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Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases

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 March 2026) | Viewed by 20647

Special Issue Editor

Dr. Hirayuki Enomoto

E-Mail Website
Guest Editor
Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan
Interests: viral hepatitis; liver cirrhosis; portal hypertension; ascites; esophageal varices; liver fibrosis; hepatocellular carcinoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic liver diseases develop through a wide range of causes, including hepatitis B virus (HBV) and C virus (HCV) infection, alcoholic-related liver disease, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver diseases. Due to recent advancements in antiviral therapies and lifestyle changes, the clinical importance of non-viral chronic liver diseases is increasing. However, viral hepatitis is still a major cause of chronic liver diseases.

Recent advances in molecular and cellular techniques have succeeded in providing new perspectives related to the diagnosis and treatment of chronic liver diseases.

This Special Issue aims to cover state-of-the-art research on chronic liver diseases, inviting authors to submit original and review articles on recent findings in this area, particularly molecular approaches for the diagnosis and treatment of these diseases. Potential topics include, but are not limited to, the following:

  • Biomarkers for chronic liver diseases;
  • Genomic research for chronic liver diseases, including gene SNPs (single-nucleotide polymorphisms);
  • Molecular mechanisms of chronic liver diseases;
  • Recent advances in the management of chronic liver diseases, including liver cirrhosis;
  • Molecularly targeted therapy for liver cancer.

Dr. Hirayuki Enomoto
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-blind 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

  • biomarker
  • genomic research
  • epigenomic research
  • molecular mechanisms
  • viral hepatitis
  • alcoholic-related liver disease
  • non-alcoholic fatty liver disease
  • autoimmune liver diseases
  • liver cirrhosis
  • hepatocellular carcinoma

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Related Special Issue

Published Papers (6 papers)

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Research

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27 pages, 7336 KB  
Article
Hepatitis C Virus 5′UTR Sequences That Bind eIF3 and Ribosomal 40S Subunits Confer Stimulation of Minus-Strand RNA Synthesis
by Attiya Qadoos Malik, Lyudmila Shalamova, Mozhdeh Khajouei, Jonas Budnik, Anna-Lena Hell, Elena Jost, Gesche K. Gerresheim, Oliver Rossbach and Michael Niepmann
Int. J. Mol. Sci. 2026, 27(7), 3234; https://doi.org/10.3390/ijms27073234 - 2 Apr 2026
Viewed by 451
Abstract
Hepatitis C Virus (HCV) is a plus-strand RNA virus that replicates its genome via a minus-strand intermediate, which in turn is the template for the synthesis of progeny plus-strand genomes. In order to characterize sequence elements in the HCV 5′-untranslated region (5′UTR) that [...] Read more.
Hepatitis C Virus (HCV) is a plus-strand RNA virus that replicates its genome via a minus-strand intermediate, which in turn is the template for the synthesis of progeny plus-strand genomes. In order to characterize sequence elements in the HCV 5′-untranslated region (5′UTR) that are possibly involved in the regulation of minus-strand RNA synthesis starting at the genome’s 3′end, we used a replicon system in which a possible function of these sequences is uncoupled from other functions like translation regulation. For the specific detection by RT-qPCR of minus strands newly synthesized in the cells from the transfected replicon RNAs, we carefully eliminated the contaminating DNA and transfected RNA and avoided self-priming caused by hairpin formation. We found that the absence of any HCV sequences at the 5′end does not allow genome replication. Stem-loop I-II sequences only allow extremely low-level replication, whereas the presence of stem-loops I-III or the complete 5′UTR allows efficient replication. The mutation of sequences required for the binding of translation initiation factor 3 (eIF3) and the ribosomal 40S subunit in the 5′UTR of the plus strand severely impairs minus-strand synthesis. This suggests that eIF3 and the 40S subunit are involved in plus-strand 5′-3′-end communication and the regulation of minus-strand synthesis. Full article
(This article belongs to the Special Issue Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases)
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Review

