{"title":"Mechanistic Basis and Translational Potential of Traditional Chinese Medicine in the Treatment of Cholestasis: A Narrative Review.","authors":"Shuai Yuan, Shuang Zhou","doi":"10.2147/HMER.S609530","DOIUrl":"10.2147/HMER.S609530","url":null,"abstract":"<p><strong>Background: </strong>Cholestasis results from impaired bile formation, secretion, or flow and contributes to heterogeneous hepatobiliary disorders, including primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cholestatic drug-induced liver injury, and cholestasis-associated fibrosis. Persistent bile acid retention drives hepatocyte and cholangiocyte injury, immune activation, gut-liver axis disruption, and fibrogenesis. Traditional Chinese medicine (TCM) has been investigated as a multi-component therapeutic approach, but its evidence strength and translational readiness remain uncertain.</p><p><strong>Objective: </strong>To synthesize mechanistic, clinical, and translational evidence on TCM-based interventions for cholestasis and identify evidence gaps relevant to future development.</p><p><strong>Methods: </strong>PubMed, Web of Science Core Collection, CNKI, Wanfang, VIP, and SinoMed were searched for publications from 1 January 2016 to 25 January 2026, supplemented by backward citation chasing. A sensitivity search of CNKI, Wanfang, VIP, and SinoMed was performed to reduce language bias. Eligible studies were mapped by cholestatic condition or model, intervention type, study design, mechanistic domain, clinical relevance, and evidence strength.</p><p><strong>Results: </strong>Eighty studies were included in the core evidence set. The evidence base was dominated by preclinical animal, in vitro, omics, pharmacokinetic, quality-control, and toxicology studies, with limited mature clinical evidence. Recurrent mechanisms involved FXR-centered bile acid homeostasis, transporter regulation, inflammatory and immune pathways, oxidative stress and regulated cell death, fibrogenic signaling, and gut-liver axis modulation. Clinical evidence was most developed for intrahepatic cholestasis of pregnancy, where adjunctive TCM plus ursodeoxycholic acid was associated with improvements in bile acids and pruritus. However, heterogeneity in formula composition, trial quality, endpoint selection, and safety reporting limits inference, particularly for maternal-fetal outcomes. Evidence for other cholestatic indications remains limited or largely preclinical.</p><p><strong>Conclusion: </strong>TCM provides pathway-linked therapeutic hypotheses and candidate compounds for cholestasis, but high-confidence translation requires standardized products, exposure-response characterization, causal target validation, robust safety and herb-drug interaction assessment, and adequately powered disease-specific trials using clinically meaningful endpoints.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"18 ","pages":"609530"},"PeriodicalIF":2.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Relevance and Utility of Serum APOC2 Levels in Patients with Type 2 Diabetes Mellitus: A Comparative Study on Subjects with and without Pyogenic Liver Abscess.","authors":"Ying Huang, Xiaoqin Chen, Hongyan Guo, Yuhai Hu, Tianbin Chen","doi":"10.2147/HMER.S580195","DOIUrl":"10.2147/HMER.S580195","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the diagnostic value of serum APOC2 in patients with diabetes mellitus combined with pyogenic liver abscess.</p><p><strong>Methods: </strong>From April 2023 to July 2023, 77 type 2 diabetes mellitus patients were included which divided into two groups: diabetes mellitus (n=55) and diabetes mellitus combined with pyogenic liver abscess (n=22). Additionally, 27 healthy individuals served as the control group. Serum APOC2 levels were detected and compared among the groups. ROC curve and logistic regression analysis were performed to evaluate the diagnostic value of serum APOC2.</p><p><strong>Results: </strong>Serum APOC2 levels were significantly higher in diabetes mellitus patients compared to the healthy control group (<i>P</i>=0.008). In diabetes mellitus combined with pyogenic liver abscess patients, APOC2 levels were significantly reduced (<i>P</i><0.001) while increased post-treatment (<i>P</i><0.001). ROC curve analysis showed high diagnostic accuracy for serum APOC2 in diabetes mellitus combined with pyogenic liver abscess (AUC=0.945). Logistic regression analysis revealed that reduced serum APOC2 levels were a risk factor for diabetes mellitus combined with pyogenic liver abscess (OR=0.02, 95% CI=0.01~0.16, <i>P</i>=0.012). The diabetes mellitus combined with pyogenic liver abscess patients with lower APOC2 levels had higher ALT (<i>P</i>=0.038) and AST levels (<i>P</i>=0.007), suggesting that reduced serum APOC2 levels were associated with liver damage.