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Biomedicines
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Emerging Trends in Liver Diseases and Cirrhosis Research
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Emerging Trends in Liver Diseases and Cirrhosis Research

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

Deadline for manuscript submissions: 30 November 2026 | Viewed by 6310

Editor

Dr. Hariklia Kranidioti

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Guest Editor
2nd Academic Department of Internal Medicine, General Hospital of Athens “Hippokratio”, Medical School of National and Kapodistrian University of Athens, Athens, Greece
Interests: viral hepatitis; liver diseases and immunology; cirrhosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I am pleased to invite you to contribute to this Special Issue, entitled “Emerging Trends in Liver Diseases and Cirrhosis Research”. Liver diseases remain a growing global health challenge, with cirrhosis being one of the leading causes of morbidity and mortality worldwide. The clinical landscape is rapidly changing, driven by the rising prevalence of metabolic-associated steatotic liver disease (MASLD), autoimmune conditions like primary biliary cholangitis (PBC), and persistent viral hepatitis. At the same time, advances in diagnostic tools, molecular understanding, and therapeutic strategies are providing new hope for earlier intervention and better outcomes. This Special Issue provides an opportunity to highlight recent advancements and emerging frontiers in hepatology research.

We aim to gather cutting-edge research and comprehensive reviews focusing on new developments in the diagnosis, pathophysiology, and management of cirrhosis. Special attention will be given to innovations in the diagnosis and treatment of MASLD, PBC, and other chronic liver conditions. The collection aligns with the journal's commitment to publishing high-quality research that advances clinical and scientific understanding of complex disease processes.

We look forward to receiving your contributions.

Dr. Hariklia Kranidioti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pathogenesis of liver fibrosis and cirrhosis
  • MASLD
  • hepatitis B, C and D
  • primary biliary cholangitis (PBC): immunopathology and treatment advances
  • alcohol-associated liver disease
  • liver regeneration and stem-cell-based therapies
  • biomarkers for early diagnosis and prognosis
  • emerging antifibrotic treatments
  • liver complications and systemic comorbidities
  • personalized medicine in liver disease

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Published Papers (5 papers)

