Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Liver Diseases: From Pathophysiology to Novel Therapeutic Approaches

Editor
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 April 2026) | Viewed by 4676

Share This Special Issue

Editor

Dr. Clare Selden

E-Mail Website
Guest Editor

UCL Medical School, London, UK
Interests: liver disease; molecular mechanisms; treatments for liver disease; somatic cell therapy; ATMP; medical device; molecular approaches; molecular signatures

Special Issue Information

Dear Colleagues,

The prevalence of liver disease is increasing worldwide. More than sixty years ago, Thomas Starzl performed the first whole-organ liver transplant, which was successfully repeated in the UK and Europe within 5 years. Transplantation can be curative for many patients; however, donor organs are limited and many patients do not receive this curative treatment. Nonetheless, new treatments for liver disease are crucial as liver disease is widespread and growing. Recent advances in understanding the pathophysiology of many liver diseases offer hope for many new therapeutic approaches. With a better understanding of disease pathology at the molecular level, ideas that were a pipe dream 20 years ago are becoming a reality today. Examples in liver disease include anti-fibrotic and cirrhosis-resolving pharmaceuticals. Novel cell therapies in liver cancer include immune modulation therapies and somatic cell therapies, or the use of RNA nanomedicine, wherein gene or protein expression is altered without a corresponding alteration in DNA sequences. Moreover, several delivery technologies are required for these new treatments to be used in patients, whether they be medical devices, nano-carriers, GalNAc based conjugates that target the asialo-glycoprotein receptor, cell and organoid cryopreservation, or cell transplantation into a stem cell niche.

This Special Issue aims to bring together new technological approaches to produce and deliver novel therapies for liver disease as well as to further investigate the molecular patterns associated with liver disease using appropriate “omics” for exploring liver disease pathology further.

Dr. Clare Selden
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

liver disease molecular mechanisms treatments for liver disease somatic cell therapy
ATMP medical device molecular approaches
molecular signatures
RNA therapies
“omics” for liver disease pathobiology

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

22 pages, 26139 KB

Open AccessArticle

Transcriptomic Identification of Diagnostic Biomarkers for Alcohol-Associated Liver Cirrhosis: Integration of Population-Level Epidemiology with Multi-Cohort Transcriptomic Analysis

by Hao Wang, Wenzhang Ding, Linjie Zhang, Muyang Xu and Jing Sui

Int. J. Mol. Sci. 2026, 27(13), 5809; https://doi.org/10.3390/ijms27135809 - 26 Jun 2026

Viewed by 305

Abstract

Alcohol-associated liver cirrhosis (ALC) lacks aetiology-specific molecular diagnostic biomarkers. This study aims to quantify the association between alcohol and cirrhosis risk, and to identify transcriptomic diagnostic biomarkers and candidate therapeutics. Methods: Survey-weighted logistic regression was applied to 17,007 adults from NHANES (2017–2023) to quantify alcohol-cirrhosis associations. ALC transcriptomic data from four GEO datasets were analysed using weighted gene co-expression network analysis (WGCNA) and three parallel machine learning algorithms (LASSO, Random Forest, SVM-RFE). External validation was performed in an independent cohort of 93 samples. Candidate therapeutics were identified via drug signature database querying and validated by molecular docking. Heavy drinking conferred a 5.14-fold increased cirrhosis risk (95% CI: 2.60–10.20, p < 0.001). Transcriptomic analysis revealed global downregulation of long non-coding RNAs (with 91.7% of dysregulated lncRNAs being suppressed). A five-gene diagnostic signature (IL1B, CCL3, LUM, SPP1, ITGA6), specifically developed to distinguish ALC from histologically normal liver tissue, achieved an area under the receiver operating characteristic curve (AUC) of 0.824 in an external validation cohort. Immune infiltration analysis uncovered global contraction of macrophage-associated transcriptomic signatures across M0, M1, and M2 subtypes, inversely correlated with fibrotic hub gene upregulation. Fluvastatin and honokiol were identified as candidate therapeutic agents, with strong binding affinities to IL1B and CCL3, respectively. This study confirms a dose-dependent alcohol-cirrhosis association and establishes a five-gene diagnostic signature (distinguishing ALC from normal liver tissue) alongside candidate therapeutics, warranting prospective clinical validation. The identified tissue-derived signature and therapeutic candidates provide a foundation for future ALC-specific diagnostic and therapeutic strategies; their translation into a non-invasive (e.g., blood-based) assay will require dedicated validation in circulating samples. Full article

(This article belongs to the Special Issue Liver Diseases: From Pathophysiology to Novel Therapeutic Approaches)

► Show Figures

Figure 1

27 pages, 2779 KB

Open AccessArticle

Cinnamic Acid: A Shield Against High-Fat-Diet-Induced Liver Injury—Exploring Nrf2’s Protective Mechanisms

by Asmahan Taher Alahdal, Laila Naif Al-Harbi, Ghedeir M. Alshammari, Ali Saleh and Mohammed Abdo Yahya

Int. J. Mol. Sci. 2025, 26(16), 7940; https://doi.org/10.3390/ijms26167940 - 17 Aug 2025

