scholarly journals Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 610 ◽  
Author(s):  
Volker Kinast ◽  
Stefan L. Leber ◽  
Richard J. P. Brown ◽  
Gabrielle Vieyres ◽  
Patrick Behrendt ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Ectopic Expression ◽  
Host Factor ◽  
Hcv Infection ◽  
Mrna Levels ◽  
Structural Support ◽  
Protein Levels ◽  
Inducible Protein

Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus.

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Limit Of Detection ◽  
Position Paper ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Diagnostic Tools ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

2017 ◽  
Vol 26 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranța Iacob ◽  
Roxana Șirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Real Life ◽  
Virologic Response ◽  
Position Paper ◽  
Hcv Infection ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

Testing for Hepatitis C Virus Infection Among Adults Aged ≥18 in the United States, 2013-2017

2021 ◽  
pp. 003335492110472
Author(s):  
Hope King ◽  
J. E. Soh ◽  
William W. Thompson ◽  
Jessica Rogers Brown ◽  
Karina Rapposelli ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
The United States ◽  
Hcv Infection ◽  
High School Education ◽  
Related Risk ◽  
Hcv Testing

Objective Approximately 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. The objective of our study was to describe demographic and socioeconomic characteristics, liver disease–related risk factors, and modifiable health behaviors associated with self-reported testing for HCV infection among adults. Methods Using data on adult respondents aged ≥18 from the 2013-2017 National Health Interview Survey, we summarized descriptive data on sociodemographic characteristics and liver disease–related risk factors and stratified data by educational attainment. We used weighted logistic regression to examine predictors of HCV testing. Results During the study period, 11.7% (95% CI, 11.5%-12.0%) of adults reported ever being tested for HCV infection. Testing was higher in 2017 than in 2013 (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.36). Adults with ≥some college were significantly more likely to report being tested (aOR = 1.60; 95% CI, 1.52-1.69) than adults with ≤high school education. Among adults with ≤high school education (but not adults with ≥some college), those who did not have health insurance were less likely than those with private health insurance (aOR = 0.78; 95% CI, 0.68-0.89) to get tested, and non–US-born adults were less likely than US-born adults to get tested (aOR = 0.77; 95% CI, 0.68-0.87). Conclusions Rates of self-reported HCV testing increased from 2013 to 2017, but testing rates remained low. Demographic characteristics, health behaviors, and liver disease–related risk factors may affect HCV testing rates among adults. HCV testing must increase to achieve hepatitis C elimination targets.

scholarly journals Chronic Hepatitis C Virus Infection After Treatment for Pediatric Malignancy

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1315-1320 ◽  
Author(s):  
Simone Cesaro ◽  
Maria Grazia Petris ◽  
Flavio Rossetti ◽  
Riccardo Cusinato ◽  
Corrado Pipan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Virus Infection ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Hcv Infection ◽  
Pediatric Malignancy ◽  
Infection Markers

Abstract Sera of 658 patients who had completed treatment for pediatric malignancy were analyzed by a second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay test to assess the prevalence of hepatitis C virus (HCV)-seropositivity. All HCV-seropositive patients underwent detailed clinical, laboratory, virologic, and histologic study to analyze the course of HCV infection. One hundred seventeen of the 658 patients (17.8%) were positive for HCV infection markers. Among the 117 anti-HCV+ patients, 41 (35%) were also positive for markers of hepatitis B virus infection with or without delta virus infection markers, 91 (77.8%) had previously received blood product transfusions, and 25 (21.4%) showed a normal alanine aminotransferase (ALT) level during the last 5-year follow-up (11 of them never had abnormal ALT levels). The remaining 92 patients showed ALT levels higher than the upper limit of normal range. Eighty-one of 117 (70%) anti-HCV+ patients were HCV-RNA+, with genotype 1b being present in most patients (54%). In univariate analysis, no risk factor for chronic liver disease was statistically significant. In this study, the prevalence of HCV infection was high in patients who were treated for a childhood malignancy. In about 20% of anti-HCV+ patients, routes other than blood transfusions are to be considered in the epidemiology of HCV infection. After a 14-year median follow-up, chronic liver disease of anti-HCV+ positive patients did not show progression to liver failure.

scholarly journals Hepatitis C Virus Attenuates Mitochondrial Lipid β-Oxidation by Downregulating Mitochondrial Trifunctional-Protein Expression

2015 ◽  
Vol 89 (8) ◽  
pp. 4092-4101 ◽  
Author(s):  
Yutaka Amako ◽  
Tsubasa Munakata ◽  
Michinori Kohara ◽  
Aleem Siddiqui ◽  
Chris Peers ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Persistent Infection ◽  
Liver Steatosis ◽  
Hcv Infection ◽  
Host Cells ◽  
Type I ◽  
Mrna Levels ◽  
Mitochondrial Lipid ◽  
Mitochondrial Trifunctional Protein

