Hepatology Research最新文献

{"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","doi":"10.1111/hepr.70035","DOIUrl":"https://doi.org/10.1111/hepr.70035","url":null,"abstract":"<p><strong>Aim: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"https://doi.org/10.1111/hepr.70037","url":null,"abstract":"<p><strong>Aim: </strong>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><p><strong>Methods: </strong>A retrospective analysis was conducted on 13,045 patients who underwent HCV screening using the Elecsys HCV Duo immunoassay.</p><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"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}

{"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","doi":"10.1111/hepr.70033","DOIUrl":"https://doi.org/10.1111/hepr.70033","url":null,"abstract":"<p><strong>Aims: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Dur/Tre may be a viable treatment option for patients with Vp4 and HTB.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"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}

{"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":"https://doi.org/10.1111/hepr.70020","url":null,"abstract":"<p><strong>Aim: </strong>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><p><strong>Methods: </strong>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><p><strong>Results and conclusion: </strong>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>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"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}

{"title":"Rechallenge of Atezolizumab Plus Bevacizumab Therapy in Patients With Unresectable Hepatocellular Carcinoma.","authors":"Yuichiro Suzuki, Teiji Kuzuya, Leona Osawa, Yasuyuki Komiyama, Hitomi Takada, Shuya Matsuda, Masaru Muraoka, Mitsuaki Sato, Shinya Maekawa, Nobuyuki Enomoto, Hisanori Muto, Yoshihiko Tachi, Yoshiki Hirooka, Atsunori Tsuchiya","doi":"10.1111/hepr.70024","DOIUrl":"https://doi.org/10.1111/hepr.70024","url":null,"abstract":"<p><strong>Background: </strong>Atezolizumab plus bevacizumab (AB) is a standard first-line therapy for unresectable hepatocellular carcinoma (HCC). However, data on the efficacy and safety of AB rechallenge (re-AB) after discontinuation are limited.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 13 patients with unresectable HCC who received initial AB treatment and re-AB at the University of Yamanashi and Fujita Health University. Rechallenge was defined as reinitiating AB after prior discontinuation followed by one or more other systemic therapies. Tumor responses were assessed using RECIST v1.1 and modified RECIST (mRECIST), and adverse events (AEs) were evaluated according to CTCAE v5.0.</p><p><strong>Results: </strong>During initial AB, the objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS) were 15%, 69%, and 3.7 months, respectively. AB was discontinued due to disease progression or immune-related AEs. Re-AB was administered after a median of two intervening regimens. In the re-AB phase, ORR, DCR, and mPFS were 15%, 54%, and 4.7 months, respectively. Despite prior progression, two patients achieved partial response and five had stable disease. No worsening of previously observed AEs occurred during re-AB.</p><p><strong>Conclusions: </strong>AB rechallenge may be a safe and potentially effective treatment option for selected patients with unresectable HCC, even after discontinuation due to disease progression or adverse events.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952040","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":"Mac-2 Binding Protein Glycosylation Isomer as a Dynamic Biomarker in Obstructive Cholestasis","authors":"Takanobu Iwadare,&nbsp;Takefumi Kimura","doi":"10.1111/hepr.70029","DOIUrl":"10.1111/hepr.70029","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 10","pages":"1333-1334"},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952075","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":"MetALD Was a More Notable Independent Risk Factor for Reflux Esophagitis Than MASLD: A Multicenter Cohort Study Using Directed Acyclic Graphs.","authors":"Hiroshi Tanaka, Shuhei Fukunaga, Michita Mukasa, Tomoyuki Nakane, Tomonori Cho, Shinpei Minami, Daiki Ohzono, Tomokazu Yoshio, Yusei Watanabe, Dan Nakano, Tsubasa Tsutsumi, Shinobu Yoshinaga, Ryuichi Nouno, Hidetoshi Takedatsu, Takumi Kawaguchi","doi":"10.1111/hepr.70028","DOIUrl":"https://doi.org/10.1111/hepr.70028","url":null,"abstract":"<p><strong>Aim: </strong>Metabolic abnormalities are recognized as risk factors for reflux esophagitis. Recently, the definition of MASLD and MetALD has been proposed. However, the effect of moderate alcohol consumption on its development remains unclear. We aimed to investigate independent risk factors for reflux esophagitis, including MASLD and MetALD.</p><p><strong>Methods: </strong>The present multicenter observational cohort study enrolled 5441 consecutive health check-up examinees between 2008 and 2021. Participants were classified into the non-SLD, MASLD, or MetALD groups. Independent risk factors for reflux esophagitis were evaluated using multivariate Cox regression analysis. Directed acyclic graphs were constructed to identify direct risk factors for reflux esophagitis.</p><p><strong>Results: </strong>Age, male sex, and hiatus hernia were independent risk factors for reflux esophagitis. MASLD (HR 1.1534, 95% CI 1.0069-1.3213, p = 0.0395) and MetALD (HR 1.9026, 95% CI 1.3554-2.6707, p = 0.0002) were also identified as independent risk factors compared to non-SLD. Furthermore, the MetALD group showed a significantly higher risk than the MASLD group (HR 1.6495, 95% CI 1.1668-2.3319, p = 0.0046). The cumulative incidence in the MetALD group was significantly higher than in the MASLD group (85.1/1000 vs. 55.8/1000 person-years, p = 0.0111). Directed acyclic graphs revealed that moderate alcohol consumption was identified as a direct risk factor for reflux esophagitis.