Hepatology Communications最新文献

{"title":"Age-dependent differences in FIB-4 predictions of fibrosis in patients with MASLD referred from primary care.","authors":"Shuen Sung, Mustafa Al-Karaghouli, Matthew Tam, Yu Jun Wong, Saumya Jayakumar, Tracy Davyduke, Mang Ma, Juan G Abraldes","doi":"10.1097/HC9.0000000000000609","DOIUrl":"10.1097/HC9.0000000000000609","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis 4 (FIB-4) is widely used to triage patients with metabolic dysfunction-associated steatotic liver disease. Given that age is part of FIB-4, higher scores may be expected in the elderly population. This led to the proposal of using a higher threshold of FIB-4 to triage patients aged ≥65. Our main objective is to evaluate how age modifies the association between the FIB-4 index and disease severity based on the vibration-controlled transient elastography (VCTE) \"rule of 5s.\"</p><p><strong>Methods: </strong>In this cross-sectional study, we prospectively analyzed data from a primary care referral pathway. We used liver stiffness measurement by VCTE as a reference standard for liver risk. We modeled with ordinal regression the exceedance probabilities of finding different liver stiffness measurement thresholds according to FIB-4, and how age modifies FIB-4 predictions.</p><p><strong>Results: </strong>Nine hundred eighty-five participants with complete data were used for modeling. Participants aged ≥65 had a higher prevalence of advanced liver disease estimated by VCTE and higher FIB-4 values than those <65 (85.9% vs. 20.2% for FIB-4 ≥1.3, and 46.5% vs. 6.5% for FIB-4 ≥2.0). In participants age ≥65, the negative predictive value for VCTE ≥10 kPa of FIB-4 <1.3 was 100% versus FIB-4 <2.0 was 83%. Age significantly modified FIB-4-based prediction of fibrosis, but predictions at a threshold of 1.3 or 2 were only minimally altered. For higher FIB-4 threshold (ie, 2.7), age strongly modified FIB-4 predictions of liver stiffness measurement.</p><p><strong>Conclusions: </strong>Age does not relevantly modify FIB-4 predictions when using the common threshold of 1.3. Our data suggest no rationale for increasing the FIB-4 threshold to 2 for undergoing further testing in patients aged ≥65. However, the meaning of a FIB-4 of 2.7 strongly changes with age. This cutoff for ages over 65 is not enough to define high-risk and would not warrant direct referral.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817866","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":"Depression and anxiety management in cirrhosis.","authors":"Paula C Zimbrean, Simona S Jakab","doi":"10.1097/HC9.0000000000000600","DOIUrl":"10.1097/HC9.0000000000000600","url":null,"abstract":"<p><p>Depressive and anxiety symptoms are more prevalent in patients with cirrhosis compared to the general population. Between 2009 and 2019, the prevalence of depression in cirrhosis increased by 80%, while the prevalence of generalized anxiety disorder increased by over 400%. When present, anxiety and depression are linked to lower health-related quality of life, more severe symptoms (eg, fatigue), and poorer response to medical treatment. Screening instruments for depression and anxiety have shown acceptable validity in patients with cirrhosis. However, the diagnosis of depression and anxiety disorder remains challenging in this population and should follow the established criteria for general populations. Treatment interventions are numerous and include patient education and support around liver disease, pharmacological agents, and psychotherapy. Antidepressants are the treatment of choice for patients with depressive or anxiety disorder and cirrhosis. However, consideration must be given to dose adjustment and choice of agent due to changes in their metabolism in patients with liver disease. Psychotherapy may be used as a stand-alone therapy or concomitantly with pharmacotherapy. The high prevalence and complexity of depressive and anxiety symptoms in patients with cirrhosis support the integrated care approach in which patients are cared for by multidisciplinary teams.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817873","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":"High-fat/high-sucrose diet results in a high rate of MASH with HCC in a mouse model of human-like bile acid composition.","authors":"Hajime Ueda, Akira Honda, Teruo Miyazaki, Yukio Morishita, Takeshi Hirayama, Junichi Iwamoto, Tadashi Ikegami","doi":"10.1097/HC9.0000000000000606","DOIUrl":"10.1097/HC9.0000000000000606","url":null,"abstract":"<p><strong>Background: </strong>Wild-type (WT) mice fed a conventional high-fat/high-sucrose diet (HFHSD) rarely develop metabolic dysfunction-associated steatohepatitis (MASH) with HCC. Because mouse bile acid (BA) is highly hydrophilic, we hypothesized that making it hydrophobic would lead to MASH with HCC.