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17 pages, 560 KB  
Review
Accuracy of Diagnostic Investigations in Monitoring Hepatitis B Virus Infection: Strengths, Limitations, and Emerging Biomarkers
by Laura Iulia Bozomitu, Ancuta Lupu, Vasile Valeriu Lupu, Nicoleta Gimiga, Dana Teodora Anton Paduraru, Dana Elena Mîndru, Mihaela Mihai, Carmen Anton, Emil Anton, Mihaela Mitrea, Anca Adam-Raileanu and Lorenza Forna
Int. J. Mol. Sci. 2026, 27(5), 2464; https://doi.org/10.3390/ijms27052464 - 7 Mar 2026
Viewed by 527
Abstract
In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) updated the biomarker framework; they underscored major advances in the understanding of viral and immunologic markers, yet highlighted persistent gaps in their clinical integration. This is particularly the case in low- [...] Read more.
In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) updated the biomarker framework; they underscored major advances in the understanding of viral and immunologic markers, yet highlighted persistent gaps in their clinical integration. This is particularly the case in low- and middle-income regions, where HBV remains a substantial public health problem, including in the pediatric population. To synthesize contemporary evidence, a structured literature search was performed across PubMed/MEDLINE, Scopus, and Web of Science. Classical biomarkers—including HBeAg, HBV DNA, and quantitative HBsAg—remain central for disease staging and therapeutic monitoring, while emerging markers enhance precision in risk stratification: HBcrAg, which correlates strongly with intrahepatic cccDNA activity and virological rebound after NA discontinuation; serum HBV RNA, which offers additional insight into transcriptional activity, which is particularly relevant for RNA-targeted therapies; and quantitative anti-HBc (qAnti-HBc), which reflects stronger humoral imprinting and more competent HBV-specific immune memory, and is consistently associated with fewer ALT flares and reduced virological rebound at end of treatment. Despite these advances, assay standardization, genotype-related variability, and limited pediatric data constrain broad clinical application. Integrating classical and emerging biomarkers into personalized therapeutic algorithms offers substantial potential for refining treatment decisions, predicting post-treatment outcomes, and advancing HBV elimination strategies in diverse clinical settings. Full article
(This article belongs to the Special Issue Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases)
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22 pages, 9696 KB  
Review
Liver Disease in Common Variable Immunodeficiency: Current Evidence and Knowledge Gaps
by Irena Nedelea, Oana Nicoara-Farcau, Bogdan Procopet, Horia Stefanescu, Corina Radu, Radu Balan, Ana-Maria Fit, Ioana Rusu and Diana Deleanu
Int. J. Mol. Sci. 2026, 27(3), 1518; https://doi.org/10.3390/ijms27031518 - 3 Feb 2026
Viewed by 991
Abstract
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency or inborn error of immunity (IEI) encountered in clinical practice. Characterized by a remarkably broad clinical spectrum, CVID presents with phenotypes spanning from “infection only” to significant non-infectious complications. The frequent overlap [...] Read more.
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency or inborn error of immunity (IEI) encountered in clinical practice. Characterized by a remarkably broad clinical spectrum, CVID presents with phenotypes spanning from “infection only” to significant non-infectious complications. The frequent overlap between these classifications underscores that their distinction is more accurately viewed as a continuous spectrum, rather than a binary categorization. CVID-associated liver disease is a significant source of morbidity, yet often poses diagnostic challenges due to its insidious and clinically silent nature, typically becoming apparent only upon the development of complications. Manifestations range from abnormal liver tests to irreversible organ damage, with reports including granulomas, autoimmune hepatitis, fibrosis, and porto-sinusoidal vascular disorder (PSVD). Regenerative nodular hyperplasia (RNH), commonly associated with PSVD, is a frequent histopathological finding. Management requires a multidisciplinary approach, including cause-directed immunosuppression and supportive treatment for non-cirrhotic portal hypertension. Despite significant advances in comprehending CVID-associated liver involvement, substantial gaps persist concerning its pathogenesis, its optimal management, and the correlation between histological findings and clinical outcomes. A heightened awareness of CVID-associated liver disease is paramount for multidisciplinary teams across IEI centers. Furthermore, given its prevalence, its insidious clinical phenotype until advanced complications, and the significant diagnostic delay and underdiagnosis, such awareness is critical across a broader range of medical specialties. In this paper, we aim to consolidate current knowledge regarding CVID-related liver disease, examining its clinical presentation, recent genetic and pathogenetic advancements along with current diagnostic methodologies, and therapeutic strategies. Full article
(This article belongs to the Special Issue Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases)
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35 pages, 10516 KB  
Review
Histological and Molecular Evaluation of Liver Biopsies: A Practical and Updated Review
by Joon Hyuk Choi
Int. J. Mol. Sci. 2025, 26(16), 7729; https://doi.org/10.3390/ijms26167729 - 10 Aug 2025
