Hepatology Research最新文献

{"title":"Chronic Kidney Disease Risk Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Nationwide Cohort Study in Korea.","authors":"Dong Wook Kim, Minkook Son, Hye Jung Lee, Chi Hyeon Choi, Yeo Wool Kang, Sang Yi Moon, Myeongseok Koh, Jong Yoon Lee, Yang Hyun Baek, Won Suk An","doi":"10.1111/hepr.14226","DOIUrl":"https://doi.org/10.1111/hepr.14226","url":null,"abstract":"<p><strong>Aim: </strong>The shift in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) highlights its association with metabolic dysfunction. MASLD is defined by hepatic steatosis and at least one cardiometabolic risk factor (CMRF), which contribute to chronic kidney disease (CKD). This study examines the relationship between MASLD and CKD, the independent impact of CMRFs on CKD risk, and the cumulative effect of multiple CMRFs on CKD development.</p><p><strong>Methods: </strong>The present retrospective cohort study utilized data from the Korean National Health Insurance System (NHIS), analyzing 211,992 individuals aged ≥ 40 years who underwent health screenings between 2009 and 2010. The average observation period was 9.1 years. Participants were classified into groups: no steatotic liver disease (SLD) without CMRF, no SLD with CMRF, MASLD, and metabolic dysfunction-associated steatotic liver disease with increased alcohol intake (MetALD).</p><p><strong>Results: </strong>Compared to the no SLD without CMRF group, the adjusted hazard ratios (HRs) for CKD were 1.27 (95% CI: 1.18-1.37) for no SLD with CMRF, 1.70 (95% CI: 1.58-1.83) for MASLD, and 1.47 (95% CI: 1.33-1.63) for MetALD. CKD risk increased with the number of CMRFs, with adjusted HRs increasing from 1.12 (one CMRF) to 1.97 (four CMRFs).</p><p><strong>Conclusions: </strong>MASLD is independently associated with increased CKD risk. Each CMRF independently contributes to CKD development, and the cumulative effect of multiple CMRFs further amplifies this. This suggests that MASLD is an effective predictor of CKD risk. Given the rising burden of MASLD and its complications, early identification and management of risk factors are crucial for reducing CKD incidence.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301928","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":"Microwave Thermosphere Ablation Versus Radiofrequency Ablation in Hepatocellular Carcinoma: Optimizing Treatment Strategies for Tumor Size and Malignancy Grade.","authors":"Hideyuki Tamai, Jumpei Okamura","doi":"10.1111/hepr.14221","DOIUrl":"https://doi.org/10.1111/hepr.14221","url":null,"abstract":"<p><strong>Aim: </strong>The next-generation microwave thermosphere ablation (MTA) system was developed to overcome the limitations of conventional microwave ablation. However, the comparative oncologic efficacy of MTA versus radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remains uncertain. This study aimed to evaluate the oncologic benefits of MTA.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 310 patients with primary HCC meeting the Milan criteria, treated with either RFA (n = 71) or MTA (n = 239). Metastatic recurrence was defined as ≥ 4 intrahepatic recurrences suggestive of intrahepatic metastases, extrahepatic metastases, or dissemination. High-grade malignant HCC was classified as non-single nodular type or alpha-fetoprotein lens culinaris-agglutinin reactive fraction (AFP-L3) positive (> 10%).</p><p><strong>Results: </strong>MTA was associated with significantly lower metastatic recurrence and HCC-specific mortality rates compared to RFA. Multivariate analysis identified the ablation method as an independent factor contributing to metastatic recurrence and HCC mortality. Among patients with HCC ≤ 2 cm, metastatic recurrence rates did not differ significantly between groups. However, for HCC > 2 cm, MTA showed significantly lower metastatic recurrence rates than RFA. In non-single nodular or AFP-L3-positive HCC, metastatic recurrence rates were similar between groups, whereas in single nodular or AFP-L3-negative HCC, MTA significantly reduced metastatic recurrence.</p><p><strong>Conclusions: </strong>MTA provides superior oncologic outcomes compared to RFA, particularly in reducing HCC-specific mortality and metastatic recurrence rates. MTA should be considered the preferred ablative therapy for select HCC patients, in particular those with tumors > 2 cm or those without high-grade malignancy.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293663","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":"Letter to the Editor: \"Effectiveness and Safety of Antithrombin for Treatment of Portal Vein Thrombosis: Nationwide Prospective Surveillance of 4 Years of Clinical Experience in Japan\".","authors":"Pelin Telli, Aynura Rustamzade, Bilger Çavuş","doi":"10.1111/hepr.14222","DOIUrl":"https://doi.org/10.1111/hepr.14222","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293662","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":"Current Status and Challenges of Antithrombin Administrations in Cases of Portal Vein Thrombosis With Decreased Antithrombin Concentration in Japan.","authors":"Hisashi Hidaka","doi":"10.1111/hepr.14220","DOIUrl":"https://doi.org/10.1111/hepr.14220","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293660","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":"CXCL6 Is a Novel Biliary Marker and a Downstream Target of MMP7 in Biliary Atresia.","authors":"Fanyang Kong, Jingying Jiang, Min Du, Rui Dong, Gong Chen, Shan Zheng, Junfeng Wang","doi":"10.1111/hepr.14217","DOIUrl":"https://doi.org/10.1111/hepr.14217","url":null,"abstract":"<p><strong>Aim: </strong>MMP7 has been identified as a potential biomarker for biliary atresia (BA) diagnosis. However, the mechanism of MMP7 and its downstream signaling pathway remain unknown in the pathogenesis of BA. Herein, this study was performed to figure out MMP7's downstream target.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was performed to screen out MMP7's downstream molecule CXCL6. QRT-PCR, immunohistochemistry, western blot, and ELISA were used to determine the expressions of MMP7 and CXCL6 in the liver and serum of BA and controls. Immunofluorescence was conducted to validate the hepatic cellular expressions of MMP7 and CXCL6. In vitro, overexpression and knockdown of MMP7 in biliary epithelial cells (BECs) were established to verify the MMP7's regulation on CXCL6.</p><p><strong>Results: </strong>ScRNA-seq demonstrated that MMP7 and CXCL6 were exclusively expressed on cholangiocytes and up-regulated in BA when compared with normal controls (NC). QRT-PCR, immunohistochemistry, western blot and ELISA validated the higher expressions of MMP7 and CXCL6 in the liver and serum of BA when compared with non-BA cholestasis (CS) and NC. Immunofluorescence further verified the biliary localization of MMP7 and CXCL6 in BA. Hepatic and serum CXCL6 expressions were positively correlated with MMP7 expressions, and both expressions were correlated with the stages of fibrosis in BA. Overexpression of MMP7 promoted CXCL6 expression, while knocking down MMP7 inhibited CXCL6 expression in BECs.</p><p><strong>Conclusion: </strong>CXCL6 is a downstream target of MMP7, and is identified as a novel biliary marker in BA. The production of CXCL6 by MMP7 may exert pathological roles in the liver fibrogenesis of BA.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293661","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":"Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab.","authors":"Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo","doi":"10.1111/hepr.14224","DOIUrl":"https://doi.org/10.1111/hepr.14224","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre).</p><p><strong>Methods: </strong>A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted. Additionally, hazard ratio (HR) spline curve analysis was used to determine the optimal NLR cut-off values for predicting overall survival (OS).</p><p><strong>Results: </strong>The median progression-free survival (PFS) was 3.5 months (95% confidence interval [CI]: 2.7-4.4), whereas the median OS was not reached (95% CI: 12.1 months-not reached). Multivariate analysis demonstrated that treatment with Dur/Tre as a second-line therapy or beyond was independently associated with worse PFS (HR: 1.819; 95% CI: 1.230-2.688; p = 0.003). Furthermore, an NLR of ≥ 2.56 was identified as an independent predictor of reduced OS (HR: 1.919; 95% CI: 1.033-3.566; p = 0.039). The median OS was not reached (95% CI: 12.3 months-not reached) in patients with an NLR of < 2.56, compared with 12.1 months (95% CI: 9.0 months-not reached) in those with an NLR of ≥ 2.56 (p = 0.016). A Sankey diagram illustrating post-treatment outcomes revealed that a significantly larger proportion of patients with high NLRs did not proceed to subsequent therapies but instead received best supportive care (p = 0.046). Spline curve analysis showed that an NLR range of approximately 2.3-3.0 represents an appropriate cut-off for predicting OS.</p><p><strong>Conclusions: </strong>The NLR is a significant prognostic biomarker for OS in patients with HCC treated with Dur/Tre.