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Cancers
Special Issues
HCC and Virus: From Carcinogenesis to New Therapeutic Approaches
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HCC and Virus: From Carcinogenesis to New Therapeutic Approaches

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Survivorship and Quality of Life".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 11873

Special Issue Editors

Dr. Luca Rinaldi

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Guest Editor
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138, Naples, Italy
Interests: HCC; viral hepatitis; NAFLD; ultrasound; type 2 diabetes; gene delivery
Dr. Riccardo Nevola

E-Mail Website
Guest Editor
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138 Naples, Italy
Interests: chronic HCV hepatitis; viral hepatitis; non-alcoholic fatty liver disease; metabolic syndrome; SARS-CoV-2
Special Issues, Collections and Topics in MDPI journals
Dr. Secondo Lastoria

E-Mail
Guest Editor
Department of Hematology Research and Innovative Therapies, National Cancer Institute, G. Pascale, Naples, Italy.

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that accounts for about 6% of all new cancers diagnosed worldwide. It is the third and fifth leading cause of death from cancer worldwide in men and women, respectively. Risk factors historically best known include Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and the resulting complications. Despite the potential decline of HCV cirrhosis in the coming years due to the advent of new antiviral therapies, the increase in metabolic and non-alcoholic fatty liver disease (NASH) constitutes an additional element of risk. The World Health Organization (WHO) estimates that 130–170 million people are infected with HCV worldwide with 400,000 people dying each year to HCV-related liver diseases. Despite the scientific evidence in the last decades highlighting the role of virus infection in HCC-related diseases, the time mechanisms are unclear. Although Directly Acting Antivirals (DAA) treatments for the HCV eradication were acclaimed as the potential panacea for HCC prevention, it is now evident that even in HCV-eradicated patients, the risk of HCC remains. The plot behind this pathology evolution is a miscellany of biological, genetic, biochemical, and epigenetic factors.
Further understanding of viral–host interaction, HCC initiation, progression, and fate with the old and innovative treatments are therefore mandatory for the future of precise medicine.
This Special Issue of Cancers aims to collect new research articles and timely reviews on all aspects of HCC and virus.

Dr. Luca Rinaldi
Dr. Riccardo Nevola
Dr. Secondo Lastoria
Guest Editors

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • hepatocellular carcinoma
  • viral hepatitis
  • direct acting antivirals
  • HBV
  • HCV
  • epigenetic modulators
  • precise medicine
  • oncolytic virus

Published Papers (4 papers)

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Research

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17 pages, 2828 KiB  
Article
HCV Activates Somatic L1 Retrotransposition—A Potential Hepatocarcinogenesis Pathway
by Praveen D. Sudhindar, Daniel Wainwright, Santu Saha, Rachel Howarth, Misti McCain, Yvonne Bury, Sweta S. Saha, Stuart McPherson, Helen Reeves, Arvind H. Patel, Geoffrey J. Faulkner, John Lunec and Ruchi Shukla
Cancers 2021, 13(20), 5079; https://doi.org/10.3390/cancers13205079 - 11 Oct 2021
Cited by 5 | Viewed by 2524
Abstract
Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present [...] Read more.
Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance. Full article
(This article belongs to the Special Issue HCC and Virus: From Carcinogenesis to New Therapeutic Approaches)
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14 pages, 1541 KiB  
Article
Liver Transplantation for HCC in HIV-Infected Patients: Long-Term Single-Center Experience
by Gian Piero Guerrini, Massimiliano Berretta, Giovanni Guaraldi, Paolo Magistri, Giuseppe Esposito, Roberto Ballarin, Valentina Serra, Stefano Di Sandro and Fabrizio Di Benedetto
Cancers 2021, 13(18), 4727; https://doi.org/10.3390/cancers13184727 - 21 Sep 2021
Cited by 8 | Viewed by 1866
Abstract
Background: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results [...] Read more.
Background: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results of liver transplantation (LT) for HCC in HIV-infected patients. Methods: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. Results: Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. Conclusion: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list. Full article
(This article belongs to the Special Issue HCC and Virus: From Carcinogenesis to New Therapeutic Approaches)
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16 pages, 553 KiB  
Article
Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes
by Magda Rybicka, Anna Woziwodzka, Alicja Sznarkowska, Tomasz Romanowski, Piotr Stalke, Marcin Dręczewski, Eloi R. Verrier, Thomas F. Baumert and Krzysztof Piotr Bielawski
Cancers 2020, 12(11), 3295; https://doi.org/10.3390/cancers12113295 - 07 Nov 2020
Cited by 8 | Viewed by 2457
Abstract
Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, [...] Read more.
Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course. DNA repair enzymes can affect dynamics of liver damage and are involved in HBV covalently closed circular DNA (cccDNA) formation, an essential step for viral replication. This study aimed to evaluate the possible role of genes representing key DNA-repair pathways in HBV-induced liver damage. MALDI-TOF MS genotyping platform was applied to evaluate variations within XRCC1, XRCC4, ERCC2, ERCC5, RAD52, Mre11, and NBN genes. Apart from older age (p < 0.001), female sex (p = 0.021), portal hypertension (p < 0.001), thrombocytopenia (p < 0.001), high HBV DNA (p = 0.001), and high aspartate aminotransferase (AST) (p < 0.001), we found that G allele at rs238406 (ERCC2, p = 0.025), T allele at rs25487 (XRCC1, p = 0.012), rs13181 GG genotype (ERCC2, p = 0.034), and C allele at rs2735383 (NBN, p = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (p = 0.005) and rs238406 TT (p = 0.027) were independently associated with lower risk of LC. This study provides evidence for the impact of functional and potentially functional variations in key DNA-repair genes XRCC1 and ERCC2 in HBV-induced liver damage in a Caucasian population. Full article
(This article belongs to the Special Issue HCC and Virus: From Carcinogenesis to New Therapeutic Approaches)
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Review

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31 pages, 781 KiB  
Review
Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives
by Annalisa Chianese, Biagio Santella, Annalisa Ambrosino, Debora Stelitano, Luca Rinaldi, Massimiliano Galdiero, Carla Zannella and Gianluigi Franci
Cancers 2021, 13(11), 2761; https://doi.org/10.3390/cancers13112761 - 02 Jun 2021
Cited by 20 | Viewed by 4145
Abstract
According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a [...] Read more.
According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies). Full article
(This article belongs to the Special Issue HCC and Virus: From Carcinogenesis to New Therapeutic Approaches)
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