Yuta Maruki, Yasushi Yatabe, Chiharu Mizoguchi, Kathleen Yasmin de Almeida, Aumkhae Sookprasert, Charuwan Akewanlop, Ming-Huang Chen, Ekaphop Sirachainan, Dao Van Tu, Rozita Abdul Malik, Chaiyut Charoentum, Hwoei Fen Soo Hoo, Suhana Yusak, Tsung-Hao Liu, Rangasamy Ramachandran, Patrapim Sunpaweravong, Pei Jye Voon, Najihah Abu Bakar, Junki Mizusawa, Hitomi Sumiyoshi Okuma, Kenichi Nakamura, Chigusa Morizane, Takuji Okusaka
Aim
Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications.
Methods
This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).
Results
Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0–897), platinum-based + GEM (240 days, 95% CI: 197–282), and other treatments (168 days, 95% CI: 11–325; p = 0.017).
Conclusion
The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.
目的：胆道肿瘤，包括肝内胆管癌（ICC），具有侵袭性，治疗方案有限，预后差。最近的试验（TOPAZ-1, Keynote-966）显示ICIs联合吉西他滨和顺铂可改善生存率。包括FGFR抑制剂在内的靶向治疗对于FGFR2基因融合或重排的胆管癌患者是有希望的，尽管在亚洲很少有关于FGFR2阳性和临床数据的报道。本研究旨在通过评估亚洲肝内和肝门周围胆管癌患者的FGFR2融合或重排来解决这一差距，为其临床意义和潜在的治疗意义提供见解。方法：这项多中心研究利用荧光原位杂交（FISH）和Todai OncoPanel2 （TOP2）的全面基因组图谱分析，评估了亚洲（泰国、马来西亚、越南和台湾）ICC和肝门周围胆管癌中FGFR2重排和融合基因的频率。结果：113例患者中，102例符合条件；FISH发现FGFR2重排/融合占3.9%（4例），所有这些也被TOP2小组证实，与日本PRELUDE研究一致。年龄较小与FGFR2阳性显著相关（34.5±3.17 vs 62.69±1.04;p = 0.0003），而与肝炎感染、饮酒或吸烟史无相关性。基因组分析鉴定了TP53、KRAS和ARID1A的频繁突变，具有显著的区域差异。与其他治疗方法相比，接受ICIs治疗的患者显示出更长的无进展生存期：ICI +细胞毒（348天，95% CI: 0-897），铂基+ GEM（240天，95% CI: 197-282）和其他治疗（168天，95% CI: 11-325; p = 0.017）。结论：亚洲的FGFR2阳性率略低，但与日本的报道一致，并且在年轻的ICC患者中更为常见。不同的基因改变可能是亚洲人群的特征。
{"title":"FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan-Asian Study","authors":"Yuta Maruki, Yasushi Yatabe, Chiharu Mizoguchi, Kathleen Yasmin de Almeida, Aumkhae Sookprasert, Charuwan Akewanlop, Ming-Huang Chen, Ekaphop Sirachainan, Dao Van Tu, Rozita Abdul Malik, Chaiyut Charoentum, Hwoei Fen Soo Hoo, Suhana Yusak, Tsung-Hao Liu, Rangasamy Ramachandran, Patrapim Sunpaweravong, Pei Jye Voon, Najihah Abu Bakar, Junki Mizusawa, Hitomi Sumiyoshi Okuma, Kenichi Nakamura, Chigusa Morizane, Takuji Okusaka","doi":"10.1111/hepr.70031","DOIUrl":"10.1111/hepr.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with <i>FGFR</i>2 gene fusions or rearrangements, although few reports exist on <i>FGFR</i>2 positivity and clinical data in Asia. This study aims to address this gap by evaluating <i>FGFR</i>2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter study evaluated the frequency of <i>FGFR</i>2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 113 patients, 102 were eligible; <i>FGFR2</i> rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with <i>FGFR</i>2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; <i>p</i> = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in <i>TP</i>53, <i>KRAS</i>, and <i>ARID1A</i> with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0–897), platinum-based + GEM (240 days, 95% CI: 197–282), and other treatments (168 days, 95% CI: 11–325; <i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The <i>FGFR</i>2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"78-88"},"PeriodicalIF":3.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075191","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 examined mortality patterns and their association with liver fibrosis in Japanese patients with biopsy-confirmed metabolic dysfunction–associated steatotic liver disease (MASLD).