</p><p><strong>Methods: </strong>Eleven-week-old WT and Cyp2a12/Cyp2c70 double knockout (DKO) mice were divided into two groups, including one which was fed a normal chow diet, and one which was fed an HFHSD. Samples were collected after 15, 30, 47, and 58 weeks for histological, biochemical, and immunological analyses.</p><p><strong>Results: </strong>In the HFHSD group, body weight gain did not differ in WT versus DKO mice, although HFHSD-fed DKO mice exhibited markedly accelerated liver inflammation, fibrosis, and carcinogenesis. HFHSD upregulated lipogenesis and downregulated fatty acid oxidation in both WT and DKO mice, which increased liver lipid accumulation and lipotoxicity. However, the increase in reactive oxygen species production and carcinogenesis observed in DKO mice could not be explained by abnormal lipid metabolism alone. Regarding BA metabolism, DKO mice had a higher hydrophobicity index. They exhibited an age-associated increase in chenodeoxycholic acid (CDCA) levels because of CYP8B1 activity inhibition due to the farnesoid X receptor activation. HFHSD further downregulated CYP8B1, presumably by activating the Liver X receptor. Liver CDCA accumulation was associated with increased inflammation, reactive oxygen species production, and hepatocyte FGF15 induction. Moreover, in noncancerous liver tissues, HFHSD appeared to activate STAT3, an oncogenic transcription factor, which was enhanced by a CDCA-rich environment.</p><p><strong>Conclusions: </strong>Here, we developed a new model of MASH with HCC using mice with human-like BA composition and found that HFHSD and elevated hepatic CDCA synergistically increased the risk of MASH with HCC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817878","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":"Key role of macrophages in the progression of hepatic fibrosis.","authors":"Jinqiu Ran, Shengxia Yin, Rahma Issa, Qianwen Zhao, Guangqi Zhu, Huan Zhang, Qun Zhang, Chao Wu, Jie Li","doi":"10.1097/HC9.0000000000000602","DOIUrl":"10.1097/HC9.0000000000000602","url":null,"abstract":"<p><p>Liver fibrosis is a pathological change characterized by excessive deposition of extracellular matrix caused by chronic liver injury, and the mechanisms underlying its development are associated with endothelial cell injury, inflammatory immune cell activation, and HSC activation. Furthermore, hepatic macrophages exhibit remarkable heterogeneity and hold central functions in the evolution of liver fibrosis, with different subgroups exerting dual effects of promotion and regression. Currently, targeted macrophage therapy for reversing hepatic fibrosis has been extensively studied and has shown promising prospects. In this review, we will discuss the dual role of macrophages in liver fibrosis and provide new insights into reversing liver fibrosis based on macrophages.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817889","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":"Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.","authors":"Lianne M Nieuwenhuis, Yanni Li, Bao-Li Loza, Annechien J A Lambeck, Shixian Hu, Ranko Gacesa, Michiel D Voskuil, Bouke G Hepkema, Bernadien H Jansen, Hans Blokzijl, Henk-Jan Verkade, Marius C van den Heuvel, Sumeet Asrani, Giuliano Testa, Goran Klintmalm, James Trotter, Kim M Olthoff, Abraham Shaked, Brendan J Keating, Rinse K Weersma, Eleonora A M Festen, Vincent E de Meijer","doi":"10.1097/HC9.0000000000000601","DOIUrl":"10.1097/HC9.0000000000000601","url":null,"abstract":"<p><strong>Background: </strong>Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation.</p><p><strong>Methods: </strong>We conducted an international multicenter case-control genome-wide association study of donor-recipient liver transplant pairs in 3 independent cohorts, totaling 1846 pairs. To assess genetic mismatch burden, we calculated sum scores for single-nucleotide polymorphism (SNP) mismatch based on all non-HLA functional SNPs, specifically SNPs coding for transmembrane or secreted proteins as they more likely affect the immune system. We analyzed the association between the non-HLA mismatch scores and ACR in a multivariable Cox regression model per cohort, followed by a weighted meta-analysis.