scholarly journals Haplotype HLA-B8-DR3 Confers Susceptibility to Hepatitis C Virus-Related Mixed Cryoglobulinemia

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2062-2066 ◽  
Author(s):  
Marco Lenzi ◽  
Magda Frisoni ◽  
Vilma Mantovani ◽  
Paolo Ricci ◽  
Luigi Muratori ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Blood Chemistry ◽  
Mixed Cryoglobulinemia ◽  
Hcv Rna ◽  
Hla Polymorphism ◽  
Number Of Patients ◽  
Host Genetic ◽  
Chronic Hcv ◽  
Normal Controls

Abstract Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10.1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected= .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.

scholarly journals Haplotype HLA-B8-DR3 Confers Susceptibility to Hepatitis C Virus-Related Mixed Cryoglobulinemia

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2062-2066 ◽  
Author(s):  
Marco Lenzi ◽  
Magda Frisoni ◽  
Vilma Mantovani ◽  
Paolo Ricci ◽  
Luigi Muratori ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Blood Chemistry ◽  
Mixed Cryoglobulinemia ◽  
Hcv Rna ◽  
Hla Polymorphism ◽  
Number Of Patients ◽  
Host Genetic ◽  
Chronic Hcv ◽  
Normal Controls

Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10.1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected= .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.

scholarly journals Characterization of Resistance to the Nonnucleoside NS5B Inhibitor Filibuvir in Hepatitis C Virus-Infected Patients

2011 ◽  
Vol 56 (3) ◽  
pp. 1331-1341 ◽  
Author(s):  
Philip J. F. Troke ◽  
Marilyn Lewis ◽  
Paul Simpson ◽  
Katrina Gore ◽  
Jennifer Hammond ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Site Directed Mutagenesis ◽  
Phenotypic Resistance ◽  
Number Of Patients ◽  
Chronic Hcv ◽  
Selection Of

ABSTRACTFilibuvir (PF-00868554) is an investigational nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural 5B (NS5B) RNA-dependent RNA polymerase currently in development for treating chronic HCV infection. The aim of this study was to characterize the selection of filibuvir-resistant variants in HCV-infected individuals receiving filibuvir as short (3- to 10-day) monotherapy. We identified amino acid M423 as the primary site of mutation arising upon filibuvir dosing. Through bulk cloning of clinical NS5B sequences into a transient-replicon system, and supported by site-directed mutagenesis of the Con1 replicon, we confirmed that mutations M423I/T/V mediate phenotypic resistance. Selection in patients of an NS5B mutation at M423 was associated with a reduced replicative capacityin vitrorelative to the pretherapy sequence; consistent with this, reversion to wild-type M423 was observed in the majority of patients following therapy cessation. Mutations at NS5B residues R422 and M426 were detected in a small number of patients at baseline or the end of therapy and also mediate reductions in filibuvir susceptibility, suggesting these are rare but clinically relevant alternative resistance pathways. Amino acid variants at position M423 in HCV NS5B polymerase are the preferred pathway for selection of viral resistance to filibuvirin vivo.

scholarly journals Distribution of hepatitis C virus genotypes and subtypes in a group of patients with chronic hepatitis C from Canton Sarajevo, 2012-2018

2019 ◽  
Vol 49 ◽  
Author(s):  
Irma Salimović- Bešić ◽  
Adna Kahriman ◽  
Suzana Arapčić ◽  
Amela Dedeić- Ljubović
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hcv Rna ◽  
Genotype 3 ◽  
Hcv Genotype ◽  
Hcv Genotypes ◽  
Number Of Patients ◽  
Subtype 1B

Background: Hepatitis C virus (HCV) genotypes and subtypes exhibit significant geographic variations.Aim: To analyse the distribution of genotypes/subtypes of HCV in a group of patients with chronic hepatitis C from Canton Sarajevo during 2012-2018.Material and methods:The study enrolled 247 human plasma samples of HCV-RNA positive patients with available results of HCV genotyping test.Results: During 2012-2018, the domination of subtypes 1a (34.01%), 1b (28.34%) and genotype 3 (23.89%) was registered. In 2012 and 2013, HCV subtype 1a was the most common (27/63; 42.86% and 17/40; 42.50%, respectively). In 2014, the leading HCV genotype/subtype were 3 and 1b (17/57; 29.82%). In 2015, the dominance of HCV genotype 3 (14/39; 35.90%) continued, while in 2016, the same number of HCV subtypes 1a and 1b (11/30; 36.67%) was recorded. Although in a small number of tested, during 2017, HCV subtype 1b was the most prevalent (7/14; 50.00%), and in 2018, it was replaced by a HCV subtype 1a (3/4; 75.00%). Distribution of HCV genotypes/subtypes by age group of patients varied significantly (p=0.000). The largest number of patients (71/247; 28.74%) belonged to the age category 30-39 years and HCV genotypes/subtypes 1, 3, 4, 1a and 1b were identified. Except in 2017, male gender significantly dominated (p=0.000). In males, HCV subtype 1a (68/170; 40.00%) was the most common, while in women it was HCV subtype 1b (44/77; 57.14%).Conclusion: This six-year retrospective study showed the time variations of the circulating HCV genotypes/subtypes among patients with chronic hepatitis C in Canton Sarajevo. Genotyping of the HCV has an important implications for diagnosis and treatment of the patients.

Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4296-4301 ◽  
Author(s):  
F Silvestri ◽  
C Pipan ◽  
G Barillari ◽  
F Zaja ◽  
R Fanin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Close Association ◽  
Mixed Cryoglobulinemia ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Hodgkin's Lymphomas ◽  
Hcv Genotyping

It has been recently hypothesized that the hepatitis C virus (HCV) might be involved in the pathogenesis of malignant B-cell non-Hodgkin's lymphomas (NHL). On the basis of this observation we sought to determine the prevalence of HCV infection in the patients affected by B- cell NHL and extended our analysis to all the patients affected by lymphoproliferation disorders seen at our institution in the last 30 months. Five hundred and thirty-seven unselected, consecutive patients were studied. HCV infection was investigated through detection of anti- HCV antibodies and HCV-RNA. HCV genotyping was performed on HCV-RNA positive specimens. The risk of being infected by HCV was compared with that of the general population of our area. Among all lymphoproliferative disorders, the prevalence and the relative risk (RR) of being infected by HCV were increased only among B-cell NHL (9%; RR 3.24; p < .0001). Among these, a strong prevalence of HCV was found only in the subgroup of immunocytomas (30%; RR 10.27; P < .0001), while other histotypes were associated with it only occasionally. Because HCV- positive lymphomas clinically behave as essential mixed cryoglobulinemia (EMC), the close association between HCV infection and EMC is confirmed, and evidence is provided that the pathological substrate of EMC corresponds to the immunocytoma. HCV genomic sequences were found in 84% of patients analyzed. Viral genotypes were those more frequent in our area.

scholarly journals Characterization of Hepatitis C Virus Deletion Mutants Circulating in Chronically Infected Patients

2007 ◽  
Vol 81 (22) ◽  
pp. 12496-12503 ◽  
Author(s):  
Suwanna Noppornpanth ◽  
Saskia L. Smits ◽  
Truong Xuan Lien ◽  
Yong Poovorawan ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Rna ◽  
Deletion Mutants ◽  
Genotype 3 ◽  
Long Distance ◽  
Bona Fide ◽  
Chronic Hcv ◽  
High Level

ABSTRACT Hepatitis C virus (HCV) has a linear positive-stranded RNA genome of ∼9,600 nucleotides in length and displays a high level of sequence diversity caused by high mutation rates and recombination. However, when we performed long distance reverse transcription-PCRs on HCV RNA isolated from serum of chronic HCV patients, not only full-length HCV genomes but also HCV RNAs which varied in size from 7,600 to 8,346 nucleotides and contained large in-frame deletions between E1 and NS2 were amplified. Carefully designed control experiments indicated that these deletion mutants are a bona fide natural RNA species, most likely packaged in virions. Moreover, deletion mutants were detected in sera of patients infected with different HCV genotypes. We observed that 7/37 (18.9%) of genotype 1, 5/43 (11.6%) of genotype 3, and 4/13 (30.7%) of genotype 6 samples contained HCV deletion mutant genomes. These observations further exemplify HCV's huge genetic diversity and warrant studies to explore their biological relevance.

scholarly journals Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection

2001 ◽  
Vol 45 (2) ◽  
pp. 517-524 ◽  
Author(s):  
Jeffrey M. Jacobson ◽  
Lawrence Feinman ◽  
Leonard Liebes ◽  
Nancy Ostrow ◽  
Victoria Koslowski ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Pharmacokinetic Data ◽  
Serious Adverse Events ◽  
Dosing Schedule ◽  
Diarrhea Virus ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.

scholarly journals Replication of Hepatitis C Virus (HCV) RNA in Mouse Embryonic Fibroblasts: Protein Kinase R (PKR)-Dependent and PKR-Independent Mechanisms for Controlling HCV RNA Replication and Mediating Interferon Activities

2006 ◽  
Vol 80 (15) ◽  
pp. 7364-7374 ◽  
Author(s):  
Kyung-Soo Chang ◽  
Zhaohui Cai ◽  
Chen Zhang ◽  
Ganes C. Sen ◽  
Bryan R. G. Williams ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Replication ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Protein Kinase R ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. The underlying mechanisms of chronic HCV infection and IFN-based therapies, however, have not been defined. Protein kinase R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced antiviral response. In this report, we demonstrate that a subgenomic RNA replicon of genotype 2a HCV replicated efficiently in mouse embryonic fibroblasts (MEFs), as determined by cell colony formation efficiency and the detection of HCV proteins and both positive- and negative-strand RNAs. Additionally, the subgenomic HCV RNA was found to replicate more efficiently in the PKR knockout (PKR−/−) MEF than in the wild-type (PKR+/+) MEF. The knockdown expression of PKR by specific small interfering RNAs significantly enhanced the level of HCV RNA replication, suggesting that PKR is involved in the control of HCV RNA replication. The level of ISG56 (p56) was induced by HCV RNA replication, indicating the activation of PKR-independent antiviral pathways. Furthermore, IFN-α/β inhibited HCV RNA replication in PKR−/− MEFs as efficiently as in PKR+/+ MEFs. These findings demonstrate that PKR-independent antiviral pathways play important roles in controlling HCV replication and mediating IFN-induced antiviral effect. Our findings also provide a foundation for the development of transgenic mouse models of HCV replication and set a stage to further define the roles of cellular genes in the establishment of chronic HCV infection and the mediation of intracellular innate antiviral response by using MEFs derived from diverse gene knockout animals.

scholarly journals Chronic hepatitis C virus infection: Is there a correlation between HCV genotypes and the level of viremia?