Methods
We analyzed 1104 MASLD-eligible individuals from the Suita SLD cohort (2004–2023). Mortality rates were assessed using Kaplan–Meier analysis and compared between patients with and without fibrosis (Stages 1–4 vs. 0) and between metabolic dysfunction–associated steatohepatitis (MASH) and non-MASH groups, adjusting for age and sex. Associations between fibrosis or inflammation levels and cause-specific mortality were also evaluated.
Results
Of the initial 1109 patients, 1104 met the MASLD criteria. Among these patients (544 men, 560 women; mean age: 57.2 years; mean follow-up period: 6.9 years), 93 patients died, primarily from hepatocellular carcinoma (HCC) (n = 17), liver failure (n = 16), extrahepatic malignancies (n = 17), cardio-cerebrovascular diseases (n = 7), and other causes (n = 36). Fibrosis was associated with higher all-cause (11.4% vs. 3.6%) and liver-related mortality (4.8% vs. 0%, both p < 0.0001), but not with nonliver-related mortality after adjustment. All-cause mortality was higher in the MASH group (11.2% vs. 2.6%, p < 0.0001), with increased risk of both liver- and nonliver-related deaths (adjusted hazard ratios: liver-related = 1.34 × 1017, 95% CI: NE, nonliver-related = 2.20, 95% confidence interval [CI]: 1.07–4.53).
Conclusion
HCC and extrahepatic malignancies were the leading causes of death in Japanese patients with MASLD. Liver fibrosis was a significant predictor of both all-cause and liver-related mortalities, but not nonliver-related mortality, highlighting its importance in follow-up strategies for MASLD. MASH may contribute to increased nonliver-related deaths. Further long-term studies are warranted.
{"title":"Association Between Liver Fibrosis and Cause-Specific Mortality in Japanese Patients With Biopsy-Confirmed Metabolic Dysfunction–Associated Steatotic Liver Disease: A Prospective Cohort Study / Liver Fibrosis and Mortality in Japanese MASLD","authors":"Kyoko Sakai, Toshihide Shima, Hirohisa Oya, Takahiro Miura, Shohei Amioka, Takahiro Nonaka, Shinsaku Fujiishi, Keiichiro Okuda, Kei Terasaki, Kohei Fukumoto, Yasuhide Mitsumoto, Masayuki Mizuno, Takeshi Okanoue","doi":"10.1111/hepr.70034","DOIUrl":"10.1111/hepr.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study examined mortality patterns and their association with liver fibrosis in Japanese patients with biopsy-confirmed metabolic dysfunction–associated steatotic liver disease (MASLD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 1104 MASLD-eligible individuals from the Suita SLD cohort (2004–2023). Mortality rates were assessed using Kaplan–Meier analysis and compared between patients with and without fibrosis (Stages 1–4 vs. 0) and between metabolic dysfunction–associated steatohepatitis (MASH) and non-MASH groups, adjusting for age and sex. Associations between fibrosis or inflammation levels and cause-specific mortality were also evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the initial 1109 patients, 1104 met the MASLD criteria. Among these patients (544 men, 560 women; mean age: 57.2 years; mean follow-up period: 6.9 years), 93 patients died, primarily from hepatocellular carcinoma (HCC) (<i>n</i> = 17), liver failure (<i>n</i> = 16), extrahepatic malignancies (<i>n</i> = 17), cardio-cerebrovascular diseases (<i>n</i> = 7), and other causes (<i>n</i> = 36). Fibrosis was associated with higher all-cause (11.4% vs. 3.6%) and liver-related mortality (4.8% vs. 0%, both <i>p</i> < 0.0001), but not with nonliver-related mortality after adjustment. All-cause mortality was higher in the MASH group (11.2% vs. 2.6%, <i>p</i> < 0.0001), with increased risk of both liver- and nonliver-related deaths (adjusted hazard ratios: liver-related = 1.34 × 10<sup>17</sup>, 95% CI: NE, nonliver-related = 2.20, 95% confidence interval [CI]: 1.07–4.53).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HCC and extrahepatic malignancies were the leading causes of death in Japanese patients with MASLD. Liver fibrosis was a significant predictor of both all-cause and liver-related mortalities, but not nonliver-related mortality, highlighting its importance in follow-up strategies for MASLD. MASH may contribute to increased nonliver-related deaths. Further long-term studies are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"33-49"},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069478","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}
Atezolizumab plus bevacizumab (Atezo+Bev) therapy is the preferred first-line treatment for advanced hepatocellular carcinoma (HCC). However, the efficacy of Atezo+Bev is limited in patients with a CRAFITY score of 2 (C-reactive protein ≥ 1 mg/dL and alpha-fetoprotein [AFP] ≥ 100 ng/mL). This study compared the efficacy and safety of lenvatinib and Atezo+Bev in these patients.