Cited by 6 | Viewed by 10072
Abstract
Liver biopsy remains an indispensable diagnostic modality in contemporary hepatology because most classification systems and pathogenetic concepts are grounded in morphology. The diagnostic yield of a biopsy hinges on specimen adequacy and meticulous tissue processing; however, interpretation often challenges even experienced pathologists. This [...] Read more.
Liver biopsy remains an indispensable diagnostic modality in contemporary hepatology because most classification systems and pathogenetic concepts are grounded in morphology. The diagnostic yield of a biopsy hinges on specimen adequacy and meticulous tissue processing; however, interpretation often challenges even experienced pathologists. This narrative review summarizes practical aspects of histological and molecular assessment for both clinicians and pathologists. Key topics include specimen handling, selection of ancillary stains, recognition of pivotal patterns of hepatic injury, and a systematic approach to differential diagnosis. Mastery of both histological and molecular principles is essential for accurate diagnosis, appropriate therapy, and reliable prognostication. Full article
(This article belongs to the Special Issue Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases)
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29 pages, 340 KB  
Review
Systemic Therapy for Unresectable Hepatocellular Carcinoma: Current Landscape and Future Directions
by Zachary Philippi, Keerthi D. Reddy, Sheza Malik, Zeina Al-Khalil and Nader Dbouk
Int. J. Mol. Sci. 2025, 26(13), 5994; https://doi.org/10.3390/ijms26135994 - 22 Jun 2025
Cited by 2 | Viewed by 3732
Abstract
Hepatocellular carcinoma (HCC), the most common primary liver cancer, remains a leading cause of cancer-related mortality worldwide. Its often-silent progression results in late-stage diagnosis, limiting curative options and necessitating systemic therapy for many patients. The presence of underlying cirrhosis in most cases further [...] Read more.
Hepatocellular carcinoma (HCC), the most common primary liver cancer, remains a leading cause of cancer-related mortality worldwide. Its often-silent progression results in late-stage diagnosis, limiting curative options and necessitating systemic therapy for many patients. The presence of underlying cirrhosis in most cases further complicates treatment decisions. While the approval of sorafenib in 2007 marked a major milestone in systemic therapy for HCC, the treatment landscape has since evolved significantly, particularly with the advent of immune checkpoint inhibitors and anti-angiogenic agents. Combination regimens, such as atezolizumab plus bevacizumab, have demonstrated superior outcomes and are now considered standard first-line options. Despite these advances, efforts to translate insights from HCC’s molecular pathogenesis into personalized treatments have been limited. This narrative review explores the current systemic therapy options for HCC, from first-line to subsequent-line treatments, and highlights emerging strategies, including novel immunotherapies and targeted agents. We emphasize the need for individualized treatment approaches that consider tumor biology, liver function, and performance status, and we outline future directions for research aimed at improving outcomes in this complex and evolving field. Full article
(This article belongs to the Special Issue Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases)
12 pages, 897 KB  
Review
The Role of Myokines in Liver Diseases
by Hiroki Nishikawa, Soo Ki Kim and Akira Asai
Int. J. Mol. Sci. 2025, 26(3), 1043; https://doi.org/10.3390/ijms26031043 - 25 Jan 2025
Cited by 6 | Viewed by 3913
Abstract
Myokine is a general term for hormones, peptides, and other substances secreted by skeletal muscle. Myokine has attracted much attention in recent years as a key substance for understanding the mechanism of “exercise and health”. Skeletal muscle accounts for about 40% of the [...] Read more.
Myokine is a general term for hormones, peptides, and other substances secreted by skeletal muscle. Myokine has attracted much attention in recent years as a key substance for understanding the mechanism of “exercise and health”. Skeletal muscle accounts for about 40% of the total human weight and is now recognized as an endocrine organ that produces myokines, which have physiological activity. Representative myokines include IL-6, myostatin, irisin, brain-derived neurotropic factor, fibroblast growth factor-21, and decorin. On the other hand, sarcopenia, defined by quantitative and qualitative loss of skeletal muscle, is a condition that has received much attention in recent years because of its close correlation with prognosis. In patients with chronic liver disease (CLD), sarcopenia is a common complication. Mechanisms underlying sarcopenia in CLD patients have been reported to involve protein-energy malnutrition, which is characteristic of patients with cirrhosis, signaling involved in protein synthesis and degradation, myokines such as myostatin and decorin, the ubiquitin-proteasome pathway, sex hormones such as testosterone, dysbiosis, and insulin resistance, etc., in addition to aging. Each of these pathological conditions is thought to be intricately related to each other, leading to sarcopenia. This review will summarize the relationship between CLD and myokines. Full article
(This article belongs to the Special Issue Advanced Molecular Research on the Diagnosis and Treatment of Chronic Liver Diseases)
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