Hepatitis C Virus Infection in Humans and Animals: Pathogenesis, Prevention and Treatment

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (15 December 2024) | Viewed by 17310

Special Issue Editor


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Guest Editor
Johns Hopkins School of Medicine, Baltimore, MD, USA
Interests: maternal fetal transmission; linkage to care; direct antiviral agents (DAAs); global health burden; viral hepatitis elimination

Special Issue Information

Dear Colleagues,

Viral hepatitis (a disease caused by inflammation of the liver) is one of the major threats to human health worldwide. Different groups of viruses that spread via different routes and have a wide range of hosts can cause human hepatitis, causing death and disability. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most common causes of chronic liver disease worldwide. It is estimated that hundreds of millions of people are infected with HBV or HCV, and some of them are infected with both viruses. For HCV infection, the approval of oral antiviral drugs without interferon direct action has revolutionized the treatment of chronic hepatitis C and achieved a cure for HCV infection. However, there is currently no effective vaccine to prevent HCV infection.

Due to co-evolution and species selection between virus and host, humans are the only natural host of HCV. This makes it difficult to construct suitable and easily accessible in vivo animal models of viral infection. For cell culture models, although some cell models can be successfully infected with HCV, there are certain limitations, especially in the study of virus–host interactions or HCV vaccines. As a result, these limitations have greatly hindered research into the underlying mechanisms of HCV infection, as well as the identification of potential targets for HCV vaccines. In addition, the host's different genetic background and the genetic diversity of viruses driven by genomic mutations may also lead to clinical uncertainty in some patients. As a result, there are still many unsolved challenges to achieving the WHO's goal of “eliminating hepatitis”. In view of this, this Special Issue is aimed at elucidating the pathogenesis of HCV infection and providing new ideas for prevention and treatment.

This Special Issue includes, but is not limited to, the following topics:

  1. Molecular viral pathogenesis of HCV;
  2. Cell and animal models of HCV infection;
  3. Effects of host and viral genetic variation on HCV infection and treatment;
  4. Clinical treatment strategies for HCV;
  5. Research on molecular epidemiology and predictive models of HCV;
  6. Global health burden and hepatitis C elimination—poor linkage to care (both infants and adults).

Dr. Wikrom W. Karnsakul
Guest Editor

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Keywords

  • hepatitis C virus
  • host
  • prevention
  • treatment
  • viral hepatitis

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Published Papers (9 papers)

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Research

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15 pages, 3328 KiB  
Article
Alterations in N-glycosylation of HCV E2 Protein in Children Patients with IFN-RBV Therapy Failure
by Karolina Zimmer, Alicja M. Chmielewska, Paulina Jackowiak, Marek Figlerowicz and Krystyna Bienkowska-Szewczyk
Pathogens 2024, 13(3), 256; https://doi.org/10.3390/pathogens13030256 - 15 Mar 2024
Viewed by 2029
Abstract
The glycosylation of viral envelope proteins plays an important role in virus biology and the immune response of the host to infection. Hepatitis C virus (HCV) envelope proteins E1 and E2, key players in virus entry and spread, are highly N-glycosylated and possess [...] Read more.
The glycosylation of viral envelope proteins plays an important role in virus biology and the immune response of the host to infection. Hepatitis C virus (HCV) envelope proteins E1 and E2, key players in virus entry and spread, are highly N-glycosylated and possess 4 (5 in certain genotypes) to 11 conserved glycosylation sites, respectively. Many published results based on recombinant proteins indicate that the glycan shield can mask the epitopes targeted by neutralizing antibodies. Glycan shifting within the conserved linear E2 region (412–423) could be one of the escape strategies used by HCV. In the present report, we isolated E2 genes from samples (collected before the IFN-RBV therapy) originating from pediatric patients infected with HCV gt 1a. We analyzed the biochemical properties of cloned E2 glycoprotein variants and investigated their glycosylation status. The sequencing of E2 genes isolated from patients who did not respond to therapy revealed mutations at N-glycosylation sites, thus leading to a lower molecular weight and a low affinity to both linear and conformational neutralizing antibodies. The loss of the glycosylation site within the conserved epitope (amino acid 417) impaired the binding with AP33, an antibody that potently neutralizes all genotypes of HCV. Our findings, based on clinical samples, confirm the influence of N-glycosylation aberrations on the antigenic and conformational properties of HCV E1/E2, which may possibly correlate with the outcome of therapy in patients. Full article
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Review

