Clinical and Experimental Hepatology最新文献

{"title":"Pemafibrate as a therapeutic option for metabolic dysfunction-associated steatotic liver disease resistant to dietary intervention.","authors":"Hideyuki Tamai, Jumpei Okamura","doi":"10.5114/ceh.2025.155314","DOIUrl":"https://doi.org/10.5114/ceh.2025.155314","url":null,"abstract":"<p><strong>Aim of the study: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a lifestyle-related disease. However, many patients appear resistant to treatment despite dietary counseling. Pemafibrate is a novel lipidlowering pharmaceutical agent that was developed as a selective peroxisome proliferator-activated receptor α modulator. The present study aimed to clarify the efficacy of pemafibrate in diet-resistant MASLD patients with persistent hyperlipidemia.</p><p><strong>Material and methods: </strong>Participants comprised 91 MASLD patients with persistent alanine aminotransferase (ALT) elevation and hyperlipidemia despite counseling on moderate-carbohydrate restriction (150-200 g/day) for more than one year, who received pemafibrate (0.2 mg/day) for 6 months. Complete response (CR) was defined as ALT normalization (≤ 33 IU/l in males, ≤ 25 IU/l in females). Partial response (PR) was defined as a ≥ 30% reduction in ALT level from baseline, without achieving CR. No response (NR) was defined as achieving neither CR nor PR. Dietary counseling was maintained every 3 months throughout pemafibrate treatment.</p><p><strong>Results: </strong>CR, PR, and NR rates were 40% (36/91), 24% (22/91), and 36% (33/91), respectively. The response rate (CR + PR) was 64%. Although no significant change in body weight was observed, significant reductions were seen in lipid profiles (including triglycerides and low-density lipoprotein cholesterol) and liver enzymes (including ALT, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase). The concentration of glycosylated isomers of Mac-2-binding protein was significantly reduced, but no significant change in liver shear wave velocity was observed.</p><p><strong>Conclusions: </strong>Pemafibrate may be a potential second-line therapeutic option for diet-resistant MASLD patients with hyperlipidemia.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"344-351"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764088","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":"Metabolic dysfunction-associated steatotic liver disease in children.","authors":"Malgorzata Pawlowska","doi":"10.5114/ceh.2025.155319","DOIUrl":"https://doi.org/10.5114/ceh.2025.155319","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the main chronic liver pathology in children and adolescents. The incidence of MASLD is increasing with the obesity pandemic; MASLD affects approximately 40% of obese children. The article presents diagnostic criteria for MASLD in children, studies of potential screening markers and suggestions for treatment procedures.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"333-336"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764104","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":"Association of thyroid function and thyroid hormone sensitivity with all-cause and cardiovascular mortality in euthyroid patients with MASLD.","authors":"Xinghua Zhang, Xiaoling Xing, Sheng Mao, Min Qi, Yanrui Xin, Xinyu Ma, Rui Huang","doi":"10.5114/ceh.2025.155479","DOIUrl":"https://doi.org/10.5114/ceh.2025.155479","url":null,"abstract":"<p><strong>Aim of the study: </strong>To prospectively investigate the association of individual thyroid function and sensitivity with cardiovascular and all-cause mortality in adult euthyroid patients with metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Material and methods: </strong>Data for the study came from 1198 MASLD participants with normal thyroid function in the National Health and Nutrition Examination Survey (NHANES 2007-2012). The Thyroid-Stimulating Hormone Index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), and Thyroid Feedback Quantile-based Index (TFQI_FT4) were used to assess thyroid hormone sensitivity. Kaplan-Meier survival curves, Cox proportional hazard regression models, restricted cubic splines, subgroup analyses, and a series of sensitivity analyses were used to explore the association of thyroid function and thyroid hormone sensitivity with cardiovascular and all-cause mortality.</p><p><strong>Results: </strong>During a median follow-up of 11.1 years (12,188.8 person-years), 178 (14.9%) all-cause deaths were recorded, of which 46 (3.8%) were cardiovascular deaths. After adjusting for multiple factors, such as demographic characteristics, lifestyle, economic and social factors, and blood indices, free thyroxine (FT4) was independently correlated with all-cause mortality, and the risk of all-cause mortality increased by 16.2% for each unit increase in FT4 (95% CI: 1.044-1.293). For every one-unit increase in FT4, the risk of all-cause death was increased by 35.3% (95% CI: 1.168-1.567). Furthermore, when stratified by age, sex, race, body mass index (BMI), hypertension, and diabetes, the results were not uniformly significant.</p><p><strong>Conclusions: </strong>In MASLD patients with normal thyroid hormones, higher FT4 levels were significantly associated with increased risk of all-cause mortality, while higher FT4 levels were significantly linearly associated with cardiovascular mortality.