Methods
We retrospectively analyzed 774 patients treated with lenvatinib or Atezo+Bev as first-line treatment for advanced HCC between October 2020 and December 2023 across 11 hospitals in Japan. Among them, 90 patients (11.6%) had a CRAFITY score of 2. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profiles were compared.
Results
Baseline characteristics were similar, except tumor size and AFP levels, which were higher in the Atezo+Bev group. Median PFS was significantly longer in the lenvatinib group compared to the Atezo+Bev group (6.0 vs. 2.3 months; hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.32–0.95]; p = 0.032). The median OS was not significantly different between the two groups (9.8 vs. 5.2 months; HR: 0.66, 95% CI: 0.41–1.08; p = 0.101). The DCR (62.0% vs. 30.0%; p = 0.003) and the occurrence of grade ≥ 3 treatment-related adverse events (46.0% vs. 20.0%; p = 0.014) were significantly higher in the lenvatinib group than in the Atezo+Bev group.
Conclusion
Lenvatinib provided a significantly longer PFS than Atezo+Bev in patients with HCC and a baseline CRAFITY score of 2, whereas OS did not significantly differ between the two groups. These findings may serve as a cornerstone for developing biomarker-based strategies in first-line treatment selection for this patient population.
{"title":"Lenvatinib Versus Atezolizumab Plus Bevacizumab as First-Line Treatment for Advanced Hepatocellular Carcinoma With a CRAFITY Score of 2: A Multi-Center Retrospective Study","authors":"Masayuki Ueno, Haruhiko Takeda, Atsushi Takai, Makoto Umeda, Hiroki Morimura, Shunsuke Okuyama, Norihiro Nishijima, Satoru Iwamoto, Shigeharu Nakano, Shu Nagatomo, Takeshi Seta, Tomoyuki Goto, Atsuyuki Ikeda, Takahisa Kayahara, Shin'ichi Miyamoto, Shujiro Yazumi, Taro Ueo, Yoshito Uenoyama, Kazuyoshi Matsumura, Masako Mishima, Tadashi Inuzuka, Yuji Eso, Ken Takahashi, Hiroyuki Marusawa, Yukio Osaki, Etsuro Hatano, Hiroshi Seno","doi":"10.1111/hepr.70040","DOIUrl":"10.1111/hepr.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Atezolizumab plus bevacizumab (Atezo+Bev) therapy is the preferred first-line treatment for advanced hepatocellular carcinoma (HCC). However, the efficacy of Atezo+Bev is limited in patients with a CRAFITY score of 2 (C-reactive protein ≥ 1 mg/dL and alpha-fetoprotein [AFP] ≥ 100 ng/mL). This study compared the efficacy and safety of lenvatinib and Atezo+Bev in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 774 patients treated with lenvatinib or Atezo+Bev as first-line treatment for advanced HCC between October 2020 and December 2023 across 11 hospitals in Japan. Among them, 90 patients (11.6%) had a CRAFITY score of 2. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profiles were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline characteristics were similar, except tumor size and AFP levels, which were higher in the Atezo+Bev group. Median PFS was significantly longer in the lenvatinib group compared to the Atezo+Bev group (6.0 vs. 2.3 months; hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.32–0.95]; <i>p</i> = 0.032). The median OS was not significantly different between the two groups (9.8 vs. 5.2 months; HR: 0.66, 95% CI: 0.41–1.08; <i>p</i> = 0.101). The DCR (62.0% vs. 30.0%; <i>p</i> = 0.003) and the occurrence of grade ≥ 3 treatment-related adverse events (46.0% vs. 20.0%; <i>p</i> = 0.014) were significantly higher in the lenvatinib group than in the Atezo+Bev group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lenvatinib provided a significantly longer PFS than Atezo+Bev in patients with HCC and a baseline CRAFITY score of 2, whereas OS did not significantly differ between the two groups. These findings may serve as a cornerstone for developing biomarker-based strategies in first-line treatment selection for this patient population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"100-110"},"PeriodicalIF":3.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052890","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}
{"title":"HCV Elimination Strategies for Maximum Effectiveness, Tailored to National and Regional Circumstances","authors":"Ken Sato","doi":"10.1111/hepr.70038","DOIUrl":"10.1111/hepr.70038","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"9-10"},"PeriodicalIF":3.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052946","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}
{"title":"Effect of Tirzepatide Treatment on Hepatic Biomarkers in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus","authors":"Dilara Tekin Uzman, Gizem Dağcı","doi":"10.1111/hepr.70039","DOIUrl":"10.1111/hepr.70039","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"131-132"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033273","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}
Bradycardic responses frequently occur during radiofrequency ablation (RFA) and microwave ablation (MWA) for hepatocellular carcinoma (HCC), but the impact of procedural pain severity and patient-specific factors remains unclear. This study aimed to evaluate the incidence and risk factors for bradycardic responses, focusing on procedural pain and autonomic regulation.
