{"title":"Response to “Which Cells Play a Protective Role in Primary Biliary Cholangitis: Dendritic Cells or Others?”","authors":"Jiaqi Zhang, Yoshihiro Hirata","doi":"10.1111/hepr.70053","DOIUrl":"10.1111/hepr.70053","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"258-259"},"PeriodicalIF":3.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274319","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}
No reports described the deep-learning (DL) models using computed tomography (CT) as an imaging biomarker for predicting postoperative long-term outcomes in patients with hepatocellular carcinoma (HCC). This study aimed to validate the DL models for individualized prognostication after HCC resection using CT as an imaging biomarker.
Methods
This study included 1733 patients undergoing hepatic resection for solitary HCC. Participants were classified into training, validation, and test datasets. DL predictive models were developed using clinical variables and CT imaging to predict recurrence within 2 and 5 years and overall survival (OS) of > 5 and > 10 years postoperatively. Youden index was utilized to identify cutoff values. Permutation importance was used to calculate the importance of each explanatory variable.
Results
DL predictive models for recurrence within 2 and 5 years and OS of > 5 and > 10 years postoperatively were developed in the test datasets, with the area under the curve of 0.70, 0.70, 0.80, and 0.80, respectively. Permutation importance demonstrated that CT imaging analysis revealed the highest importance value. The postoperative recurrence rates within 2 and 5 years were 52.6% versus 18.5% (p < 0.001) and 78.9% versus 46.7% (p < 0.001) and overall mortality within 5 and 10 years postoperatively were 45.1% versus 9.2% (p < 0.001) and 87.1% versus 43.2% (p < 0.001) in the high-risk versus low-risk groups, respectively.
Conclusions
Our DL models using CT as an imaging biomarker are useful for individualized prognostication and may help optimize treatment planning for patients with HCC.
{"title":"Individualized Prognostication Based on Deep-Learning Models Using Computed Tomography as an Imaging Biomarker After Hepatocellular Carcinoma Resection","authors":"Hiroji Shinkawa, Daiju Ueda, Sota Kurimoto, Masaki Kaibori, Masaki Ueno, Satoshi Yasuda, Hisashi Ikoma, Tsukasa Aihara, Takuya Nakai, Masahiko Kinoshita, Hisashi Kosaka, Shinya Hayami, Yasuko Matsuo, Ryo Morimura, Takayoshi Nakajima, Chihoko Nobori, Takeaki Ishizawa","doi":"10.1111/hepr.70055","DOIUrl":"10.1111/hepr.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>No reports described the deep-learning (DL) models using computed tomography (CT) as an imaging biomarker for predicting postoperative long-term outcomes in patients with hepatocellular carcinoma (HCC). This study aimed to validate the DL models for individualized prognostication after HCC resection using CT as an imaging biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 1733 patients undergoing hepatic resection for solitary HCC. Participants were classified into training, validation, and test datasets. DL predictive models were developed using clinical variables and CT imaging to predict recurrence within 2 and 5 years and overall survival (OS) of > 5 and > 10 years postoperatively. Youden index was utilized to identify cutoff values. Permutation importance was used to calculate the importance of each explanatory variable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DL predictive models for recurrence within 2 and 5 years and OS of > 5 and > 10 years postoperatively were developed in the test datasets, with the area under the curve of 0.70, 0.70, 0.80, and 0.80, respectively. Permutation importance demonstrated that CT imaging analysis revealed the highest importance value. The postoperative recurrence rates within 2 and 5 years were 52.6% versus 18.5% (<i>p</i> < 0.001) and 78.9% versus 46.7% (<i>p</i> < 0.001) and overall mortality within 5 and 10 years postoperatively were 45.1% versus 9.2% (<i>p</i> < 0.001) and 87.1% versus 43.2% (<i>p</i> < 0.001) in the high-risk versus low-risk groups, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our DL models using CT as an imaging biomarker are useful for individualized prognostication and may help optimize treatment planning for patients with HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"204-213"},"PeriodicalIF":3.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274359","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}
Acute pancreatitis is a recognized complication of acute liver failure (ALF), but its incidence and predictive factors remain poorly defined. Current risk stratification relies primarily on conventional laboratory markers with limited discriminatory ability for pancreatic complications. This study aimed to determine the incidence and prognostic impact of acute pancreatitis in ALF patients and evaluate whether liver volumetry improves prediction beyond conventional markers.