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Research

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13 pages, 1974 KB  
Article
Effect of Short-Chain Fatty Acids In Vivo on the Treatment of CCL4-Induced Hepatic Fibrosis
by Kétlin Fernanda Rodrigues, Giovana Vivan Tonial, Matheus Scherer Bastos, Giovanna Mezzomo Pavanato, Carolina Luft, Maria Cláudia Rosa Garcia, Fábio Luiz Dal Moro Maito, Maria Martha Campos and Jarbas Rodrigues de Oliveira
Biomedicines 2026, 14(7), 1477; https://doi.org/10.3390/biomedicines14071477 (registering DOI) - 29 Jun 2026
Abstract
Background/Objectives: Hepatic fibrosis is a progressive pathological condition characterized by excessive extracellular matrix deposition in the liver, which may progress to cirrhosis and liver failure. Short-chain fatty acids (SCFAs) have demonstrated anti-inflammatory and anti-fibrotic properties; however, their therapeutic potential in hepatic fibrosis remains [...] Read more.
Background/Objectives: Hepatic fibrosis is a progressive pathological condition characterized by excessive extracellular matrix deposition in the liver, which may progress to cirrhosis and liver failure. Short-chain fatty acids (SCFAs) have demonstrated anti-inflammatory and anti-fibrotic properties; however, their therapeutic potential in hepatic fibrosis remains incompletely understood. This study aimed to evaluate the effects of acetate, propionate, and butyrate on carbon tetrachloride (CCl4)-induced hepatic fibrosis in Balb/C mice. Methods: Hepatic fibrosis was induced in Balb/C mice using CCl4, and the animals were treated with acetate, propionate, or butyrate administered via drinking water for four weeks. Biochemical parameters, histological alterations, and the expression of fibrogenic and inflammatory markers were evaluated and compared with a silymarin-treated group. Results: Treatment with SCFAs significantly reduced serum transaminase levels (AST and ALT) compared to the untreated fibrotic group. Histological analyses demonstrated the preservation of hepatic architecture and reduced inflammatory infiltrates, particularly in the butyrate-treated group. In addition, SCFAs significantly decreased the gene and protein expression of fibrogenic markers (ACTA2 and COL1A1) and inflammatory markers (NOS1, NF-κB, and IL-10), with propionate showing the most pronounced effects. Overall, the therapeutic effects observed with SCFAs were comparable or superior to those obtained with silymarin treatment. Conclusions: The findings suggest that SCFAs, especially butyrate and propionate, exert hepatoprotective, anti-inflammatory, and anti-fibrotic effects in CCl4-induced hepatic fibrosis. These compounds represent promising therapeutic candidates for the treatment of liver fibrosis. Full article
(This article belongs to the Special Issue Emerging Trends in Liver Diseases and Cirrhosis Research)
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26 pages, 957 KB  
Article
Machine Learning-Based Prediction of Ultrasound-Detected Hepatic Steatosis Within the Metabolic Dysfunction-Associated Steatotic Liver Disease Spectrum Using Routine Clinical and Biochemical Parameters
by Canan Akkus, Gamze Sonmez, Ali Sahin, Yigit Yazarkan, Melis Gokgoz, Feride Caglar and Sanem Kayhan
Biomedicines 2026, 14(5), 1154; https://doi.org/10.3390/biomedicines14051154 - 20 May 2026
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Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease globally, mirroring the increasing prevalence of obesity, insulin resistance, and type 2 diabetes. Early detection of hepatic steatosis is vital for cardiometabolic risk assessment; however, conventional imaging [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease globally, mirroring the increasing prevalence of obesity, insulin resistance, and type 2 diabetes. Early detection of hepatic steatosis is vital for cardiometabolic risk assessment; however, conventional imaging is costly and impractical for population screening. This study aimed to develop interpretable machine-learning models to predict ultrasound-detected hepatic steatosis within the MASLD spectrum using routinely available clinical and biochemical data. Methods: We analyzed data from 644 adults, 50% of whom had ultrasound-detected hepatic steatosis. Preprocessing, imputation, and feature selection were implemented within a single scikit-learn pipeline to avoid information leakage. An Elastic Net-regularized logistic regression identified the top 20 predictors, which were subsequently used across nine supervised machine learning (ML) classifiers. Model performance was evaluated via repeated stratified 5-fold cross-validation (25 resamples) using accuracy, F1 score, sensitivity, specificity, Youden’s J, balanced accuracy, and Area Under the Receiver Operating Characteristic Curve (AUROC). Interpretability was assessed using SHapley Additive exPlanations (SHAP). Results: Participants with ultrasound-detected hepatic steatosis exhibited greater adiposity, insulin resistance, and dyslipidemia compared with controls [p < 0.05 for body mass index (BMI), waist circumference, glucose, glycated hemoglobin (HbA1c), triglycerides]. Elastic Net selection highlighted Weight, Ponderal Index, Fibrosis-4 Index (FIB-4), blood urea nitrogen (BUN)/Creatinine ratio, Aspartate Aminotransferase to Platelet Ratio Index (APRI), and Visceral Adiposity Index as the strongest predictors. Logistic Regression and Gradient Boosting achieved the best performance (accuracy = 0.65 ± 0.03; AUROC = 0.71 ± 0.04; balanced accuracy = 0.66 ± 0.06), outperforming rule-based indices such as Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) reported in the literature. SHAP analysis confirmed clinically coherent feature effects, with higher anthropometric and hepatic injury indices increasing the predicted probability of ultrasound-detected hepatic steatosis. Conclusions: Routinely available clinical and biochemical parameters can predict hepatic steatosis with moderate accuracy using transparent, interpretable ML models. Logistic Regression and Gradient Boosting provided best discrimination and robust internal performance, offering a pragmatic, low-cost approach for early identification of ultrasound-detected hepatic steatosis within the MASLD spectrum in primary and metabolic care settings. Full article
(This article belongs to the Special Issue Emerging Trends in Liver Diseases and Cirrhosis Research)
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Review