Methods
This retrospective study included 267 patients with solitary HCC who underwent RFA or MWA between 2019 and 2024. Bradycardic responses were defined as a ≥ 30% decrease in heart rate from baseline or < 50 bpm. Patients were categorized by procedural pain severity using patient-controlled analgesia (PCA) bolus administration. Risk factors for bradycardia were assessed by logistic regression.
Results
Bradycardic responses occurred in 70 patients (26.2%). Severe procedural pain (odds ratio [OR], 2.26 and p = 0.007) and primary HCC (OR, 2.68 and p = 0.002) were independent risk factors. In patients without severe pain, absence of angiotensin II receptor blocker (ARB) use increased bradycardia risk (OR, 0.14 and p = 0.013). Most bradycardic events (61.4%) occurred within 3 min of ablation initiation.
Conclusions
Bradycardic responses during RFA and MWA are common and linked to procedural pain severity and autonomic imbalance. Comprehensive management, including pain control, medication review, and addressing procedural anxiety through counseling or sedation, may reduce risks and enhance procedural safety.
目的：在肝细胞癌（HCC）的射频消融（RFA）和微波消融（MWA）治疗过程中经常发生心动过缓反应，但手术疼痛严重程度和患者特异性因素的影响尚不清楚。本研究旨在评估心动过缓反应的发生率和危险因素，重点关注程序性疼痛和自主调节。方法：本回顾性研究包括267例2019年至2024年间接受RFA或MWA治疗的单发HCC患者。心动过缓反应定义为心率较基线降低≥30%。结果：70例患者（26.2%）发生心动过缓反应。严重的手术疼痛（比值比[OR]， 2.26, p = 0.007）和原发性肝癌（比值比[OR]， 2.68, p = 0.002）是独立的危险因素。在没有剧烈疼痛的患者中，不使用血管紧张素II受体阻滞剂（ARB）会增加心动过缓的风险（OR， 0.14和p = 0.013）。大多数心动过缓事件（61.4%）发生在消融开始后3分钟内。结论：RFA和MWA期间的心动过缓反应是常见的，并与程序性疼痛严重程度和自主神经失衡有关。综合管理，包括疼痛控制，药物审查，通过咨询或镇静解决程序焦虑，可以降低风险并提高程序安全性。
{"title":"Bradycardic Responses During Thermal Ablation for Hepatocellular Carcinoma: Impact of Procedural Pain Severity and Autonomic Imbalance","authors":"Yasuyuki Komiyama, Masaru Muraoka, Tetsuya Iijima, Leona Osawa, Hitomi Takada, Yuichiro Suzuki, Mitsuaki Sato, Shinichi Takano, Shinya Maekawa, Atsunori Tsuchiya, Nobuyuki Enomoto","doi":"10.1111/hepr.70013","DOIUrl":"10.1111/hepr.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Bradycardic responses frequently occur during radiofrequency ablation (RFA) and microwave ablation (MWA) for hepatocellular carcinoma (HCC), but the impact of procedural pain severity and patient-specific factors remains unclear. This study aimed to evaluate the incidence and risk factors for bradycardic responses, focusing on procedural pain and autonomic regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 267 patients with solitary HCC who underwent RFA or MWA between 2019 and 2024. Bradycardic responses were defined as a ≥ 30% decrease in heart rate from baseline or < 50 bpm. Patients were categorized by procedural pain severity using patient-controlled analgesia (PCA) bolus administration. Risk factors for bradycardia were assessed by logistic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bradycardic responses occurred in 70 patients (26.2%). Severe procedural pain (odds ratio [OR], 2.26 and <i>p</i> = 0.007) and primary HCC (OR, 2.68 and <i>p</i> = 0.002) were independent risk factors. In patients without severe pain, absence of angiotensin II receptor blocker (ARB) use increased bradycardia risk (OR, 0.14 and <i>p</i> = 0.013). Most bradycardic events (61.4%) occurred within 3 min of ablation initiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Bradycardic responses during RFA and MWA are common and linked to procedural pain severity and autonomic imbalance. Comprehensive management, including pain control, medication review, and addressing procedural anxiety through counseling or sedation, may reduce risks and enhance procedural safety.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 11","pages":"1518-1530"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033211","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}