Methods
This cross-sectional retrospective study utilized data from a nationwide survey-based registry conducted by the Intractable Hepato-Biliary Disease Study Group of Japan (2011–2021). We analyzed 142 ALF patients with available liver volumetry data and 90-day outcome information. Patients with pre-existing acute pancreatitis were excluded. Predictive models were developed comparing conventional markers (MELD score) versus an enhanced model incorporating computed tomography liver volume to standard liver volume ratio (CTLV/SLV). Model performance was evaluated using ROC analysis, net reclassification index, and clinical validation.
Results
Acute pancreatitis developed in 19 patients (13.4%), typically within the first 8 weeks (84.3% of cases). Logistic regression identified acute pancreatitis as an independent risk factor for poor prognosis (β = 0.2556, p = 0.031). The CTLV/SLV ratio was significantly lower in patients developing pancreatitis (0.80 vs. 1.07, p < 0.001). The enhanced model (MELD + CTLV/SLV) achieved superior discrimination (AUC 0.810) compared to MELD alone (AUC 0.704), with 81% relative risk reduction in the low-risk category.
Conclusion
Incorporating liver volumetry significantly improves acute pancreatitis prediction in ALF patients, enabling more precise risk stratification and potentially optimizing clinical management strategies.
背景和目的：急性胰腺炎是公认的急性肝衰竭（ALF）并发症，但其发病率和预测因素仍不明确。目前的风险分层主要依赖于传统的实验室标志物，对胰腺并发症的区分能力有限。本研究旨在确定ALF患者急性胰腺炎的发生率和预后影响，并评估肝容量测定是否比传统标志物更能改善预测。方法：这项横断面回顾性研究利用了日本顽固性肝胆疾病研究组（2011-2021）在全国范围内进行的基于调查的登记数据。我们分析了142例ALF患者的可用肝容量数据和90天预后信息。排除既往存在急性胰腺炎的患者。建立了比较传统标志物（MELD评分）和结合计算机断层扫描肝体积与标准肝体积比（CTLV/SLV）的增强模型的预测模型。采用ROC分析、净重分类指数和临床验证来评估模型的性能。结果：19例（13.4%）患者发生急性胰腺炎，主要发生在发病前8周（84.3%）。Logistic回归发现急性胰腺炎是预后不良的独立危险因素（β = 0.2556, p = 0.031）。发生胰腺炎患者的CTLV/SLV比值显著降低（0.80 vs. 1.07, p）。结论：结合肝容量测定可显著提高ALF患者急性胰腺炎的预测，实现更精确的风险分层，并有可能优化临床管理策略。
{"title":"Liver Volumetry Enhances Prediction of Acute Pancreatitis in Acute Liver Failure: A Nationwide Registry Study","authors":"Keisuke Kakisaka, Nobuaki Nakayama, Tokio Sasaki, Kotaro Kumagai, Hidekatsu Kuroda, Ryuzo Abe, Taro Takami, Kazuaki Chayama, Masahito Shimizu, Takuya Genda, Shuji Terai, Kazuaki Inoue, Atsushi Tanaka, Takayuki Matsumoto, Satoshi Mochida","doi":"10.1111/hepr.70054","DOIUrl":"10.1111/hepr.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>Acute pancreatitis is a recognized complication of acute liver failure (ALF), but its incidence and predictive factors remain poorly defined. Current risk stratification relies primarily on conventional laboratory markers with limited discriminatory ability for pancreatic complications. This study aimed to determine the incidence and prognostic impact of acute pancreatitis in ALF patients and evaluate whether liver volumetry improves prediction beyond conventional markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional retrospective study utilized data from a nationwide survey-based registry conducted by the Intractable Hepato-Biliary Disease Study Group of Japan (2011–2021). We analyzed 142 ALF patients with available liver volumetry data and 90-day outcome information. Patients with pre-existing acute pancreatitis were excluded. Predictive models were developed comparing conventional markers (MELD score) versus an enhanced model incorporating computed tomography liver volume to standard liver volume ratio (CTLV/SLV). Model performance was evaluated using ROC analysis, net reclassification index, and clinical validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Acute pancreatitis developed in 19 patients (13.4%), typically within the first 8 weeks (84.3% of cases). Logistic regression identified acute pancreatitis as an independent risk factor for poor prognosis (<i>β</i> = 0.2556, <i>p</i> = 0.031). The CTLV/SLV ratio was significantly lower in patients developing pancreatitis (0.80 vs. 1.07, <i>p</i> < 0.001). The enhanced model (MELD + CTLV/SLV) achieved superior discrimination (AUC 0.810) compared to MELD alone (AUC 0.704), with 81% relative risk reduction in the low-risk category.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Incorporating liver volumetry significantly improves acute pancreatitis prediction in ALF patients, enabling more precise risk stratification and potentially optimizing clinical management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"233-245"},"PeriodicalIF":3.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250831","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}
Hepatocellular carcinoma (HCC) with Vp4 portal vein tumor thrombosis (PVTT) has an extremely poor prognosis, and evidence for effective systemic therapy is limited. Preclinical studies suggest that hypofractionated radiation therapy (HFRT) may enhance immune checkpoint inhibitor (ICI) efficacy through immunogenic cell death and modulation of the tumor microenvironment.