Cited by 4 | Viewed by 2202

Abstract

This study investigated the hepatoprotective effects of cinnamic acid (CA) against liver injury and fat accumulation induced by a high-fat diet (HFD), focusing on the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Male Wistar rats were divided into six groups: a control group receiving carboxymethylcellulose; a CA control group (40 mg/kg); an HFD group; two HFD groups treated with CA (20 mg/kg or 40 mg/kg); and a HFD group co-treated with CA (40 mg/kg) and brusatol (2 mg/kg, i.p.), a selective Nrf2 inhibitor. CA was administered orally, and brusatol intraperitoneally, both twice per week for twelve weeks. CA had no effect on serum glucose or insulin but improved serum and hepatic profiles in HFD rats. It also attenuated liver vacuolization and normalized serum levels of ALT, AST, and γ-GT. CA also reduced hepatic apoptosis by increasing Bcl2 and reducing Bax and caspase-3 levels. CA mitigated oxidative stress by reducing MDA and enhancing SOD and GSH levels. It suppressed inflammatory mediators, including TNF-α, IL-6, and NF-κB. CA also downregulated SREBP1, FAS, ACC-1, and Keap1 while increasing mRNA and nuclear translocation of Nrf2. All these effects were dose-dependent. Similar molecular effects of CA were also seen in control rats while CA protection in HFD rats was abolished with brusatol indicating Nrf2-dependency. Such findings highlight CA as a promising nutraceutical candidate for preventing HFD-induced liver injury. Further studies are warranted to explore its clinical applicability in metabolic liver diseases. Full article

(This article belongs to the Special Issue Liver Diseases: From Pathophysiology to Novel Therapeutic Approaches)

► Show Figures

Figure 1

Review

Jump to: Research

19 pages, 1390 KB

Open AccessReview

Deubiquitinating Enzymes as Therapeutic Candidates in Hepatocellular Carcinoma and Other Liver Disease

by Young-Hoon Jeong, Hwa-Hyeong Lee, Young-Jun Kim, Hye-Rim Lee and Key-Hwan Lim

Int. J. Mol. Sci. 2026, 27(12), 5625; https://doi.org/10.3390/ijms27125625 - 22 Jun 2026

Viewed by 237

Abstract

Hepatocellular carcinoma is challenging to detect at an early stage, and its severity increases over time. Recently, the incidence of hepatocellular carcinoma has increased, partly due to lifestyle-related factors such as excessive alcohol intake, sedentary behavior, and diets high in fat, which contribute to the growing prevalence of fatty liver and hepatitis. Various therapeutic strategies are being explored for hepatocellular carcinoma, among which therapies targeting deubiquitinating enzymes (DUBs) have attracted growing attention. Ubiquitination acts as a crucial modulator in the regulation of intracellular signaling across many diseases. E3 ligase recognizes the target protein and transfers ubiquitin, received from the E2 enzyme, to the lysine residues of the substrate, thereby conferring specificity to the ubiquitination process. Once a ubiquitin chain is attached to a target protein by an E3 ligase, the protein is directed to the ubiquitin–proteasome system (UPS) for degradation. In this process, the 26S proteasome complex recognizes the ubiquitin chain and degrades the target protein, thereby serving as a major mechanism for maintaining protein homeostasis. Through this pathway, cells regulate signal transduction, eliminate abnormal proteins, and perform various essential functions. On the other hand, deubiquitinating enzymes (DUBs) recognize the ubiquitin chains on target proteins and remove them by hydrolyzing the isopeptide bonds of ubiquitin, thereby enabling the target proteins to evade degradation by the proteasome system. Furthermore, deubiquitinating enzymes independently remove ubiquitin from proteins and can serve as central regulators in signaling pathways related to hepatocellular carcinoma. Full article

(This article belongs to the Special Issue Liver Diseases: From Pathophysiology to Novel Therapeutic Approaches)

► Show Figures

Figure 1

10 pages, 551 KB

Open AccessReview

Redox Modulation in Hepatic Fibrosis: Translating NOX1/4 Inhibition to Therapy

by Ghaith K. Mansour, Ahmad W. Hajjar, Irene Marafini and Giovanni Monteleone

Int. J. Mol. Sci. 2026, 27(1), 158; https://doi.org/10.3390/ijms27010158 - 23 Dec 2025

Viewed by 1403

Abstract

Chronic liver disease (CLD) encompasses a spectrum of progressive disorders, including metabolic dysfunction steatotic-associated liver disease (MASLD) and primary biliary cholangitis (PBC), which together represent a significant global health burden with few effective therapeutic options. The fibrogenic process, common to most forms of CLD, is driven by a complex interplay of cellular stress, inflammation, and wound-healing responses. Nicotinamide adenine dinucleotide phosphate oxidase isoforms 1 and 4 (NOX1 and NOX4) have emerged as key enzymatic sources of reactive oxygen species (ROS), serving as central mediators of hepatic oxidative stress, fibrogenesis, and inflammation. Setanaxib is a first-in-class, orally bioavailable, selective dual inhibitor of NOX1 and NOX4 that has progressed to clinical evaluation. This review synthesizes current knowledge on the molecular pharmacology of the NOX1/4 axis, preclinical evidence from translational models, and clinical trial outcomes to critically assess the therapeutic potential of targeted NOX inhibition in hepatic fibrosis. By attenuating hepatic stellate cell activation, modulating TGF-β signaling, reducing extracellular matrix (ECM) deposition, and regulating hepatic macrophage polarization, setanaxib exhibits pleiotropic antifibrotic effects. The compound also demonstrates favorable pharmacokinetic properties and a good safety profile in patients with PBC, with emerging evidence suggesting meaningful improvements in fatigue and quality of life. Finally, we examine the complex, and sometimes paradoxical, roles of NOX4 in liver pathophysiology, compare the evolving therapeutic landscape with other approaches such as farnesoid X receptor (FXR) agonists, and propose future paradigms integrating artificial intelligence–driven predictive modeling to optimize patient stratification and therapeutic response in this new era of redox-targeted hepatoprotective therapy. Full article

(This article belongs to the Special Issue Liver Diseases: From Pathophysiology to Novel Therapeutic Approaches)

► Show Figures

Journal Menu

Journal Browser

Liver Diseases: From Pathophysiology to Novel Therapeutic Approaches

Share This Special Issue

Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (4 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI