Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Research in Viral Hepatitis and Liver Cancer

Special Issue Editors
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 May 2025) | Viewed by 11259

Share This Special Issue

Special Issue Editor

Prof. Dr. Teh-Ia Huo

E-Mail Website
Guest Editor

Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
Interests: hepatocellular carcinoma; viral hepatitis; liver cancer

Special Issue Information

Dear Colleagues,

Viral hepatitis (mainly hepatitis B, C, and D) has continued to be a global threat. New mechanisms in the pathogenesis of inducing liver diseases have been discovered over the past few decades. One of the major complications of viral hepatitis is hepatocellular carcinoma (HCC), and its mortality rates are rapidly increasing worldwide. Cirrhosis, a chronic complication of viral hepatitis, is also known to be a major risk factor for HCC. Although hepatitis B vaccination and antiviral therapy for hepatitis B and C are effective the for primary prevention of HCCs, unmet clinical needs require further in-depth studies centred around molecular mechanisms. Primary HCC may arise out of synergy between chronic viral infection and other carcinogenic stimuli that induce increased hepatic mitotic activity. Common mechanisms shared by HBV, HCV, and HDV in causing liver cancer include persistent liver inflammation with an impaired anti-viral immune response, viral protein-mediated oxidative stress, and dysregulated cellular signaling pathways. In this Special Issue, investigators provide further evidence in this important field.

Prof. Dr. Teh-Ia Huo
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

hepatitis B
hepatitis C
hepatitis D
hepatocellular carcinoma

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 (5 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

15 pages, 1309 KiB

Open AccessArticle

Distinct Biomarker Profiles of B-Cell Activation in Metabolic and Viral Hepatic Fibrosis

by Umberto Basile, Valeria Carnazzo, Valerio Basile, Stefano Pignalosa, Francesca D’Ambrosio, Ilaria Vinante, Marzia Tagliaferro, Benedetta Niccolini, Riccardo Di Santo, Gian Ludovico Rapaccini, Enrico Rosa, Marco De Spirito, Mariapaola Marino and Gabriele Ciasca

Int. J. Mol. Sci. 2025, 26(13), 5942; https://doi.org/10.3390/ijms26135942 - 20 Jun 2025

Viewed by 161

Abstract

Increasing evidence underlines the role of B-cells in the development of hepatic fibrogenesis following viral infections and metabolic dysfunction, through different mechanisms depending on the etiology. Circulating biomarkers of B-cell activation—such as B-cell activating factor (BAFF), immunoglobulin G (IgG) subclasses, and free light chains (FLCs)—may be associated with different results between viral and metabolic hepatic fibrosis, supporting their use as diagnostic tools. We conducted a case-control study including 100 patients with liver fibrosis, 50/100 of metabolic etiology and 50/100 of viral etiology. A reference group of 30 healthy donors was included as control. Serum levels of BAFF were measured using ELISA, while IgG subclasses (IgG1, IgG2, IgG3, IgG4), κ-FLC, λ-FLC, and the κ/λ ratio were quantified by turbidimetric methods. In univariate analysis, κ-FLC, λ-FLC, and BAFF levels were significantly elevated in both patient groups, with the highest concentrations consistently observed in metabolic fibrosis. IgG2 was selectively increased in metabolic fibrosis, whereas IgG3 was specifically elevated in viral fibrosis. Multivariate analysis confirmed these findings, showing a clear clustering of the three groups and identifying increased BAFF and κ-FLC as key features of metabolic fibrosis, while elevated IgG3 emerged as the most distinctive marker of viral etiology. These results reveal distinct B-cell-related immunological signatures in metabolic and viral hepatic fibrosis supporting the role of BAFF, FLCs, and IgG subclasses as biomarkers of etiological differentiation, and provide novel insights into the immune mechanisms driving fibrosis progression, potentially contributing to the identification of new therapeutic targets. Full article

(This article belongs to the Special Issue Molecular Research in Viral Hepatitis and Liver Cancer)

► Show Figures

Figure 1

14 pages, 843 KiB

Open AccessArticle

Genome-Wide Association Study to Identify Genetic Factors Linked to HBV Reactivation Following Liver Transplantation in HBV-Infected Patients

by Joonhong Park, Dong Yun Kim, Heon Yung Gee, Hee Chul Yu, Jae Do Yang, Shin Hwang, YoungRok Choi, Jae Geun Lee, Jinsoo Rhu, Donglak Choi, Young Kyoung You, Je Ho Ryu, Yang Won Nah, Bong-Wan Kim, Dong-Sik Kim, Jai Young Cho and The Korean Organ Transplantation Registry (KOTRY) Study Group