Methods
We conducted a retrospective feasibility study of HFRT combined with ICIs for unresectable HCC. Patients receiving atezolizumab plus bevacizumab (Atz/Bev) or durvalumab plus tremelimumab (Dur/Tre) as first-line therapy between October 2020 and March 2025 were analyzed. Since July 2022, those with Vp4 PVTT received HFRT (5 Gy × 5) targeting PVTT with ICIs. Outcomes were compared among Vp4 patients with HFRT, Vp4 patients without HFRT, and patients without Vp4 invasion (non-Vp4).
Results
Eight Vp4 patients received HFRT plus ICIs (Atz/Bev, n = 5; Dur/Tre, n = 3). The best responses of the main intrahepatic lesions by RECIST 1.1 were complete response (CR) in 1 (12.5%), partial response (PR) in 6 (75%), and stable disease in 1 (12.5%), yielding a high objective response rate (ORR) of 87.5%. By mRECIST, CR was achieved in 3 patients (37.5%). Overall survival in Vp4 patients with HFRT was comparable to non-Vp4 patients and significantly better than Vp4 patients without HFRT. No gastrointestinal bleeding or perforation occurred, and ALBI scores were preserved at 12 weeks.
Conclusions
HFRT combined with ICIs is feasible, well tolerated, and may improve outcomes in HCC with Vp4 PVTT. Prospective studies are warranted to confirm efficacy and determine optimal treatment protocols.
{"title":"Efficacy and Safety of Hypofractionated Radiation Therapy Combined With Immunotherapy for Hepatocellular Carcinoma With Vp4 Portal Vein Tumor Thrombosis","authors":"Masahiko Tameda, Hideaki Tanaka, Yutaka Toyomasu, Mizuki Kawachi, Hirono Owa, Mone Tsukimoto, Yasuyuki Tamai, Naoto Fujiwara, Ryuta Shigefuku, Suguru Ogura, Yoshihito Nomoto, Hayato Nakagawa","doi":"10.1111/hepr.70051","DOIUrl":"10.1111/hepr.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) with Vp4 portal vein tumor thrombosis (PVTT) has an extremely poor prognosis, and evidence for effective systemic therapy is limited. Preclinical studies suggest that hypofractionated radiation therapy (HFRT) may enhance immune checkpoint inhibitor (ICI) efficacy through immunogenic cell death and modulation of the tumor microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective feasibility study of HFRT combined with ICIs for unresectable HCC. Patients receiving atezolizumab plus bevacizumab (Atz/Bev) or durvalumab plus tremelimumab (Dur/Tre) as first-line therapy between October 2020 and March 2025 were analyzed. Since July 2022, those with Vp4 PVTT received HFRT (5 Gy × 5) targeting PVTT with ICIs. Outcomes were compared among Vp4 patients with HFRT, Vp4 patients without HFRT, and patients without Vp4 invasion (non-Vp4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight Vp4 patients received HFRT plus ICIs (Atz/Bev, <i>n</i> = 5; Dur/Tre, <i>n</i> = 3). The best responses of the main intrahepatic lesions by RECIST 1.1 were complete response (CR) in 1 (12.5%), partial response (PR) in 6 (75%), and stable disease in 1 (12.5%), yielding a high objective response rate (ORR) of 87.5%. By mRECIST, CR was achieved in 3 patients (37.5%). Overall survival in Vp4 patients with HFRT was comparable to non-Vp4 patients and significantly better than Vp4 patients without HFRT. No gastrointestinal bleeding or perforation occurred, and ALBI scores were preserved at 12 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HFRT combined with ICIs is feasible, well tolerated, and may improve outcomes in HCC with Vp4 PVTT. Prospective studies are warranted to confirm efficacy and determine optimal treatment protocols.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"246-252"},"PeriodicalIF":3.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250799","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}
The effects of partial splenic embolization (PSE) on hepatic encephalopathy, a portal hypertension-related disease, are not well established. This study aimed to investigate changes in ammonia levels by PSE and to identify determinants of postprocedural changes in patients with or without portosystemic shunts (PSSs).