Yuki Kugiyama, Masanori Abe, Tadashi Namisaki, Hitoshi Yoshiji, Kazumichi Abe, Hiromasa Ohira, Ryosaku Shirahashi, Keiji Yokoyama, Atsushi Fukunaga, Kazuhito Kawata, Masahiro Umemura, Akira Honda, Tadashi Ikegami, Shiho Miyase, Toshiaki Nakano, Atsumasa Komori, Atsushi Tanaka, the Japan PBC Study Group
Aim
The Japan Primary Biliary Cholangitis Study Group (JPBCSG) has conducted nationwide surveys of primary biliary cholangitis (PBC) since 1980. Due to the progress in the management of PBC, a more comprehensive survey platform is desired.
Methods
The JPBCSG conducted the 17th survey of PBC by using an electronic data capture (EDC) system: The patients' clinical demography at diagnosis and the outcomes of newly and past registered cases (till the 16th) were entered jointly in the EDC system. A questionnaire for treatment response was included in the survey. Using the new platform, the trends in clinical demography and the long-term prognosis of PBC were analyzed.
Results
The percentage of male patients with PBC showed a significant increase from the period before the end of 2010 [Period 1, 12.4% (n = 772)] to the period after 2021 [Period 4, 20.6% (n = 345), p < 0.001] (n = 2579, in total). The mean age at diagnosis also rose significantly from 56.8 years old in Period 1 to 61.8 years in Period 4 (p < 0.001). There were no significant changes in the prevalence of symptoms at diagnosis. In a multivariate Cox-regression analysis, older age (hazard ratio [HR] 3.48, p = 0.001), female sex (HR 0.46, p = 0.046), total bilirubin (HR 3.84, p = 0.009), fluid retention (HR 5.69, p < 0.001), and esophagogastric varices (HR 2.66, p = 0.015) were significantly associated with liver-related mortality and liver transplantation.
Conclusion
We have established the 2nd-generation nationwide survey of PBC in Japan. The survey results revealed not only demographical trends in Japanese patients with PBC but also risk factors for their prognosis.
目的：日本原发性胆道胆管炎研究组（JPBCSG）自1980年以来在全国范围内开展了原发性胆道胆管炎（PBC）调查。由于中国人民银行管理的进步，需要一个更全面的调查平台。方法：采用电子数据采集（electronic data capture， EDC）系统进行第17次PBC调查，将患者诊断时的临床人口学资料以及新登记病例和既往登记病例（截止至16日）的结果联合录入EDC系统。调查中包括一份治疗反应问卷。利用新平台，分析临床人口学趋势和PBC的长期预后。结果：男性PBC患者的比例从2010年底前[第1期，12.4% (n = 772)]到2021年之后[第4期，20.6% (n = 345)]显著增加，p结论：我们在日本建立了第二代全国PBC调查。调查结果不仅揭示了日本PBC患者的人口趋势，还揭示了影响其预后的危险因素。
{"title":"Clinical Characteristics and Long-Term Prognosis of Primary Biliary Cholangitis in Japan: Results of the 2nd-Generation Nationwide Survey","authors":"Yuki Kugiyama, Masanori Abe, Tadashi Namisaki, Hitoshi Yoshiji, Kazumichi Abe, Hiromasa Ohira, Ryosaku Shirahashi, Keiji Yokoyama, Atsushi Fukunaga, Kazuhito Kawata, Masahiro Umemura, Akira Honda, Tadashi Ikegami, Shiho Miyase, Toshiaki Nakano, Atsumasa Komori, Atsushi Tanaka, the Japan PBC Study Group","doi":"10.1111/hepr.70035","DOIUrl":"10.1111/hepr.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The Japan Primary Biliary Cholangitis Study Group (JPBCSG) has conducted nationwide surveys of primary biliary cholangitis (PBC) since 1980. Due to the progress in the management of PBC, a more comprehensive survey platform is desired.