Int. J. Mol. Sci. 2025, 26(1), 259; https://doi.org/10.3390/ijms26010259 - 30 Dec 2024

Cited by 2 | Viewed by 1527

Abstract

This study utilized a genome-wide association study (GWAS) to investigate the genetic variations linked to the risk of hepatitis B virus (HBV) reactivation in patients who have undergone liver transplantation (LT), aiming to enhance understanding and improve clinical outcomes. Genotyping performed on a selected patients from the Korean Organ Transplantation Registry (KOTRY) data using high-throughput platforms with the Axiom Korea Biobank array 1.1. The discovery cohort included 21 patients who experienced HBV reactivation (cases) and 888 patients without HBV reactivation (controls) following LT. The replication cohort consisted of 5 patients with HBV reactivation (cases) and 312 patients without HBV reactivation (controls) after LT. Additive logistic regression analysis was conducted using PLINK software ver 1.9, with adjustments for age and gender. The GWAS findings from the discovery cohort were validated using the replication cohort. The GWAS identified several single-nucleotide polymorphisms (SNPs) in the RGL1, CDCA7L, and AQP9 genes that were significantly linked to HBV reactivation after LT, with genome-wide significance thresholds set at p < 10⁻⁷. Down-regulation of RGL1 cDNAs was observed in primary duck hepatocytes infected with duck HBV. Overexpression of CDCA7L was found to promote hepatocellular carcinoma cell proliferation and colony formation, whereas knocking down CDCA7L inhibited these processes. Additionally, the absence of AQP9 triggered immune and inflammatory responses, leading to mild and scattered liver cell pyroptosis, accompanied by compensatory liver cell proliferation. This study provides critical insights into the genetic factors influencing HBV reactivation after LT, identifying significant associations with SNPs in RGL1, CDCA7L, and AQP9. These findings hold promise for developing predictive biomarkers and personalized management strategies to improve outcomes for HBV-infected LT recipients. Full article

(This article belongs to the Special Issue Molecular Research in Viral Hepatitis and Liver Cancer)

► Show Figures

Figure 1

18 pages, 10107 KiB

Open AccessArticle

Single-Cell RNA Sequencing Reveals the Spatial Heterogeneity and Functional Alteration of Endothelial Cells in Chronic Hepatitis B Infection

by Jingqi Shi, Qingyu Li, Jian Li, Jianglin Zhou, Xiaochang Zhang, Shengqi Wang and Liang Guo

Int. J. Mol. Sci. 2024, 25(13), 7016; https://doi.org/10.3390/ijms25137016 - 27 Jun 2024

Cited by 3 | Viewed by 3621

Abstract

Chronic Hepatitis B virus (CHB) infection is a global health challenge, causing damage ranging from hepatitis to cirrhosis and hepatocellular carcinoma. In our study, single-cell RNA sequencing (scRNA-seq) analysis was performed in livers from mice models with chronic inflammation induced by CHB infection and we found that endothelial cells (ECs) exhibited the largest number of differentially expressed genes (DEGs) among all ten cell types. NF-κB signaling was activated in ECs to induce cell dysfunction and subsequent hepatic inflammation, which might be mediated by the interaction of macrophage-derived and cholangiocyte-derived VISFATIN/Nampt signaling. Moreover, we divided ECs into three subclusters, including periportal ECs (EC_Z1), midzonal ECs (EC_Z2), and pericentral ECs (EC_Z3) according to hepatic zonation. Functional analysis suggested that pericentral ECs and midzonal ECs, instead of periportal ECs, were more vulnerable to HBV infection, as the VISFATIN/Nampt- NF-κB axis was mainly altered in these two subpopulations. Interestingly, pericentral ECs showed increasing communication with macrophages and cholangiocytes via the Nampt-Insr and Nampt-Itga5/Itgb1 axis upon CHB infection, which contribute to angiogenesis and vascular capillarization. Additionally, ECs, especially pericentral ECs, showed a close connection with nature killer (NK) cells and T cells via the Cxcl6-Cxcr6 axis, which is involved in shaping the microenvironment in CHB mice livers. Thus, our study described the heterogeneity and functional alterations of three subclusters in ECs. We revealed the potential role of VISFATIN/Nampt signaling in modulating ECs characteristics and related hepatic inflammation, and EC-derived chemokine Cxcl16 in shaping NK and T cell recruitment, providing key insights into the multifunctionality of ECs in CHB-associated pathologies. Full article