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293664","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":"The new assay type IV collagen 7S (CLEIA) is a useful test to identify progressive fibrosis in chronic liver disease: A study based on magnetic resonance elastography","authors":"Miwa Kawanaka,&nbsp;Takashi Fushimi,&nbsp;Tomohiro Tanikawa,&nbsp;Noriiyo Urata,&nbsp;Ken Haruma,&nbsp;Hirofumi Kawamoto,&nbsp;Motoyuki Otsuka","doi":"10.1111/hepr.14202","DOIUrl":"10.1111/hepr.14202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Liver fibrosis is a critical prognostic factor for chronic liver disease that influences morbidity and mortality. Type IV collagen 7S, measured using a chemiluminescent enzyme immunoassay, was evaluated as a novel noninvasive biomarker with its cutoff value determined via magnetic resonance elastography (MRE) to eliminate sampling bias. A two-step approach combining the fibrosis-4 (FIB-4) index and type IV collagen 7S demonstrated potential in enhancing risk stratification and clinical utility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 307 patients with chronic liver disease and 235 with metabolic dysfunction-associated steatotic liver disease. Type IV collagen 7S was compared with biomarkers such as FIB-4 index, M2BPGi, and hyaluronic acid. Diagnostic accuracy was assessed using AUROC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value, with cutoffs determined via the Youden Index. Subgroup analyses evaluated performance based on ALT levels (≤30 and &gt;30 U/L) and age (≤60 and &gt;60 years). A two-step risk stratification model incorporating type IV collagen 7S was developed for intermediate FIB-4 index groups (1.3–2.66) to assess its utility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For liver stiffness assessed using MRE, type IV collagen 7S showed the highest correlation (<i>ρ</i> = 0.591, <i>p</i> &lt; 0.001) and outperformed other biomarkers, particularly for <i>F</i> ≥ 2. Its performance was notable in patients with low ALT levels (≤30 U/L) and in elderly patients (&gt;60 years). In the intermediate FIB-4 index group, the two-stage model reduced over triage by 20%, increased specificity from 55% to 78% and enhanced PPV by 13%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The novel assay, type IV collagen 7S, is a highly effective and noninvasive biomarker for liver fibrosis. The performance of type IV collagen 7S tends to have robustness under the difference of ALT. Its combination with the FIB-4 index enhances diagnostic precision, particularly in intermediate-risk patients, reinforcing its role in refining fibrosis staging and optimizing patient management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 7","pages":"994-1004"},"PeriodicalIF":3.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266133","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":"Predicting the risk of developing diabetes in steatotic liver disease using controlled attenuation parameter in a health checkup population.","authors":"Takuma Nakatsuka, Yutaka Yamaji, Ryosuke Tateishi, Takako Ogasawara, Rena Mihara, Yoshiaki Kawashima, Tetsuharu Ono, Tomoharu Yamada, Tatsuya Minami, Masaya Sato, Takeshi Hayashi, Yuki Matsushita, Kazuyoshi Funato, Tatsuya Sato, Tomotaka Saito, Yotaro Kudo, Hirofumi Kogure, Hayato Nakagawa, Yoshinari Asaoka, Yasuo Tanaka, Yousuke Nakai, Hideaki Ijichi, Mitsuhiro Fujishiro","doi":"10.1111/hepr.14216","DOIUrl":"https://doi.org/10.1111/hepr.14216","url":null,"abstract":"<p><strong>Introduction: </strong>Excessive hepatic steatosis is linked to systemic metabolic disorders. We investigated the association between hepatic steatosis quantified by controlled attenuation parameter (CAP) and the development of type 2 diabetes mellitus (T2DM) in a health checkup population.</p><p><strong>Methods: </strong>The present retrospective cohort study included 1636 participants without T2DM who underwent CAP measurement and were followed up at annual health checkups. Cox proportional hazards regression was used to identify risk factors for T2DM development.</p><p><strong>Results: </strong>During a mean follow-up of 3.2 years, 181 participants developed T2DM. The cumulative incidence rates of T2DM were significantly higher in participants with severe steatosis (CAP ≥ 280 dB/m) compared with those without (13.9% vs. 4.8% at 3 years, p < 0.001). Multivariate analysis identified CAP as an independent predictor of new-onset T2DM (adjusted hazard ratio [aHR], 1.04 per 10 dB/m increase; 95% confidence interval [CI], 1.01-1.08, p = 0.01), along with fasting plasma glucose (aHR, 2.13 per 10 mg/dL; 95% CI, 1.77-2.55, p < 0.001), HbA1c (aHR, 1.25 per 0.1% increase; 95% CI, 1.19-1.32, p < 0.001), and platelet count (aHR, 0.95 per 10⁴/μL increase; 95% CI, 0.92-0.98, p = 0.001). A dose-response relationship was observed between CAP level and T2DM risk. In addition, suspected compensated advanced chronic liver disease (liver stiffness ≥10 kPa) and at-risk steatohepatitis (FibroScan-AST score ≥0.67) were associated with a higher incidence of T2DM (p < 0.001 for both).