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The JPBCSG conducted the 17th survey of PBC by using an electronic data capture (EDC) system: The patients' clinical demography at diagnosis and the outcomes of newly and past registered cases (till the 16th) were entered jointly in the EDC system. A questionnaire for treatment response was included in the survey. Using the new platform, the trends in clinical demography and the long-term prognosis of PBC were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The percentage of male patients with PBC showed a significant increase from the period before the end of 2010 [Period 1, 12.4% (<i>n</i> = 772)] to the period after 2021 [Period 4, 20.6% (<i>n</i> = 345), <i>p <</i> 0.001] (<i>n</i> = 2579, in total). The mean age at diagnosis also rose significantly from 56.8 years old in Period 1 to 61.8 years in Period 4 (<i>p</i> < 0.001). There were no significant changes in the prevalence of symptoms at diagnosis. In a multivariate Cox-regression analysis, older age (hazard ratio [HR] 3.48, <i>p</i> = 0.001), female sex (HR 0.46, <i>p</i> = 0.046), total bilirubin (HR 3.84, <i>p</i> = 0.009), fluid retention (HR 5.69, <i>p <</i> 0.001), and esophagogastric varices (HR 2.66, <i>p</i> = 0.015) were significantly associated with liver-related mortality and liver transplantation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We have established the 2nd-generation nationwide survey of PBC in Japan. The survey results revealed not only demographical trends in Japanese patients with PBC but also risk factors for their prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"50-59"},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033250","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}
Hepatitis C virus (HCV) infection remains a global health concern. Although the World Health Organization (WHO) proposed a strategy to eliminate HCV by 2030, Japan faces challenges owing to limited access and insufficient support for high-risk populations. Previously, HCV diagnoses required a two-step process, delaying results and increasing costs. In 2024, Japan introduced the Elecsys HCV Duo immunoassay, which enables the qualitative dual detection of HCV core antigen (HCV Ag) and antibodies against HCV (anti-HCV). This study aimed to evaluate its effectiveness in identifying patients with an active HCV infection.
Methods
A retrospective analysis was conducted on 13,045 patients who underwent HCV screening using the Elecsys HCV Duo immunoassay.
Results
Of these, 244 were positive for HCV Duo. All 14 patients who were positive for HCV Ag and anti-HCV had active infection, as confirmed by HCV-RNA testing. Five HCV Ag-positive but anti-HCV-negative patients were identified as false positives. In contrast, five anti-HCV-positive but HCV Ag-negative patients had active infections with detectable HCV-RNA. A low viral load and possible antibody interference were identified as potential reasons for false-negative HCV Ag results.
Conclusion
The Elecsys HCV Duo immunoassay effectively simplified HCV diagnosis and facilitated early detection and treatment initiation. Although false-negative HCV Ag results occurred, the assay ensured linkage to care for patients with both HCV Ag and anti-HCV positivity. These advancements may contribute to enhanced HCV care and support national elimination efforts.