(This article belongs to the Special Issue Molecular Research in Viral Hepatitis and Liver Cancer)

► Show Figures

Figure 1

11 pages, 993 KiB

Open AccessArticle

Albumin-Based Liver Reserve Models vs. MELD 3.0 in Prognostic Prediction for Hepatocellular Carcinoma Patients with Renal Insufficiency

by Shu-Yein Ho, Po-Hong Liu, Chia-Yang Hsu, Hung-Ting Tseng, Yi-Hsiang Huang, Chien-Wei Su, Ming-Chih Hou and Teh-Ia Huo

Int. J. Mol. Sci. 2023, 24(23), 16987; https://doi.org/10.3390/ijms242316987 - 30 Nov 2023

Cited by 5 | Viewed by 1624

Abstract

The severity of liver functional reserve is an important prognostic predictor in hepatocellular carcinoma (HCC). The albumin–bilirubin (ALBI), easy (EZ)-ALBI, platelet-albumin–bilirubin (PALBI), platelet–albumin (PAL) score, and MELD 3.0 score are used to evaluate the severity of liver dysfunction. However, their prognostic role in HCC patients, specifically with renal insufficiency (RI), is unclear. We aimed to investigate the predictive accuracy of the five models in these patients. A total of 1120 newly diagnosed HCC patients with RI were enrolled. A multivariate Cox proportional analysis was used to identify independent predictors associated with survival. In the Cox model, older age, an α-fetoprotein ≥20 ng/mL, vascular invasion, a medium and high tumor burden score, poor performance status, a higher ALBI grade, an EZ-ALBI grade, a PALBI grade, a PAL grade, and MELD 3.0 score were all independently associated with decreased overall survival (all p < 0.001). Among the five liver reserve models, the ALBI grade is the best surrogate marker to represent liver functional reserve in terms of outcome prediction. The albumin-based liver reserve models (ALBI, EZ-ALBI, PALBI, and PAL) and MELD 3.0 are all feasible prognostic markers to indicate liver injury, specifically in HCC patients with RI. Among them, the ALBI grade is the most robust tool for survival prediction in these patients. Full article

(This article belongs to the Special Issue Molecular Research in Viral Hepatitis and Liver Cancer)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 1627 KiB

Open AccessReview

Inflammatory Response in the Pathogenesis and Treatment of Hepatocellular Carcinoma: A Double-Edged Weapon

by Linda Galasso, Lucia Cerrito, Valeria Maccauro, Fabrizio Termite, Irene Mignini, Giorgio Esposto, Raffaele Borriello, Maria Elena Ainora, Antonio Gasbarrini and Maria Assunta Zocco

Int. J. Mol. Sci. 2024, 25(13), 7191; https://doi.org/10.3390/ijms25137191 - 29 Jun 2024

Cited by 9 | Viewed by 3538

Abstract

Hepatocellular carcinoma (HCC) is the most frequent among primary liver tumors (90%) and one of the main causes of cancer-related death. It develops usually in a chronically inflamed environment, ranging from compensatory parenchymal regeneration to fibrosis and cirrhosis: carcinogenesis can potentially happen in each of these stages. Inflammation determined by chronic viral infection (hepatitis B, hepatitis C, and hepatitis delta viruses) represents an important risk factor for HCC etiology through both viral direct damage and immune-related mechanisms. The deregulation of the physiological liver immunological network determined by viral infection can lead to carcinogenesis. The recent introduction of immunotherapy as the gold-standard first-line treatment for HCC highlights the role of the immune system and inflammation as a double-edged weapon in both HCC carcinogenesis and treatment. In this review we highlight how the inflammation is the key for the hepatocarcinogenesis in viral, alcohol and metabolic liver diseases. Full article

(This article belongs to the Special Issue Molecular Research in Viral Hepatitis and Liver Cancer)

► Show Figures

Journal Menu

Journal Browser

Molecular Research in Viral Hepatitis and Liver Cancer

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (5 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI