scholarly journals ANALYSIS OF THE INFLUENCE OF GENETIC FACTORS OF HEPATITIS C VIRUS AND GENE POLYMORPHISM IN INFECTED PATIENTS ON THE DEVELOPMENT OF LIVER FIBROSIS

2012 ◽  
Vol 17 (5) ◽  
pp. 7-13 ◽  
Author(s):  
L. I. Nikolaeva ◽  
A. V. Kolotvin ◽  
L. M. Samokhodskaya ◽  
G. V. Sapronov ◽  
V. V. Makashova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Genetic Factors ◽  
Rapid Development ◽  
Hereditary Hemochromatosis ◽  
Hcv Rna ◽  
Snp Analysis ◽  
Slow Development

The purpose of the study - to reveal the dependence of the rate of development of liver fibrosis (LF) on genetic factors of hepatitis C virus (HCV) and single nucleotide polymorphisms (SNPs) of the genes of infected people. In the three groups of patients with different rates of development of LF, HCV subtype, viral load, the number of quasi- variant forms and the presence of intergenotype recombinantion, SNPs of human cytokine genes (IL-1ß, IL-6, IL-10, IL-28B, TNF-a , TGF-ß1), hereditary hemochromatosis (HFE), genes involved in the development of endothelial dysfunction (eNOS) and oxidative stress (CYBA) were analyzed. In all groups of patients with HCV subtype 1b prevailed. In the groups with moderate and fast speed of development of LF viral load was revealed to be higher than in the group with the slow development of fibrosis. The number of genetic variants within E2 protein zone in the latter group of patients is characterized to be more than in other groups. Recombinant HCV RNA (2k/1b) was found in the groups with moderate and rapid development of LF. SNP analysis of genes of patients showed a statistically significant relationship between the rapid formation of LF and allelic variants of IL-1ß (-511 TT), IL-10 (-1082 AA), TNF-a (-238 GA or AA) and HFE (S282Y or Y282Y )genes. In other SNPs of analyzed gene there no association with speed of LF was found.

scholarly journals Hepatitis C Virus Clearance after Discontinuation of Pegylated Interferon Alpha-2a Monotherapy in a Child

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Takeshi Endo ◽  
Koichi Ito ◽  
Tokio Sugiura ◽  
Kenji Goto
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Antiviral Treatment ◽  
Pegylated Interferon ◽  
Hcv Rna ◽  
Pegylated Interferon Alpha ◽  
Present Patient

The present patient was a 4-year-old boy. His hepatitis C virus genotype was 2a, and his viral load was high (1400,000 U/mL). The pretreatment liver biopsy revealed no fibrosis or malignancy and mild chronic hepatitis; his Knodell's histological activity (HAI) score was 4. Single nucleotide polymorphism of IL28B (rs8099917) was major type. The patient began antiviral treatment with pegylated interferon alpha 2a (90 μg/week). At week 9, serum HCV RNA became undetectable, with a sensitivity of 50 copies/mL. Antiviral treatment was discontinued at week 11 because the ALT level increased to 610 U/L. After discontinuation of therapy, the patient’s serum HCV RNA status became positive again. The serum viral load increased to 100,000 U/mL. During this period, he had been observed without medication. Sixteen months after stopping treatment, serum HCV became undetectable. Over a 4-year period, HCV RNA became negative and his anti-HCV antibody titer gradually decreased. In conclusion, though antiviral therapy resulted in failure or incomplete therapy, a reduced viral load resulted in viral clearance in the present patient. Interleukin 28B genotype might have association with the clearance of hepatitis C virus after discontinuation of antiviral therapy.

scholarly journals Short-Term Monotherapy with IDX184, a Liver-Targeted Nucleotide Polymerase Inhibitor, in Patients with Chronic Hepatitis C Virus Infection

2012 ◽  
Vol 56 (12) ◽  
pp. 6372-6378 ◽  
Author(s):  
Jacob Lalezari ◽  
David Asmuth ◽  
Arnaldo Casiró ◽  
Hugo Vargas ◽  
Shannon Lawrence ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Adverse Events ◽  
Antiviral Activity ◽  
Chronic Hepatitis C ◽  
Hcv Rna ◽  
Plasma Exposure ◽  
Chronic Hepatitis C Virus

ABSTRACTIDX184 is a liver-targeted prodrug of 2′-methylguanosine (2′-MeG) monophosphate. This study investigated the safety, tolerability, antiviral activity, and pharmacokinetics of IDX184 as a single agent in treatment-naïve patients with genotype-1 chronic hepatitis C virus (HCV) infection. Forty-one patients with baseline HCV RNA ≥ 5 log10IU/ml, alanine aminotransferase (ALT) ≤ 2.5× the upper limit of normal, and compensated liver disease were dosed. Sequential cohorts of 10 patients, randomized 8:2 (active:placebo), received 25, 50, 75, and 100 mg of IDX184 once daily for 3 days, with a 14-day follow-up. There were no safety-related treatment discontinuations or serious adverse events. The adverse events and laboratory abnormalities observed for IDX184- and placebo-treated patients were similar. At the end of the 3-day treatment period, changes from baseline in HCV RNA levels (means ± standard deviations) were −0.5 ± 0.6, −0.7 ± 0.2, −0.6 ± 0.3, and −0.7 ± 0.5 log10for the 25-, 50-, 75-, and 100-mg doses, respectively, while viral load remained unchanged for the pooled placebo patients (−0.05 ± 0.3 log10). Patients with genotype-1a and patients with genotype-1b responded similarly. Serum ALT levels decreased, especially at daily doses ≥ 75 mg. During the posttreatment period, plasma viremia and serum aminotransferase levels returned to near pretreatment levels. No resistance mutations associated with IDX184 were detected. Plasma exposure of IDX184 and its nucleoside metabolite 2′-MeG was dose related and low. Changes in plasma viral load correlated with plasma exposure of 2′-MeG. In conclusion, the results from this proof-of-concept study show that small doses of the liver-targeted prodrug IDX184 were able to deliver significant antiviral activity and support further clinical evaluation of the drug candidate.

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 Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

2012 ◽  
Vol 45 (4) ◽  
pp. 444-447 ◽  
Author(s):  
Fábio Heleno de Lima Pace ◽  
Lincoln Eduardo Vieira de Castro Ferreira ◽  
Antonio Eduardo Benedito Silva ◽  
Maria Lucia Gomes Ferraz
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Hepatitis B Surface Antigen ◽  
Hcv Rna ◽  
Progression Rate ◽  
Fibrosis Progression ◽  
Normal Alanine Aminotransferase ◽  
Normal Alt

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis

2003 ◽  
Vol 98 (5) ◽  
pp. 1150-1154 ◽  
Author(s):  
Jean Michel Petit ◽  
Muriel Benichou ◽  
Laurence Duvillard ◽  
Valerie Jooste ◽  
Jean Baptiste Bour ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Plasma Viral Load

scholarly journals Seroprevalance of hepatitis-c infection in multi-transfused thalassemic children: study from a West Indian tertiary care center

2017 ◽  
Vol 4 (5) ◽  
pp. 1871 ◽  
Author(s):  
Sheesham Agrawal ◽  
Pawan Kumar Sulaniya ◽  
Kapil Garg ◽  
Ramesh Choudhary ◽  
Chandrakanta Sulaniya
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Serum Ferritin ◽  
Tertiary Care ◽  
Antibody Detection ◽  
P Value ◽  
Hcv Rna ◽  
Age Group ◽  
Hcv Antibody

Background: To study the prevalence of hepatitis-C virus infection in multi-transfused thalassemic children and to correlate these patients with age, number of transfusion, serum ferritin levels and transaminases levels.Methods: This study was conducted in the Department of Pediatrics of a Teaching Institute of Rajasthan. It was a hospital based cross sectional study, conducted over a period of 12 months (April 2016- March 2017). Blood sample for Ant-HCV antibody detection was taken at time of follow-up visit in the subspeciality clinic. These samples were processed in central laboratory for hep-C antibody, serum ferritin and transaminases levels. Anti-HCV antibody detection was done by BI-DOT machine. HCV RNA PCR was done to access viral load in all positive cases.Results: A total of 300 patients were enrolled in the study. There were 219 (73%) males and 81 (27%) females. The mean age of the study group was 7.59±3.6 years (range 1.5-18years). At the time of our study 277 (92.4%) cases were on one or the other chelating agent whereas 23 (7.6%) cases were not taking any kind of chelation therapy. Out of 300 patients, 72(24%) cases tested positive for anti HCV antibody. Out of 72 patients only 36(12%) patients had detectable viral load in RNA PCR.  Mean age of the HCV positive cases (9.58±3.28) years was higher as compared to HCV negative cases (6.98±3.54). Maximum HCV positivity 20/38 (52.6%) was seen in 12-18 year age group; followed by 33/76 (43.4%) in 9-12yr age group. Significant association was observed between advancing age and prevalence of hepatitis C in thalassemia major patients (p=0.002). The number of blood transfusions received by anti-HCV positive children (Avg. Transfusion 185±98.40 ml/kg/year) was significantly higher than that by anti-HCV negative patients (Avg. Transfusion 102.8±71.20) (p value<0.001). Maximum HCV positive cases 33 (45.83%) had total transfusions >200 in a year followed by 15 (20.83%) cases with 151-200 transfusions (p<0.001).Conclusions: Despite ELISA screening of blood donors, our study demonstrated high (24%) prevalence of transfusion transmitted hepatitis-C virus in thalassemic children which increases with increasing number of transfusions, it also correlates with rising serum ferritin level and SGPT level. 

scholarly journals Activity of a Potent Hepatitis C Virus Polymerase Inhibitor in the Chimpanzee Model

2007 ◽  
Vol 51 (12) ◽  
pp. 4290-4296 ◽  
Author(s):  
Chih-Ming Chen ◽  
Yupeng He ◽  
Liangjun Lu ◽  
Hock Ben Lim ◽  
Rakesh L. Tripathi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Half Life ◽  
Nonstructural Protein ◽  
Hcv Rna ◽  
Antiviral Efficacy ◽  
Genotype 1A ◽  
Genotype 1B ◽  
Infected Chimpanzee

ABSTRACT A-837093 is a potent and specific nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase. It possesses nanomolar potencies in both enzymatic and replicon-based cell culture assays. In rats and dogs this compound demonstrated an oral plasma half-life of greater than 7 h, and its bioavailability was >60%. In monkeys it had a half-life of 1.9 h and 15% bioavailability. Its antiviral efficacy was evaluated in two chimpanzees infected with HCV in a proof-of-concept study. The design included oral dosing of 30 mg per kg of body weight twice a day for 14 days, followed by a 14-day posttreatment observation. Maximum viral load reductions of 1.4 and 2.5 log10 copies RNA/ml for genotype 1a- and 1b-infected chimpanzees, respectively, were observed within 2 days after the initiation of treatment. After this initial drop in the viral load, a rebound of plasma HCV RNA was observed in the genotype 1b-infected chimpanzee, while the genotype 1a-infected chimpanzee experienced a partial rebound that lasted throughout the treatment period. Clonal analysis of NS5B gene sequences derived from the plasma of A-837093-treated chimpanzees revealed the presence of several mutations associated with resistance to A-837093, including Y448H, G554D, and D559G in the genotype 1a-infected chimpanzee and C316Y and G554D in the genotype 1b-infected chimpanzee. The identification of resistance-associated mutations in both chimpanzees is consistent with the findings of in vitro selection studies, in which many of the same mutations were selected. These findings validate the antiviral efficacy and resistance development of benzothiadiazine HCV polymerase inhibitors in vivo.

scholarly journals Clinical Evaluation of the Automated COBAS AMPLICOR HCV MONITOR Test Version 2.0 for Quantifying Serum Hepatitis C Virus RNA and Comparison to the Quantiplex HCV Version 2.0 Test

