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Viral Hepatitis and Risk of Hepatocellular Carcinoma
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Viral Hepatitis and Risk of Hepatocellular Carcinoma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 39849

Special Issue Editors

Dr. Joachim Lupberger

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Guest Editor
Institut National de la Santé et de la Recherche Médicale, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg, Strasbourg, France
Interests: pathogenesis of viral hepatitis; signal transduction; liver disease; hepatocellular carcinoma; biomarkers
Prof. Dr. Thomas F. Baumert

E-Mail Website
Guest Editor
Institut National de la Santé et de la Recherche Médicale, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Pôle Hépato-digestif, Institut Hopitalo-Universitaire, Strasbourg, Université de Strasbourg, Strasbourg, France
Interests: hepatology; liver fibrosis; non-alcoholic fatty liver disease (NAFLD); hepatocellular carcinoma; chemoprevention; viral hepatitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Three decades after the discovery of the virus, treatment of hepatitis C virus infection with the new generation of direct-acting antivirals have turned this health burden into a curable disease. Virus-associated hepatic and extrahepatic complications of chronic infection, i.e., metabolic syndrome, fibrosis, and hepatocellular carcinoma (HCC), are significantly decreasing in clinical cohorts after sustained virologic response. However, the risk of developing HCC cannot be fully eradicated, especially in patients with advanced liver disease. This suggests persistent alternations in the liver, which are induced during chronic infection with HCV that cumulate in a tip-over, a point of no return for individual patients. It is estimated that although viral cure can be achieved in almost all patients treated with DAAs, the peak of HCV-associated liver diseases and HCC is yet to come. These facts highlight important, yet unsolved problems: How can we identify the fraction of HCV-cured patients at still-elevated HCC risk? And how can we help these patients that we stratified for a closer follow up with novel clinical strategies? In chronic hepatitis B, antivirals efficiently control viral infection but rarely eliminate the viral genome. While control of HBV infection has been shown to result in a decrease in liver disease progression and HCC risk, a fraction of patients still develop cancer.

In recent years, it has become clear that only a joint effort of translational scientists and clinicians will be able to provide answers to these eminent questions and develop innovative strategies for reliable biomarkers novel chemopreventive strategies aiming at halting liver disease progression and preventing HCC.

Thus, the present Special Issue aims to provide an interdisciplinary view of the current challenges in the post-HCV cure era and to define the next steps urgently required to tackle the aftermath of the HCV epidemic and to accompany and help HCV-cured patients at risk of developing HCC. Furthermore, this Special Issue will address the risk of HCC in the treatment of patients with chronic hepatitis B.

Dr. Joachim Lupberger
Prof. Dr. Thomas F. Baumert
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. Journal of Clinical Medicine 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 2600 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

  • HCC risk estimation in clinical populations with sustained viral response
  • HCC risk in patients with chronic hepatitis B
  • Persistent epigenetic footprints of Hepatitis C virus infection
  • Biomarkers for HCC risk
  • Implementation of personalized medicine in clinical practice
  • Chemoprevention of HCC development and recurrence
  • What can we learn from HCV for other liver disease etiologies?

Published Papers (12 papers)

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Editorial

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3 pages, 189 KiB  
Editorial
Virus-Induced Risk of Hepatocellular Carcinoma: Recent Progress and Future Challenges
by Joachim Lupberger and Thomas F. Baumert
J. Clin. Med. 2022, 11(1), 208; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11010208 - 31 Dec 2021
Viewed by 1043
Abstract
Chronic viral hepatitis is a key risk factor for liver fibrosis and hepatocellular carcinoma (HCC) [...] Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)

