scholarly journals Interferon lambda 4 impacts broadly on hepatitis C virus diversity

2018 ◽  
Author(s):  
M Azim Ansari ◽  
Elihu Aranday-Cortes ◽  
Camilla LC Ip ◽  
Ana da Silva Filipe ◽  
Lau Siu Hin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Amino Acid ◽  
Active Form ◽  
Hcv Infection ◽  
Virus Diversity ◽  
Genome Wide ◽  
Amino Acid Diversity

AbstractType III interferons (IFN-λ) are part of the innate immune response to hepatitis C virus (HCV) infection however the specific role of IFN-λ4 and the nature of the viral adaption to this pressure have not been defined. Here we use paired genome-wide human and viral genetic data in 485 patients infected with HCV genotype 3a to explore the role of IFN-λ4 on HCV evolution during chronic infection. We show that genetic variations within the host IFNL4 locus have a broad and systematic impact on HCV amino acid diversity. We also demonstrate that this impact is larger in patients producing a more active form of IFN-λ4 protein compared to the less active form. A similar observation was noted for viral load. We conclude that IFN-λ4 protein is a likely causal agent driving widespread HCV amino acid changes and associated with viral load and possibly other clinical and biological outcomes of HCV infection.

Hepatitis C Virus Infection and B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4668-4668
Author(s):  
Janet G. Grudeva
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Hcv Infection ◽  
Control Group ◽  
Cell Infection ◽  
Serum Samples ◽  
Pathogenetic Role ◽  
Significant Difference

Backgroud: An increasing number of bacterial and viral infections have been linked with specific subtypes of lymphoma. Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as a subset of B-cell non-Hodgkin, s lymphomas (B-NHL), often with extranodal localization. Design and methods: The study was conducted in the Department of Hematology and consisted 149 (86 male, 63 female) untreated patients with a new diagnosis of B-NHL for 5-years period (2000–2004). HCV infection was investigated by testing for HCV antibodies in serum samples. The controls were 587 patients (without intravenous drug users) in other departments of the same hospital. Results: HCV infection was documented in 13 cases (8,4%) with NHL. The infected patients were not clinically relevant cryoglobulinemic activity, increased rate of autoimmune disorders and extranodal localizations prevalence. There was statistically significant difference between the NHL and control group (p<0,01) and no statistically significant difference between man/women carriers (p>0,05) into the NHL group. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant liver injury may predict a worse prognosis in these cases. Conclusions: Our date suggest that HCV infection may be associated with B-NHL. With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most date support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.

scholarly journals ‘Favourable’ IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype 3a infection and do not predict a sustained virological response after 24 weeks of therapy

2013 ◽  
Vol 94 (6) ◽  
pp. 1259-1265 ◽  
Author(s):  
Cristina Bucci ◽  
Annette von Delft ◽  
Annabel Christian ◽  
Vicki M. Flemming ◽  
Abby Harrison ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Virological Response ◽  
Response To Therapy ◽  
Baseline Viral Load ◽  
Median Viral Load ◽  
Host Genetic

IL28B host genetic make-up is known to play a critical role in the outcome of genotype 1 hepatitis C virus (HCV) infection in the context of both primary infection and therapy. However, the role of IL28B in subtype 3a infection remains unclear, and has not yet been assessed in the UK population where subtype 3a is dominant. In this study, we evaluated the role of the IL28B single-nucleotide polymorphism rs8099917 in 201 patients recruited from two well-defined cohorts (from Nottingham and Oxford), treated with the standard-of-care therapy of pegylated interferon and ribavirin for 24 weeks. We showed that the ‘favourable’ IL28B gene was associated with a rapid virological response to therapy at 4 weeks (P<0.0001), but not with a sustained virological response to therapy. The median viral load at baseline, before therapy, was markedly increased in people with the ‘favourable’ IL28B genotype [median viral load for the TT allele, 925 961 IU ml−1 (range 2200–21 116 965 IU ml−1), and for the GT or GG allele, 260 284 IU ml−1 (range 740–7 560 000 IU ml−1); P = 0.0010]. Our results suggest that the host genetic response plays an important role in early viral clearance of subtype 3a virus from the blood. However, significant reservoirs of infection must persist, as viral relapse is common, even in those with the favourable host genotype.

Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience

2005 ◽  
Vol 23 (3) ◽  
pp. 468-473 ◽  
Author(s):  
Daniele Vallisa ◽  
Patrizia Bernuzzi ◽  
Luca Arcaini ◽  
Stefano Sacchi ◽  
Vittorio Callea ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Treatment ◽  
Complete Response ◽  
Hcv Infection ◽  
Low Grade ◽  
Hcv Treatment ◽  
Hematologic Response

Purpose Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated. Patients and Methods Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months. Results Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 ± 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response. Conclusion This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.

scholarly journals Clinical, Biochemical and Virological Profile of Patients with Chronic Hepatitis C Virus Infection - A Study from University Hospital in Nepal

2015 ◽  
Vol 4 (1) ◽  
pp. 32-35
Author(s):  
Dipesh Gurubacharya ◽  
Mohan Khadka ◽  
Khadga B Shreshta ◽  
Prem Khadga ◽  
Sashi Sharma
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Drug Use ◽  
Injection Drug Use ◽  
Hcv Infection ◽  
Genotype 3 ◽  
Hcv Genotypes ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Introduction: Hepatitis C virus (HCV) infection is a major public health challenge. It is a major cause for cirrhosis and hepatocellular carcinoma worldwide. Both the genotype and viral load of HCV determine the choice of therapy as well as outcome of therapy. The aim of this study was to evaluate clinical, biochemical and virological profile and association of HCV genotypes with viral load and liver biochemical profile.Material and Methods: This was descriptive observational study of chronic HCV infected patients who attended at the outpatient clinic of Department of Gastroenterology of TUTH, IOM from April 2013 to November 2014. During this study period 38 patients with chronic HCV infection were analyzed. Clinical profile, possible risk factors for transmission of HCV infection and liver biochemical profile were recorded. Virological profile included HCV viral load and HCV genotypes.Results: Out of 38 patients 34(89.5%) were male and 4(10.5%) were female. Injection drug use (IDU) was the most common mode for acquisition of HCV infection (55.3%). Genotype 3 was found in 21(55.26%) patients and genotype 1 was found in 17(44.74%) patients. There was no significant association between HCV genotypes and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. And also there was no significant association between HCV viral load and different HCV genotypes.Conclusions: In our study HCV genotype 3 was the most prevalent genotype in patients with chronic HCV infection. Injection drug use was identified as most common identifiable risk factor for transmission of HCV infection. There was no significant association between different HCV genotypes and serum ALT, AST level and HCV viral load. Journal of Nobel College of Medicine Vol.4(1) 2015: 32-35

scholarly journals Elevated Levels of IL-33, IL-17 and IL-25 Indicate the Progression from Chronicity to Hepatocellular Carcinoma in Hepatitis C Virus Patients

Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 57
Author(s):  
Momen Askoura ◽  
Hisham A. Abbas ◽  
Hadeel AlSadoun ◽  
Wesam H. Abdulaal ◽  
Amr S. Abu Lila ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Serum Level ◽  
Viral Infections ◽  
Serum Levels ◽  
Chronic Patients

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.

scholarly journals The role of neutralizing antibodies in hepatitis C virus infection

2012 ◽  
Vol 93 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Victoria C. Edwards ◽  
Alexander W. Tarr ◽  
Richard A. Urbanowicz ◽  
Jonathan K. Ball
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Neutralizing Antibodies ◽  
Primary Liver Cancer ◽  
Protective Role ◽  
Hcv Infection ◽  
Comprehensive Overview ◽  
Therapeutic Benefits ◽  
Natural Target

Hepatitis C virus (HCV) is a blood-borne virus estimated to infect around 170 million people worldwide and is, therefore, a major disease burden. In some individuals the virus is spontaneously cleared during the acute phase of infection, whilst in others a persistent infection ensues. Of those persistently infected, severe liver diseases such as cirrhosis and primary liver cancer may develop, although many individuals remain asymptomatic. A range of factors shape the course of HCV infection, not least host genetic polymorphisms and host immunity. A number of studies have shown that neutralizing antibodies (nAb) arise during HCV infection, but that these antibodies differ in their breadth and mechanism of neutralization. Recent studies, using both mAbs and polyclonal sera, have provided an insight into neutralizing determinants and the likely protective role of antibodies during infection. This understanding has helped to shape our knowledge of the overall structure of the HCV envelope glycoproteins – the natural target for nAb. Most nAb identified to date target receptor-binding sites within the envelope glycoprotein E2. However, there is some evidence that other viral epitopes may be targets for antibody neutralization, suggesting the need to broaden the search for neutralization epitopes beyond E2. This review provides a comprehensive overview of our current understanding of the role played by nAb in HCV infection and disease outcome and explores the limitations in the study systems currently used. In addition, we briefly discuss the potential therapeutic benefits of nAb and efforts to develop nAb-based therapies.

scholarly journals Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection

2016 ◽  
Vol 90 (21) ◽  
pp. 9632-9643 ◽  
Author(s):  
Zaili Yang ◽  
Xiaoning Wang ◽  
Xiumei Chi ◽  
Fanfan Zhao ◽  
Jinxu Guo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Surface ◽  
Apolipoprotein E ◽  
Virus Assembly ◽  
Hcv Infection ◽  
Apoe Level ◽  
New Perspective ◽  
Apoe Expression

ABSTRACT Hepatitis C virus (HCV) is a major cause of chronic liver disease, infecting approximately 170 million people worldwide. HCV assembly is tightly associated with the lipoprotein pathway. Exchangeable apolipoprotein E (apoE) is incorporated on infectious HCV virions and is important for infectious HCV virion morphogenesis and entry. Moreover, the virion apoE level is positively correlated with its ability to escape E2 antibody neutralization. However, the role of apoE exchange in the HCV life cycle is unclear. In this study, the relationship between apoE expression and cell permissiveness to HCV infection was assessed by infecting apoE knockdown and derived apoE rescue cell lines with HCV. Exchange of apoE between lipoproteins and HCV lipoviral particles (LVPs) was evaluated by immunoprecipitation, infectivity testing, and viral genome quantification. Cell and heparin column binding assays were applied to determine the attachment efficiency of LVPs with different levels of incorporated apoE. The results showed that cell permissiveness for HCV infection was determined by exogenous apoE-associated lipoproteins. Furthermore, apoE exchange did occur between HCV LVPs and lipoproteins, which was important to maintain a high apoE level on LVPs. Lipid-free apoE was capable of enhancing HCV infectivity for apoE knockdown cells but not apoE rescue cells. A higher apoE level on LVPs conferred more efficient LVP attachment to both the cell surface and heparin beads. This study revealed that exogenous apoE-incorporating lipoproteins from uninfected hepatocytes safeguarded the apoE level of LVPs for more efficient attachment during HCV infection. IMPORTANCE In this study, a neglected but important role of apoE exchange in HCV LVP infectivity after virus assembly and release was identified. The data indicated that apoE expression level in uninfected cells is important for high permissiveness to HCV infection. Secreted apoE-associated lipoprotein specifically enhances infection of HCV LVPs. apoE exchange between HCV LVP and lipoproteins is important to maintain an adequate apoE level on LVPs for their efficient attachment to cell surface. These data defined for the first time an extracellular role of exchangeable apoE in HCV infection and suggested that exchangeable apolipoproteins reach a natural equilibrium between HCV LVPs and lipoprotein particles, which provides a new perspective to the understanding of the heterogeneity of HCV LVPs in composition.

The Impact of Hepatitis C Virus Infection on Buprenorphine Dose in Pregnancy

2019 ◽  
Vol 37 (01) ◽  
pp. 073-078
Author(s):  
Misty L. McDowell ◽  
Tiffany R. Tonismae ◽  
James E. Slaven ◽  
Mary P. Abernathy ◽  
Anthony L. Shanks ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Liver Enzymes ◽  
Hcv Infection ◽  
Third Trimester ◽  
Correlation Tests ◽  
The Impact ◽  
The Relationship ◽  
In Pregnancy

Abstract Objective Buprenorphine (BUP) is commonly used for opioid maintenance therapy in pregnancy. Our goal was to determine whether liver dysfunction related to hepatitis C virus (HCV) infection impacts BUP dosing requirements in pregnancy. Study Design This was a retrospective cohort study of pregnant women with antenatal exposure to BUP to compare dosing between individuals positive versus negative for HCV infection. Spearman correlation tests were used to assess the relationship between BUP dose and HCV status. Results HCV infection was present in 103 (39%) of the patients. Patients with HCV infection required lower dose increases of BUP throughout pregnancy (p = 0.02). HCV viral load was positively correlated with the liver enzymes aspartate transaminase (r = 0.30, p = 0.003) and alanine transaminase (r = 0.25, p = 0.01). There was a negative correlation between HCV viral load and BUP dose during the second trimester (r = −0.27, p = 0.01) and third trimester (r = −0.20, p = 0.04). Conclusion Women with HCV infection required less of an increase in BUP dose throughout pregnancy compared with women without HCV infection. Severity of HCV infection, as measured by viral load and liver enzymes, was also associated with BUP dosing.

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