2000 ◽  
Vol 38 (8) ◽  
pp. 2933-2939 ◽  
Author(s):  
Ming-Lung Yu ◽  
Wan-Long Chuang ◽  
Chia-Yen Dai ◽  
Shinn-Cherng Chen ◽  
Zu-Yau Lin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hcv Rna ◽  
Interferon Treatment ◽  
Test Version ◽  
Version 2.0 ◽  
Chronic Hepatitis C Patients

A second-generation hepatitis C virus (HCV) quantitative assay (COBAS AMPLICOR HCV MONITOR Test, version 2.0; COBAS HCM-2) has been developed, with the intention of achieving equivalent quantification of all HCV genotypes and improving assay performance. To evaluate the clinical performance of COBAS HCM-2 and its utility in predicting the response to alpha interferon treatment, sera from 215 chronic hepatitis C patients were analyzed and the results were compared with those obtained by the Quantiplex bDNA HCV RNA, version 2.0, assay (bDNA-2). The COBAS HCM-2 had significantly greater sensitivity than bDNA-2 (94.9 versus 88.4%; P < 0.001) when performed with sera from chronic hepatitis C patients who were viremic by a qualitative PCR test. The standard deviations for the within-run and between-run reproducibilities of COBAS HCM-2 were <0.1 and <0.2, respectively, and it showed an improved linear range between genotypes with the threefold serial dilutions tested (r 2 = 0.986 to 0.995). The COBAS HCM-2 results were positively correlated with the bDNA-2 results, but the values for COBAS HCM-2 were on average 0.96 log lower than the values for bDNA-2. The mean difference in quantification values between these two assays did not differ among samples with different genotypes (0.70 to 1.00 log). No genotype-dependent difference in viral load was observed. The pretreatment viral load was significantly lower in complete responders. By using multivariate analysis, the viral load 2 weeks after the initiation of alpha interferon treatment was the strongest predictor of a complete response. In conclusion, COBAS HCM-2 demonstrated good sensitivity, linearity, and reproducibility and efficiency equal to that of bDNA-2 for the quantification of HCV genotypes 1 and 2. Hence, this assay provides a rapid and reliable method for the quantification of HCV RNA in serum and is useful for the planning of interferon treatment.

scholarly journals Significant Improvement in Diagnosis of Hepatitis C Virus Infection by a One-Step Strategy in a Central Laboratory: an Optimal Tool for Hepatitis C Elimination?

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Rosa López-Martínez ◽  
Andrea Arias-García ◽  
Francisco Rodríguez-Algarra ◽  
Laura Castellote-Bellés ◽  
Ariadna Rando-Segura ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Global Strategy ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Central Laboratory ◽  
Antiviral Therapies ◽  
One Step ◽  
Reflex Testing

ABSTRACT The remarkable effectivity of current antiviral therapies has led to consider the elimination of hepatitis C virus (HCV) infection. However, HCV infection is highly underdiagnosed; therefore, a global strategy for eliminating it requires improving the effectiveness of HCV diagnosis to identify hidden cases. In this study, we assessed the effectiveness of a protocol for HCV diagnosis based on viral load reflex testing of anti-HCV antibody-positive patients (known as one-step diagnosis) by analyzing all diagnostic tests performed by a central laboratory covering an area of 1.5 million inhabitants in Barcelona, Spain, before (83,786 cases) and after (45,935 cases) the implementation of the reflex testing protocol. After its implementation, the percentage of anti-HCV-positive patients with omitted HCV RNA determination remarkably decreased in most settings, particularly in drug treatment centers and primary care settings, where omitted HCV RNA analyses had absolute reductions of 76.4 and 20.2%, respectively. In these two settings, the percentage of HCV RNA-positive patients identified as a result of reflex testing accounted for 55 and 61% of all anti-HCV-positive patients. HCV RNA results were provided in a mean of 2 days. The presence of HCV RNA and age of ≥65 years were significantly associated with advanced fibrosis, assessed using the serological FIB-4 index (odds ratio [OR], 5.92; 95% confidence interval [CI], 3.4 to 10.4). The implementation of viral load reflex testing in a central laboratory is feasible and significantly increases the diagnostic effectiveness of HCV infections, while allowing the identification of underdiagnosed cases.

Sign in / Sign up

Export Citation Format

Share Document