</p><p><strong>Results: </strong>During the first year post-transplantation, 90 of 689 (13%), 161 of 720 (22%), and 48 of 437 (11%) recipients experienced ACR in cohorts 1-3, respectively. Weighted meta-analyses showed that higher mismatch in functional non-HLA SNPs was associated with an increased incidence of ACR (HR 5.99; 95% CI: 1.39-20.08; p=0.011). Moreover, we found a larger effect of mismatch in SNPs coding for transmembrane or secreted proteins on ACR (HR 7.54; 95% CI 1.95-28.79; p=0.003). Sensitivity analyses showed that imputed HLA mismatch did not affect the associations between both non-HLA mismatch scores and ACR.</p><p><strong>Conclusions: </strong>Donor-recipient mismatch of functional non-HLA SNPs overall and, especially, of SNPs encoding transmembrane or secreted proteins correlated with 1-year ACR post-liver transplantation. Identifying high-risk immunological burdens between pairs may prevent early graft rejection and aid in personalizing immunosuppressive therapy. Future studies are, however, needed to validate our findings using a genotyped HLA cohort.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817822","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":"Vessels encapsulating tumor clusters contribute to the intratumor heterogeneity of HCC on Gd-EOB-DTPA-enhanced MRI.","authors":"Kosuke Matsuda, Akihisa Ueno, Junya Tsuzaki, Yutaka Kurebayashi, Yohei Masugi, Ken Yamazaki, Masashi Tamura, Yuta Abe, Yasushi Hasegawa, Minoru Kitago, Masahiro Jinzaki, Michiie Sakamoto","doi":"10.1097/HC9.0000000000000593","DOIUrl":"10.1097/HC9.0000000000000593","url":null,"abstract":"<p><strong>Background: </strong>Vessels encapsulating tumor clusters (VETC) pattern is tumor vasculature of HCC and is a predictor of prognosis and therapeutic efficacy. Recent radiological studies have demonstrated the predictability of VETC from preoperative images, but the mechanisms of image formation are not elucidated. This study aims to determine the relationship between VETC and intratumor heterogeneity in Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) and to provide its pathological evidence.</p><p><strong>Methods: </strong>Radiologists visually classified preoperative arterial- and hepatobiliary-phase EOB-MRI images of 204 surgically resected HCCs into patterns based on heterogeneity and signal intensity; these classifications were validated using texture analysis. Single and multiplex immunohistochemistry for CD34, h-caldesmon, and OATP1B3 were performed to evaluate VETC, arterial vessel density (AVD), and OATP1B3 expression. Recurrence-free survival was assessed using the generalized Wilcoxon test. The contribution of clinicoradiological factors to the prediction of VETC was evaluated by random forest and least absolute shrinkage and selection operator regression.</p><p><strong>Results: </strong>VETC was frequently found in tumors with arterial-phase heterogeneous hyper-enhancement patterns and in tumors with hepatobiliary-phase heterogeneous hyperintense/isointense patterns (HBP-Hetero). AVD and OATP1B3 expression positively correlated with signal intensity in the arterial and hepatobiliary phases, respectively. Intratumor spatial analysis revealed that AVD and OATP1B3 expression were lower in VETC regions than in tumor regions without VETC. Patients with HBP-Hetero tumors had shorter recurrence-free survival. Machine learning models highlighted the importance of serum PIVKA-II, tumor size, and enhancement pattern of arterial and hepatobiliary phase for VETC prediction.</p><p><strong>Conclusions: </strong>VETC is associated with local reductions of both AVD and OATP1B3 expression, likely contributing to heterogeneous enhancement patterns in EOB-MRI. Evaluation of the arterial and hepatobiliary phases of EOB-MRI would enhance the predictability of VETC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817961","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":"Accuracy of type IV collagen 7S versus Enhanced Liver Fibrosis score for diagnosing fibrosis in patients with metabolic dysfunction-associated steatotic liver disease.","authors":"Hiroshi Ishiba, Hideki Fujii, Yoshihiro Kamada, Yoshio Sumida, Hirokazu Takahashi, Yuya Seko, Hidenori Toyoda, Hideki Hayashi, Kanji Yamaguchi, Michihiro Iwaki, Masato Yoneda, Taeang Arai, Toshihide Shima, Asahiro Morishita, Kazuhito Kawata, Kengo Tomita, Miwa Kawanaka, Yuichi Yoshida, Tadashi Ikegami, Kazuo Notsumata, Satoshi Oeda, Hideaki Fukushima, Eiji Miyoshi, Shinichi Aishima, Yoshito Itoh, Takeshi Okanoue, Atsushi Nakajima","doi":"10.1097/HC9.0000000000000563","DOIUrl":"10.1097/HC9.0000000000000563","url":null,"abstract":"<p><strong>Background: </strong>Various noninvasive tests can be used to identify high-risk groups of patients with metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD). In this study, we compared the diagnostic performance of serum type 4 collagen 7S (COL4-7S) and the Enhanced Liver Fibrosis (ELF) score for detecting fibrosis in patients with MASLD.