on AH development and outcome.</p><p><strong>Results: </strong>Data from 1356 participants in two prospective cohorts (926 AH cases and 430 HDC) were combined and analyzed. Parental alcohol use disorder was found in 56.9% of AH cases and 61.1% of HDC; parental death due to liver disease was reported in 7.5% of AH cases and 5.7% of HDC. Multivariable logistic regression showed that parental liver disease-related mortality was associated with more than a doubled risk of AH development in the offspring after controlling for their demographic characteristics and drinking behavior (OR=2.26, 95% CI: [1.22, 4.20]). Moreover, among the AH cases, having a parent die of liver disease significantly increased the 90-day mortality of study participants after adjusting for the effects of other risk factors (HR=2.26, 95% CI: [1.05, 4.86]).</p><p><strong>Conclusions: </strong>The study highlights the influences of parental death due to liver disease on AH development and mortality. Identifying patients at risk of AH through family history might help facilitate discussions on reducing alcohol consumption.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132315","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}