</p><p><strong>Conclusion: </strong>CAP quantification of hepatic steatosis effectively stratifies the risk of developing T2DM, facilitating timely intervention and prevention strategies.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186952","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":"Associations of serum carotenoids with cardiovascular disease mortality among patients with metabolic dysfunction-associated steatotic liver disease.","authors":"Qian-Qian Wang, Jing Zhu, Lin-Jun Miao, Si-Ang Lv, Guo-Yin Shen, Jun Wu","doi":"10.1111/hepr.14215","DOIUrl":"https://doi.org/10.1111/hepr.14215","url":null,"abstract":"<p><strong>Aim: </strong>High cardiovascular disease (CVD) mortality occurred among metabolic dysfunction-associated steatotic liver disease (MASLD) patients with few approved therapies. The aim of this study was to reveal the associations of serum carotenoid concentrations with CVD mortality among MASLD patients.</p><p><strong>Methods: </strong>The two prospective cohort analyses included 1175 MASLD patients from the National Health and Nutrition Examination Survey (NHANES) and 1725 MASLD patients from NHANES III. CVD mortality was ascertained through December 31, 2019. Multivariable Cox proportional hazards regression analysis was carried out to evaluate the associations of serum carotenoid levels with CVD mortality.</p><p><strong>Results: </strong>After multivariable adjustment, per one-unit increment in natural log-transformed serum β-cryptoxanthin was associated with an 85% lower risk of CVD mortality (p = 0.03) among MASLD patients aged <60 years from NHANES and a 92% lower risk of CVD mortality (p = 0.003) among MASLD patients aged <60 years from NHANES III. The adjusted HRs (95% CIs) across tertiles of serum β-cryptoxanthin concentrations were 1.00 (reference), 0.55 (0.12-2.41), 0.02 (0.002-0.24), P trend = 0.03 and 1.00 (reference), 0.47 (0.14-1.58), 0.05 (0.01-0.31), P trend = 0.002, among MASLD patients aged <60 years from NHANES and NHANES III, respectively.</p><p><strong>Conclusions: </strong>In MASLD patients aged <60 years, high serum β-cryptoxanthin concentrations were inversely associated with CVD mortality.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181383","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":"A novel approach to evaluate the therapeutic efficacy of durvalumab and tremelimumab combination therapy in hepatocellular carcinoma.","authors":"Tetsu Tomonari, Shigeo Shimose, Issei Saeki, Joji Tani, Yuichi Honma, Takanori Ito, Mamiko Takeuchi, Takehito Naito, Yasuto Takeuchi, Ryu Sasaki, Kyo Sasaki, Takeshi Hatanaka, Satoru Kakizaki, Yuki Kanayama, Atsushi Naganuma, Norikazu Tanabe, Hironori Tanaka, Yutaka Kawano, Yasushi Sato, Sohji Nishina, Hisamitsu Miyaaki, Motoyuki Otsuka, Hiroki Kawashima, Masaru Harada, Hideki Kobara, Taro Takami, Takumi Kawaguchi, Tetsuji Takayama","doi":"10.1111/hepr.14212","DOIUrl":"https://doi.org/10.1111/hepr.14212","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real-world clinical practice, characterize \"stable disease (SD),\" and identify SD responders (SD-R) who benefit from Dur + Tre treatment.</p><p><strong>Methods: </strong>This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u-HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first-line and 117 later-line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression-free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders.</p><p><strong>Results: </strong>Disease control rate (DCR) and PFS were significantly better in the first-line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤-10% were classified as SD-R, as they had long-term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD-R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD-R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11).</p><p><strong>Conclusions: </strong>In real-world clinical practice, Dur + Tre is highly effective as a first-line treatment for u-HCC. Additionally, patients with SD who met the SD-R criteria (PFS ≥84 days or RECIST DOR ≤-10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158308","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}