Advances in Hepatology

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 6258

Special Issue Editor


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Guest Editor
Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai 200040, China
Interests: metabolic dysfunction-associated steatotic liver disease (MASLD); metabolic dysfunction-associated steatohepatitis (MASH); alcohol-associated liver disease; alcohol-associated hepatitis; liver fibrosis; gut microbiota; macrophages; neutrophils

Special Issue Information

Dear Colleagues,

This Special Issue, “Advances in Hepatology”, aims to highlight cutting-edge research and emerging concepts across the spectrum of liver diseases. We welcome original research and comprehensive reviews on metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), alcoholic hepatitis, and related complications such as fibrosis, cirrhosis, and portal hypertension. In addition, this Special Issue seeks to include significant advances in the understanding and management of viral hepatitis, liver cancer, and autoimmune liver diseases.

Recent research has underscored the pivotal roles of adipose tissue, the gut microbiota, neuroimmune interactions, and the regulation of inflammatory cells—including macrophages and neutrophils—in the pathogenesis and progression of liver diseases. We encourage the submission of papers that investigate these novel pathways and translational and clinical studies that may inform future therapeutic strategies across all categories of major liver disease.

By compiling the latest findings in hepatology, this Special Issue seeks to foster interdisciplinary dialogue and provide a platform for innovative research that will advance our understanding and treatment of liver diseases in all their complexity.

Dr. Yuanwen Chen
Guest Editor

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Keywords

  • metabolic dysfunction-associated steatotic liver disease (MASLD)
  • metabolic dysfunction-associated steatohepatitis (MASH)
  • alcohol-associated liver disease (ALD)
  • alcohol-associated hepatitis
  • viral hepatitis
  • liver cancer
  • autoimmune liver diseases
  • liver fibrosis
  • gut microbiota
  • neuroimmune
  • inflammatory mechanisms
  • oxidative stress
  • reversibly oxidized human non-mercaptalbumin-1
  • irreversibly oxidized human non-mercaptalbumin-2 (HNA2)

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Published Papers (7 papers)

