Hepatology Research最新文献

{"title":"Trajectories of hepatic steatosis and incidence of cardiovascular disease over a 29-year follow-up.","authors":"Ming-Whei Yu, Wan-Jung Wu, Chih-Lin Lin, Chun-Jen Liu, Wei-Ya Peng, Pin-Yu Huang, Yi-Wen Huang, Jui-Ting Hu, Hung-Chuen Chang, Jyh-Ming Liou","doi":"10.1111/hepr.14101","DOIUrl":"https://doi.org/10.1111/hepr.14101","url":null,"abstract":"<p><strong>Aim: </strong>To examine the dynamic change in hepatic steatosis status during repeated assessments over time, and its potential impact on the risk of developing cardiovascular disease (CVD).</p><p><strong>Methods: </strong>We assessed trajectories of hepatic steatosis and other metabolic disorders in 3134 middle-aged adults undergoing longitudinal assessment of ultrasonography during a pre-baseline period (1993-2009) in a population-based cohort study of liver health. Subsequently, we determined the association of hepatic steatosis trajectories with the incidence of CVD among 2185 CVD-free individuals, followed until 2021. Metabolic risk factors and cardiovascular events (including coronary heart disease and stroke) were determined through medical examination and linkage with nationwide health databases.</p><p><strong>Results: </strong>We identified three discrete trajectories of hepatic steatosis according to changing pattern over time through group-based trajectory modeling: \"stable, non-steatosis\" (n = 1298), \"intermittent\" (n = 921), and \"persistent steatosis\" (n = 915). During the pre-baseline period, hepatic steatosis trajectories were associated with trajectories of developing diabetes and hypertension, and persistent steatosis (vs. other trajectories) was associated with higher risks and rapidly progressive disease patterns. At a median 13.6 years of follow-up, 629 CVD events occurred. A persistent (vs. non-steatosis: HR 1.44, 95% CI 1.17-1.76), but not intermittent, steatosis pattern predicted the future risk of CVD, after adjustment for age, sex, smoking, and obesity. This association was independent of genetic background, and remained after accounting for pre-baseline body-mass index, other cardiometabolic risk factors, Framingham risk score, medications, and hepatic fibrosis score.</p><p><strong>Conclusions: </strong>The persistence of hepatic steatosis is associated with trajectories of metabolic disorder development and increased risk of CVD. These data have important implications for practice and further research.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999773","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":"Significance of changes in tumor markers in patients treated with durvalumab plus tremelimumab combination therapy as a surrogate marker for tumor response to unresectable hepatocellular carcinoma.","authors":"Shinsuke Uchikawa, Tomokazu Kawaoka, Serami Murakami, Ryoichi Miura, Yuki Shirane, Yusuke Johira, Masanari Kosaka, Yasutoshi Fujii, Hatsue Fujino, Atsushi Ono, Eisuke Murakami, Daiki Miki, C Nelson Hayes, Masataka Tsuge, Shiro Oka","doi":"10.1111/hepr.14104","DOIUrl":"https://doi.org/10.1111/hepr.14104","url":null,"abstract":"<p><strong>Aim: </strong>When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response.</p><p><strong>Methods: </strong>Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur + Tre) were enrolled. Their functional reserve was Child-Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8 weeks after the start of treatment. The first radiological evaluation was carried out at 4 weeks and the second evaluation at 8-12 weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors.</p><p><strong>Results: </strong>In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8 weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4 weeks. The optimal cut-off value to divide responders and nonresponders at 4 weeks was approximately -40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4 weeks.</p><p><strong>Conclusions: </strong>The change in tumor markers is a more useful predicter of tumor response to Dur + Tre than imaging evaluation alone.