2006 ◽  
Vol 59 (5-6) ◽  
pp. 230-234 ◽  
Author(s):  
Dragan Delic ◽  
Zorica Nesic ◽  
Jasmina Simonovic ◽  
Neda Svirtlih ◽  
Ljubisa Dokic ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Objective Assessment ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Genotype 4 ◽  
Hcv Genotypes ◽  
Genotype 2 ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Introduction. Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. Material and methods. For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested. Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype lb infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. Results. Patients infected by genotype lb had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p<0.05). Over 70% of patients infected by genotype lb had more than 2xl06 virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7x10.6 virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3xl06 copies/ml; p<0.05). Conclusion. Our results are in concordance with the results of other authors reporting that genotype lb is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype lb infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems. .

scholarly journals Association between chronic hepatitis C virus infection and myocardial infarction in people living with HIV in the United States

2018 ◽  
Author(s):  
Jessica Williams-Nguyen ◽  
Stephen E Hawes ◽  
Robin M Nance ◽  
Sara Lindström ◽  
Susan R Heckbert ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
The United States ◽  
Hcv Rna ◽  
High Risk Population ◽  
People Living With Hiv ◽  
Extrahepatic Manifestations ◽  
Chronic Hcv ◽  
Living With Hiv

AbstractHepatitis C virus (HCV) is common among people living with HIV (PLWH). The potential for extrahepatic manifestations of HCV, including myocardial infarction (MI), is a topic of active research. MI is classified into types, predominantly atheroembolic Type 1 MI (T1MI) and supply-demand mismatch Type 2 MI (T2MI). We examined the association between HCV and MI in the CFAR Network of Integrated Clinical Systems (CNICS), a multi-center clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Universal MI definition. We estimated the association between chronic HCV (RNA+) and time to MI adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics and substance use. Among 24,755 PLWH aged ≥18, there were 336 T1MI and 330 T2MI during a median of 4.2 years of follow-up. HCV was associated with a 68% greater risk of T2MI (adjusted hazard ratio (aHR) 1.68, 95% CI: 1.22, 2.30) but not T1MI (aHR 0.96, 95% CI: 0.63, 1.45). In a cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR 2.26, 95% CI: 1.34, 3.81). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Risks of hepatitis C virus reactivation in a real-life population of oncology patients treated in an academic center

2020 ◽  
pp. 107815522096979
Author(s):  
Catherine-Audrey Boutin ◽  
Jean-Philippe Adam ◽  
Dominic Martel ◽  
Stéphane Doucet ◽  
Valérie Martel-Laferrière
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real Life ◽  
Viral Reactivation ◽  
Hcv Rna ◽  
Hepatic Decompensation ◽  
Oncology Patients ◽  
Chronic Hcv ◽  
The Impact ◽  
Hepatic Flare

Background Chemotherapy has been associated with a theoretical risk of hepatitis C virus (HCV) reactivation. However, little is known about the amplitude of viral replication and the incidence of subsequent hepatic exacerbation. Method We aimed to describe the occurrence of hepatitis flare and HCV reactivation at our center. We included, over a period of 5 years, adult patients with chronic HCV receiving intravenous chemotherapy. We excluded patients with undetectable HCV RNA, hepatocellular carcinoma, liver metastases or other etiologies of hepatic disease. The primary objective was to identify hepatic flares (elevation of alanine aminotransferase 3 times above the upper limit of normal). Secondary objectives were to assess viral reactivation (HCVr, HCV-RNA ≥1 log10 IU/mL when compared to baseline value), hepatic decompensation, mortality and the impact on the chemotherapy. Descriptive statistics were used. Results A total of 11 patients with chronic HCV were identified among the 5761 oncology patients. Five patients experienced a hepatic flare with median maximal ALT value of 139 U/L (IQR 133-237). Only 2 patients met criteria for HCVr with a median RNA increase of 1.16 log IU/mL (IQR 1.1-1.2). One patient presented with both HCVr and a hepatic flare. Only one patient required chemotherapy discontinuation following hepatic flare. No hepatic decompensation or related mortality were observed. Conclusion We identified a very small number of HCV cases among our population. We observed HCVr and hepatic flares, but only one consequence on cancer treatment. Nonetheless, HCV screening is encouraged among patients undergoing chemotherapy to allow close follow-up of hepatic function.

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