{"title":"Clinical Evaluation of Initial Experiences With the Qualitative Dual Detection of Core Antigen and Antibodies Immunoassay for Hepatitis C Virus Screening Test","authors":"Rihwa Om, Shunsuke Sato, Kei Kondo, Naoki Ashikawa, Hiroki Nago, Masahiro Yamaguchi, Yoko Kato, Yuichiro Terai, Yuji Kita, Yuji Ikeda, Sho Sato, Ayato Murata, Yuji Shimada, Yumiko Kodama, Takuya Genda","doi":"10.1111/hepr.70037","DOIUrl":"10.1111/hepr.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Hepatitis C virus (HCV) infection remains a global health concern. Although the World Health Organization (WHO) proposed a strategy to eliminate HCV by 2030, Japan faces challenges owing to limited access and insufficient support for high-risk populations. Previously, HCV diagnoses required a two-step process, delaying results and increasing costs. In 2024, Japan introduced the Elecsys HCV Duo immunoassay, which enables the qualitative dual detection of HCV core antigen (HCV Ag) and antibodies against HCV (anti-HCV). This study aimed to evaluate its effectiveness in identifying patients with an active HCV infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was conducted on 13,045 patients who underwent HCV screening using the Elecsys HCV Duo immunoassay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of these, 244 were positive for HCV Duo. All 14 patients who were positive for HCV Ag and anti-HCV had active infection, as confirmed by HCV-RNA testing. Five HCV Ag-positive but anti-HCV-negative patients were identified as false positives. In contrast, five anti-HCV-positive but HCV Ag-negative patients had active infections with detectable HCV-RNA. A low viral load and possible antibody interference were identified as potential reasons for false-negative HCV Ag results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The Elecsys HCV Duo immunoassay effectively simplified HCV diagnosis and facilitated early detection and treatment initiation. Although false-negative HCV Ag results occurred, the assay ensured linkage to care for patients with both HCV Ag and anti-HCV positivity. These advancements may contribute to enhanced HCV care and support national elimination efforts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"125-130"},"PeriodicalIF":3.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029753","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}
This study aimed to evaluate the therapeutic efficacy of durvalumab and tremelimumab (Dur/Tre) in patients with hepatocellular carcinoma (HCC) who had a tumor thrombus in the main portal vein trunk (Vp4) or high tumor burden (HTB).
Methods
A total of 309 patients with BCLC stage B or C HCC who received Dur/Tre between March 2023 and October 2024 were included. HTB was defined as the presence of at least one of the following radiological findings: ≥ 50% liver involvement by HCC, bile duct invasion, or the presence of Vp4.
Results
Both the patients with Vp4 and HTB-positive group had significantly higher proportions of BCLC stage C disease (p = 0.01 and 0.007, respectively) and serum DCP levels ≥ 100 mAU/mL (p = 0.03 and < 0.001, respectively), and significantly higher neutrophil-to-lymphocyte ratio (p = 0.04 and p = 0.004, respectively) compared to their respective counterparts. While the objective response rate did not significantly differ between the HTB-positive and HTB-negative groups (21.6% vs. 16.2%, p = 0.5), it was significantly higher in patients with Vp4 than in those without (42.9% vs. 15.6%, p = 0.02). There were no significant differences in progression-free survival or overall survival (OS) between patients with and without Vp4 (p = 0.1 and 0.3, respectively) and nor between the HTB-positive and HTB-negative groups (both p = 0.3). Among patients with both Vp4 and HTB, responders had longer OS than non-responders.
Conclusions
Dur/Tre may be a viable treatment option for patients with Vp4 and HTB.
{"title":"Efficacy and Safety of Durvalumab Plus Tremelimumab in Hepatocellular Carcinoma Patients With Portal Vein Thrombosis and High Tumor Burden: A Multicenter Retrospective Analysis","authors":"Takeshi Hatanaka, Yutaka Yata, Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Satoru Kakizaki, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hidenori Toyoda, Yuichi Koshiyama, Chikara Ogawa, Hiroki Nishikawa, Takashi Nishimura, Kazuhito Kawata, Hisashi Kosaka, Kosuke Matsui, Atsushi Naganuma, Hironori Tanaka, Hideko Ohama, Hidekatsu Kuroda, Tomomitsu Matono, Tomoko Aoki, Hironori Ochi, Michitaka Imai, Shinichiro Nakamura, Shohei Komatsu, Hideyuki Tamai, Jumpei Okamura, Yuki Kanayama, Kazunari Tanaka, Fujimasa Tada, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takanori Matsuura, Hidenao Noritake, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada, Real-life Practice Experts for HCC (RELPEC) Study Group, and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)","doi":"10.1111/hepr.70033","DOIUrl":"10.1111/hepr.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to evaluate the therapeutic efficacy of durvalumab and tremelimumab (Dur/Tre) in patients with hepatocellular carcinoma (HCC) who had a tumor thrombus in the main portal vein trunk (Vp4) or high tumor burden (HTB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 309 patients with BCLC stage B or C HCC who received Dur/Tre between March 2023 and October 2024 were included. HTB was defined as the presence of at least one of the following radiological findings: ≥ 50% liver involvement by HCC, bile duct invasion, or the presence of Vp4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both the patients with Vp4 and HTB-positive group had significantly higher proportions of BCLC stage C disease (<i>p</i> = 0.01 and 0.007, respectively) and serum DCP levels ≥ 100 mAU/mL (<i>p</i> = 0.03 and < 0.001, respectively), and significantly higher neutrophil-to-lymphocyte ratio (<i>p</i> = 0.04 and <i>p</i> = 0.004, respectively) compared to their respective counterparts. While the objective response rate did not significantly differ between the HTB-positive and HTB-negative groups (21.6% vs. 16.2%, <i>p</i> = 0.5), it was significantly higher in patients with Vp4 than in those without (42.9% vs. 15.6%, <i>p</i> = 0.02). There were no significant differences in progression-free survival or overall survival (OS) between patients with and without Vp4 (<i>p</i> = 0.1 and 0.3, respectively) and nor between the HTB-positive and HTB-negative groups (both <i>p</i> = 0.3). Among patients with both Vp4 and HTB, responders had longer OS than non-responders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dur/Tre may be a viable treatment option for patients with Vp4 and HTB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 1","pages":"89-99"},"PeriodicalIF":3.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008264","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}
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that can cause vascular malformations in multiple organs, including the liver. Although liver involvement typically remains asymptomatic until adulthood, severe cases can progress to high-output cardiac failure (HOCF). Although liver transplantation (LT) is a well-established curative option for adult patients with HHT, pediatric data are limited.