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33 pages, 2054 KB  
Review
Current Drug Development Pipeline for MASLD and MASH: Focusing on Cardiovascular Comorbidities
by Veronika A. Prikhodko and Sergey V. Okovityi
Biomedicines 2026, 14(4), 909; https://doi.org/10.3390/biomedicines14040909 - 16 Apr 2026
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an exceptionally high global prevalence that is projected to continue rising in the near future. MASLD is strongly associated with a spectrum of cardiometabolic risk factors, and may itself, in turn, contribute to cardiovascular [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an exceptionally high global prevalence that is projected to continue rising in the near future. MASLD is strongly associated with a spectrum of cardiometabolic risk factors, and may itself, in turn, contribute to cardiovascular morbidity and mortality. This interconnection warrants the development of integrated treatment strategies targeting shared pathophysiological processes and addressing both hepatic, metabolic, and cardiovascular outcomes. In this work, we review the modern MASLD clinical development pipeline and highlight the most prominent drug candidates with known or purported cardiovascular benefits, discussing mechanistic links and supporting evidence ranging from preclinical experiments to real-world data. Although the drug development pipeline is extensive and diverse, evidence supporting cardiovascular benefits for most candidate molecules remains limited. Both of the FDA-approved therapies, resmetirom and semaglutide, have been found to significantly reduce the risk of major adverse cardiovascular events as well as cardiovascular and all-cause mortality in patients with MASH. In addition, significant improvements were observed in patients with heart failure with preserved ejection fraction treated with semaglutide, highlighting incretin mimetics as a promising class for managing cardiovascular disease concomitant with MASLD/MASH. Other investigational compounds, targeting the farnesoid X receptor, peroxisome proliferator-activated receptors, de novo lipogenesis enzymes, and fibroblast growth factors, have demonstrated improvements in blood lipid spectrum and glycemic control; however, their clinical effectiveness in patients at cardiovascular risk has yet to be established. Full article
(This article belongs to the Special Issue Emerging Trends in Liver Diseases and Cirrhosis Research)
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30 pages, 1829 KB  
Review
When Atrial Fibrillation Meets Alcoholic Liver Cirrhosis: Can Direct Oral Anticoagulants Bridge the Therapeutic Gap?
by Iulia Cristina Marginean, Sergiu Marian Cazacu, Cristina Maria Marginean, Mihaela Popescu, George Alexandru Iacob, Marian Sorin Popescu and Cristin Constantin Vere
Biomedicines 2026, 14(3), 531; https://doi.org/10.3390/biomedicines14030531 - 27 Feb 2026
Viewed by 1288
Abstract
A significant clinical challenge is represented by the use of anticoagulants in patients with chronic liver diseases—such as metabolic steatohepatitis (MASH), metabolic associated steatotic liver disease (MASLD), and liver cirrhosis (LC). There is a well-established association between alcohol-related LC and atrial fibrillation (AF). [...] Read more.
A significant clinical challenge is represented by the use of anticoagulants in patients with chronic liver diseases—such as metabolic steatohepatitis (MASH), metabolic associated steatotic liver disease (MASLD), and liver cirrhosis (LC). There is a well-established association between alcohol-related LC and atrial fibrillation (AF). These individuals often require anticoagulation, but treatment must carefully balance the heightened risks of both thrombosis and bleeding. Direct oral anticoagulants (DOACs) are recognized as effective and safe alternatives to warfarin, offering superior stroke prevention and a more favorable safety profile regarding major bleeding. They are generally considered safe for use in patients with LC classified as Child–Pugh A and B—excluding rivaroxaban—but are contraindicated in those with Child–Pugh C cirrhosis. DOACs also offer practical advantages, including convenience of administration, fewer drug interactions, and a high level of safety and efficacy. Comprehensive randomized controlled trials with well-defined cirrhosis stages and standardized anticoagulation protocols are essential to guide clinical decision-making. Until then, a multidisciplinary, individualized approach remains critical in managing patients with both AF and LC. The present review aims to explore the complex interplay between alcohol-related LC and the therapeutic use of direct oral anticoagulants (DOACs), particularly in the presence of cardiovascular risk factors such as atrial fibrillation, and the associated thrombotic complications. Full article
(This article belongs to the Special Issue Emerging Trends in Liver Diseases and Cirrhosis Research)
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Other