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13 pages, 502 KiB  
Review
Hepatitis C Virus–Pediatric and Adult Perspectives in the Current Decade
by Nanda Kerkar and Kayla Hartjes
Pathogens 2025, 14(1), 11; https://doi.org/10.3390/pathogens14010011 - 29 Dec 2024
Viewed by 1479
Abstract
Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting [...] Read more.
Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting antiviral agents (DAA) have made the cure of HCV possible, and fortunately, these medications are approved down to three years of age. However, treatment in the pediatric population has its own set of challenges. The World Health Organization (WHO) has made a pledge to eliminate HCV as a public health threat by 2030. Despite this, HCV continues to remain a global health burden, leading to cirrhosis as well as hepatocellular carcinoma, and is a reason for liver transplantation in the adult population. Although rare, these complications can also affect the pediatric population. A variety of new technologies t have become available in the current era and can advance our understanding of HCV are discussed. Artificial intelligence, machine learning, liver organoids, and liver-on-chip are some examples of techniques that have the potential to contribute to our understanding of the disease and treatment process in HCV. Despite efforts over several decades, a successful vaccine against HCV has yet to be developed. This would be an important tool to help in worldwide efforts to eliminate the virus. Full article
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27 pages, 1737 KiB  
Review
Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy
by Po-Yuan Ke and Chau-Ting Yeh
Pathogens 2024, 13(11), 980; https://doi.org/10.3390/pathogens13110980 - 8 Nov 2024
Viewed by 1724
Abstract
Many types of RNA viruses, including the hepatitis C virus (HCV), activate autophagy in infected cells to promote viral growth and counteract the host defense response. Autophagy acts as a catabolic pathway in which unnecessary materials are removed via the lysosome, thus maintaining [...] Read more.
Many types of RNA viruses, including the hepatitis C virus (HCV), activate autophagy in infected cells to promote viral growth and counteract the host defense response. Autophagy acts as a catabolic pathway in which unnecessary materials are removed via the lysosome, thus maintaining cellular homeostasis. The HCV non-structural 5A (NS5A) protein is a phosphoprotein required for viral RNA replication, virion assembly, and the determination of interferon (IFN) sensitivity. Recently, increasing evidence has shown that HCV NS5A can induce autophagy to promote mitochondrial turnover and the degradation of hepatocyte nuclear factor 1 alpha (HNF-1α) and diacylglycerol acyltransferase 1 (DGAT1). In this review, we summarize recent progress in understanding the detailed mechanism by which HCV NS5A triggers autophagy, and outline the physiological significance of the balance between host–virus interactions. Full article
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9 pages, 198 KiB  
Review
Use of Hepatitis C Viremic Donors to Expand the Pediatric Donor Pool
by Natasha Dilwali, Christopher Hartley, Paul K. Sue and Wikrom Karnsakul
Pathogens 2024, 13(11), 947; https://doi.org/10.3390/pathogens13110947 - 30 Oct 2024
Viewed by 1035
Abstract
The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors [...] Read more.
The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors for organ transplantation. The recent data show that transplant centers are progressively accepting HCV-positive donors for various organs, including kidneys, livers, and hearts, given the efficacy of post-transplant antiviral treatment. Using these donors has helped mitigate the organ shortage crisis, increasing the donor pool and reducing waitlist times. Despite these advantages, the approach raises concerns about viral transmission, long-term outcomes, and the cost-effectiveness of post-transplant DAA therapy. Furthermore, this review highlights the ethical implications of informed consent and the monitoring of HCV-negative recipients following transplantation. The outcomes from recent studies suggest that with proper management, transplantations from HCV-positive donors to HCV-negative recipients can be safe and effective, leading to excellent graft function and patient survival. This review synthesizes existing research and offers insights into optimizing protocols for future transplants involving HCV-positive donors. Full article
8 pages, 438 KiB  
Review
Hepatitis C in Children—An Asia–Pacific Concise Perspective
by Lynette Goh and Winita Hardikar
Pathogens 2024, 13(10), 860; https://doi.org/10.3390/pathogens13100860 - 1 Oct 2024
Viewed by 1198
Abstract
Since the discovery of hepatitis C virus (HCV) in 1989, we now have curative treatment options with direct-acting antiviral therapies. By increasing the rate of treatment and reducing transmission, the eradication of HCV is potentially achievable. Nonetheless, the feasibility and implementation of this [...] Read more.
Since the discovery of hepatitis C virus (HCV) in 1989, we now have curative treatment options with direct-acting antiviral therapies. By increasing the rate of treatment and reducing transmission, the eradication of HCV is potentially achievable. Nonetheless, the feasibility and implementation of this goal remains challenging. This article sums up the approach to managing children with HCV in the Asia–Pacific region and lists some of the difficulties and complexities surrounding this issue. Full article
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9 pages, 239 KiB  
Review
Hepatitis C Virus Infection in Europe
by Margarida Simão and Cristina Gonçalves
Pathogens 2024, 13(10), 841; https://doi.org/10.3390/pathogens13100841 - 28 Sep 2024
Viewed by 1639
Abstract
The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. [...] Read more.
The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection’s distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe. Full article
9 pages, 817 KiB  
Review
Hepatitis C Virus and Molecular Mimicry
by Lynette Goh and Nanda Kerkar
Pathogens 2024, 13(7), 527; https://doi.org/10.3390/pathogens13070527 - 22 Jun 2024
Viewed by 1421
Abstract
This review delves into the interactions between hepatitis C virus (HCV) and the host immune system, shedding light on how by using the mechanism of molecular mimicry, the virus strategically evades the immune system, resulting in a cascade of diverse complications. HCV, notorious [...] Read more.
This review delves into the interactions between hepatitis C virus (HCV) and the host immune system, shedding light on how by using the mechanism of molecular mimicry, the virus strategically evades the immune system, resulting in a cascade of diverse complications. HCV, notorious for its ability to persistently infect hepatocytes, employs molecular mimicry to resemble host proteins, thereby avoiding immune detection and mounting an effective defense. This mimicry also triggers systemic autoimmune responses that lead to various sequelae. The objective of this review is to comprehensively explore the role of HCV-induced molecular mimicry, which not only facilitates viral survival but is also instrumental in developing autoimmune and inflammatory disorders. By mimicking host proteins, HCV triggers an immune response that inadvertently attacks the host, fostering the development of autoimmune and other inflammatory disorders. Understanding the nuanced mechanisms of HCV-mediated molecular mimicry provides crucial insights into the multifaceted sequelae of viral infections on host immune responses. Unravelling these complexities is paramount for advancing therapeutic strategies that not only target the virus directly but also mitigate the secondary autoimmune and inflammatory complications induced by HCV. Full article
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14 pages, 974 KiB  
Review
Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication
by Andrea Pascual-Oliver, Diego Casas-Deza, Carmen Yagüe-Caballero, Jose M. Arbones-Mainar and Vanesa Bernal-Monterde
Pathogens 2024, 13(4), 278; https://doi.org/10.3390/pathogens13040278 - 25 Mar 2024
Cited by 3 | Viewed by 2626
Abstract
The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate [...] Read more.
The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals. Full article
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15 pages, 691 KiB  
Review
Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children
by Chaowapong Jarasvaraparn, Christopher Hartley and Wikrom Karnsakul
Pathogens 2024, 13(2), 180; https://doi.org/10.3390/pathogens13020180 - 16 Feb 2024
Cited by 6 | Viewed by 3144
Abstract
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, [...] Read more.
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children. Full article
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