</p><p><strong>Conclusions: </strong>MASLD and MetALD were independent risk factors for reflux esophagitis. Patients with MetALD had a higher risk than patients with MASLD. Furthermore, moderate alcohol consumption was a direct risk factor for reflux esophagitis in patients with SLD. These findings highlight the importance of both MASLD and moderate alcohol consumption in the pathogenesis of reflux esophagitis.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952035","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":"Mitochondrial Oxidative Stress in Circulating Leukocytes as a Prognostic Marker in Hepatocellular Carcinoma.","authors":"Víctor Merino, Carlos Abril, Gloria Segarra, Maria Pilar Ballester, Joan Tosca, Pilar Aguilar, Pascual Medina, Paloma Lluch","doi":"10.1111/hepr.70026","DOIUrl":"https://doi.org/10.1111/hepr.70026","url":null,"abstract":"<p><strong>Background and aims: </strong>The relationship between oxidative stress (OS) and hepatocellular carcinoma (HCC) is well known, influencing both, hepatocarcinogenesis and subsequent tumor progression. Less understood is its potential role in antitumor defense mechanisms. This study examines the production of OS in circulating leukocytes in HCC patients, its anti or pro-tumoral capacity, and its potential utility as a prognostic marker.</p><p><strong>Approach and results: </strong>The intracellular production of mitochondrial superoxide, total superoxide, hydrogen peroxide (H₂O₂), and glutathione was analyzed by flow cytometry in peripheral blood samples from 36 HCC patients and 18 HCC-free cirrhotic patients. Levels of mitochondrial superoxide in neutrophils and H₂O₂ in lymphocytes and neutrophils from HCC patients were higher than in the same cell populations from HCC-free cirrhotic patients (p < 0.05). Glutathione was higher in lymphocytes, monocytes, and neutrophils from HCC patients (p < 0.05). In HCC patients, for each 1000-unit increase in mitochondrial superoxide in lymphocytes, monocytes, and neutrophils, the risk of death is reduced by 49.4%, 49.5%, and 34.8%, respectively, demonstrating its role as a protective factor. A cutoff point in each leukocyte subset allowed the estimation of survival at 6 months and 1 year. Mitochondrial superoxide also proved to be a protective factor against disease progression (HR 0.314, 95% CI 0.113-0.872).</p><p><strong>Conclusions: </strong>Circulating leukocytes in HCC patients exhibit increased OS compared to HCC-free cirrhotic patients. Specifically, the increase in mitochondrial OS in HCC patients shows a strong correlation with survival and could thus be considered a prognostic factor.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952012","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":"Prediction of Metabolic, Cardiovascular, and Liver Health With Controlled Attenuation Parameter: A Potential Screening Tool for Preventive Hepatologists.","authors":"Ajay Kumar Mishra","doi":"10.1111/hepr.70025","DOIUrl":"https://doi.org/10.1111/hepr.70025","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952024","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":"Canagliflozin Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease via Mitochondrial Protection and Enhanced Mitophagy.","authors":"Ming Lu, Yixin Zhao, Zhihong Liu, Yanrong Zhang, Jing Liu","doi":"10.1111/hepr.70021","DOIUrl":"https://doi.org/10.1111/hepr.70021","url":null,"abstract":"<p><strong>Background: </strong>Canagliflozin shows anti-inflammatory and antioxidant properties. However, whether canagliflozin can mitigate metabolic dysfunction-associated steatotic liver disease (MASLD) by modulating mitochondrial dysfunction remains to be explored.</p><p><strong>Methods: </strong>Canagliflozin was administered daily for MASLD mice at 10 mg/kg from Week 5 to Week 15. Biochemical assays were performed to assess serum triglyceride, total cholesterol, and liver damage markers. RT-qPCR was used to quantify the genes' expression involved in lipid synthesis and metabolism, whereas oil red O staining was utilized to visualize hepatic lipid accumulation. Western blot analysis was conducted to evaluate the expression of key proteins involved in mitochondrial damage and mitophagy.</p><p><strong>Results: </strong>Canagliflozin treatment reduced liver hypertrophy, as shown by a lower liver weight/body weight ratio, and alleviated hepatic lipid accumulation with decreased triglyceride and total cholesterol levels. It improved the serum lipid profile by lowering low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol through inhibiting lipid metabolism genes, including Srebf1, Fasn, and Cd36. Canagliflozin also reduced oxidative stress, as shown by lower malondialdehyde levels, and restored superoxide dismutase and catalase activity. Mitochondrial function was improved with increased ATP production and mitochondrial DNA content. Additionally, canagliflozin activated Parkin/PINK1-mediated mitophagy, as evidenced by upregulation of key mitophagy-related proteins such as PINK1, Parkin, and Atg7, as well as enhanced colocalization of LC3 and TOM20.</p><p><strong>Conclusion: </strong>Our results demonstrate that canagliflozin may effectively treat MASLD by reducing liver fat and oxidative stress and improving mitochondrial function. It could be a promising treatment option for MASLD, particularly in diabetic patients.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952051","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}