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995654","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":"Genetic alteration of SLCO1B3 defines constitutional indocyanine green excretory defect in patients who underwent hepatectomy.","authors":"Meguri Tanimoto, Yujiro Nishioka, Yoshinori Inagaki, Takashi Kokudo, Takeaki Ishizawa, Junichi Arita, Nobuhisa Akamatsu, Junichi Kaneko, Kiyoshi Hasegawa","doi":"10.1111/hepr.14099","DOIUrl":"https://doi.org/10.1111/hepr.14099","url":null,"abstract":"<p><strong>Aim: </strong>Constitutional indocyanine green (ICG) excretory defects must be distinguished when assessing liver function. The absence of OATP1B3 expression due to homogenous alterations in the SLCO1B3 gene has been recently reported to induce ICG excretory defects; however, its association with the clinical examinations and the clinical implications of heterogeneous SLCO1B3 gene alteration remain unclear.</p><p><strong>Methods: </strong>OATP1B3 expression was evaluated in 49 patients who underwent hepatectomy after evaluation of the ICG retention rate at 15 min (ICGR15) and technetium-99 m-galactosyl serum albumin (99mTc-GSA) hepatic scintigraphy. Additionally, alterations in SLCO1B3 were analyzed in patients without OATP1B3 expression. Subsequently, 59 patients who underwent hepatectomy for colorectal liver metastasis (CRLM) were analyzed.</p><p><strong>Results: </strong>Of 49 patients, 6 (12%) had absent OATP1B3 expression. They had significantly higher ICGR15 value (74.7% vs. 23.5%; p < 0.0001), better modified albumin-bilirubin (ALBI) grade (≤grade 2A, 100% vs. 42%; p = 0.010), more normal 99mTc-GSA hepatic scintigraphy (100% vs. 28%; p = 0.0003), and better pathological liver fibrosis (F0-1, 100% vs. 49%; p = 0.027) compared to those with OATP1B3 expression. Three available frozen blocks of cases without OATP1B3 expression showed homozygous alterations in SLCO1B3. Of 59 patients with CRLM in normal liver background, five (8.5%) had heterozygous insertion in SLCO1B3, however they had no difference in ICGR15 values or other clinical findings compared to the other patients.</p><p><strong>Conclusions: </strong>Constitutional ICG excretory defects may be defined by the complete absence of OATP1B3 expression. The modified ALBI grade and 99mTc-GSA hepatic scintigraphy were useful for detecting constitutional ICG excretory defects.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971004","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":"What can we create by adding robotic assistance to conventional laparoscopic liver resection?","authors":"Zenichi Morise","doi":"10.1111/hepr.14103","DOIUrl":"10.1111/hepr.14103","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971007","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":"Reply to Letter to the Editor: Regarding the \"Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy\".","authors":"Ritsuzo Kozuka, Masaru Enomoto","doi":"10.1111/hepr.14105","DOIUrl":"https://doi.org/10.1111/hepr.14105","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971006","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":"Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis.","authors":"Yuki Imaoka, Masahiro Ohira, Kouki Imaoka, Tomoaki Bekki, Ryosuke Nakano, Takuya Yano, Yuka Tanaka, Toshihiro Nakayama, Miho Akabane, Tetsuya Tajima, Shinichiro Yokota, Sheri M Krams, Olivia M Martinez, Carlos O Esquivel, Kazunari Sasaki, Hideki Ohdan","doi":"10.1111/hepr.14102","DOIUrl":"https://doi.org/10.1111/hepr.14102","url":null,"abstract":"<p><strong>Aim: </strong>Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway.</p><p><strong>Methods: </strong>Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl₄)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity.</p><p><strong>Results: </strong>The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence.</p><p><strong>Conclusion: </strong>Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971005","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":"Metabolic dysfunction-associated steatotic liver disease (SLD) and alcohol-associated liver disease, but not SLD without metabolic dysfunction, are independently associated with new onset of chronic kidney disease during a 10-year follow-up period.","authors":"Kazuma Mori, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Keisuke Endo, Toshifumi Ogawa, Toru Suzuki, Hiroki Aida, Wataru Kawaharata, Kei Nakata, Itaru Hosaka, Araya Umetsu, Nagisa Hanawa, Masato Furuhashi","doi":"10.1111/hepr.14097","DOIUrl":"https://doi.org/10.1111/hepr.14097","url":null,"abstract":"<p><strong>Aims: </strong>The new nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD).</p><p><strong>Methods: </strong>We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or positive for urinary protein, during a 10-year period in 12 138 Japanese subjects (men / women, 7984/4154; mean age, 48 years) who received annual health examinations including abdominal ultrasonography.</p><p><strong>Results: </strong>The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men / women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p = 0.001) and those with ALD (1.41 [1.05-1.88], p = 0.022), but not those with MetALD (1.11 [0.90-1.36], p = 0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p = 0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity.</p><p><strong>Conclusions: </strong>MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901574","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":"High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma.","authors":"Miyako Murakawa, Mina Nakagawa, Hisaaki Nishimura, Shun Kaneko, Masato Miyoshi, Fukiko Kawai-Kitahata, Sayuri Nitta, Jun Tsuchiya, Taro Shimizu, Keiya Watakabe, Tomohiro Mochida, Kento Inada, Yasuhiro Iizuka, Hideki Sakai, Yuki Sakurai, Ayako Sato, Seishin Azuma, Takahiro Kawamura, Chiaki Maeyashiki, Masayuki Kurosaki, Fumihiko Kusano, Hideki Watanabe, Hitoshi Kurata, Yuko Karakama, Takeo Fujiwara, Yuki Nagata, Toshihiro Tanaka, Sei Kakinuma, Ryuichi Okamoto, Yasuhiro Asahina","doi":"10.1111/hepr.14094","DOIUrl":"https://doi.org/10.1111/hepr.14094","url":null,"abstract":"<p><strong>Aim: </strong>Gamma-glutamyltransferase (GGT) is known as an oxidative stress marker, induced by alcohol consumption and metabolic disorders, and is reported as a predictor of hepatocellular carcinoma (HCC) development after hepatitis C virus (HCV) elimination. However, it is not clear whether GGT serves simply as a surrogate marker for overlapping metabolic diseases or reflects HCV-specific carcinogenicity. We investigated the association between GGT and hepatocarcinogenesis after achieving a sustained viral response (SVR), accounting for drinking habits or diabetes, and examined predisposing factors associated with GGT levels after SVR.</p><p><strong>Methods: </strong>This is a prospective, multicenter, and observational study using the database of 1001 patients after HCV eradication with direct-acting antiviral agents. The association of GGT at SVR with cumulative HCC development was examined in a multivariate analysis using Cox proportional hazard models after adjustment for covariates including alcohol and diabetes. The association between oxidative stress markers or genetic factors and GGT levels was analyzed.</p><p><strong>Results: </strong>High GGT levels at SVR were associated with HCC development (HR] 2.38, 95% CI 1.10-5.17). This association was also significant when restricted to patients without alcohol consumption or diabetes (HR 8.38, 95% CI 2.87-24.47). GGT levels were correlated with serum growth differentiation factor 15 levels, a marker of mitochondrial dysfunction. Single-nucleotide polymorphisms of ZNF827 and GDF15 were associated with high GGT levels.</p><p><strong>Conclusions: </strong>High GGT levels at SVR were associated with HCC development after accounting for alcohol consumption and diabetes. GGT levels are influenced by genetic predisposition and may reflect mitochondrial dysfunction after HCV eradication.