Methods
We present a case of a 3-month-old boy with HOCF due to hepatic arteriovenous malformations (AVMs) caused by HHT. Prenatal imaging revealed hepatic AVMs and a ventricular septal defect (VSD), necessitating a semi-emergent cesarean delivery due to rapid cardiac enlargement. To reduce blood flow to the AVMs, hepatic artery ligation and transcatheter embolization were performed within the first week of life. At 3 weeks, progressive pulmonary blood flow led to pulmonary artery banding to address the tricuspid regurgitant gradient exceeding 50 mmHg. Given the life-threatening nature of the high-output state due to the hepatic AVMs, LT was deemed essential and was strategically performed prior to VSD closure. The patient successfully transitioned off continuous catecholamine support by postoperative Day 3 and has remained stable for 2 years without recurrence of heart failure.
Results and Conclusion
This is the first report demonstrating the feasibility and effectiveness of LT in pediatric HHT patients with severe cardiac complications, including right-to-left shunting. The case highlights the natural history of HHT in childhood and provides guidance on optimal treatment strategies, particularly a decision to perform LT first while leaving right-to-left shunting and operative procedures to prevent perioperative complications.
{"title":"Living Donor Liver Transplantation for Symptomatic Liver Involvement in Infant With Hereditary Hemorrhagic Telangiectasia","authors":"Ryuji Komine, Seisuke Sakamoto, Hajime Uchida, Yusuke Yanagi, Masato Kojima, Akinari Fukuda, Chiduko Haga, Takako Yoshioka, Mureo Kasahara","doi":"10.1111/hepr.70020","DOIUrl":"10.1111/hepr.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that can cause vascular malformations in multiple organs, including the liver. Although liver involvement typically remains asymptomatic until adulthood, severe cases can progress to high-output cardiac failure (HOCF). Although liver transplantation (LT) is a well-established curative option for adult patients with HHT, pediatric data are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present a case of a 3-month-old boy with HOCF due to hepatic arteriovenous malformations (AVMs) caused by HHT. Prenatal imaging revealed hepatic AVMs and a ventricular septal defect (VSD), necessitating a semi-emergent cesarean delivery due to rapid cardiac enlargement. To reduce blood flow to the AVMs, hepatic artery ligation and transcatheter embolization were performed within the first week of life. At 3 weeks, progressive pulmonary blood flow led to pulmonary artery banding to address the tricuspid regurgitant gradient exceeding 50 mmHg. Given the life-threatening nature of the high-output state due to the hepatic AVMs, LT was deemed essential and was strategically performed prior to VSD closure. The patient successfully transitioned off continuous catecholamine support by postoperative Day 3 and has remained stable for 2 years without recurrence of heart failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>This is the first report demonstrating the feasibility and effectiveness of LT in pediatric HHT patients with severe cardiac complications, including right-to-left shunting. The case highlights the natural history of HHT in childhood and provides guidance on optimal treatment strategies, particularly a decision to perform LT first while leaving right-to-left shunting and operative procedures to prevent perioperative complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 12","pages":"1683-1690"},"PeriodicalIF":3.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951992","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}
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