Editorial

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2 pages, 168 KiB

Open AccessEditorial

Addressing the Challenges of Hepatitis C Cure and Persistent Risk of Hepatocellular Carcinoma

by Thomas F. Baumert and Yujin Hoshida

Viruses 2019, 11(5), 441; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050441 - 15 May 2019

Cited by 5 | Viewed by 2701

Chronic hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma (HCC)—the second leading, and rising, cause of death due to cancer world-wide [...] Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

Review

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13 pages, 1531 KiB

Open AccessReview

Hepatocellular Carcinoma Recurrence in HCV Patients Treated with Direct Antiviral Agents

by Marco Sanduzzi-Zamparelli, Loreto Boix, Cassia Leal and María Reig

Viruses 2019, 11(5), 406; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050406 - 01 May 2019

Cited by 13 | Viewed by 3354

Abstract

The risk of hepatocellular carcinoma recurrence is universal regardless of the treatment modality applied, and secondary prevention is still an unmet issue even though the elimination of hepatitis C (HCV) with direct antiviral agents (DAAs) was expected to be one of the new [...] Read more.

The risk of hepatocellular carcinoma recurrence is universal regardless of the treatment modality applied, and secondary prevention is still an unmet issue even though the elimination of hepatitis C (HCV) with direct antiviral agents (DAAs) was expected to be one of the new options. Unfortunately, the impact of DAAs on hepatocellular carcinoma (HCC) development (de novo and recurrence) is still controversial. Since the first publication on the subject in 2016, almost all groups worldwide have carried out research in this field with hundreds of publications now available. This revision is focused on the impact of DAAs on HCC recurrence and aims to discuss the potential underlying mechanisms and host factors pointing out the time association phenomenon between DAA treatment and HCC recurrence. Moreover, we comment on the methodological issues that could affect the different interpretations of the published results. In conclusion, this is an area of research with potential in the understanding of the impact of factors not previously considered, and may also help change hepatocarcinogenesis tenets, such as the belief that the elimination of HCV should be used as a second prevention treatment. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

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18 pages, 1215 KiB

Open AccessReview

Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

by Nathalie Alazard-Dany, Solène Denolly, Bertrand Boson and François-Loïc Cosset

Viruses 2019, 11(1), 30; https://0-doi-org.brum.beds.ac.uk/10.3390/v11010030 - 06 Jan 2019

Cited by 57 | Viewed by 10918

Abstract

Hepatitis C infection is the leading cause of liver diseases worldwide and a major health concern that affects an estimated 3% of the global population. Novel therapies available since 2014 and 2017 are very efficient and the WHO considers HCV eradication possible by [...] Read more.

Hepatitis C infection is the leading cause of liver diseases worldwide and a major health concern that affects an estimated 3% of the global population. Novel therapies available since 2014 and 2017 are very efficient and the WHO considers HCV eradication possible by the year 2030. These treatments are based on the so-called direct acting antivirals (DAAs) that have been developed through research efforts by academia and industry since the 1990s. After a brief overview of the HCV life cycle, we describe here the functions of the different targets of current DAAs, the mode of action of these DAAs and potential future inhibitors. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

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15 pages, 718 KiB

Open AccessReview

HCV-Specific T Cell Responses During and After Chronic HCV Infection

by Hendrik Luxenburger, Christoph Neumann-Haefelin, Robert Thimme and Tobias Boettler

Viruses 2018, 10(11), 645; https://0-doi-org.brum.beds.ac.uk/10.3390/v10110645 - 17 Nov 2018

Cited by 39 | Viewed by 4788

Abstract

Hepatitis C virus (HCV)-specific T cell responses are closely linked to the clinical course of infection. While T cell responses in self-limiting infection are typically broad and multi-specific, they display several distinct features of functional impairment in the chronic phase. Moreover, HCV readily [...] Read more.

Hepatitis C virus (HCV)-specific T cell responses are closely linked to the clinical course of infection. While T cell responses in self-limiting infection are typically broad and multi-specific, they display several distinct features of functional impairment in the chronic phase. Moreover, HCV readily adapts to immune pressure by developing escape mutations within epitopes targeted by T cells. Much of our current knowledge on HCV-specific T cell responses has been gathered under the assumption that this might eventually pave the way for a therapeutic vaccine. However, with the development of highly efficient direct acting antivirals (DAAs), there is less interest in the development of a therapeutic vaccine for HCV and the scope of T cell research has shifted. Indeed, the possibility to rapidly eradicate an antigen that has persisted over years or decades, and has led to T cell exhaustion and dysfunction, provides the unique opportunity to study potential T cell recovery after antigen cessation in a human in vivo setting. Findings from such studies not only improve our basic understanding of T cell immunity but may also advance immunotherapeutic approaches in cancer or chronic hepatitis B and D infection. Moreover, in order to edge closer to the WHO goal of HCV elimination by 2030, a prophylactic vaccine is clearly required. Thus, in this review, we will summarize our current knowledge on HCV-specific T cell responses and also provide an outlook on the open questions that require answers in this field. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

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15 pages, 1109 KiB

Open AccessReview

Non-Coding RNAs and Hepatitis C Virus-Induced Hepatocellular Carcinoma

by Marie-Laure Plissonnier, Katharina Herzog, Massimo Levrero and Mirjam B. Zeisel

Viruses 2018, 10(11), 591; https://0-doi-org.brum.beds.ac.uk/10.3390/v10110591 - 30 Oct 2018

Cited by 25 | Viewed by 3669

Abstract

Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Despite recent improvements, effective treatments for HCC are still missing and new tools for early detection are [...] Read more.

Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Despite recent improvements, effective treatments for HCC are still missing and new tools for early detection are needed. Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and key players in human carcinogenesis, including HCC. Aberrant expression of ncRNAs is associated with HCC metastasis, invasion, dissemination, and recurrence. This review will focus on the recent advances in ncRNA expression profiles, their dysregulation in HCV-related HCC, and the clinical perspective of ncRNA signatures for the early detection of HCC. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

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18 pages, 287 KiB

Open AccessReview

Epidemiology and Elimination of HCV-Related Liver Disease

by Pierre Pradat, Victor Virlogeux and Eric Trépo

Viruses 2018, 10(10), 545; https://0-doi-org.brum.beds.ac.uk/10.3390/v10100545 - 06 Oct 2018

Cited by 48 | Viewed by 4574

Abstract

Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects nearly 1.0% of the worldwide population. The main risk factors include unsafe injection drug use and iatrogenic infections. Chronic HCV infection can promote liver damage, cirrhosis and hepatocellular carcinoma (HCC) [...] Read more.

Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects nearly 1.0% of the worldwide population. The main risk factors include unsafe injection drug use and iatrogenic infections. Chronic HCV infection can promote liver damage, cirrhosis and hepatocellular carcinoma (HCC) in affected individuals. The advent of new second-generation, direct-acting antiviral (DAA) agents allow a virological cure in more than 90% of treated patients, and therefore prevent HCV-related complications. Recently, concerns have been raised regarding the safety of DAA-regimens in cirrhotic patients with respect to the occurrence and the recurrence of HCC. Here, we review the current available data on HCV epidemiology, the beneficial effects of therapy, and discuss the recent controversy with respect to the potential link with liver cancer. We also highlight the challenges that have to be overcome to achieve the ambitious World Health Organization objective of HCV eradication by 2030. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

21 pages, 869 KiB

Open AccessReview

Oncogenic Signaling Induced by HCV Infection

by Alessia Virzì, Armando Andres Roca Suarez, Thomas F. Baumert and Joachim Lupberger

Viruses 2018, 10(10), 538; https://0-doi-org.brum.beds.ac.uk/10.3390/v10100538 - 02 Oct 2018

Cited by 20 | Viewed by 4864

Abstract

The liver is frequently exposed to toxins, metabolites, and oxidative stress, which can challenge organ function and genomic stability. Liver regeneration is therefore a highly regulated process involving several sequential signaling events. It is thus not surprising that individual oncogenic mutations in hepatocytes [...] Read more.

The liver is frequently exposed to toxins, metabolites, and oxidative stress, which can challenge organ function and genomic stability. Liver regeneration is therefore a highly regulated process involving several sequential signaling events. It is thus not surprising that individual oncogenic mutations in hepatocytes do not necessarily lead to cancer and that the genetic profiles of hepatocellular carcinomas (HCCs) are highly heterogeneous. Long-term infection with hepatitis C virus (HCV) creates an oncogenic environment by a combination of viral protein expression, persistent liver inflammation, oxidative stress, and chronically deregulated signaling events that cumulate as a tipping point for genetic stability. Although novel direct-acting antivirals (DAA)-based treatments efficiently eradicate HCV, the associated HCC risk cannot be fully eliminated by viral cure in patients with advanced liver disease. This suggests that HCV may persistently deregulate signaling pathways beyond viral cure and thereby continue to perturb cancer-relevant gene function. In this review, we summarize the current knowledge about oncogenic signaling pathways derailed by chronic HCV infection. This will not only help to understand the mechanisms of hepatocarcinogenesis but will also highlight potential chemopreventive strategies to help patients with a high-risk profile of developing HCC. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

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24 pages, 1110 KiB

Open AccessReview

Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection

by C. Nelson Hayes, Peiyi Zhang, Yizhou Zhang and Kazuaki Chayama

Viruses 2018, 10(10), 531; https://0-doi-org.brum.beds.ac.uk/10.3390/v10100531 - 28 Sep 2018

Cited by 32 | Viewed by 6679

Abstract

Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is [...] Read more.

Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers >90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis. Full article

(This article belongs to the Special Issue Cure of Hepatitis C Virus Infection and Hepatocellular Carcinoma)

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