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Molecular Research in Viral Hepatitis and Liver Cancer

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: 20 December 2024 | Viewed by 4739

Special Issue Editor


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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

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Keywords

  • hepatitis B
  • hepatitis C
  • hepatitis D
  • hepatocellular carcinoma

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Published Papers (3 papers)

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Research

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18 pages, 10107 KiB  
Article
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
Viewed by 1674
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 [...] Read more.
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)
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11 pages, 993 KiB  
Article
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 1 | Viewed by 955
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 [...] Read more.
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)
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Review

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22 pages, 1627 KiB  
Review
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 3 | Viewed by 1283
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 [...] Read more.
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)
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