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"371-386"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764060","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":"Associations between diffusion-weighted imaging and immunohistochemical features in hepatocellular carcinoma: a preliminary analysis of tumor-infiltrating lymphocytes and microvessel density expression.","authors":"Daniele Romeo, Theresa Richter, Anne-Kathrin Höhn, Hans-Michael Tautenhahn, Daniel Seehofer, Uwe Scheuermann, Timm Denecke, Hans-Jonas Meyer","doi":"10.5114/ceh.2025.155477","DOIUrl":"https://doi.org/10.5114/ceh.2025.155477","url":null,"abstract":"<p><strong>Introduction: </strong>Imaging modalities can predict histopathological characteristics of tumors such as cellularity and proliferation potential, which has also been shown for hepatocellular carcinoma (HCC). Diffusion-weighted imaging can reflect cellularity of tumors and provide apparent diffusion coefficient (ADC) values as a quantitative imaging marker. This analysis elucidates possible associations between ADC values and several immunohistochemical features of HCC.</p><p><strong>Material and methods: </strong>A cohort of 25 patients (4 female; 16%) with a mean age of 63 ±8.9 years met the inclusion criteria of this analysis. The main inclusion criteria were the availability of an MRI pre-interventional examination within 9 months before surgery and the availability of the histopathologic analysis. Immunohistochemical features included programmed cell death-ligand 1 (PD-L1) scores (immune cell score [ICS], tumor proportion score [TPS], and combined positive score [CPS]), glypican-3, tumor-infiltrating lymphocytes (TIL), stroma infiltrating lymphocytes (SIL), CD68 positive cells and microvessel density (MVD). ADC values were measured as ADC_max, ADC_mean, and ADC_min.</p><p><strong>Results: </strong>CD3+ TIL showed a moderate inverse correlation with ADC_max (<i>r</i> = -0.50, <i>p</i> = 0.01), ADC_mean (<i>r</i> = -0.52, <i>p</i> = 0.008). CD34+ MVD showed higher expression in the group that showed diffusion restriction (mean 40 ±10.8 vs. 54 ±5.5, <i>p</i> = 0.0046). There was no correlation between ADC values and CD68+ positive cells, PDL-1, glypican-3 expression, or CD3+ SIL.</p><p><strong>Conclusions: </strong>The present analysis demonstrated an inverse correlation between CD3-positive tumor-infiltrating lymphocytes and ADC_mean and ADC_max. Diffusion restriction is correlated with increased microvessel density in HCC. ADC values could help to better characterize the tumor microenvironment of HCC in a non-invasive manner.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"352-359"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764094","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":"Current approach to diagnosis and treatment of focal nodular hyperplasia in children with a management algorithm.","authors":"Anna Chudoba, Joanna Pawłowska, Joanna Cielecka-Kuszyk, Dorota Majak, Irena Jankowska, Dorota Broniszczak-Czyszek, Jakub Barański, Piotr Czubkowski","doi":"10.5114/ceh.2025.155044","DOIUrl":"https://doi.org/10.5114/ceh.2025.155044","url":null,"abstract":"<p><p>Focal nodular hyperplasia (FNH) is a benign tumor of the liver rarely reported in children. It requires differentiation from malignant liver lesions, which are more common in the pediatric population. The pathogenesis of the disease remains unknown, but previous oncological treatment of non-liver neoplasms or vascular abnormalities may predispose to FNH development. Differential diagnosis is based on radiological imaging with rare indications for diagnostic biopsy or resection. There are no specific management guidelines for FNH in children, but in most cases watchful waiting is most appropriate. In symptomatic, rapidly growing cases, surgical or radiological intervention may be considered. In this review, we present the clinical features, natural course, and current management patterns in pediatric FNH.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"324-332"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764072","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":"Potential pharmacotherapy pathways in metabolic dysfunction-associated steatotic liver disease.","authors":"Paweł Rajewski, Jakub Cieściński, Piotr Rajewski, Szymon Suwała, Alicja Rajewska, Maciej Potasz","doi":"10.5114/ceh.2025.154956","DOIUrl":"https://doi.org/10.5114/ceh.2025.154956","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, one of the leading causes of cirrhosis, hepatocellular carcinoma and liver transplantation in developed countries, and an important cardiovascular risk factor. It affects about 30% of the adult population and about 10% of the paediatric population. These figures may be underestimated due to the long-standing asymptomatic or oligosymptomatic course of the disease, the lack of nationwide screening for MASLD in patients with risk factors for its development, and the low awareness of both patients and physicians themselves. According to projections, this number could double by 2030 due to the growing obesity epidemic and the associated development of other weight-dependent metabolic complications, such as insulin resistance, pre-diabetic state, type 2 diabetes, lipid disorders and hypertension. The basis for prevention and treatment of MASLD is weight reduction with diet and regular physical activity and modern pharmacotherapy for obesity-related disease, as well as treatment aimed at reducing the cardiometabolic factors - diabetes, hyperlipidaemia and hypertension. Pharmacological treatment of hepatic steatosis, steatohepatitis or liver fibrosis alone is limited, and many drugs are currently in clinical trials. This article presents the current pharmacological options and potential pharmacotherapy pathways for the hepatic complications of MASLD - steatosis, steatohepatitis and incipient liver fibrosis.