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Research

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20 pages, 3275 KB  
Article
Machine Learning-Based Models for the Prediction of Postoperative Recurrence Risk in MVI-Negative HCC
by Chendong Wang, Qunzhe Ding, Mingjie Liu, Rundong Liu, Qiang Zhang, Bixiang Zhang and Jia Song
Biomedicines 2025, 13(10), 2507; https://doi.org/10.3390/biomedicines13102507 - 15 Oct 2025
Viewed by 222
Abstract
Background: Hepatocellular carcinoma (HCC) patients without microvascular invasion (MVI) face significant postoperative early recurrence (ER) risks, yet prognostic determinants remain understudied. Existing models often rely on linear assumptions. This study aimed to develop and validate an interpretable machine learning model using routine [...] Read more.
Background: Hepatocellular carcinoma (HCC) patients without microvascular invasion (MVI) face significant postoperative early recurrence (ER) risks, yet prognostic determinants remain understudied. Existing models often rely on linear assumptions. This study aimed to develop and validate an interpretable machine learning model using routine clinical parameters to predict early recurrence (ER) in MVI-negative HCC patients. Methods: We retrospectively analyzed 578 MVI-negative HCC patients undergoing radical resection. Seven machine learning (ML) algorithms were systematically benchmarked using clinical/laboratory/imaging features optimized via recursive feature elimination (RFE) and hyperparameter tuning. Model interpretability was achieved via SHapley Additive exPlanations (SHAP). Results: The CatBoost model demonstrated superior performance (AUC: 0.7957, Accuracy: 0.7290). SHAP analysis identified key predictors: tumor capsule absence, elevated HBV-DNA and CA125 levels, larger tumor diameter, and lower body weight significantly increased ER risk. Individualized SHAP force plots enhanced clinical interpretability. Conclusions: The CatBoost model exhibits robust predictive performance for ER in MVI-negative HCC, offering a clinically interpretable tool for personalized risk stratification and optimization of postoperative management strategies. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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10 pages, 944 KB  
Article
Pharmacokinetics of Sofosbuvir and Velpatasvir for Hepatitis C Treatment in Pregnancy
by Michelle L. Giles, Alexandra Dunbar, Sushena Krishnaswamy, Joe Sasadeusz, Joanne M. Said, Laura Roon, Lane R. Bushman and Kristina M. Brooks
Biomedicines 2025, 13(10), 2462; https://doi.org/10.3390/biomedicines13102462 - 10 Oct 2025
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Abstract
Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity [...] Read more.
Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity for healthcare interventions such as treatment for hepatitis C virus (HCV) infection. Methods: This was a multi-site, prospective, open-label, pharmacokinetic (PK) study conducted at two large maternity hospitals in Melbourne, Australia, to evaluate the safety and pharmacokinetics of antenatal sofosbuvir (SOF) and velpatasvir (VEL) treatment administered for 12 weeks during the second and third trimester. Five women were recruited and underwent detailed PK assessments across three visits. Results: Compared to historical data in non-pregnant women, SOF area under the concentration curve (AUC) and maximum concentrations (Cmax) were 60% and 49% higher in pregnancy, respectively. In contrast, exposure to the inactive metabolite of SOF, GS-331007, was 43% lower in pregnancy. Both Cmax and AUC for VEL in pregnancy were similar to values reported in historic non-pregnant women (~21% lower in pregnant women). SOF/VEL was safe and well tolerated. Conclusions: These results add to the limited published experience prescribing antivirals in pregnancy and provide further support for a larger ongoing prospective study and other efforts to support HCV treatment in pregnancy. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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12 pages, 642 KB  
Article
Distinctive Clinical Features of Portal Hypertension in Children with Portal Vein Thrombosis Following Liver Transplantation
by Naire Sansotta, Angelo Di Giorgio, Mara Marcella Colusso, Marco Salvi, Paolo Marra, Domenico Pinelli, Alessandra Carobbio and Lorenzo D’Antiga
Biomedicines 2025, 13(9), 2061; https://doi.org/10.3390/biomedicines13092061 - 24 Aug 2025
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Abstract
Background: Portal vein thrombosis (PVT) occurs in nearly 8% of pediatric liver transplants (LT), leading to portal hypertension (PH). This study aims to describe the clinical features and management of PVT in children post-transplant (PVTt) compared to those with PVT in native [...] Read more.
Background: Portal vein thrombosis (PVT) occurs in nearly 8% of pediatric liver transplants (LT), leading to portal hypertension (PH). This study aims to describe the clinical features and management of PVT in children post-transplant (PVTt) compared to those with PVT in native livers (PVTn). Methods: All children diagnosed with PVTt between January 2002 and October 2021 were included. The control group comprised pediatric patients with PVTn diagnosed and managed at our center during the same period. Results: PVTt was diagnosed in 37 out of 610 children (6%), while 36 children with PVTn were included as controls. At 5-year follow-up, medium-to-large esophageal varices (grade II–III) developed in 15/37 (38%) PVTt patients compared to 23/36 (64%) PVTn patients (p = 0.002). Among 11 patients who bled, upper gastrointestinal bleeding occurred in 2/7 (29%) with PVTt, versus 4/4 (100%) PVTn patients (p = 0.06). Mean spleen length was 9.3 cm in PVTt versus 7.4 cm in PVTn (p = 0.039). Mean platelet count was 76 × 103/L in PVTt versus 93 × 103/L in PVTn (p = 0.16). Conclusions: Despite more severe PH and marked hypersplenism, children with PVTt have a reduced risk of developing esophageal varices, but an increased risk of bleeding from the lower gastrointestinal tract. This suggests the need for a different surveillance strategy in this patient group. Individualized care is key, mainly in PVTt, where hypersplenism does not correlate with risk of bleeding from esophageal varices. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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20 pages, 374 KB  
Article
Genetic Variants, Metabolic Dysfunction-Associated Fatty Liver Disease, and Major Health Outcomes in Older Adults
by Daniel Clayton-Chubb, Ammar Majeed, William W. Kemp, Chenglong Yu, Peter W. Lange, Jessica A. Fitzpatrick, Robyn L. Woods, Andrew M. Tonkin, Andrew T. Chan, Mark R. Nelson, Joanne Ryan, Alexander D. Hodge, John S. Lubel, Hans G. Schneider, John J. McNeil and Stuart K. Roberts
Biomedicines 2025, 13(8), 1977; https://doi.org/10.3390/biomedicines13081977 - 14 Aug 2025
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Abstract
Background and Aims: Multiple genetic variants have been associated with disease prevalence and outcomes in middle-aged people with metabolic dysfunction-associated fatty liver disease (MAFLD). However, genetic studies in older adults have been lacking. We aimed to understand their clinical relevance in healthy [...] Read more.
Background and Aims: Multiple genetic variants have been associated with disease prevalence and outcomes in middle-aged people with metabolic dysfunction-associated fatty liver disease (MAFLD). However, genetic studies in older adults have been lacking. We aimed to understand their clinical relevance in healthy older persons. Methods: A secondary analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized trial involving community-dwelling older adults ≥ 70 years without prior cardiovascular disease events or life-limiting illness at enrolment. The Fatty Liver Index (FLI) was used to identify MAFLD at baseline. We assessed the associations between six previously reported MAFLD-associated genetic variants with prevalent MAFLD at baseline, and the associations of these variants with cardiovascular disease events and all-cause mortality. Results: A total of 8756 participants with genetic data were stratified according to the FLI, with 3310 having MAFLD at baseline. The follow-up was for a median of 8.4 (IQR 7.3–9.5) years. Variants in two genes (GCKR and HSD17B13) were associated with prevalent MAFLD (p < 0.05); PNPLA3, TM6SF2, LYPLAL1, and MBOAT7 were not. PNPLA3, TM6SF2, HSD17B13, GCKR, and LYPLAL1 were not associated with major adverse cardiovascular events (MACEs) or mortality in the overall cohort or in participants with MAFLD during the follow-up (all p > 0.05). Within the MAFLD group, homozygosity for the rs641738 C > T variant in the MBOAT7 gene was associated with a reduced risk of MACEs (HR 0.68 [95% CI 0.48–0.97]), but not all-cause mortality (HR 1.14 [95% CI 0.89–1.47]). This protective association remained significant after adjusting for multiple key covariates (aHR 0.64 [95% CI 0.44–0.92]). The results were similar when using the metabolic dysfunction-associated steatotic liver disease definition rather than MAFLD. Conclusions: The rs641738 C > T variant in MBOAT7 may confer protection against MACEs in older adults with MAFLD, independent of other clinical risk factors. Further validation using external cohorts is needed. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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25 pages, 2693 KB  
Article
Adipokine and Hepatokines in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Current and Developing Trends
by Salvatore Pezzino, Stefano Puleo, Tonia Luca, Mariacarla Castorina and Sergio Castorina
Biomedicines 2025, 13(8), 1854; https://doi.org/10.3390/biomedicines13081854 - 30 Jul 2025
Cited by 1 | Viewed by 1234
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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18 pages, 8113 KB  
Article
An Interpretable Machine Learning Model Based on Inflammatory–Nutritional Biomarkers for Predicting Metachronous Liver Metastases After Colorectal Cancer Surgery
by Hao Zhu, Danyang Shen, Xiaojie Gan and Ding Sun
Biomedicines 2025, 13(7), 1706; https://doi.org/10.3390/biomedicines13071706 - 12 Jul 2025
Viewed by 902
Abstract
Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods [...] Read more.
Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods: This study enrolled 680 patients with CRC who underwent curative resection, randomly allocated into a training set (n = 477) and a validation set (n = 203) in a 7:3 ratio. Feature selection was performed using Boruta and Lasso algorithms, identifying nine core prognostic factors through variable intersection. Seven machine learning (ML) models were constructed using the training set, with the optimal predictive model selected based on comprehensive evaluation metrics. An interactive visualization tool was developed to interpret the dynamic impact of key features on individual predictions. The partial dependence plots (PDPs) revealed a potential dose–response relationship between inflammatory–nutritional markers and MLM risk. Results: Among 680 patients with CRC, the cumulative incidence of MLM at 6 months postoperatively was 39.1%. Multimodal feature selection identified nine key predictors, including the N stage, vascular invasion, carcinoembryonic antigen (CEA), systemic immune–inflammation index (SII), albumin–bilirubin index (ALBI), differentiation grade, prognostic nutritional index (PNI), fatty liver, and T stage. The gradient boosting machine (GBM) demonstrated the best overall performance (AUROC: 0.916, sensitivity: 0.772, specificity: 0.871). The generalized additive model (GAM)-fitted SHAP analysis established, for the first time, risk thresholds for four continuous variables (CEA > 8.14 μg/L, PNI < 44.46, SII > 856.36, ALBI > −2.67), confirming their significant association with MLM development. Conclusions: This study developed a GBM model incorporating inflammatory-nutritional biomarkers and clinical features to accurately predict MLM in colorectal cancer. Integrated with dynamic visualization tools, the model enables real-time risk stratification via a freely accessible web calculator, guiding individualized surveillance planning and optimizing clinical decision-making for precision postoperative care. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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Review