</p><p><strong>Conclusion: </strong>Serum APOC2 levels are significantly decreased in patients with diabetes mellitus combined with pyogenic liver abscess, serving as a potential marker for predicting the occurrence of this condition. Lower levels of APOC2 are strongly linked to liver function impairment.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"18 ","pages":"580195"},"PeriodicalIF":2.5,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Zaozhu Yinchen Decoction on a Rat Model of Nonalcoholic Steatohepatitis via Regulation of Myeloid-Derived Suppressor Cells.","authors":"Wenyang Zhang, Yujie Wang, Yaoyu Liu, Xiaoting Zheng, Tianxiang Wang, Xinyi Kwan, Ruobing Liu, Qi Liu, Hongli Zhuang, Huiqing Liang, Shaodong Chen","doi":"10.2147/HMER.S605761","DOIUrl":"10.2147/HMER.S605761","url":null,"abstract":"<p><strong>Objective: </strong>To observe the therapeutic effect of Zaozhu Yinchen Decoction (ZZYC) on rats with non-alcoholic steatohepatitis (NASH) and explore its mechanism of action related to myeloid-derived suppressor cells (MDSCs).</p><p><strong>Methods: </strong>A NASH rat model was established by feeding a high-fat diet for 16 weeks, and drug intervention was initiated from the 9th week of modeling, lasting for 8 weeks. The general status of rats was observed. Biochemical methods were used to detect the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as the triglyceride (TG) content in liver tissue. Hematoxylin-eosin (HE) staining and Oil Red O staining were performed to observe the pathological changes of liver tissue. Flow cytometry was used to detect the expression level of MDSCs in peripheral blood. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the protein expression levels of arginase 1 (ARG-1) and the pro-inflammatory factor S100 calcium-binding protein A9 (S100A9) in liver tissue.</p><p><strong>Results: </strong>Compared with the normal group, rats in the model group exhibited typical histological features of NASH. After treatment with ZZYC decoction, hepatocellular steatosis and inflammatory infiltration were significantly alleviated. Compared with the normal group, the model group showed a significant increase in liver weight, serum ALT and AST activities, liver TG and free fatty acid (FFA) content, peripheral blood MDSC level, and the expression of ARG-1 and S100A9 in liver tissue (all P<0.01). These indicators were significantly reduced after ZZYC decoction treatment (all P<0.05).</p><p><strong>Conclusion: </strong>ZZYC decoction exerts a significant pharmacological effect on improving hepatocellular steatosis, ballooning degeneration, and inflammation in NASH rats. Meanwhile, it can markedly reduce the level of peripheral blood MDSCs and the expression of ARG-1 and S100A9 in liver tissue. These findings suggest that the therapeutic mechanism of ZZYC decoction for NASH is closely associated with the regulation of MDSCs.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"18 ","pages":"605761"},"PeriodicalIF":2.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"2 Cases of Large Cystic-Solid Perivascular Epithelioid Cell Tumor: Case Report and Literature Review.","authors":"Tian-Tian Dong, Xue-Liang Yan, Fang Nie","doi":"10.2147/HMER.S471745","DOIUrl":"10.2147/HMER.S471745","url":null,"abstract":"<p><p>Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that tend to occur in multiple organs and the biological behavior of it between benign and malignant. They are even less common in the liver and there is still no effective treatment method established. In particular, how to deal with it when the imaging manifestations of the lesion are predominantly giant cystic are a question that we need to investigate. We present PEComas in two female patients with large cystic-solid lesions on ultrasound with clinical signs of nonspecific pain and a large mass in the right upper quadrant. Both patients underwent contrast-enhanced ultrasound (CEUS) and interventional ultrasound to assist in diagnosis and treatment. Depending on the patient's condition, we take a different approach to treatment. To our knowledge, such reports have never been documented before.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"18 ","pages":"471745"},"PeriodicalIF":2.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Zhou, Baoyi Sun, Zongyuan Xuan, Guanning Zhong, Xiaolei Sun, Jun Yan
