Hepatology Communications最新文献

{"title":"Erratum: Gut microbiota and metabolic biomarkers in metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"","doi":"10.1097/HC9.0000000000000493","DOIUrl":"10.1097/HC9.0000000000000493","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534280","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 and genetic risk factors for progressive fibrosis in metabolic dysfunction-associated steatotic liver disease.","authors":"David E Kaplan, Craig C Teerlink, Tae-Hwi Schwantes-An, Trina M Norden-Krichmar, Scott L DuVall, Timothy R Morgan, Philip S Tsao, Benjamin F Voight, Julie A Lynch, Marijana Vujković, Kyong-Mi Chang","doi":"10.1097/HC9.0000000000000487","DOIUrl":"10.1097/HC9.0000000000000487","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, \"slope\" of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort.</p><p><strong>Methods: </strong>In this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4 <2.67 at baseline. FIB4 slope was correlated with demographic parameters and clinical outcomes using logistic regression and Cox proportional hazard models. FIB4 slope as a quantitative phenotype was used in a genome-wide association analysis in ancestry-specific analysis and multiancestry meta-analysis using METAL.</p><p><strong>Results: </strong>FIB4 slopes, generated from 98,361 subjects with MASLD (16,045 African, 74,320 European, and 7996 Hispanic), showed significant associations with sex, ancestry, and cardiometabolic risk factors (p < 0.05). FIB4 slopes also correlated strongly with hepatic outcomes and were independently associated with time to cirrhosis. Five genetic loci showed genome-wide significant associations (p < 5 × 10-8) with FIB4 slope among European ancestry subjects, including 2 known (PNPLA3 and TM6SF2) and 3 novel loci (TERT 5.1 × 10-11; LINC01088, 3.9 × 10-8; and MRC1, 2.9 × 10-9).</p><p><strong>Conclusions: </strong>Linear trajectories of FIB4 correlated significantly with time to progression to cirrhosis, with liver-related outcomes among individuals with MASLD and with known and novel genetic loci. FIB4 slope may be useful as a surrogate measure of fibrosis progression.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534278","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":"Erratum: Correlation between clinical and pathological findings of liver injury in 27 patients with lethal COVID-19 infections in Brazil.","authors":"","doi":"10.1097/HC9.0000000000000492","DOIUrl":"10.1097/HC9.0000000000000492","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456375","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":"Hepatocyte-specific loss of DDB1 attenuates hepatic steatosis but aggravates liver inflammation and fibrosis in MASH.","authors":"Qiuxia Gu, Yushun Chang, Yan Jin, Jing Fang, Tong Ji, Jie Lin, Xi Zhu, Binzhi Dong, Hanning Ying, Xiaoxiao Fan, Zheyong Li, Zerui Gao, Yongfen Zhu, Yifan Tong, Xiujun Cai","doi":"10.1097/HC9.0000000000000474","DOIUrl":"10.1097/HC9.0000000000000474","url":null,"abstract":"<p><strong>Background: </strong>MASH is a common clinical disease that can lead to advanced liver conditions, but no approved pharmacotherapies are available due to an incomplete understanding of its pathogenesis. Damaged DNA binding protein 1 (DDB1) participates in lipid metabolism. Nevertheless, the function of DDB1 in MASH is unclear.</p><p><strong>Methods: </strong>Clinical liver samples were obtained from patients with MASH and control individuals by liver biopsy. Hepatocyte-specific Ddb1-knockout mice and liver Hmgb1 knockdown mice were fed with a methionine-and choline-deficient diet to induce MASH.</p><p><strong>Results: </strong>We found that the expression of DDB1 in the liver was significantly decreased in MASH models. Hepatocyte-specific ablation of DDB1 markedly alleviated methionine-and choline-deficient diet-induced liver steatosis but unexpectedly exacerbated inflammation and fibrosis. Mechanistically, DDB1 deficiency attenuated hepatic steatosis by downregulating the expression of lipid synthesis and uptake genes. We identified high-mobility group box 1 as a key candidate target for DDB1-mediated liver injury. DDB1 deficiency upregulated the expression and extracellular release of high-mobility group box 1, which further increased macrophage infiltration and activated HSCs, ultimately leading to the exacerbation of liver inflammation and fibrosis.</p><p><strong>Conclusions: </strong>These data demonstrate the independent regulation of hepatic steatosis and injury in MASH. These findings have considerable clinical implications for the development of therapeutic strategies for MASH.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456378","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":"Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites.","authors":"Rasmus H Gantzel, Emilie E Møller, Niels K Aagaard, Hugh Watson, Peter Jepsen, Henning Grønbæk","doi":"10.1097/HC9.0000000000000481","DOIUrl":"10.1097/HC9.0000000000000481","url":null,"abstract":"<p><strong>Background: </strong>Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites.</p><p><strong>Methods: </strong>We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30 ng/kg/min, though later reduced to 20 for safety reasons.</p><p><strong>Results: </strong>In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5 mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. -6.2 mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2-35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness.</p><p><strong>Conclusions: </strong>Ularitide in doses of 20-30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456379","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":"Selective internal radiation therapy for unresectable HCC: The SIRT downstaging study.","authors":"Hélène Regnault, Julia Chalaye, Athena Galetto-Pregliasco, Clara Perrin, Haytham Derbel, Giuliana Amaddeo, Sébastien Mulé, Marie Lequoy, Hicham Kobeiter, Edouard Reizine, Emmanuel Itti, Christophe Duvoux, Alexis Laurent, Vincent Leroy, Daniele Sommacale, Diana Rasolonirina, Alain Luciani, Julien Calderaro, Vania Tacher, Raffaele Brustia","doi":"10.1097/HC9.0000000000000475","DOIUrl":"10.1097/HC9.0000000000000475","url":null,"abstract":"<p><strong>Background: </strong>Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs.</p><p><strong>Methods: </strong>We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT.</p><p><strong>Results: </strong>One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014).</p><p><strong>Conclusions: </strong>These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456338","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":"Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.","authors":"Ye Wang, Zhi-Hui Jiang, Yu-Wei Zhou, Tian-Tian Qiu, Han Wang, Min-Sheng Zhu, Xin Chen, Xue-Na Zhang","doi":"10.1097/HC9.0000000000000473","DOIUrl":"10.1097/HC9.0000000000000473","url":null,"abstract":"<p><strong>Background: </strong>The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.</p><p><strong>Methods: </strong>Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).</p><p><strong>Results: </strong>Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.</p><p><strong>Conclusions: </strong>We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456377","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":"Screening patients in general practice for advanced chronic liver disease using an innovative IT solution: The Liver Toolkit.","authors":"David S Prince, Shakira Hoque, Christy Kim, Salim Maher, Jane Miller, Phoebe Chomley, Janice Pritchard-Jones, Sally Spruce, Nathan McGarry, David Baker, Penelope Elix, Ken Liu, Simone I Strasser, Brendan Goodger, Amany Zekry, Geoffrey W McCaughan","doi":"10.1097/HC9.0000000000000482","DOIUrl":"10.1097/HC9.0000000000000482","url":null,"abstract":"<p><strong>Background: </strong>Identifying patients with undiagnosed advanced chronic liver disease (ACLD) is a public health challenge. Patients with advanced fibrosis or compensated cirrhosis have much better outcomes than those with decompensated disease and may be eligible for interventions to prevent disease progression.</p><p><strong>Methods: </strong>A cloud-based software solution (\"the Liver Toolkit\") was developed to access primary care practice software to identify patients at risk of ACLD. Clinical history and laboratory results were extracted to calculate aspartate aminotransferase-to-platelet ratio index and fibrosis 4 scores. Patients identified were recalled for assessment, including Liver Stiffness Measurement (LSM) via transient elastography. Those with an existing diagnosis of cirrhosis were excluded.</p><p><strong>Results: </strong>Existing laboratory results of more than 32,000 adults across nine general practices were assessed to identify 703 patients at increased risk of ACLD (2.2% of the cohort). One hundred seventy-nine patients (26%) were successfully recalled, and 23/179 (13%) were identified to have ACLD (LSM ≥10.0 kPa) (10% found at indeterminate risk [LSM 8.0-9.9 kPa] and 77% low risk of fibrosis [LSM <8.0 kPa]). In most cases, the diagnosis of liver disease was new, with the most common etiology being metabolic dysfunction-associated steatotic liver disease (n=20, 83%). Aspartate aminotransferase-to-platelet ratio index ≥1.0 and fibrosis 4 ≥3.25 had a positive predictive value for detecting ACLD of 19% and 24%, respectively. Patients who did not attend recall had markers of more severe disease with a higher median aspartate aminotransferase-to-platelet ratio index score (0.57 vs. 0.46, p=0.041).</p><p><strong>Conclusions: </strong>This novel information technology system successfully screened a large primary care cohort using existing laboratory results to identify patients at increased risk ACLD. More than 1 in 5 patients recalled were found to have liver disease requiring specialist follow-up.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456337","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":"Erratum: Rifaximin plus lactulose versus lactulose alone for reducing the risk of HE recurrencey.","authors":"","doi":"10.1097/HC9.0000000000000501","DOIUrl":"10.1097/HC9.0000000000000501","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456376","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":"Severe obesity is associated with worse outcomes than lean metabolic dysfunction-associated steatotic liver disease.","authors":"Jaideep Behari, Renwei Wang, Hung N Luu, David McKenzie, Michele Molinari, Jian-Min Yuan","doi":"10.1097/HC9.0000000000000471","DOIUrl":"10.1097/HC9.0000000000000471","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with obesity. We aimed to study the association of body mass index (BMI) with clinical outcomes in patients with MASLD.</p><p><strong>Methods: </strong>A retrospective cohort of 32,900 patients with MASLD, identified through the International Classification of Diseases-9 and 10 codes within the electronic health records of a large US-based health system, with a mean follow-up of 5.5 years (range: 1-15 y), was stratified into 6 BMI categories, <25, 25-<30, 30-<40, 40-<50, and ≥50 kg/m2.</p><p><strong>Results: </strong>The risk of liver decompensation and extrahepatic obesity-associated cancers had a J-shaped profile (both ps for linear and quadratic terms <0.05). Compared to patients with BMI 25-<30 kg/m2, the adjusted HRs (95% CIs) for liver decompensation of patients with BMI <25 and BMI ≥50 kg/m2 were 1.44 (1.17-1.77) and 2.27 (1.66-3.00), respectively. The corresponding figures for obesity-associated extrahepatic cancer were 1.15 (0.97-1.36) and 1.29 (1.00-1.76). There was an inverse association for BMI with liver transplantation and non-obesity-associated cancer (both ps for linear terms <0.05), but no association with HCC or all types of cancers combined. A similar J-shaped association between BMI and all-cause mortality was observed; adjusted HRs (95% CIs) for BMI <25 and ≥50 kg/m2 were 1.51 (1.32-1.72) and 3.24 (2.67-3.83), respectively, compared with BMI 25-<30 kg/m2 (both ps for linear and quadratic terms <0.001).</p><p><strong>Conclusions: </strong>Patients with MASLD and very severe obesity (BMI ≥50 kg/m2) had the highest risk, exceeding that of patients with lean MASLD, for developing liver decompensation, obesity-associated extrahepatic cancers, or dying from any cause.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456339","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}