Liver and spleen stiffness (LS and SS) measurements in predicting high risk varices (HRVs) are reported useful in biliary atresia (BA). In children, inability to temporarily hold their breath may pose challenges in obtaining accurate measurements. This cross-sectional prospective study aimed to evaluate the diagnostic accuracy of LS and SS measurements obtained under general anesthesia during brief pauses in ventilation compared with those obtained in the awake state, in predicting HRVs.
Methods
Among patients with BA aged 15 years or younger who underwent esophagogastroduodenoscopy under general anesthesia for evaluation of varices, 43 patients with LS and SS measured both in the awake and anaesthetized states were enrolled. HRVs were defined as large esophagogastric varices or esophagogastric varices of any size with red color signs.
Results
The median age was 4 years. Nineteen patients had HRVs. In the HRVs group compared with the non-HRVs group, awake-LS, awake-SS, anesthesia-LS, and anesthesia-SS were significantly higher: 2.23 versus 1.71, 4.40 versus 3.45, 2.56 versus 1.73, and 4.13 versus 3.62 m/s, respectively. The area under the curve for awake-LS, awake-SS, anesthesia-LS, and anesthesia-SS were 0.784, 0.794, 0.814, and 0.698, respectively. Awake-LS and anesthesia-LS showed a strong positive correlation (ρ = 0.894), whereas awake-SS and anesthesia-SS showed a weak correlation (ρ = 0.468).
Conclusions
As anesthetics and mechanical ventilation affect abdominal hemodynamics, SS measurements obtained under general anesthesia deviated from those obtained during the awake state. Further research is needed to determine whether mild sedation could help optimize measurement conditions.
Trial Registration
This study was registered on the University Hospital Medical Information Network (UMIN000033123)
{"title":"Effect of General Anesthesia on Liver and Spleen Stiffness for Predicting High-Risk Varices in Biliary Atresia","authors":"Shinya Yokoyama, Takashi Honda, Yoji Ishizu, Norihiro Imai, Takanori Ito, Kenta Yamamoto, Chiyoe Shirota, Takahisa Tainaka, Satoshi Makita, Masanao Nakamura, Hiroo Uchida, Hiroki Kawashima","doi":"10.1111/hepr.70049","DOIUrl":"10.1111/hepr.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Liver and spleen stiffness (LS and SS) measurements in predicting high risk varices (HRVs) are reported useful in biliary atresia (BA). In children, inability to temporarily hold their breath may pose challenges in obtaining accurate measurements. This cross-sectional prospective study aimed to evaluate the diagnostic accuracy of LS and SS measurements obtained under general anesthesia during brief pauses in ventilation compared with those obtained in the awake state, in predicting HRVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Among patients with BA aged 15 years or younger who underwent esophagogastroduodenoscopy under general anesthesia for evaluation of varices, 43 patients with LS and SS measured both in the awake and anaesthetized states were enrolled. HRVs were defined as large esophagogastric varices or esophagogastric varices of any size with red color signs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age was 4 years. Nineteen patients had HRVs. In the HRVs group compared with the non-HRVs group, awake-LS, awake-SS, anesthesia-LS, and anesthesia-SS were significantly higher: 2.23 versus 1.71, 4.40 versus 3.45, 2.56 versus 1.73, and 4.13 versus 3.62 m/s, respectively. The area under the curve for awake-LS, awake-SS, anesthesia-LS, and anesthesia-SS were 0.784, 0.794, 0.814, and 0.698, respectively. Awake-LS and anesthesia-LS showed a strong positive correlation (<i>ρ</i> = 0.894), whereas awake-SS and anesthesia-SS showed a weak correlation (<i>ρ</i> = 0.468).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>As anesthetics and mechanical ventilation affect abdominal hemodynamics, SS measurements obtained under general anesthesia deviated from those obtained during the awake state. Further research is needed to determine whether mild sedation could help optimize measurement conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This study was registered on the University Hospital Medical Information Network (UMIN000033123)</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"223-232"},"PeriodicalIF":3.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with chronic liver disease often experience significant physical, psychological, and financial burdens. These burdens result from repeated long-term hospital visits or admissions caused by progression to decompensated cirrhosis or hepatocellular carcinoma. Patients with viral liver disease may fear discrimination or social prejudice. This study aimed to clarify the employment status of patients with liver disease in Japan and provide basic data to promote support for balancing treatment and work responsibilities.
Methods
A cross-sectional questionnaire survey on employment was conducted among patients attending 22 hospitals across Japan.
Results
Of the 4022 respondents, 2183 were analyzed, including 1694 (77.6%) participants with liver disease. Patients with liver disease were predominantly male and in their 60 s. Disclosure of health information to the workplace was significantly lower among patients with viral liver disease (80.8%) than among those without liver disease or with nonviral liver disease. The intention to continue working after diagnosis was significantly higher among patients with malignancies than among those without. However, this intention did not significantly differ between liver disease and non-liver disease groups. The awareness rate of the support system for balancing treatment and work program was 27.1%, with no significant difference observed between the liver disease and malignancy groups. Awareness was significantly higher in large workplaces, where full-time occupational health physicians are mandated.
Conclusion
Workers with viral liver disease may hesitate to disclose their condition owing to fear of discrimination or prejudice. Therefore, raising awareness of support systems that protect all workers with illnesses, while considering stigma and discrimination, is essential.
{"title":"Employment Status of Patients With Liver Disease: A Nationwide Questionnaire Survey in Japan","authors":"Yoshio Tokumoto, Yoichi Hiasa, Yoshihito Uchida, Takashi Oono, Atsushi Yukimoto, Takao Watanabe, Ryo Sasaki, Sachiko Tatsuki, Hironori Tanaka, Takako Inoue, Mika Horino, Akira Hirose, Tadashi Ikegami, Jun Inoue, Hiroshi Isoda, Hirokazu Takahashi, Yoshihisa Arao, Isao Hidaka, Hiroki Tojima, Satoru Kakizaki, Tetsuro Shimakami, Masayuki Tatemichi, Tatehiro Kagawa, Koji Ogawa, Masatsugu Ohara, Ritsuzo Kozuka, Masaru Enomoto, Mizuki Endo, Yuichiro Eguchi, Kenji Nagata, Masaaki Korenaga","doi":"10.1111/hepr.70048","DOIUrl":"10.1111/hepr.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Patients with chronic liver disease often experience significant physical, psychological, and financial burdens. These burdens result from repeated long-term hospital visits or admissions caused by progression to decompensated cirrhosis or hepatocellular carcinoma. Patients with viral liver disease may fear discrimination or social prejudice. This study aimed to clarify the employment status of patients with liver disease in Japan and provide basic data to promote support for balancing treatment and work responsibilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional questionnaire survey on employment was conducted among patients attending 22 hospitals across Japan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 4022 respondents, 2183 were analyzed, including 1694 (77.6%) participants with liver disease. Patients with liver disease were predominantly male and in their 60 s. Disclosure of health information to the workplace was significantly lower among patients with viral liver disease (80.8%) than among those without liver disease or with nonviral liver disease. The intention to continue working after diagnosis was significantly higher among patients with malignancies than among those without. However, this intention did not significantly differ between liver disease and non-liver disease groups. The awareness rate of the support system for balancing treatment and work program was 27.1%, with no significant difference observed between the liver disease and malignancy groups. Awareness was significantly higher in large workplaces, where full-time occupational health physicians are mandated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Workers with viral liver disease may hesitate to disclose their condition owing to fear of discrimination or prejudice. Therefore, raising awareness of support systems that protect all workers with illnesses, while considering stigma and discrimination, is essential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"214-222"},"PeriodicalIF":3.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liver stiffness measurement (LSM) values decrease after hepatitis C virus eradication. However, whether this reduction translates into a reduced risk of hepatocellular carcinoma (HCC) development in patients who achieve sustained virological response (SVR) remains unclear.
Methods
We retrospectively analyzed 501 patients with chronic hepatitis C who achieved SVR after direct-acting antiviral (DAA) treatment. LSM and FIB-4 levels were measured before DAA treatment and at multiple follow-up points. Time-dependent Cox proportional hazards models evaluated the association between these time-dependent markers and HCC development.
Results
LSM and FIB-4 significantly decreased after DAA treatment in 80.4% and 70.8% of patients, respectively. During a mean follow-up of 5.7 years, 28 patients developed HCC, and in 57% of them, LSM was reduced to < 10 kPa and FIB-4 to < 3.25 at HCC diagnosis. Multivariable analysis revealed higher pre-treatment LSM (adjusted hazard ratio [aHR], 8.10; 95% confidence interval [CI], 1.82–35.95) and higher pre-treatment FIB-4 (aHR, 1.29; 95% CI, 1.11–1.51) as independent predictors of HCC, while post-treatment values at any time point showed no significant association. Patients with LSM < 10 kPa at HCC diagnosis showed better liver function and less fibrosis, but more metabolic risk factors and excessive alcohol consumption than those with LSM ≥ 10 kPa.
Conclusion
Pre-treatment LSM and FIB-4 were stronger predictors of post-SVR HCC risk than post-treatment values. Patients with higher pre-treatment values remained at an increased risk of HCC development even if these values decreased after DAA treatment, emphasizing the importance of continued HCC surveillance in this group.
{"title":"Pre-Treatment Liver Stiffness Is a Stronger Predictor of Hepatocellular Carcinoma Development Than Post-Treatment Liver Stiffness After Hepatitis C Virus Eradication","authors":"Takuma Nakatsuka, Ryo Nakagomi, Keisuke Mabuchi, Yuki Matsushita, Tomoharu Yamada, Kazuya Okushin, Tatsuya Minami, Masaya Sato, Koji Uchino, Yotaro Kudo, Mitsuhiro Fujishiro, Kazuhiko Koike, Ryosuke Tateishi","doi":"10.1111/hepr.70047","DOIUrl":"10.1111/hepr.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Liver stiffness measurement (LSM) values decrease after hepatitis C virus eradication. However, whether this reduction translates into a reduced risk of hepatocellular carcinoma (HCC) development in patients who achieve sustained virological response (SVR) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 501 patients with chronic hepatitis C who achieved SVR after direct-acting antiviral (DAA) treatment. LSM and FIB-4 levels were measured before DAA treatment and at multiple follow-up points. Time-dependent Cox proportional hazards models evaluated the association between these time-dependent markers and HCC development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LSM and FIB-4 significantly decreased after DAA treatment in 80.4% and 70.8% of patients, respectively. During a mean follow-up of 5.7 years, 28 patients developed HCC, and in 57% of them, LSM was reduced to < 10 kPa and FIB-4 to < 3.25 at HCC diagnosis. Multivariable analysis revealed higher pre-treatment LSM (adjusted hazard ratio [aHR], 8.10; 95% confidence interval [CI], 1.82–35.95) and higher pre-treatment FIB-4 (aHR, 1.29; 95% CI, 1.11–1.51) as independent predictors of HCC, while post-treatment values at any time point showed no significant association. Patients with LSM < 10 kPa at HCC diagnosis showed better liver function and less fibrosis, but more metabolic risk factors and excessive alcohol consumption than those with LSM ≥ 10 kPa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pre-treatment LSM and FIB-4 were stronger predictors of post-SVR HCC risk than post-treatment values. Patients with higher pre-treatment values remained at an increased risk of HCC development even if these values decreased after DAA treatment, emphasizing the importance of continued HCC surveillance in this group.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"161-171"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to identify and establish novel biomarkers for human drug-induced liver injury (DILI).
Methods
Patients with DILI (N = 52) or other liver diseases (N = 486) and healthy participants (N = 60) were recruited from the hospitals enrolled in this study. Metabolomics was conducted using serum samples from patients with DILI and healthy participants to screen for candidate DILI biomarkers. Subsequently, the serum concentrations of the candidate biomarkers were determined using a validated assay to characterize their properties and evaluate their ability to differentiate the patients with DILI from those who recovered from DILI and those with other liver diseases.
Results
Three metabolites, pyroglutamylglycine (pyroGluGly), phenylalanine (Phe), and phenylalanyltryptophan (PheTrp), were identified as candidate DILI biomarkers. The serum concentrations of pyroGluGly, Phe, and PheTrp demonstrated a high and similar differentiating ability (area under the receiver-operating characteristic curve [ROC-AUC] > 0.9) in patients with mixed and cholestatic DILI compared with those in patients who recovered from DILI, suggesting that these three metabolites are biomarkers for mixed/cholestatic DILI. All or some of them demonstrated a substantially high differentiating ability (ROC-AUC > 0.8) in patients with mixed/cholestatic DILI compared with patients with other liver diseases, except for obstructive jaundice.
Conclusions
We identified novel DILI biomarkers that can be used to clinically assess patients with mixed/cholestatic DILI and to differentiate these patients from recovered patients and those with other liver diseases.
{"title":"Identification and Characterization of Three Novel Biomarkers for Mixed/Cholestatic Drug-Induced Liver Injury","authors":"Kosuke Saito, Tatehiro Kagawa, Keiji Tsuji, Yuji Kumagai, Ken Sato, Shotaro Sakisaka, Naoya Sakamoto, Mitsuhiko Aiso, Shunji Hirose, Nami Mori, Toshio Uraoka, Kazuhide Takata, Koji Ogawa, Kazuhiko Mori, Motonobu Sato, Takayoshi Nishiya, Kazuhiko Takamatsu, Noriaki Arakawa, Takashi Izumi, Ruri Kikura-Hanajiri, Yasuo Ohno, Yoshiro Saito, Hajime Takikawa","doi":"10.1111/hepr.70043","DOIUrl":"10.1111/hepr.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to identify and establish novel biomarkers for human drug-induced liver injury (DILI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with DILI (<i>N</i> = 52) or other liver diseases (<i>N</i> = 486) and healthy participants (<i>N</i> = 60) were recruited from the hospitals enrolled in this study. Metabolomics was conducted using serum samples from patients with DILI and healthy participants to screen for candidate DILI biomarkers. Subsequently, the serum concentrations of the candidate biomarkers were determined using a validated assay to characterize their properties and evaluate their ability to differentiate the patients with DILI from those who recovered from DILI and those with other liver diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three metabolites, pyroglutamylglycine (pyroGluGly), phenylalanine (Phe), and phenylalanyltryptophan (PheTrp), were identified as candidate DILI biomarkers. The serum concentrations of pyroGluGly, Phe, and PheTrp demonstrated a high and similar differentiating ability (area under the receiver-operating characteristic curve [ROC-AUC] > 0.9) in patients with mixed and cholestatic DILI compared with those in patients who recovered from DILI, suggesting that these three metabolites are biomarkers for mixed/cholestatic DILI. All or some of them demonstrated a substantially high differentiating ability (ROC-AUC > 0.8) in patients with mixed/cholestatic DILI compared with patients with other liver diseases, except for obstructive jaundice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We identified novel DILI biomarkers that can be used to clinically assess patients with mixed/cholestatic DILI and to differentiate these patients from recovered patients and those with other liver diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"111-124"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Which Cells Play a Protective Role in Primary Biliary Cholangitis: Dendritic Cells or Others?","authors":"Zhencheng Zhang, Zaixing Yang","doi":"10.1111/hepr.70045","DOIUrl":"10.1111/hepr.70045","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bile acid (BA) signaling plays an important role in the pathogenesis of hepatic encephalopathy (HE), including covert (CHE) and overt HE (OHE). However, few studies have examined its clinical impact in patients with cirrhosis.
Methods
This retrospective study included patients with cirrhosis who underwent CHE assessment using a computer-aided neuropsychiatric test. BAs were quantified using liquid chromatography-tandem mass spectrometry. Patients were divided into high and low groups according to their BA levels. Independent factors, namely CHE, OHE development, and mortality, were assessed using logistic, Fine–Gray competing risk, and Cox proportional hazards regression models.
Results
Among the 189 patients, the median age was 71 years, 74.1% were male, and 28.0% were diagnosed with CHE. During a median follow-up period of 3.1 years, 15.9% (n = 30) developed OHE, and 33.3% (n = 63) died. Considering mortality as a competing risk, multivariable analysis identified a high conjugated primary BA level (subdistribution hazard ratio [HR] 3.44; 95% confidence interval [CI] 1.08–10.97) as an independent factor for OHE development. Additionally, a high non-conjugated primary BA level (odds ratio 2.18; 95% CI 1.06–4.46) was an independent factor of CHE. Furthermore, a high conjugated primary BA level (HR 2.06; 95% CI 1.11–3.83) was an independent predictor of mortality.
Conclusions
Elevated serum conjugated primary BA levels are an independent factor for OHE development and mortality in patients with cirrhosis. Additionally, elevated non-conjugated primary BA levels were an independent factor for CHE in these patients.
目的：胆汁酸（BA）信号在肝性脑病（HE）的发病机制中起重要作用，包括隐性（CHE）和显性（OHE）。然而，很少有研究考察其对肝硬化患者的临床影响。方法：本回顾性研究纳入了使用计算机辅助神经精神测试进行CHE评估的肝硬化患者。采用液相色谱-串联质谱法对BAs进行定量。根据BA水平将患者分为高、低两组。独立因素，即CHE、OHE发展和死亡率，采用logistic、Fine-Gray竞争风险和Cox比例风险回归模型进行评估。结果：189例患者中位年龄为71岁，男性占74.1%，诊断为CHE的比例为28.0%。在中位随访3.1年期间，15.9% （n = 30）发生OHE， 33.3% （n = 63）死亡。考虑到死亡率作为竞争风险，多变量分析确定高共轭原发性BA水平（亚分布风险比[HR] 3.44； 95%置信区间[CI] 1.08-10.97）是OHE发展的独立因素。此外，高非共轭原发性BA水平（优势比2.18;95% CI 1.06-4.46）是CHE的独立因素。此外，高共轭原发BA水平（HR 2.06; 95% CI 1.11-3.83）是死亡率的独立预测因子。结论：血清结合原发性BA水平升高是肝硬化患者OHE发展和死亡率的独立因素。此外，非共轭原发性BA水平升高是这些患者CHE的独立因素。
{"title":"Altered Serum Bile Acid Pattern as an Independent Factor for Covert and Overt Hepatic Encephalopathy in Patients With Cirrhosis","authors":"Takao Miwa, Hajime Ueda, Teruo Miyazaki, Akira Honda, Tadashi Ikegami, Shinji Unome, Tatsunori Hanai, Yohei Shirakami, Masahito Shimizu","doi":"10.1111/hepr.70036","DOIUrl":"10.1111/hepr.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Bile acid (BA) signaling plays an important role in the pathogenesis of hepatic encephalopathy (HE), including covert (CHE) and overt HE (OHE). However, few studies have examined its clinical impact in patients with cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included patients with cirrhosis who underwent CHE assessment using a computer-aided neuropsychiatric test. BAs were quantified using liquid chromatography-tandem mass spectrometry. Patients were divided into high and low groups according to their BA levels. Independent factors, namely CHE, OHE development, and mortality, were assessed using logistic, Fine–Gray competing risk, and Cox proportional hazards regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 189 patients, the median age was 71 years, 74.1% were male, and 28.0% were diagnosed with CHE. During a median follow-up period of 3.1 years, 15.9% (<i>n</i> = 30) developed OHE, and 33.3% (<i>n</i> = 63) died. Considering mortality as a competing risk, multivariable analysis identified a high conjugated primary BA level (subdistribution hazard ratio [HR] 3.44; 95% confidence interval [CI] 1.08–10.97) as an independent factor for OHE development. Additionally, a high non-conjugated primary BA level (odds ratio 2.18; 95% CI 1.06–4.46) was an independent factor of CHE. Furthermore, a high conjugated primary BA level (HR 2.06; 95% CI 1.11–3.83) was an independent predictor of mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated serum conjugated primary BA levels are an independent factor for OHE development and mortality in patients with cirrhosis. Additionally, elevated non-conjugated primary BA levels were an independent factor for CHE in these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"60-69"},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Successful Retreatment of Glecaprevir-Pibrentasvir for Hepatitis C Virus Genotype 2a Infection in Patient Whose Cirrhosis Improved From Decompensation to Compensation After Sofosbuvir–Velpatasvir Therapy","authors":"Tatsuo Kanda, Ryota Masuzaki, Naoki Matsumoto, Reina Sasaki-Tanaka, Hirofumi Kogure","doi":"10.1111/hepr.70046","DOIUrl":"10.1111/hepr.70046","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"253-255"},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic liver diseases (CLD) arising from various etiologies including viral hepatitis, excessive alcohol intake, alcoholic associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), are associated with persistent hepatic injury ultimately resulting in fibrosis. Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM). This pathological ECM deposition increases tissue stiffness, disrupts normal tissue architecture and impairs liver functions leading to cirrhosis which constitutes a major risk factor for the onset of hepatocellular carcinoma (HCC). The characteristics of the ECM in liver fibrosis have been extensively investigated, particularly with the use of recent proteomic approaches that provide a large overview of ECM changes during disease progression. Alongside large collagen fiber molecules, established as a hallmark of fibrotic tissues, numerous other matrix components are significantly altered. These include the fibulin family. These glycoproteins are distributed across various tissues and involved in numerous physiological processes including embryonic development and tissue repair. They are implicated in a range of pathological processes such as hypertrophic cardiomyopathy, chronic fibrotic disorders, and cancer. In healthy a liver, low levels of fibulins can be detected; however, the expression of a number of fibulin family members is markedly induced during the progression of fibrosis. Beyond their role in the organization and structure integrity of elastic fibers, their contribution to the pathogenesis of liver fibrosis and HCC remains poorly understood. The present review provides an up-to-date overview of the literature on fibulins in the context of chronic liver diseases with particular insights from new omics meta-analyses.
{"title":"Fibulin Family Members: New Players in Liver Fibrosis and Potential Biomarkers in Chronic Liver Diseases","authors":"Fidaa Bouezzedine, Célia Thomas, Nathalie Théret","doi":"10.1111/hepr.70032","DOIUrl":"10.1111/hepr.70032","url":null,"abstract":"<p>Chronic liver diseases (CLD) arising from various etiologies including viral hepatitis, excessive alcohol intake, alcoholic associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), are associated with persistent hepatic injury ultimately resulting in fibrosis. Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM). This pathological ECM deposition increases tissue stiffness, disrupts normal tissue architecture and impairs liver functions leading to cirrhosis which constitutes a major risk factor for the onset of hepatocellular carcinoma (HCC). The characteristics of the ECM in liver fibrosis have been extensively investigated, particularly with the use of recent proteomic approaches that provide a large overview of ECM changes during disease progression. Alongside large collagen fiber molecules, established as a hallmark of fibrotic tissues, numerous other matrix components are significantly altered. These include the fibulin family. These glycoproteins are distributed across various tissues and involved in numerous physiological processes including embryonic development and tissue repair. They are implicated in a range of pathological processes such as hypertrophic cardiomyopathy, chronic fibrotic disorders, and cancer. In healthy a liver, low levels of fibulins can be detected; however, the expression of a number of fibulin family members is markedly induced during the progression of fibrosis. Beyond their role in the organization and structure integrity of elastic fibers, their contribution to the pathogenesis of liver fibrosis and HCC remains poorly understood. The present review provides an up-to-date overview of the literature on fibulins in the context of chronic liver diseases with particular insights from new omics meta-analyses.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 11","pages":"1425-1436"},"PeriodicalIF":3.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frailty is emerging as a prognostic factor in chronic liver disease (CLD). However, its clinical impact remains underexplored, particularly in Japan. This study aimed to evaluate the prognostic significance of frailty in Japanese patients with CLD. In addition, the prevalence and clinical characteristics of frailty in this population were assessed.