Research

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10 pages, 1678 KiB  
Article
PCSK9 Levels Are Raised in Chronic HCV Patients with Hepatocellular Carcinoma
by Silvano Fasolato, Sabrina Pigozzo, Patrizia Pontisso, Paolo Angeli, Massimiliano Ruscica, Edoardo Savarino, Sara De Martin, Maria Giovanna Lupo and Nicola Ferri
J. Clin. Med. 2020, 9(10), 3134; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9103134 - 28 Sep 2020
Cited by 21 | Viewed by 2064
Abstract
Background: Since emerging evidence suggests a protective role of proprotein convertase subtilisin/kexin type 9 (PCSK9) on hepatitis C virus (HCV) infection, the aim of the present study was to evaluate the correlation between PCSK9 and HCV infection in hepatocellular carcinoma (HCC) patients. Methods: [...] Read more.
Background: Since emerging evidence suggests a protective role of proprotein convertase subtilisin/kexin type 9 (PCSK9) on hepatitis C virus (HCV) infection, the aim of the present study was to evaluate the correlation between PCSK9 and HCV infection in hepatocellular carcinoma (HCC) patients. Methods: In this retrospective study, PCSK9 levels were evaluated by ELISA, in plasma samples from control (n = 24) and 178 patients diagnosed for HCC, cirrhosis, or chronic hepatitis, either positive or negative for HCV. Results: HCV positive patients (HCV+) presented with higher PCSK9 levels compared to HCV negative individuals (HCV-), 325.2 ± 117.7 ng/mL and 256.7 ± 139.5 ng/mL, respectively. This difference was maintained in the presence of HCC, although this disease significantly reduced PCSK9 levels. By univariate analysis, a positive correlation between PCSK9 and HCV viral titer was found, being G2 genotype the most-potent inducer of PCSK9 among other genotypes. This induction was not associated with changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). A negative correlation was also found between PCSK9 levels and liver impairment, assessed by Model for End-Stage Liver Disease (MELD). Finally, a multivariate correlation analysis corrected for age, TC, LDL-C, and sex, demonstrated, in the whole cohort, a positive association between PCSK9 and HCV and a negative with HCC. Conclusions: taken together, our study reveals that HCV raised PCSK9 in both the presence and absence of HCC. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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14 pages, 1223 KiB  
Article
Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study
by Chung-Man Moon, Sang Soo Shin, Suk Hee Heo and Yong Yeon Jeong
J. Clin. Med. 2020, 9(3), 765; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030765 - 12 Mar 2020
Cited by 8 | Viewed by 2144
Abstract
Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage [...] Read more.
Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60–80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60–80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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Review

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16 pages, 842 KiB  
Review
Genomics of Viral Hepatitis-Associated Liver Tumors
by Camille Péneau, Jessica Zucman-Rossi and Jean-Charles Nault
J. Clin. Med. 2021, 10(9), 1827; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10091827 - 22 Apr 2021
Cited by 9 | Viewed by 6295
Abstract
Virus-related liver carcinogenesis is one of the main contributors of cancer-related death worldwide mainly due to the impact of chronic hepatitis B and C infections. Three mechanisms have been proposed to explain the oncogenic properties of hepatitis B virus (HBV) infection: induction of [...] Read more.
Virus-related liver carcinogenesis is one of the main contributors of cancer-related death worldwide mainly due to the impact of chronic hepatitis B and C infections. Three mechanisms have been proposed to explain the oncogenic properties of hepatitis B virus (HBV) infection: induction of chronic inflammation and cirrhosis, expression of HBV oncogenic proteins, and insertional mutagenesis into the genome of infected hepatocytes. Hepatitis B insertional mutagenesis modifies the function of cancer driver genes and could promote chromosomal instability. In contrast, hepatitis C virus promotes hepatocellular carcinoma (HCC) occurrence mainly through cirrhosis development whereas the direct oncogenic role of the virus in human remains debated. Finally, adeno associated virus type 2 (AAV2), a defective DNA virus, has been associated with occurrence of HCC harboring insertional mutagenesis of the virus. Since these tumors developed in a non-cirrhotic context and in the absence of a known etiological factor, AAV2 appears to be the direct cause of tumor development in these patients via a mechanism of insertional mutagenesis altering similar oncogenes and tumor suppressor genes targeted by HBV. A better understanding of virus-related oncogenesis will be helpful to develop new preventive strategies and therapies directed against specific alterations observed in virus-related HCC. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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16 pages, 1178 KiB  
Review
Host Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma
by Mirjam B. Zeisel, Francesca Guerrieri and Massimo Levrero
J. Clin. Med. 2021, 10(8), 1715; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081715 - 16 Apr 2021
Cited by 12 | Viewed by 3214
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Although much progress has been made in HCC drug development in recent years, treatment options remain limited. The major cause of HCC is [...] Read more.
Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Although much progress has been made in HCC drug development in recent years, treatment options remain limited. The major cause of HCC is chronic hepatitis B virus (HBV) infection. Despite the existence of a vaccine, more than 250 million individuals are chronically infected by HBV. Current antiviral therapies can repress viral replication but to date there is no cure for chronic hepatitis B. Of note, inhibition of viral replication reduces but does not eliminate the risk of HCC development. HBV contributes to liver carcinogenesis by direct and indirect effects. This review summarizes the current knowledge of HBV-induced host epigenetic alterations and their association with HCC, with an emphasis on the interactions between HBV proteins and the host cell epigenetic machinery leading to modulation of gene expression. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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12 pages, 886 KiB  
Review
CD8+ T Cell Responses during HCV Infection and HCC
by Maike Hofmann, Catrin Tauber, Nina Hensel and Robert Thimme
J. Clin. Med. 2021, 10(5), 991; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10050991 - 02 Mar 2021
Cited by 20 | Viewed by 3323
Abstract
Chronic hepatitis C virus (cHCV) infection is a major global health burden and the leading cause of hepatocellular carcinoma (HCC) in the Western world. The course and outcome of HCV infection is centrally influenced by CD8+ T cell responses. Indeed, strong virus-specific [...] Read more.
Chronic hepatitis C virus (cHCV) infection is a major global health burden and the leading cause of hepatocellular carcinoma (HCC) in the Western world. The course and outcome of HCV infection is centrally influenced by CD8+ T cell responses. Indeed, strong virus-specific CD8+ T cell responses are associated with spontaneous viral clearance while failure of these responses, e.g., caused by viral escape and T cell exhaustion, is associated with the development of chronic infection. Recently, heterogeneity within the exhausted HCV-specific CD8+ T cells has been observed with implications for immunotherapeutic approaches also for other diseases. In HCC, the presence of tumor-infiltrating and peripheral CD8+ T cell responses correlates with a favorable prognosis. Thus, tumor-associated and tumor-specific CD8+ T cells are considered suitable targets for immunotherapeutic strategies. Here, we review the current knowledge of CD8+ T cell responses in chronic HCV infection and HCC and their respective failure with the potential consequences for T cell-associated immunotherapeutic approaches. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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Graphical abstract

16 pages, 669 KiB  
Review
Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development
by Alessia Virzì, Victor Gonzalez-Motos, Simona Tripon, Thomas F. Baumert and Joachim Lupberger
J. Clin. Med. 2021, 10(5), 977; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10050977 - 02 Mar 2021
Cited by 8 | Viewed by 2649
Abstract
Despite breakthroughs in antiviral therapies, chronic viral hepatitis B and C are still the major causes of liver fibrosis and hepatocellular carcinoma (HCC). Importantly, even in patients with controlled infection or viral cure, the cancer risk cannot be fully eliminated, highlighting a persisting [...] Read more.
Despite breakthroughs in antiviral therapies, chronic viral hepatitis B and C are still the major causes of liver fibrosis and hepatocellular carcinoma (HCC). Importantly, even in patients with controlled infection or viral cure, the cancer risk cannot be fully eliminated, highlighting a persisting oncogenic pressure imposed by epigenetic imprinting and advanced liver disease. Reliable and minimally invasive biomarkers for early fibrosis and for residual HCC risk in HCV-cured patients are urgently needed. Chronic infection with HBV and/or HCV dysregulates oncogenic and profibrogenic signaling within the host, also displayed in the secretion of soluble factors to the blood. The study of virus-dysregulated signaling pathways may, therefore, contribute to the identification of reliable minimally invasive biomarkers for the detection of patients at early-stage liver disease potentially complementing existing noninvasive methods in clinics. With a focus on virus-induced signaling events, this review provides an overview of candidate blood biomarkers for liver disease and HCC risk associated with chronic viral hepatitis and epigenetic viral footprints. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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15 pages, 767 KiB  
Review
Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis
by Tom Domovitz and Meital Gal-Tanamy
J. Clin. Med. 2021, 10(3), 551; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10030551 - 02 Feb 2021
Cited by 17 | Viewed by 3131
Abstract
Hepatitis C virus (HCV) is a major cause of death and morbidity globally and is a leading cause of hepatocellular carcinoma (HCC). Incidence of HCV infections, as well as HCV-related liver diseases, are increasing. Although now, with new direct acting antivirals (DAAs) therapy [...] Read more.
Hepatitis C virus (HCV) is a major cause of death and morbidity globally and is a leading cause of hepatocellular carcinoma (HCC). Incidence of HCV infections, as well as HCV-related liver diseases, are increasing. Although now, with new direct acting antivirals (DAAs) therapy available, HCV is a curable cancer-associated infectious agent, HCC prevalence is expected to continue to rise because HCC risk still persists after HCV cure. Understanding the factors that lead from HCV infection to HCC pre- and post-cure may open-up opportunities to novel strategies for HCC prevention. Herein, we provide an overview of the reported evidence for the induction of alterations in the transcriptome of host cells via epigenetic dysregulation by HCV infection and describe recent reports linking the residual risk for HCC post-cure with a persistent HCV-induced epigenetic signature. Specifically, we discuss the contribution of the epigenetic changes identified following HCV infection to HCC risk pre- and post-cure, the molecular pathways that are epigenetically altered, the downstream effects on expression of cancer-related genes, the identification of targets to prevent or revert this cancer-inducing epigenetic signature, and the potential contribution of these studies to early prognosis and prevention of HCC as an approach for reducing HCC-related mortality. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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13 pages, 739 KiB  
Review
Stratification of Hepatocellular Carcinoma Risk Following HCV Eradication or HBV Control
by Pierre Nahon, Erwan Vo Quang and Nathalie Ganne-Carrié
J. Clin. Med. 2021, 10(2), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020353 - 19 Jan 2021
Cited by 18 | Viewed by 2964
Abstract
Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV [...] Read more.
Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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13 pages, 712 KiB  
Review
Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection
by Pil Soo Sung and Eui-Cheol Shin
J. Clin. Med. 2021, 10(2), 221; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020221 - 10 Jan 2021
Cited by 13 | Viewed by 3672
Abstract
Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, [...] Read more.
Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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21 pages, 934 KiB  
Review
Clinical and Molecular Prediction of Hepatocellular Carcinoma Risk
by Naoto Kubota, Naoto Fujiwara and Yujin Hoshida
J. Clin. Med. 2020, 9(12), 3843; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9123843 - 26 Nov 2020
Cited by 12 | Viewed by 3440
Abstract
Prediction of hepatocellular carcinoma (HCC) risk becomes increasingly important with recently emerging HCC-predisposing conditions, namely non-alcoholic fatty liver disease and cured hepatitis C virus infection. These etiologies are accompanied with a relatively low HCC incidence rate (~1% per year or less), while affecting [...] Read more.
Prediction of hepatocellular carcinoma (HCC) risk becomes increasingly important with recently emerging HCC-predisposing conditions, namely non-alcoholic fatty liver disease and cured hepatitis C virus infection. These etiologies are accompanied with a relatively low HCC incidence rate (~1% per year or less), while affecting a large patient population. Hepatitis B virus infection remains a major HCC risk factor, but a majority of the patients are now on antiviral therapy, which substantially lowers, but does not eliminate, HCC risk. Thus, it is critically important to identify a small subset of patients who have elevated likelihood of developing HCC, to optimize the allocation of limited HCC screening resources to those who need it most and enable cost-effective early HCC diagnosis to prolong patient survival. To date, numerous clinical-variable-based HCC risk scores have been developed for specific clinical contexts defined by liver disease etiology, severity, and other factors. In parallel, various molecular features have been reported as potential HCC risk biomarkers, utilizing both tissue and body-fluid specimens. Deep-learning-based risk modeling is an emerging strategy. Although none of them has been widely incorporated in clinical care of liver disease patients yet, some have been undergoing the process of validation and clinical development. In this review, these risk scores and biomarker candidates are overviewed, and strategic issues in their validation and clinical translation are discussed. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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31 pages, 3056 KiB  
Review
Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges
by Shen Li, Antonio Saviano, Derek J. Erstad, Yujin Hoshida, Bryan C. Fuchs, Thomas Baumert and Kenneth K. Tanabe
J. Clin. Med. 2020, 9(12), 3817; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9123817 - 25 Nov 2020
Cited by 27 | Viewed by 4676
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease. Various epidemiological and experimental studies have identified candidates for secondary prevention—both etiology-specific and generic prevention strategies—including statins, aspirin, and anti-diabetic drugs. The introduction of multi-cell based omics analysis along with better characterization of the hepatic microenvironment will further facilitate the identification of targets for prevention. In this review, we will summarize HCC risk factors, pathogenesis, and discuss strategies of HCC prevention. We will focus on secondary prevention and also discuss current challenges in translating experimental work into clinical practice. Full article
(This article belongs to the Special Issue Viral Hepatitis and Risk of Hepatocellular Carcinoma)
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