{"title":"Literature Review on the Regulatory Effects of Hydrogen Sulfide in Non-Alcoholic Fatty Liver Disease (NAFLD).","authors":"Shan Zhou, Baoyi Sun, Zongyuan Xuan, Guanning Zhong, Xiaolei Sun, Jun Yan","doi":"10.2147/HMER.S574921","DOIUrl":"10.2147/HMER.S574921","url":null,"abstract":"<p><strong>Introduction: </strong>This paper reviews the regulatory effects of hydrogen sulfide (H<sub>2</sub>S) in non-alcoholic fatty liver disease (NAFLD). The research background indicates that NAFLD has become one of the most common chronic liver diseases worldwide, with a complex pathogenesis involving insulin resistance and lipid metabolism disorders. Hydrogen sulfide, as an important gaseous signaling molecule, exerts protective effects in NAFLD through multiple pathways, including antioxidant, anti-inflammatory, lipid metabolism regulation, apoptosis inhibition, and insulin resistance improvement. This article provides a detailed summary of the research overview of NAFLD, the biological characteristics of hydrogen sulfide, its mechanisms of action in NAFLD, empirical studies, and evaluates and prospects current research, aiming to provide a new theoretical basis and experimental support for the treatment of NAFLD.</p><p><strong>Purpose: </strong>This literature review aims to systematically synthesize the regulatory roles of hydrogen sulfide (H<sub>2</sub>S) in non-alcoholic fatty liver disease (NAFLD). It provides a comprehensive overview of NAFLD research, the biological characteristics of H<sub>2</sub>S, the mechanisms underlying H<sub>2</sub>S's action in NAFLD, and relevant empirical studies. Additionally, the review evaluates the current state of research and prospects future directions, with the goal of offering novel theoretical foundations and experimental support for NAFLD treatment.</p><p><strong>Patients and methods: </strong>It adopts a comprehensive literature analysis approach. Analyze literature on NAFLD pathogenesis, H<sub>2</sub>S (synthesis/function), and NAFLD treatments (in vitro, animal models, clinical studies).</p><p><strong>Results: </strong>NAFLD links to insulin resistance/inflammation; H<sub>2</sub>S protects against NAFLD by mitigating inflammation, oxidative stress, and lipid accumulation, while improving insulin sensitivity and inhibiting apoptosis. However, its precise mechanisms, stage-specific effects, and therapeutic safety require further clinical validation.</p><p><strong>Conclusion: </strong>Hydrogen sulfide (H<sub>2</sub>S), a gaseous signal, exerts multi-mechanistic protective effects in NAFLD. Current limitations include unclear signaling mechanisms and lack of targeted delivery systems. Future research should focus on stage-specific mechanisms, optimized H<sub>2</sub>S donors, and combination therapies for NAFLD treatment.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"209-218"},"PeriodicalIF":1.8,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noa Tuyikurikire, Emmanuel Tuyizere, Janvier Imanishimwe, Aime Ahishakiye, Happy Jean Bosco Asifiwe, Emmanuel Rubayiza, James Gafirita, Herbert T Mapira, Augustin Nzitakera, Araya G Wasihun, Cuthbert Musarurwa
{"title":"The Prevalence of Liver Enzyme Abnormalities Among Adult Patients with Non-Communicable Diseases in Rwanda: A Gender-Stratified Analysis.","authors":"Noa Tuyikurikire, Emmanuel Tuyizere, Janvier Imanishimwe, Aime Ahishakiye, Happy Jean Bosco Asifiwe, Emmanuel Rubayiza, James Gafirita, Herbert T Mapira, Augustin Nzitakera, Araya G Wasihun, Cuthbert Musarurwa","doi":"10.2147/HMER.S560761","DOIUrl":"10.2147/HMER.S560761","url":null,"abstract":"<p><strong>Background: </strong>Liver enzyme abnormalities are early indicators of hepatic dysfunction and are increasingly observed in individuals with non-communicable diseases (NCDs). Globally, liver diseases cause approximately 2 million deaths every year (≈4% of all deaths). In Rwanda, data on liver health and its gender-based stratification among adults with NCDs are scarce. This study assessed the prevalence and gender-specific patterns of liver enzyme abnormalities in this population to inform targeted interventions.