ABSTRACTThe course of hepatitis C virus (HCV) infection and disease progression involves alterations in lipid metabolism, leading to symptoms such as hypocholesterolemia and steatosis. Steatosis can be induced by multiple mechanisms, including increases in lipid biosynthesis and uptake, impaired lipoprotein secretion, and/or attenuation of lipid β-oxidation. However, little is known about the effects of HCV on lipid β-oxidation. A previous proteomics study revealed that HCV interacted with both the α- and β-subunits of the mitochondrial trifunctional protein (MTP), an enzyme complex which catalyzes the last 3 steps of mitochondrial lipid β-oxidation for cellular energy production. Here we show that in HCV-infected Huh7.5 cells, lipid β-oxidation was significantly attenuated. Consistently with this, MTP protein and mRNA levels were suppressed by HCV infection. A loss-of-function study showed that MTP depletion rendered cells less responsive to alpha interferon (IFN-α) treatment by impairing IFN-stimulated gene expression. These aspects of host-virus interaction explain how HCV alters host energy homeostasis and how it may also contribute to the establishment of persistent infection in the liver.IMPORTANCEHCV infection triggers metabolic alterations, which lead to significant disease outcomes, such as fatty liver (steatosis). This study revealed that HCV impairs mitochondrial lipid β-oxidation, which results in low lipid combustion. On the other hand, the HCV-induced defects in metabolic status played an important role in the control of the type I interferon system. Under the conditions of impaired lipid β-oxidation, host cells were less responsive to the ability of exogenously added IFN-α to suppress HCV replication. This suggests that interference with lipid β-oxidation may assist the virus in the establishment of a long-term, persistent infection. Further understanding of this aspect of virus-host interaction may lead to improvements in the current standard therapy.

scholarly journals The Clearance of Hepatitis C Virus Infection in Chimpanzees May Not Necessarily Correlate with the Appearance of Acquired Immunity

2003 ◽  
Vol 77 (2) ◽  
pp. 862-870 ◽  
Author(s):  
Michael Thomson ◽  
Michelina Nascimbeni ◽  
Michael B. Havert ◽  
Marian Major ◽  
Sophia Gonzales ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Distinct Pattern ◽  
Hcv Infection ◽  
Interleukin 4 ◽  
Mrna Levels ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT Clearance of hepatitis C virus (HCV) infection in humans and chimpanzees is thought to be associated with the induction of strong T-cell responses. We studied four chimpanzees infected with HCV derived from an infectious full-length HCV genotype 1b cDNA. Two of the chimpanzees cleared the infection to undetectable levels for more than 12 months of follow-up; the other two became persistently infected. Detailed analyses of HCV-specific immune responses were performed during the courses of infection in these chimpanzees. Only weak and transient T helper responses were detected during the acute phase in all four chimpanzees. A comparison of the frequency of gamma interferon (IFN-γ)-producing CD4+ and CD8+ T cells in peripheral blood by ELISpot assay did not reveal any correlation between viral clearance and T-cell responses. In addition, analyses of IFN-γ, IFN-α, and interleukin-4 mRNA levels in liver biopsies, presumably indicative of intrahepatic T-cell responses, revealed no distinct pattern in these chimpanzees with respect to infection outcome. The present study suggests that the outcome of HCV infection in chimpanzees is not necessarily attributable to HCV sequence variation and that chimpanzees may recover from HCV infection by mechanisms other than the induction of readily detectable HCV-specific T-cell responses.

Evaluation of Metabolic Changes in HCV Diabetic Patients Treated With Direct Acting Antiviral Agents

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Engy Yousry Elsayed ◽  
Hany Haroun Saad ◽  
Gina Gamal Naguib ◽  
Hazem Ibrahim Abouelela
Keyword(s):  
Uric Acid ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Chronic Liver Disease ◽  
Serum Uric Acid ◽  
Metabolic Changes ◽  
Chronic Liver ◽  
Hcv Infection ◽  
Diabetic Patients

Abstract Background Viral hepatitis is a major public health problem in need of urgent response. The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world. Seroprevalence was modeled to 10.6% and viraemic prevalence to 7.3% in 2014. The association between hepatitis C virus (HCV) infection and diabetes has been widely postulated. Prospective studies have demonstrated a higher risk of developing type 2 diabetes mellitus (T2DM) and insulin resistance in the HCV population. Objective to evaluate metabolic changes in HCV-positive diabetic patients following combination therapy of hepatitis C, clarifying the role of DAAs in these changes. Patients and Methods This study was conducted in Ain Shams University Hospital outpatient clinics who attended from March to December 2018. our study included 70 patients, and were subdivided into the following two groups: Group I: Easy to treat group. Contains 35 diabetic patients with HCV related chronic liver disease treated with sofosbuvir, daclatasvir. Group II: Difficult to treat group. Contains 35 diabetic patients with HCV related chronic liver disease treated with sofosbuvir and daclatasvir and ribavirin. Results Treatment was considered successful when patients became non-viraemic as identified by negative HCV RNA serum PCR at 12 weeks from the end of the treatment regimens (SVR). It was found that diabetic patients treated with DAAs achieved reduction of HbA1C by mean of (0.724±0.3%). The mean increase of serum uric acid level was (0.607±0.4 mg/dL). There were increases in Cholesterol (by mean of 16.85±3.4), HDL (by mean of 5.34±2.1) and LDL (by mean of 13.91±4.2) as well as a decrease in TG (by mean of 13.56±5.1). Conclusion Our study concludes that HCV eradication in diabetic patients leads to various metabolic changes in the form of: Reduction of serum HbA1c level. Elevation of serum uric acid. Elevation of serum cholesterol, HDL, LDL as well as a decrease in TG. Further and larger studies are needed to evaluate the full magnitude of RBV effects on the patients’ metabolism.

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