| 1. |
- Alestig, Erik, 1973, et al.
(författare)
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Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection
- 2011
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients. Methods: The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor. Results: No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860. Conclusions: The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.
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| 2. |
- Alestig, Erik, 1973, et al.
(författare)
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Genetic diversity of genotype D3 in acute hepatitis B
- 2013
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615. ; 85:7, s. 1148-1154
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Tidskriftsartikel (refereegranskat)abstract
- Acute hepatitis B related to injection drug use is often caused by HBV-D3, a subgenotype that probably was introduced in Western Europe in the 1960s. The aim of this study was to describe genetic change over time in injection drug use-related HBV-D3 in one geographic area. Fourteen complete genomes and partial genomic regions of 17 HBV strains of subgenotype D3 causing acute (n = 30) or chronic (n = 1) hepatitis B at different time points between 1975 and 2009 were investigated. The 14 complete genomes clustered in phylogenetic trees on a sub-branch of HBV-D3 along with a few published sequences with high bootstrap values. In contrast, the phylogenetic tree topology based on nucleotides coding for surface antigen or core was uncertain with bootstrap values below 70% or lower. Variation of nucleotides coding for amino acids 125, 136, and 143 in the a determinant of HBsAg was however linked to complete genome phylogeny, indicating that these codons might be useful as markers for clades. The results show that knowledge about circulating strains is critical for the interpretation of molecular epidemiology investigations. The low degree of genetic change over time of HBV-D3 in the studied groups suggests that outbreaks of acute hepatitis B in injection drug users might originate from a limited number of individuals with chronic infection. Classification based on core or S region phylogeny obtained poor support from bootstrap values, but the presence of clade-specific amino acid substitutions suggests that the S region may be useful for subgenomic molecular epidemiology of HBV.
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| 3. |
- Alsiö, Åsa, 1965, et al.
(författare)
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Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection
- 2012
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 31:7, s. 1631-1635
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n = 382) comparing 12 and 24 weeks of combination treatment with pegylated interferon-alpha 2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral response (SVR) rates of 86% and 84% were achieved in the 12- and 24-week arms, respectively. Similarly, among patients having received at least 80% of the target dose of both pegylated interferon alpha-2a and of ribavirin for at least 80% of the target treatment duration (per-protocol analysis), the SVR rates were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia.
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| 4. |
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| 5. |
- Alsiö, Åsa, 1965, et al.
(författare)
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Nonresponder patients with hepatitis C virus genotype 2/3 infection: a question of low systemic interferon concentrations?
- 2010
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Ingår i: Clinical infectious diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 50:4, s. e22-e25
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Tidskriftsartikel (refereegranskat)abstract
- Twelve of 303 per-protocol patients were nonresponders in a 12-week versus 24-week treatment study of hepatitis C virus (HCV) genotype 2/3 infection. The nonresponders had significantly lower interferon concentrations, as well as significantly greater mean age, body mass index, and viral load. Suboptimal drug concentrations may thus contribute to lack of response to therapy in patients with infection due to HCV genotype 2/3.
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| 6. |
- Askarieh, Galia, 1983, et al.
(författare)
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Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.
- 2010
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
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Tidskriftsartikel (refereegranskat)abstract
- High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. CONCLUSION: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.
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| 7. |
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| 8. |
- Eilard, Anders, et al.
(författare)
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Vertically acquired occult hepatitis B virus infection may become overt after several years
- 2019
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 78:3, s. 226-231
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Elsevier Ltd Objectives: To study the frequency of vertically acquired occult hepatitis B virus (HBV) infection (OBI). Methods: We investigated 44 children born to hepatitis B surface antigen (HBsAg) positive mothers. They received HBV vaccine directly after birth and at 2, 6 and 52 weeks of age; eight with HBeAg-positive mothers also received hepatitis B immunoglobulin (HBIG). HBV DNA was analyzed in blood collected at 6 weeks and 12 months of age, and HBV antibodies at 12 and 18 months of age. Results: HBV DNA, but not HBsAg or anti-HBc, was detected at 12 months of age in three children. The viral sequences were almost identical with HBV DNA from their mothers who all were HBeAg-positive and had received tenofovir during pregnancy. Follow-up at 5–7 years age showed that one of the three children had become seropositive for HBsAg and anti-HBc. This child and one of the other two had detectable HBV DNA at the follow-up, with whole genome sequences identical to those in HBV from their mothers. Conclusions: Mothers-to-child transmission of HBV can, despite adequate prophylaxis, lead to OBI which may later develop into overt HBV infection. Whether such infections are of clinical importance needs to be further investigated.
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| 9. |
- Fuchs, Dietmar, et al.
(författare)
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Increase of tryptophan in serum and in cerebrospinal fluid of patients with HIV infection during zidovudine therapy
- 1996
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Ingår i: Adv Exp Med Biol. ; 398, s. 131-4
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Tidskriftsartikel (refereegranskat)abstract
- A high percentage of patients with human immunodeficiency virus infection presents with decreased tryptophan concentrations in serum and cerebrospinal fluid. In parallel degradation products of tryptophan like kynurenine and quinolinic acid are increased. We investigated the behavior of tryptophan concentrations in 14 patients with HIV infection before and during treatment with zidovudine, and we found a significant increase of tryptophan in serum and cerebrospinal fluid after 4-14 months of therapy. In parallel, neopterin concentrations decreased significantly. Moreover, an association existed in cerebrospinal fluid between the degree of tryptophan increase and neopterin decrease. Thus, treatment with zidovudine contributes to a gradual normalization of tryptophan metabolism in patients with HIV-1 infection. The data imply that zidovudine therapy is associated not only with a reduction of virus replication but also immune activation is reduced.
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| 10. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Cerebrospinal fluid and plasma viral load in HIV-1-infected patients with various anti-retroviral treatment regimens
- 2000
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Ingår i: Scand J Infect Dis. ; 32:4, s. 365-9
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Tidskriftsartikel (refereegranskat)abstract
- Highly active anti-retroviral therapy (HAART) effectively decreases HIV-1 RNA in cerebrospinal fluid (CSF) and plasma in controlled clinical trials. To study the virological effect in CSF and plasma achieved in routine practice, HIV-1 RNA levels were analysed retrospectively in 27 patients on mono-nucleoside reversed transcriptase inhibitor (NRTI) treatment, 27 on dual-NRTI-treatment and 45 on HAART using a Roche Amplicor HIV-1 monitor quantitative PCR. A significant difference was found in the proportion of patients with a CSF viral load below 20 copies/ml between patients treated with 1 (0%) and 2 NRTIs (41%) as well as between those treated with 2 NRTIs and HAART (69%). The proportion of patients with plasma viral load below 20 copies/ml differed significantly between patients on HAART (47%) and those on 2 NRTIs (0%), but not between those with 1 (0%) or 2 NRTIs. In multivariate regression analysis, treatment regimen and prior anti-retroviral experience (but not treatment time) were independently associated with the CSF viral load. Plasma viral load was independently associated with treatment regimen and treatment time, but not with anti-retroviral experience. Dual-NRTI-treatment affects the CSF viral load substantially, while HAART is required to achieve an essential decline in plasma viral load.
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