</p><p><strong>Methods: </strong>A descriptive cross-sectional study was conducted at the NCD outpatient clinic of the University Teaching Hospital of Butare (CHUB), involving 185 adult patients with documented NCDs. A structured and pretested questionnaire was used to collect sociodemographic, behavioral, and clinical data. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were measured using the HumaLyzer 3500 semi-automated analyzer. Gender-stratified analyses were performed to assess prevalence and clustering of liver enzyme abnormalities.</p><p><strong>Results: </strong>Out of the 185 participants, liver enzyme abnormalities were observed in 51 (27.6%), with isolated GGT elevation being the most common pattern (18, 9.7%). Females exhibited significantly higher De Ritis ratios with median = 1.04, interquartile range (IQR) = 0.83-1.4, <i>p</i> = 0.019. Females showed relatively elevated GGT levels, possibly linked to non-alcoholic fatty liver disease or environmental exposures.</p><p><strong>Conclusion: </strong>Liver enzyme abnormalities are prevalent among older Rwandan adults with NCDs, with gender and occupational disparities. These findings underscore the need to integrate liver health into NCD care strategies in Rwanda.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"199-208"},"PeriodicalIF":1.8,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12691622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jia-Wei Huang, Ng Xin Man, Hong-Xin Wang, Xiang-Ting Ai, Dan-Lei Wei, Yun-Kai Dai
{"title":"Mapping the Intellectual Landscape: A 20-Year Bibliometric Analysis of Mechanisms in Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Jia-Wei Huang, Ng Xin Man, Hong-Xin Wang, Xiang-Ting Ai, Dan-Lei Wei, Yun-Kai Dai","doi":"10.2147/HMER.S562237","DOIUrl":"10.2147/HMER.S562237","url":null,"abstract":"<p><strong>Background and purpose: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD), affecting between 20% and 30% of adults around the world, represents a growing public health burden characterized by hepatic steatosis concurrent with cardiometabolic risk factors. Despite two decades of research into its pathophysiology - spanning insulin resistance, gut-liver axis dysregulation, and genetic/epigenetic mechanisms - the vast body of literature has not yet been systematically mapped. A comprehensive bibliometric analysis mapping the field's evolution, collaborative networks, and knowledge gaps remains lacking. Therefore, a 20-year bibliometric analysis (2005-2024) on the mechanism of MASLD was conducted.</p><p><strong>Patients and methods: </strong>Publications on the mechanisms of MASLD were retrieved from the Web of Science Core Collection. The search period spanned from January 1st, 2005 to December 31st, 2024. Data were analyzed with CiteSpace (v6.3.R1) and VOSviewer (v1.6.20) to assess publication trends, country/institution contributions, journal influence, author networks, keyword clusters, and reference co-citations.</p><p><strong>Results: </strong>China (40.75% of publications, n=4368) and the USA (21.18%, n=2270) dominate research output, with the Chinese Ministry of Education, Shanghai Jiao Tong University, and Harvard University as top institutions. International collaboration is prominent, particularly between China and the USA. International Journal of Molecular Sciences, Nutrients, and high-impact journals (Journal of Hepatology, IF=33.0) are key publication venues. Keyword analysis identifies five major research clusters: (1) lipid metabolism/mitochondrial dysfunction, (2) dietary factors/exercise, (3) inflammation/fibrosis, (4) metabolic comorbidities, and (5) gut-liver axis dysregulation. Temporal trends reveal a shift from insulin resistance/oxidative stress toward microbiota and molecular drivers (eg, WDR6-PPP1CB). Influential authors include Nobili Valerio (most productive) and Gerald I. Shulman (most cited; n=7703). Reference bursts highlight seminal works on disease burden (Younossi 2016) and pathogenesis (Powell 2021, Friedman 2018).</p><p><strong>Conclusion: </strong>This first comprehensive bibliometric analysis of MASLD mechanisms highlights dynamic growth, interdisciplinary collaboration, and evolving research hotspot. Persistent challenges include mechanistic heterogeneity, early diagnostic tools, and targeted therapies. In conclusion, this analysis provides a foundational roadmap for researchers and policymakers, highlighting the imperative to translate mechanistic insights into precision diagnostics and therapies to mitigate the growing global burden of MASLD.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"177-198"},"PeriodicalIF":1.8,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph Sushil Rao, Parthasarathy Rangarajan, Anala Shetty, Magie Steinhoff, Anna Tran, Andrew T Crane, Walter C Low, Clifford J Steer, Sabarinathan Ramachandran