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23 pages, 7024 KB  
Review
Metabolic Dysfunction-Associated Steatotic Liver Disease as a Risk Factor for Chronic Kidney Disease: A Narrative Review
by Marcelo do Rego Maciel Souto Maior, Nathália de Lacerda Interaminense Ribeiro, Hannah Vicentini Vitoriano Silva, Edmundo Pessoa Lopes and Emilia Chagas Costa
Biomedicines 2025, 13(9), 2162; https://doi.org/10.3390/biomedicines13092162 - 4 Sep 2025
Viewed by 1052
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD)—previously known as non-alcoholic fatty liver disease (NAFLD)—is currently the most common chronic liver disease globally. Observational studies have reported that MASLD is independently associated with extrahepatic disorders, such as chronic kidney disease (CKD). Severe forms of MASLD [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD)—previously known as non-alcoholic fatty liver disease (NAFLD)—is currently the most common chronic liver disease globally. Observational studies have reported that MASLD is independently associated with extrahepatic disorders, such as chronic kidney disease (CKD). Severe forms of MASLD (i.e., steatohepatitis and liver fibrosis) are even more strongly associated with the risk of incident kidney dysfunction. Hypothetically, MASLD could directly promote CKD through liver-derived endocrine and metabolic mediators, hemodynamic alterations, immune-mediated mechanisms, and oxidative or cellular stress. However, proving that MASLD directly causes CKD is difficult due to the multiple shared cardiometabolic and systemic risk factors, such as obesity, hypertension, and type 2 diabetes mellitus, which serve as confounding variables. Moreover, studies on the association between MASLD and CKD have differed in their designs, sampling methods, disease definitions, and inclusion criteria, precluding more robust evidence supporting a causal relationship. Furthermore, few studies have explored specific issues, such as the new nomenclature for steatotic liver disease, the relationship between these diseases in pediatric populations, the impact of MASLD plus alcohol intake (MetALD) on CKD, and therapeutic options targeting MASLD and CKD simultaneously. Answers to these issues are essential, as the appropriate management of patients with MASLD may prevent or ameliorate kidney dysfunction. The aims of the present study are to describe shared risk factors between MASLD and CKD, the possible direct pathogenic effect of MASLD on kidney structure and function, and gaps in the current literature, to indicate future research directions. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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