</p><p><strong>Methods: </strong>Among 1368 patients with MASLD who underwent liver biopsy, 794 with values for both serum COL4-7S and the ELF score were enrolled in this multicenter study. The diagnostic performance of COL4-7S and ELF for detecting fibrosis stage ≥2, fibrosis stage ≥3, and at-risk metabolic dysfunction-associated steatohepatitis were evaluated using ROC curve, continuous net reclassification improvement, and integrated discrimination improvement analyses.</p><p><strong>Results: </strong>Both COL4-7S and ELF scores increased significantly with increasing fibrosis. The AUROC for each outcome was higher for COL4-7S than ELF, but not significantly. The diagnostic performance for detecting fibrosis stage ≥2 was significantly better for COL4-7S than for the ELF score (s net reclassification improvement=16.7%, p=0.018; integrated discrimination improvement=3.9%, p<0.01). In patients without diabetes, the diagnostic performance for each outcome did not differ significantly between COL4-7S and ELF score, but in patients with diabetes, the diagnostic performance for fibrosis stage ≥2 was higher for COL4-7S than for the ELF score (AUROC=0.817 vs. 0.773, p=0.04; s net reclassification improvement=32.7%, p<0.01; integrated discrimination improvement=5.6%, p<0.01).</p><p><strong>Conclusions: </strong>The diagnostic performance of serum COL4-7S (a single marker) for identifying more advanced disease in patients with MASLD was at least equivalent to that of the ELF score (a combined marker).</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817860","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":"Pain in chronic liver disease compared to other chronic conditions: Results from a contemporary nationally representative cohort study.","authors":"Grace Y Zhang, Aly Cortella, Jennifer C Lai, Jessica B Rubin","doi":"10.1097/HC9.0000000000000605","DOIUrl":"10.1097/HC9.0000000000000605","url":null,"abstract":"<p><strong>Background: </strong>Pain is common in patients with chronic liver disease. Our limited understanding of patterns and severity of pain in this population hinders the development of effective cirrhosis-specific pain management strategies.</p><p><strong>Methods: </strong>Using cross-sectional data from the 2016-2021 National Health Interview Survey, we examined rates, severity, and functional limitations due to pain in respondents with liver disease (viral hepatitis, cirrhosis, and liver cancer), compared to the general population and those with other chronic conditions associated with pain (ie, arthritis, diabetes, and chronic kidney disease). Categorical and continuous variables were compared using χ2 and t test. Multivariable logistic regression was used to determine the predictors associated with pain and opioid use.</p><p><strong>Results: </strong>Our liver disease cohort comprised 5267 participants (63% viral hepatitis, 49% cirrhosis, and 2% liver cancer). Participants with liver disease were more likely to report pain than those without liver disease (42% vs. 22%); they were also more likely to report severe pain (42% vs. 30%) and functional limitations by pain (28% vs. 13%) (p < 0.001 for all). On multivariable logistic regression, liver disease is an independent predictor of pain (OR: 2.31, 95% CI: 2.05-2.59, p < 0.001), even after adjustment for demographic factors. Liver disease respondents had similar rates of pain as those with diabetes (p = 0.8) and were more functionally limited by pain than those with arthritis (p < 0.001). Adjusted for demographic and pain-related factors, liver disease was also an independent predictor of chronic opioid use (OR: 1.47, 95% CI: 1.12-1.92, p = 0.0054).</p><p><strong>Conclusions: </strong>Liver disease independently increases the likelihood of experiencing widespread and debilitating pain. Clinicians should consider liver disease a painful condition, ensuring that they are frequently assessing and appropriately treating pain in all liver disease patients.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817907","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":"Recent TIPS increases postoperative mortality: A national cohort study.","authors":"Helen Tang, David E Kaplan, Samir Abu-Gazala, Nadim Mahmud","doi":"10.1097/HC9.0000000000000577","DOIUrl":"10.1097/HC9.0000000000000577","url":null,"abstract":"<p><strong>Background: </strong>Patients with cirrhosis have an increased risk of postoperative mortality, which is partially attributable to portal hypertension. Preoperative TIPS placement may reduce operative risk. Studies suggesting the benefits of preoperative TIPS are limited by residual confounding and lack of longitudinal laboratory data. To address these limitations, we used granular longitudinal data from the Veterans Health Administration.