scholarly journals Hepatic Stress Response in HCV Infection Promotes STAT3-Mediated Inhibition of HNF4A-miR-122 Feedback Loop in Liver Fibrosis and Cancer Progression

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1407 ◽  
Author(s):  
Aydin ◽  
Kurt ◽  
Song ◽  
Lin ◽  
Osman ◽  
...  
Keyword(s):  
Stress Response ◽  
Cancer Progression ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Infection Model ◽  
Related Factor ◽  
Nuclear Factor ◽  
Survival Signaling ◽  
Chronic Hcv ◽  
Hepatic Stress

Hepatitis C virus (HCV) infection compromises the natural defense mechanisms of the liver leading to a progressive end stage disease such as cirrhosis and hepatocellular carcinoma (HCC). The hepatic stress response generated due to viral replication in the endoplasmic reticulum (ER) undergoes a stepwise transition from adaptive to pro-survival signaling to improve host cell survival and liver disease progression. The minute details of hepatic pro-survival unfolded protein response (UPR) signaling that contribute to HCC development in cirrhosis are unknown. This study shows that the UPR sensor, the protein kinase RNA-like ER kinase (PERK), mediates the pro-survival signaling through nuclear factor erythroid 2-related factor 2 (NRF2)-mediated signal transducer and activator of transcription 3 (STAT3) activation in a persistent HCV infection model of Huh-7.5 liver cells. The NRF2-mediated STAT3 activation in persistently infected HCV cell culture model resulted in the decreased expression of hepatocyte nuclear factor 4 alpha (HNF4A), a major liver-specific transcription factor. The stress-induced inhibition of HNF4A expression resulted in a significant reduction of liver-specific microRNA-122 (miR-122) transcription. It was found that the reversal of hepatic adaptive pro-survival signaling and restoration of miR-122 level was more efficient by interferon (IFN)-based antiviral treatment than direct-acting antivirals (DAAs). To test whether miR-122 levels could be utilized as a biomarker of hepatic adaptive stress response in HCV infection, serum miR-122 level was measured among healthy controls, and chronic HCV patients with or without cirrhosis. Our data show that serum miR-122 expression level remained undetectable in most of the patients with cirrhosis (stage IV fibrosis), suggesting that the pro-survival UPR signaling increases the risk of HCC through STAT3-mediated suppression of miR-122. In conclusion, our data indicate that hepatic pro-survival UPR signaling suppresses the liver-specific HNF4A and its downstream target miR-122 in cirrhosis. These results provide an explanation as to why cirrhosis is a risk factor for the development of HCC in chronic HCV infection.

Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Chronic Hepatitis C ◽  
Genome Wide Association Study ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Snp Analysis ◽  
Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

scholarly journals French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cécile Brouard ◽  
Josiane Pillonel ◽  
Marjorie Boussac ◽  
Victor de Lédinghen ◽  
Antoine Rachas ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
World Health ◽  
Direct Acting Antivirals ◽  
Substantial Impact ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Impact

Abstract Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

scholarly journals Challenges of transferring rural adults with chronic HCV infection for further HCV RNA confirmation and free DAAs treatment: a success story of the interdisciplinary collaboration approach

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Li ◽  
Te-Sheng Chang ◽  
Shu-Zhi Chang ◽  
Ching-Hwa Chen ◽  
Mei-Yen Chen
Keyword(s):  
Rural Areas ◽  
Medical Records ◽  
Interdisciplinary Collaboration ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Hcv Rna ◽  
National Health Insurance System ◽  
Health Clinics ◽  
Chronic Hcv ◽  
Prospective Study Design

Abstract Background Chronic hepatitis C virus (HCV), which is a concern in many countries, is the leading cause of liver cancer around the world. Since Taiwan launched its national health insurance system in 1995, it has managed to extend health coverage to 99% of the Taiwanese population, providing free but limited antiviral treatment each year since 2017. However, many people in rural areas are unaware that they have chronic HCV; nor do they realize that new drugs with high cure rates could drastically reduce their health burden. The aim of this study is to explore the implementation facilitators of and barriers to inviting potentially infected patients in rural areas to be transferred for HCV ribonucleic acid (RNA) confirmation and new drug treatment. Methods A descriptive and prospective study design with an interdisciplinary collaboration approach was implemented. After five elements of referral were developed, telephone counseling was conducted between August 2018 and May 2019 in Yunlin, Taiwan. The elements of referral developed by the research team were: (1) forming and coordinating physicians’ schedules, (2) recruiting and training volunteers, (3) training the nursing staff, (4) raising funds or resources, and (5) connecting with village leaders. Thereafter, we collaborated with two district health centers, a private local hospital, and health clinics. Based on the medical records provided by these agencies, community adults that were HCV antibody (anti-HCV) positive were invited to join the program. Results Of the 1795 adults who were serum anti-HCV positive, 1149 (64%) accepted transfer to a qualified hospital; of these, 623 (54.2%) had an HCV infection. 552 (88.6%) of those infected started receiving direct-acting antivirals (DAAs) treatment. The top four barriers to accepting transfer were: (1) they perceived themselves to be healthy (n = 98, 32.3%); (2) mistrust of treatment/healthcare (n = 60, 20.2%); (3) limited transportation to the hospital (n = 52, 17.5%); and (4) work conflict (n = 30, 10.1%). Conclusion An interdisciplinary collaboration approach significantly contributed to the invitation of CHC patients, as well as their acceptance of HCV RNA confirmation and free DAAs treatment. Using anti-HCV data from previous medical records for case-finding and collaborating with a hospital and health clinics proved to be an efficient strategy.