{"title":"Ischemia Reperfusion Injury Induced Systemic Inflammatory Response Following Interspecies Liver Transplantation.","authors":"Joseph Sushil Rao, Parthasarathy Rangarajan, Anala Shetty, Magie Steinhoff, Anna Tran, Andrew T Crane, Walter C Low, Clifford J Steer, Sabarinathan Ramachandran","doi":"10.2147/HMER.S533805","DOIUrl":"10.2147/HMER.S533805","url":null,"abstract":"<p><strong>Introduction: </strong>Xenotransplantation has advanced through porcine genetic modifications to enhance graft survival and immunological compatibility. More recently, generating of exogenic organs from recipient-derived stem cells via blastocyst complementation has emerged as a promising strategy to achieve graft-specific tolerance and reduce dependence on long-term immunosuppression. However, ischemia-reperfusion-injury (IRI) during organ donation and transplantation activates inflammatory and innate immune pathways that compromise graft function and survival. To better understand the immunological response following interspecies transplantation, we compared xeno-adaptive and acute inflammatory responses between mouse-to-rat heterotopic liver transplants and rat allotransplants. This model will serve as baseline parameters for future studies of anti-inflammatory mechanisms to mitigate IRI, especially while testing exogenic livers.</p><p><strong>Methods: </strong>Livers from retired breeder male C57BL/6 mice were heterotopically transplanted into retired breeder male Lewis rats. After 90 minutes of reperfusion, transplanted liver, recipient blood and spleen were recovered for immune and inflammatory analyses. As a control to xenografts, Sprague Dawley donor livers were transplanted into Lewis recipients to represent a clinically relevant allotransplant model. Plasma cytokine and chemokine levels were quantified, and mixed leukocyte reactions (MLR) were performed to assess CD4<sup>+</sup> and CD8<sup>+</sup> T cell proliferation.</p><p><strong>Results: </strong>Xenografts exhibited elevated plasma levels of IL-2 (p = 0.04), IL-10 (p < 0.01), IL-13 (p = 0.01), IL-17A (p < 0.01) TNF-a (p < 0.05), and RANTES (p < 0.05) compared with naïve controls. Although xenografts demonstrated higher levels after transplant, they were not statistically distinct to allotransplant results. MLR assays revealed significantly increased CD8<sup>+</sup> T cell proliferation (p = 0.01) when rat splenocytes were stimulated with mouse non-parenchymal liver cells, whereas CD4<sup>+</sup> T cell proliferation was not significant in either model.</p><p><strong>Discussion: </strong>Although xenograft induced heightened inflammatory and adaptive responses, these were comparable to allotransplants. For successful exogenic organ transplantation without maintenance immunosuppression, future strategies must focus on mitigating reperfusion-induced systemic inflammation to improve graft tolerance and survival.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"161-176"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aldose Reductase Mediated Mitophagy Promotes Epithelial-Mesenchymal Transition of Hepatocytes.","authors":"Jingjing Yan, Wenke Zhao, Haoyu Wang, Lutan Zhou, Xianwei Li, Guannan Wang","doi":"10.2147/HMER.S546357","DOIUrl":"10.2147/HMER.S546357","url":null,"abstract":"<p><strong>Background: </strong>Recent studies suggest that impaired mitophagy leading to epithelial-mesenchymal transition (EMT) in hepatocytes plays a major role in the progression of hepatic fibrosis (HF). The authors' previous study demonstrated that aldose reductase (AR) promotes radiation-induced EMT in alveolar epithelial cells. This study aims to examine whether AR influences EMT in hepatocytes by regulating defective mitophagy.