</p><p><strong>Methods: </strong>This retrospective cohort study of Veterans Health Administration patients with cirrhosis who underwent major surgery from 2008 to 2022 identified patients who underwent TIPS placement within 6 months before surgery. Demographics, comorbidities, surgery type, and longitudinal laboratory data were incorporated into a propensity score using 5:1 caliper matching for receipt of TIPS. The propensity-matched cohort included 39 patients with preoperative TIPS and 171 without.</p><p><strong>Results: </strong>Baseline characteristics were similar between groups. In Cox regression, recent TIPS was associated with an increased risk of postoperative mortality (HR: 2.69, 95% CI: 1.37-5.30, p = 0.004), redemonstrated in 500 random resampling events (median HR: 1.71). TIPS and non-TIPS patients had similar albumin, bilirubin, and international normalized ratio 6 months before surgery; however, immediately before surgery, TIPS patients had lower albumin (p = 0.009), higher bilirubin (p = 0.001), and higher international normalized ratio (p = 0.001).</p><p><strong>Conclusions: </strong>In a propensity-matched analysis of patients with cirrhosis undergoing major surgery, recent TIPS was associated with increased postoperative mortality and worsened liver synthetic function in the immediate preoperative period. TIPS placement should be carefully considered in patients with cirrhosis who may undergo surgery.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768548","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":"Serum protein risk stratification score for diagnostic evaluation of metabolic dysfunction-associated steatohepatitis.","authors":"Michelle Lai, Simon T Dillon, Xuesong Gu, Tina L Morhardt, Yuyan Xu, Noel Y Chan, Beibei Xiong, Handan Can, Long H Ngo, Lina Jin, Xuehong Zhang, Claudia C Moreira, Nathalie C Leite, Cristiane A Villela-Nogueira, Hasan H Otu, Jörn M Schattenberg, Detlef Schuppan, Nezam H Afdhal, Towia A Libermann","doi":"10.1097/HC9.0000000000000586","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000586","url":null,"abstract":"<p><strong>Background: </strong>Reliable, noninvasive tools to diagnose at-risk metabolic dysfunction-associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high-risk patients with MASH (NAFLD activity score >4 and fibrosis score >2).</p><p><strong>Methods: </strong>In this 3-phase proteomic study of biopsy-proven metabolic dysfunction-associated steatotic fatty liver disease, we first developed a multi-protein predictor for discriminating NAFLD activity score >4 based on SOMAscan proteomics quantifying 1305 serum proteins from 57 US patients. Four key predictor proteins were verified by ELISA in the expanded US cohort (N = 168) and enhanced by adding clinical variables to create the 9-feature MASH Dx score, which predicted MASH and also high-risk MASH (F2+). The MASH Dx score was validated in 2 independent, external cohorts from Germany (N = 139) and Brazil (N = 177).</p><p><strong>Results: </strong>The discovery phase identified a 6-protein classifier that achieved an AUC of 0.93 for identifying MASH. Significant elevation of 4 proteins (THBS2, GDF15, SELE, and IGFBP7) was verified by ELISA in the expanded discovery and independently in the 2 external cohorts. MASH Dx score incorporated these proteins with established MASH risk factors (age, body mass index, ALT, diabetes, and hypertension) to achieve good discrimination between MASH and metabolic dysfunction-associated steatotic fatty liver disease without MASH (AUC: 0.87-discovery; 0.83-pooled external validation cohorts), with similar performance when evaluating high-risk MASH F2-4 (vs. MASH F0-1 and metabolic dysfunction-associated steatotic fatty liver disease without MASH).</p><p><strong>Conclusions: </strong>The MASH Dx score offers the first reliable noninvasive approach combining novel, biologically plausible ELISA-based fibrosis markers and clinical parameters to detect high-risk MASH in patient cohorts from the United States, Brazil, and Europe.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"8 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768549","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}