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"313-323"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764091","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":"Diagnosing and treating fatty liver disease: strategies for hepatocellular carcinoma and cardiovascular disease prevention.","authors":"Toru Ishikawa","doi":"10.5114/ceh.2025.155228","DOIUrl":"https://doi.org/10.5114/ceh.2025.155228","url":null,"abstract":"<p><p>The link between lifestyle-related conditions and fatty liver disease has attracted considerable attention in recent years. The number of patients with metabolic dysfunction-associated steatotic liver disease (MASLD), often co-occurring with obesity, diabetes, and dyslipidemia, continues to rise. Accumulating evidence suggests that these conditions synergistically increase the risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Consequently, there is a growing need for testing to identify high-risk liver disease patients based on lifestylerelated conditions, distinct from chronic viral hepatitis or alcohol-induced liver disease, and to determine the most appropriate treatments for these conditions, especially obesity, diabetes, and dyslipidemia. This review outlines the strategy for treating fatty liver disease currently being used in community hospitals, with the goal of reducing HCC and preventing cardiovascular disease.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"307-312"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764124","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":"Annexin A2 as a marker for hepatocellular carcinoma detection among patients with hepatitis C virus-related liver cirrhosis after HCV treatment using directly acting antivirals.","authors":"Mohamed S Shater, Amr A Abd Elmoety, Yousri A A Rostom, Eman Z Elkemary, Hyam M Helal, Ahmed Kamal","doi":"10.5114/ceh.2025.154172","DOIUrl":"https://doi.org/10.5114/ceh.2025.154172","url":null,"abstract":"<p><strong>Aim of the study: </strong>Hepatocellular carcinoma (HCC) is considered the sixth most prevalent malignant tumor, while it ranks first in Egypt. Early detection of HCC is of great value, as early stages can be treated with curative modalities. Current surveillance programs depend on ultrasonography and α-fetoprotein (AFP) measurement, but both have notable limitations. This study aimed to investigate the potential role of annexin A2 in HCC detection.</p><p><strong>Material and methods: </strong>The present study included four groups: Group A: early hepatocellular carcinoma, BCLC stages 0 and A; Group B: advanced hepatocellular carcinoma, BCLC stage C; Group C: liver cirrhosis without HCC; Group D: healthy participants as a control group. Chronic hepatitis C was the cause of cirrhosis in three groups (A, B, and C). All of them attained a sustained virological response (SVR) after receiving treatment with direct-acting antiviral medications (DAAs). Both serum AFP and annexin A2 were measured in all included subjects.</p><p><strong>Results: </strong>One hundred subjects were included, 25 in each group. Annexin A2 levels were significantly higher in early- and advanced-stage HCC participants. Serum annexin A2 level was an excellent discriminator of early HCC, with an area under the ROC curve (AUC) of 0.934. The cut-off point > 7.7 ng/ml had a sensitivity of 96.00%, a specificity of 88%, a positive predictive value (PPV) of 88.9%, and a negative predictive value (NPV) of 95.7% (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>Serum annexin A2 is a promising biomarker that can improve the sensitivity of HCC detection among patients with liver cirrhosis after HCV eradication using DAAs.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"337-343"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764065","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":"Effect and prognostic factors of the double plasma molecular adsorption system combined with partial plasma exchange (DPMAS-PPE) in patients with liver failure.","authors":"Xudong Liu, Xiaofang Zhao, Chunni Liang, Ruichao Fang, Yinying Liao, Qianjun Ren, Su Li, Yuqing Chen, Xiaozu Meng, Weiqin Lu","doi":"10.5114/ceh.2025.154322","DOIUrl":"https://doi.org/10.5114/ceh.2025.154322","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;Although the dual plasma molecule adsorption system combined with partial plasma exchange (DPMAS-PPE) has been shown to be effective in the treatment of patients with liver failure (LF), short-term prognostic adverse events remain difficult to avoid in clinical practice. These events are often accompanied by severe symptoms of inflammation and elevated cytokine levels. Therefore, it is important to