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787909","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":"Improved survival outcome of curative liver resection for Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma in the era of tyrosine kinase inhibitors.","authors":"Yoh Asahi, Tatsuhiko Kakisaka, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Takeshi Aiyama, Yuzuru Sakamoto, Kazuki Wakizaka, Shunsuke Shichi, Hirofumi Kamachi, Akinobu Taketomi","doi":"10.1111/hepr.14098","DOIUrl":"https://doi.org/10.1111/hepr.14098","url":null,"abstract":"<p><strong>Aim: </strong>This study was undertaken to evaluate the outcome of curative liver resection, (LR) of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC) after tyrosine kinase inhibitors (TKIs) became approved as a treatment option for recurrent lesions.</p><p><strong>Methods: </strong>Sixty-seven patients with BCLC-C HCC who underwent curative LR were enrolled in this study. The patients were classified into two groups according to whether LR was performed before (n = 24) or after (n = 43) TKI approval (\"beforeTKI\" and \"afterTKI\" group, respectively).</p><p><strong>Results: </strong>There was no difference in the median disease-free survival time after LR between the beforeTKI and afterTKI groups (5.6 and 7.1 months, respectively; p = 0.435). However, the median survival time after LR was longer in the afterTKI than beforeTKI group (42.7 and 14.9 months, respectively; p = 0.022). Univariate and multivariate analyses showed that the date of LR was the only independent factor affecting postresection survival. When the patients were limited to those with recurrence, there were no differences in the recurrence pattern or progression of HCC at the time of recurrence between the two groups. The only difference in the treatment distribution was the administration of TKIs (14 of 34 patients in afterTKI group and only 1 of 19 patients in beforeTKI group, p < 0.001).</p><p><strong>Conclusion: </strong>These data suggest that TKI therapy for recurrent BCLC-C HCC is associated with improved overall survival. Thus, LR could be a promising option for BCLC-C HCC in the current era of TKI therapy.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765927","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":"Molecular biological role of epithelial splicing regulatory protein 1 in intrahepatic cholangiocarcinoma.","authors":"Takahiro Haruna, Mitsuhiro Kudo, Kousuke Ishino, Junji Ueda, Yukako Shintani-Domoto, Daigo Yoshimori, Takenori Fuji, Yoko Kawamoto, Kiyoshi Teduka, Taeko Kitamura, Hiroshi Yoshida, Ryuji Ohashi","doi":"10.1111/hepr.14096","DOIUrl":"https://doi.org/10.1111/hepr.14096","url":null,"abstract":"<p><strong>Aim: </strong>Epithelial splicing regulatory protein 1 (ESRP1) regulates tumor progression and metastasis through the epithelial‒mesenchymal transition by interacting with zinc finger E-box binding 1 (ZEB1) and CD44 in cancers. However, the role of ESRP1 in intrahepatic cholangiocarcinoma (iCCA) remains unclear.</p><p><strong>Methods: </strong>Three iCCA cell lines (HuCCT-1, SSP-25, and KKU-100) were analyzed using small interfering RNA to investigate the molecular biological functions of ESRP1 and ZEB1. The association between clinicopathological features and the expression of ESRP1 and ZEB1 in iCCA tissues was analyzed immunohistochemically. Proteomic analysis was performed to identify molecules related to ESRP1 expression.</p><p><strong>Results: </strong>ESRP1 expression was upregulated in HuCCT-1 and SSP-25 cells. Cell migration and invasion were enhanced, and the expression of ZEB1 and CD44s (CD44 standard) isoforms were upregulated in the ESRP1 silencing cells. Moreover, ESRP1 silencing increased the expression of N-cadherin and vimentin, indicating the presence of mesenchymal properties. Conversely, ZEB1 silencing increased the expression of ESRP1 and CD44v (CD44 variant) isoforms. Immunohistochemical analysis revealed that a lower ESRP1-to-ZEB1 expression ratio was associated with poor recurrence-free survival in patients with iCCA. Flotillin 2, a lipid raft marker related to epithelial‒mesenchymal transition, was identified as a protein related to the interactive feedback loop in proteomic analysis.</p><p><strong>Conclusions: </strong>ESRP1 suppresses tumor progression in iCCA by interacting with ZEB1 and CD44 to regulate epithelial‒mesenchymal transition.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734009","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}