Methods
The present multicenter retrospective study included patients with CLD who were admitted to three institutions in Japan. Frailty was diagnosed based on a Clinical Frailty Scale score of > 4. Factors associated with prognosis and frailty were evaluated using Cox proportional hazards regression and logistic regression models, respectively.
Results
Of 715 patients (median [interquartile range] age, 67 [56–74] years; 354 [49.5%] male; 227 [38.7%] with viral hepatitis), frailty was identified in 137 (19.2%). During the median follow-up of 2.9 years, 221 patients (28%) died. Patients with frailty had significantly shorter survival than those without frailty (median 2.4 vs. 10.6 years, p < 0.001). Multivariable Cox regression analysis showed that frailty was an independent adverse factor for mortality (hazard ratio, 1.75; 95% confidence interval, 1.25–2.45; p = 0.001) in patients with CLD. Regarding determinants of frailty, multivariable logistic regression analysis showed that older age, hepatic encephalopathy, hypoalbuminemia, thrombocytopenia, and prolonged international normalized ratio were associated with frailty.
Conclusions
Frailty is prevalent in patients with CLD and independently predicts poor survival. Given its prognostic significance, frailty assessment should be incorporated for risk stratification, early intervention, and outcome improvement in patients with CLD.
{"title":"Frailty Is an Independent Predictor of Mortality in Japanese Patients With Chronic Liver Disease: A Multicenter Retrospective Cohort Study","authors":"Shinji Unome, Mikita Oi, Yuki Utakata, Takao Miwa, Masashi Aiba, Tatsunori Hanai, Makoto Shiraki, Yasuhiro Kawashima, Naoki Katsumura, Masahito Shimizu","doi":"10.1111/hepr.70042","DOIUrl":"10.1111/hepr.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Frailty is emerging as a prognostic factor in chronic liver disease (CLD). However, its clinical impact remains underexplored, particularly in Japan. This study aimed to evaluate the prognostic significance of frailty in Japanese patients with CLD. In addition, the prevalence and clinical characteristics of frailty in this population were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present multicenter retrospective study included patients with CLD who were admitted to three institutions in Japan. Frailty was diagnosed based on a Clinical Frailty Scale score of > 4. Factors associated with prognosis and frailty were evaluated using Cox proportional hazards regression and logistic regression models, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 715 patients (median [interquartile range] age, 67 [56–74] years; 354 [49.5%] male; 227 [38.7%] with viral hepatitis), frailty was identified in 137 (19.2%). During the median follow-up of 2.9 years, 221 patients (28%) died. Patients with frailty had significantly shorter survival than those without frailty (median 2.4 vs. 10.6 years, <i>p</i> < 0.001). Multivariable Cox regression analysis showed that frailty was an independent adverse factor for mortality (hazard ratio, 1.75; 95% confidence interval, 1.25–2.45; <i>p</i> = 0.001) in patients with CLD. Regarding determinants of frailty, multivariable logistic regression analysis showed that older age, hepatic encephalopathy, hypoalbuminemia, thrombocytopenia, and prolonged international normalized ratio were associated with frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Frailty is prevalent in patients with CLD and independently predicts poor survival. Given its prognostic significance, frailty assessment should be incorporated for risk stratification, early intervention, and outcome improvement in patients with CLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"70-77"},"PeriodicalIF":3.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates, the long-term outcomes of patients with hepatitis C virus (HCV)-related cirrhosis remain variable. Growth differentiation factor 15 (GDF15), a stress-induced cytokine, has emerged as a potential biomarker for liver disease progression. This study aimed to evaluate the prognostic value of serum GDF15 levels in predicting hepatocellular carcinoma (HCC), hepatic decompensation, and mortality in patients with HCV-related cirrhosis.
Methods
We retrospectively analyzed 196 patients with HCV-related cirrhosis who achieved SVR at 18 Japanese institutions. Serum GDF15 levels were measured at baseline (BL) and 24 weeks posttreatment (p24w). A previously validated cutoff of 1.75 ng/mL was applied. The clinical outcomes included HCC occurrence, hepatic decompensation, and all-cause mortality.
Results
During a median follow-up of 46.2 months, 75 patients developed HCC, 28 experienced hepatic decompensation, and 25 died. Hepatic decompensation occurred significantly less frequently in the BL GDF15-low group. Importantly, no deaths occurred in the GDF15-low group, whereas the 5-year survival rate in the GDF15-high group was 71.7%. Similar trends were observed for GDF15 levels at p24w. In the overall cohort, GDF15 was not significantly associated with incident HCC; among HCC-naïve patients, a nonsignificant trend toward lower 3-year HCC incidence was observed in the GDF15-low group.
Conclusions
Serum GDF15 is a promising prognostic biomarker for post-SVR outcomes in patients with HCV-related cirrhosis. Its ability to predict decompensation and mortality through a validated cutoff supports its use for risk stratification and long-term management in patients with chronic liver disease.
{"title":"Serum Growth Differentiation Factor 15 Can Be a Novel Biomarker to Predict the Prognosis of Patients With Hepatitis C Virus Cirrhosis After Virus Elimination","authors":"Yuta Myojin, Hayato Hikita, Yuki Tahata, Kenji Fukumoto, Seiya Kato, Yoichi Sasaki, Shusuke Kumazaki, Atsunori Tsuchiya, Masaru Enomoto, Daiki Miki, Hiroshi Yatsuhashi, Hidekatsu Kuroda, Yoshihito Uchida, Hitoshi Yoshiji, Taro Yamashita, Seiichi Mawatari, Nobuharu Tamaki, Hisamitsu Miyaaki, Yasuhiro Asahina, Goki Suda, Kentaro Matsuura, Yasunari Nakamoto, Yoichi Hiasa, Taro Takami, Kumiko Shirai, Kazuki Maesaka, Kazuhiro Murai, Yuki Makino, Yoshinobu Saito, Takahiro Kodama, Tomohide Tatsumi, Tetsuo Takehara","doi":"10.1111/hepr.70041","DOIUrl":"10.1111/hepr.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Although direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates, the long-term outcomes of patients with hepatitis C virus (HCV)-related cirrhosis remain variable. Growth differentiation factor 15 (GDF15), a stress-induced cytokine, has emerged as a potential biomarker for liver disease progression. This study aimed to evaluate the prognostic value of serum GDF15 levels in predicting hepatocellular carcinoma (HCC), hepatic decompensation, and mortality in patients with HCV-related cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 196 patients with HCV-related cirrhosis who achieved SVR at 18 Japanese institutions. Serum GDF15 levels were measured at baseline (BL) and 24 weeks posttreatment (p24w). A previously validated cutoff of 1.75 ng/mL was applied. The clinical outcomes included HCC occurrence, hepatic decompensation, and all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a median follow-up of 46.2 months, 75 patients developed HCC, 28 experienced hepatic decompensation, and 25 died. Hepatic decompensation occurred significantly less frequently in the BL GDF15-low group. Importantly, no deaths occurred in the GDF15-low group, whereas the 5-year survival rate in the GDF15-high group was 71.7%. Similar trends were observed for GDF15 levels at p24w. In the overall cohort, GDF15 was not significantly associated with incident HCC; among HCC-naïve patients, a nonsignificant trend toward lower 3-year HCC incidence was observed in the GDF15-low group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Serum GDF15 is a promising prognostic biomarker for post-SVR outcomes in patients with HCV-related cirrhosis. Its ability to predict decompensation and mortality through a validated cutoff supports its use for risk stratification and long-term management in patients with chronic liver disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"21-32"},"PeriodicalIF":3.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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