Methods
The present retrospective study included 136 patients with hypersplenism who underwent PSE at our hospital. The patients were divided into the PSS (−) group, comprising 90 patients without PSSs with a diameter of ≥ 8 mm, and the PSS (+) group, comprising 46 patients with PSSs with a diameter of ≥ 8 mm. Ammonia levels were evaluated, and biochemical and imaging findings were assessed before and at 1 month after PSE.
Results
Overall, PSE significantly increased ammonia levels despite postprocedural hepatic function amelioration and hepatic venous pressure gradient reduction. Increased ammonia levels were observed postoperatively in 73.3% and 63.0% of patients in the PSS (−) and PSS (+) groups, respectively. The procedure induced a significant increase in ammonia levels in the PSS (−) group; in contrast, the increase was not statistically significant in the PSS (+) group. Preprocedural Child–Pugh scores of < 8 and splenic non-infarction volume of ≥ 120.32 cm3 in the PSS (−) group, as well as preprocedural splenic artery diameter-to-common hepatic artery diameter ratios of < 1.4 and concomitant splenic vein-derived shunt vessels in the PSS (+) group, were significant and independent determinants of postprocedural ammonia-level increase.
Conclusions
PSE generally poses a high risk of short-term increase in ammonia levels, particularly in patients without PSSs.
{"title":"Caution Regarding Short-Term Increases in Ammonia Levels Following Splenic Artery Embolization","authors":"Tsuyoshi Ishikawa, Aika Kirihara, Natsuko Nishiyama, Maho Egusa, Tsuyoshi Fujioka, Daiki Kawamoto, Ryo Sasaki, Tatsuro Nishimura, Norikazu Tanabe, Takuro Hisanaga, Issei Saeki, Toshihiko Matsumoto, Taro Takami","doi":"10.1111/hepr.70050","DOIUrl":"10.1111/hepr.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The effects of partial splenic embolization (PSE) on hepatic encephalopathy, a portal hypertension-related disease, are not well established. This study aimed to investigate changes in ammonia levels by PSE and to identify determinants of postprocedural changes in patients with or without portosystemic shunts (PSSs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present retrospective study included 136 patients with hypersplenism who underwent PSE at our hospital. The patients were divided into the PSS (−) group, comprising 90 patients without PSSs with a diameter of ≥ 8 mm, and the PSS (+) group, comprising 46 patients with PSSs with a diameter of ≥ 8 mm. Ammonia levels were evaluated, and biochemical and imaging findings were assessed before and at 1 month after PSE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, PSE significantly increased ammonia levels despite postprocedural hepatic function amelioration and hepatic venous pressure gradient reduction. Increased ammonia levels were observed postoperatively in 73.3% and 63.0% of patients in the PSS (−) and PSS (+) groups, respectively. The procedure induced a significant increase in ammonia levels in the PSS (−) group; in contrast, the increase was not statistically significant in the PSS (+) group. Preprocedural Child–Pugh scores of < 8 and splenic non-infarction volume of ≥ 120.32 cm<sup>3</sup> in the PSS (−) group, as well as preprocedural splenic artery diameter-to-common hepatic artery diameter ratios of < 1.4 and concomitant splenic vein-derived shunt vessels in the PSS (+) group, were significant and independent determinants of postprocedural ammonia-level increase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PSE generally poses a high risk of short-term increase in ammonia levels, particularly in patients without PSSs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 2","pages":"182-194"},"PeriodicalIF":3.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244216","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}
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}
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