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29 pages, 4504 KB  
Systematic Review
When the Liver Echoes to the Heart: Assessing Subclinical Cardiac Dysfunction in NAFLD Using Speckle Tracking Echocardiography—A Systematic Review and Meta-Analysis
by Micha Gruber, Malaz Almasri, Rania Abdulredha, Iulia Tecar, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Dan L. Dumitrascu and Abdulrahman Ismaiel
Biomedicines 2025, 13(12), 2908; https://doi.org/10.3390/biomedicines13122908 - 27 Nov 2025
Cited by 2 | Viewed by 1145
Abstract
Introduction: Worldwide, non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder, strongly associated with increased cardiovascular morbidity and mortality. Although patients have a preserved left ventricular ejection fraction (LVEF), individuals having NAFLD may demonstrate subclinical cardiac dysfunction. Speckle tracking echocardiography [...] Read more.
Introduction: Worldwide, non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder, strongly associated with increased cardiovascular morbidity and mortality. Although patients have a preserved left ventricular ejection fraction (LVEF), individuals having NAFLD may demonstrate subclinical cardiac dysfunction. Speckle tracking echocardiography (STE) enables a more sensitive evaluation, identifying even subtle alterations of myocardial strain, compared to conventional LVEF measurements. This systematic review and meta-analysis sought to examine the relationship between NAFLD and subclinical left ventricular systolic impairment, utilizing STE-derived strain parameters. Methods: A comprehensive search of the literature was undertaken using PubMed, EMBASE, and Scopus. Observational studies evaluating patients with NAFLD through STE-derived myocardial strain parameters were included. Study quality was appraised using the Newcastle-Ottawa Scale. The primary outcomes were the mean differences (MD) in global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS), and related strain rate indices between NAFLD spectrum patients and controls. Results: A total of sixteen studies, comprising 8359 participants, were included in the analysis. Compared to controls, patients with NAFLD demonstrated significant reductions in GLS (MD: −2.043; 95% CI: −2.868, −1.218), GAS (MD: −3.706; 95% CI: −4.999, −2.413), and GCS (MD: −1.415; 95% CI: −2.893, 0.064). These reductions were more substantial among individuals with moderate to severe NAFLD and those with concomitant type 2 diabetes mellitus (GLS MD: −4.385; 95% CI: −5.400, −3.369 in diabetic NAFLD vs. diabetic controls). Subgroup analysis further revealed a progressive deterioration in strain parameters from simple steatosis to more severe NAFLD. Notably, LVEF remained preserved in all groups, highlighting the subclinical nature of this dysfunction. Conclusions: This meta-analysis verifies the presence of subclinical left ventricular systolic dysfunction in individuals with NAFLD, which is identifiable by STE despite preserved LVEF. Myocardial strain metrics, particularly GLS, serve as sensitive early markers of myocardial impairment. Routine application of STE in the clinical assessment of NAFLD may support earlier cardiovascular risk detection and timely intervention. Full article
(This article belongs to the Special Issue Emerging Trends in Liver Diseases and Cirrhosis Research)
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