scholarly journals Reversal of T Cell Exhaustion in Chronic HCV Infection

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 799
Author(s):  
Sylwia Osuch ◽  
Karin J. Metzner ◽  
Kamila Caraballo Cortés
Keyword(s):  
T Cell ◽  
Antiviral Treatment ◽  
Immune Dysfunction ◽  
T Cell Response ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Long Term Consequences ◽  
Chronic Hcv

The long-term consequences of T cell responses’ impairment in chronic HCV infection are not entirely characterized, although they may be essential in the context of the clinical course of infection, re-infection, treatment-mediated viral clearance and vaccine design. Furthermore, it is unclear whether a complete reinvigoration of HCV-specific T cell response may be feasible. In most studies, attempting to reverse the effects of compromised immune response quality by specific blockades of negative immune regulators, a restoration of functional competence of HCV-specific T cells was shown. This implies that HCV-induced immune dysfunction may be reversible. The advent of highly successful, direct-acting antiviral treatment (DAA) for chronic HCV infection instigated investigation whether the treatment-driven elimination of viral antigens restores T cell function. Most of studies demonstrated that DAA treatment may result in at least partial restoration of T cell immune function. They also suggest that a complete restoration comparable to that seen after spontaneous viral clearance may not be attained, pointing out that long-term antigenic stimulation imprints an irreversible change on the T cell compartment. Understanding the mechanisms of HCV-induced immune dysfunction and barriers to immune restoration following viral clearance is of utmost importance to diminish the possible long-term consequences of chronic HCV infection.

scholarly journals Regression of a case of Multiple Myeloma with antiviral treatment in a patient with chronic HCV infection

2013 ◽  
Vol 2 (1) ◽  
pp. 39-40 ◽  
Author(s):  
Sara Panfilio ◽  
Pasqualina D'Urso ◽  
Giorgia Annechini ◽  
Gianna Maria D'Elia ◽  
Federico De Angelis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

scholarly journals Sadness and mild cognitive impairment as predictors for interferon-alpha-induced depression in patients with hepatitis C

2015 ◽  
Vol 206 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Susanne Sarkar ◽  
Rahul Sarkar ◽  
Thomas Berg ◽  
Martin Schaefer
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Rating Scale ◽  
Antiviral Treatment ◽  
Severe Depression ◽  
Hcv Infection ◽  
Clinical Predictors ◽  
Increased Risk ◽  
Chronic Hcv

BackgroundAntiviral therapy with interferon-alpha (IFN-α) for hepatitis C virus (HCV) infection is associated with increased risk for depression.AimsTo identify clinical predictors for IFN-α-induced depression during antiviral therapy for HCV infection.MethodDepression (defined with the Montgomery–åsberg Depression Rating Scale (MADRS)) was evaluated before and during antiviral treatment in 91 people with chronic HCV infection without a history of psychiatric disorders. Cognitive function was evaluated using the Trail Making Test A/B (TMT A/B). (Trial registration at ClinicalTrials.gov: NCT00136318.)ResultsDepression during antiviral therapy was significantly associated with a baseline MADRS score of 3 or higher (P = 0.006). In total, 89% (n = 16) of patients who had a baseline score >0 for the single item sadness developed depression. Poor baseline performance in the TMT A (P = 0.027) and TMT B (P=0.033) was predictive for severe depression.ConclusionsPre-treatment screening for subthreshold depressive and cognitive symptoms will help to identify those at risk for IFN-α-associated depression among patients with chronic hepatitis C.

scholarly journals Performance of HCV Antigen Testing for the Diagnosis and Monitoring of Antiviral Treatment: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 2022 ◽  
pp. 1-17
Author(s):  
Geane Lopes Flores ◽  
Jurema Corrêa Mota ◽  
Larissa Tropiano da Silva Andrade ◽  
Renata Serrano Lopes ◽  
Francisco Inácio Bastos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
High Concordance ◽  
Chronic Hcv

Background and Aims. Active hepatitis C virus (HCV) infection is based on the detection of HCV RNA that it is effective but presents high cost and the need to hire trained personnel. This systematic review and meta-analysis is aimed at evaluating the diagnostic accuracy of HCV Ag testing to identify HCV cases and to monitor antiviral treatment including DAA treatment. Methods. The studies were identified through a search in PubMed, Lilacs, and Scopus from 1990 through March 31, 2020. Cohort, cross-sectional, and randomized controlled trials were included. Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was to determine the accuracy of HCV Ag detection for the diagnosis, which we estimated using random-effects meta-analysis. Results. Of 3,062 articles identified, 54 met our eligibility criteria. The studies described cohorts from 20 countries, including 14,286 individuals with chronic HCV individuals. Studies for ECLIA technology demonstrated highest quality compared to studies that used ELISA. The pooled sensitivity and specificity (95% CI) for HCV Ag detection of active HCV infection were 98.82% ( 95 % CI = 98.04 %; 99.30%) and 98.95% ( 95 % CI = 97.84 %; 99.49%), respectively. High concordance was found between HCV Ag testing and HCV RNA detection 89.7% and 95% to evaluate antiviral treatment. Conclusions. According to our findings, HCV Ag testing could be useful to identify HCV active cases in low-resource areas. For antiviral treatment, HCV Ag testing will be useful at the end of treatment.

Sign in / Sign up

Export Citation Format

Share Document