Case 44

Author(s):  
Will Irving

Healthcare workers can transmit blood-borne virus (BBV) infections to their patients during the course of performing exposure prone procedures. To reduce the risk of this happening, healthcare workers entering the National Health Service who wish to perform EPPs in the UK must be tested for BBV infection. Hepatitis B- infected healthcare workers may perform EPPs providing they are HBE antigen negative and have a viral load below 200 IU/ml, subject to annual viral load checks. If their viral load is >200 but < 20,000 IU/ml, then they may suppress HBV replication using nucleos(t)ide analogue antiviral therapy, subject to 3-monthly viral load measurement. Healthcare workers known to be currently infected with hepatitis C virus are not allowed to perform EPPs but may do so if they are clear of HCV RNA 12 weeks after antiviral therapy. HIV-infected healthcare workers may perform EPPs if their viral load is suppressed to < 200 copies/ml whilst on combination antiretroviral therapy, subject to 3-monthly monitoring.

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Takeshi Endo ◽  
Koichi Ito ◽  
Tokio Sugiura ◽  
Kenji Goto

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.


2012 ◽  
Vol 56 (12) ◽  
pp. 6372-6378 ◽  
Author(s):  
Jacob Lalezari ◽  
David Asmuth ◽  
Arnaldo Casiró ◽  
Hugo Vargas ◽  
Shannon Lawrence ◽  
...  

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.


2012 ◽  
Vol 17 (5) ◽  
pp. 7-13 ◽  
Author(s):  
L. I. Nikolaeva ◽  
A. V. Kolotvin ◽  
L. M. Samokhodskaya ◽  
G. V. Sapronov ◽  
V. V. Makashova ◽  
...  

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.


2017 ◽  
Vol 4 (5) ◽  
pp. 1871 ◽  
Author(s):  
Sheesham Agrawal ◽  
Pawan Kumar Sulaniya ◽  
Kapil Garg ◽  
Ramesh Choudhary ◽  
Chandrakanta Sulaniya

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. 


2011 ◽  
Vol 83 (6) ◽  
pp. 1016-1022 ◽  
Author(s):  
Norio Akuta ◽  
Fumitaka Suzuki ◽  
Miharu Hirakawa ◽  
Yusuke Kawamura ◽  
Hitomi Sezaki ◽  
...  

2007 ◽  
Vol 51 (12) ◽  
pp. 4290-4296 ◽  
Author(s):  
Chih-Ming Chen ◽  
Yupeng He ◽  
Liangjun Lu ◽  
Hock Ben Lim ◽  
Rakesh L. Tripathi ◽  
...  

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.


2000 ◽  
Vol 38 (8) ◽  
pp. 2933-2939 ◽  
Author(s):  
Ming-Lung Yu ◽  
Wan-Long Chuang ◽  
Chia-Yen Dai ◽  
Shinn-Cherng Chen ◽  
Zu-Yau Lin ◽  
...  

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.


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