analyze the relationship between serological indicators, cytokines, and short-term prognosis in LF patients.The aim of the study was to monitor changes in clinical serological, haematological, and cytokine indices in patients with LF before and after DPMAS-PPE treatment. Patients were grouped according to survival outcomes, and short-term prognostic predictors were identified by analyzing relationship between routine blood parameters, serologicals indicators, and cytokines in each group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;A total of 121 LF patients treated with DPMAS-PPE were included and divided into survival and death groups based on outcomes during clinical treatment or follow-up. Data on serum levels, complete blood counts, and cytokine expression were collected and analyzed between groups before treatment, during treatment, and during follow-up. Correlations between parameters were analyzed, and a short-term prognostic model for LF patients was constructed using multivariable regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the survival group, the death group showed significantly higher of neutrophil percentage (N), neutrophil-to-lymphocyte ratio (NLR), the total bilirubin (TBIL), and creatinine (Cr) levels, as well as lower haemoglobin (HGB), albumin (ALB), and prothrombin activity (PTA) during treatment and follow-up (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Receiver operating characteristic (ROC) analysis showed that N, NLR, and TBIL had good predictive performance for short-term mortality (AUC &gt; 0.80). Elevated interleukin 6 (IL-6) expression indicated higher mortality risk within 4 weeks, whereas decreased granulocyte-colony stimulating factor (G-CSF) and increased epidermal growth factor (EGF) expression were associated with death within 12 weeks. Multivariate regression revealed that advanced disease stage and abnormal expression of IL-6, G-CSF, and EGF were independent predictors of poor short-term survival, with a C-index of 0.715 (95% confidence interval [CI]: 0.64-0.79; &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The causes of death in LF patients are often related to severe infections, coagulation dysfunction, renal insufficiency, refractory hyponatremia, and hypoalbuminemia. During DPMA-PPE treatment, laboratory indicators such as N, NLR, and TBIL can still be used as references for assessing the short-term prognosis of patients. In addition, high expression of IL-6 is a risk factor for death within 4 weeks in LF patients, while low expression of G-CSF and high expression of EGF are risk","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"387-399"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764121","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":"Identification of novel therapeutic targets for liver fibrosis, cirrhosis, and hepatocellular carcinoma <i>via</i> dual-omics analysis and preliminary exploration of regulatory mechanisms.","authors":"Jian Chen, Rongge Cao, Zhiyuan He, Zifan Li, Yanan Hong, Chuanzeng Ren, Ying Wang, Jiazhao Wu, Yongqing Liu, Honghai Xia","doi":"10.5114/ceh.2025.155448","DOIUrl":"https://doi.org/10.5114/ceh.2025.155448","url":null,"abstract":"<p><strong>Aim of the study: </strong>Liver fibrosis (LF), cirrhosis, and hepatocellular carcinoma (HCC) are strongly correlated and impose a heavy burden on the global healthcare system. Currently, there are no effective treatments, and thus we performed dual-omics analysis to identify new targets and regulatory mechanisms.</p><p><strong>Material and methods: </strong>A two-sample Mendelian randomization (MR), with cis-expression quantitative trait locus (cis-eQTL) as the genomic variables and cis-protein quantitative trait locus (cis-pQTL) as the proteomic variables, was performed to identify candidate therapeutic targets for LF, cirrhosis, and HCC at the gene and protein levels. Colocalization analysis was performed to screen for significant candidate targets. Moreover, the results were validated using summary-data-based MR (SMR) analysis. To further explore the downstream regulatory mechanisms of the targets, we performed two-step MR, with circulating metabolites, immune cells, gut microbiota, and inflammatory proteins as mediating variables.</p><p><strong>Results: </strong>Through the two-sample MR, we identified 9 candidate targets for LF, 6 targets for cirrhosis, and 12 targets for HCC. Two significant therapeutic targets for LF, 3 targets for cirrhosis, and 1 target for HCC were identified through colocalization analysis. Among them, DMWD, CDK13, ATRAID, SLC5A6, and CD300LD were validated through SMR. Further analysis revealed that ATRAID might inhibit cirrhosis by upregulating threonine levels. In contrast, CDK13 was predicted to promote LF by suppressing CD20 on naive-mature B cells.</p><p><strong>Conclusions: </strong>In this study, dual-omics analysis identified new therapeutic targets for LF, cirrhosis, and HCC, as well as potential regulatory mechanisms; these results lay the foundation for further investigations into the disease mechanisms and new drug development.</p>","PeriodicalId":10281,"journal":{"name":"Clinical and Experimental Hepatology","volume":"11 4","pages":"360-370"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764075","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}