</p><p><strong>Methods: </strong>Some histological techniques, including HE staining, Masson's trichrome staining, immunohistochemistry, and transmission electron microscopy, were employed to validate the model and examine mitochondrial injury. Subsequently, EMT was induced in hepatocytes through TGF-β1 treatment. Then experiments such as siRNA-mediated gene silencing, AR inhibition, and AR overexpression were performed. Finally, the activation status of AKT and mTOR, as well as the expression levels of proteins associated with mitophagy and EMT, were evaluated using RT-qPCR, immunofluorescence staining, and Western blotting.</p><p><strong>Results: </strong>AR knockout significantly reduced AKT and mTOR phosphorylation In vivo but increased the expression of Pink1 and Parkin in CCl<sub>4</sub>-exposed liver tissues. This was associated with an increased LC3 II/I expression ratio, decreased p62 expression, reduced mitochondrial damage, enhanced E-cadherin expression, and diminished Snail, α-SMA, and vimentin expression, which collectively alleviated HF. In vitro experiments revealed that AR knockdown significantly attenuated the activation of the TGF-β1-induced AKT/mTOR pathway, restored mitochondrial autophagy function, decreased ROS levels, increased mitochondrial membrane potential (MMP) and ATP production, and reversed EMT in hepatocytes via siRNA or pharmacological inhibition. Conversely, AR overexpression exacerbated the activation of the TGF-β1-induced AKT/mTOR pathway, impaired mitophagy efficiency, increased ROS levels, decreased MMP and ATP levels, and facilitated EMT process.</p><p><strong>Conclusion: </strong>The study findings demonstrated that AR facilitates EMT in hepatocytes and plays a major role in enhancing HF. This process may be linked to AR-induced activation of the AKT/mTOR. Consequently, this activation suppresses the expression of Pink1 and Parkin, ultimately reducing the risk of mitophagy in hepatocytes.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"141-159"},"PeriodicalIF":1.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daudi J Gyunda, James J Yahaya, Emmanuel M Sindato, Alfred J Meremo
{"title":"Seroprevalence and Predictors of Hepatitis B and C Virus Infections Among Patients with Chronic Liver Diseases in Dodoma Region, Tanzania: A Cross-Sectional Study.","authors":"Daudi J Gyunda, James J Yahaya, Emmanuel M Sindato, Alfred J Meremo","doi":"10.2147/HMER.S533485","DOIUrl":"10.2147/HMER.S533485","url":null,"abstract":"<p><strong>Background: </strong>The known major causes of chronic liver diseases (CLDs) include, hepatitis B virus (HBV) and hepatitis C virus (HCV); however, there is scarcity of data regarding their seroprevalence in Tanzania. We aimed to evaluate the seroprevalence of HBsAg and anti-HCV and their predictors among patients with CLDs. Additionally, we also described the clinical patterns of the patients.</p><p><strong>Methods: </strong>A cross-sectional analytical study design was carried at the two referral public hospitals in Dodoma region; Dodoma referral regional hospital (DRRH) and Benjamin Mkapa hospital (BMH) among 118 patients with CLDs. Rapid test immunochromatography was used to test for HBsAg whereas anti-HCV antibody positivity was tested using lateral flow chromatographic immunoassay. Multivariable binary logistic regression was used to evaluate the predictors of HbsAg positive results, and statistical significance was set at p˂0.05.</p><p><strong>Results: </strong>The seroprevalence of HBsAg and anti-HCV antibody was 28% (33/118) and 3.4% (4/118), respectively. Having a chronic illness (AOR = 2.3, 95% CI = 1.76-7.19, p = 0.041), raised level of alanine transaminase (ALT) (AOR = 3.6, 95% CI = 1.74-8.21, p = 0.025), increased AST/ALT ratio (AOR = 2.9, 95% CI = 2.57-11.57, p = 0.039), and increased level of total bilirubin (AOR = 5.1, 95% CI = 1.09-24.39, p = 0.039) remained the predictors of HBsAg positivity.</p><p><strong>Conclusion: </strong>This study reports that almost one-third of the study subjects had positive HbsAg, and the positivity of anti-HCV antibody was quite low. The positivity of HbsAg was associated with having chronic illness, increased levels of ALT, total bilirubin, and AST/ALT ratio. Therefore, emphasis should be made to maximize the screening practices for individuals with such predictors due to high possibility of being infected with HBV.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"125-140"},"PeriodicalIF":1.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}