| 1. |
- Alestig, Erik, 1973, et al.
(author)
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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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In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11
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Journal article (peer-reviewed)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.
(author)
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Genetic diversity of genotype D3 in acute hepatitis B
- 2013
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In: Journal of Medical Virology. - : Wiley. - 0146-6615. ; 85:7, s. 1148-1154
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Journal article (peer-reviewed)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.
(author)
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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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In: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 31:7, s. 1631-1635
-
Journal article (peer-reviewed)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.
(author)
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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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In: Clinical infectious diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 50:4
-
Journal article (peer-reviewed)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.
(author)
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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
-
In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
-
Journal article (peer-reviewed)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.
(author)
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Vertically acquired occult hepatitis B virus infection may become overt after several years
- 2019
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In: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 78:3, s. 226-231
-
Journal article (peer-reviewed)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.
(author)
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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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In: Adv Exp Med Biol. ; 398, s. 131-4
-
Journal article (peer-reviewed)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.
(author)
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Cerebrospinal fluid and plasma viral load in HIV-1-infected patients with various anti-retroviral treatment regimens
- 2000
-
In: Scand J Infect Dis. ; 32:4, s. 365-9
-
Journal article (peer-reviewed)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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| 11. |
- Gisslén, Magnus, 1962, et al.
(author)
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Cerebrospinal fluid viral load in HIV-1-infected patients without antiretroviral treatment: a longitudinal study
- 1998
-
In: J Acquir Immune Defic Syndr Hum Retrovirol. ; 17:4, s. 291-5
-
Journal article (peer-reviewed)abstract
- HIV-1 RNA and neopterin levels were observed longitudinally for 20 to 68 months (mean, 37.5 months) in cerebrospinal fluid (CSF) and serum in 15 HIV-1-infected patients not receiving antiretroviral treatment. During the course of infection the HIV-1 RNA levels increased significantly in CSF, from a mean of 3.08 to 3.51 log10 copies RNA/ml (p < .01). A significant positive correlation was found between the CSF levels of HIV-I RNA and neopterin (rs = 0.54; p < .001), which increased from 13.6 to 19.6 nmol/L (p < .01). No significant changes in HIV-1 RNA or neopterin levels were found in serum. We suggest that the increase of CSF viral load with time in HIV-1 infection triggers an intrathecal immune activation reflected by increased CSF levels of neopterin. These results are in accordance with the theory that a chronic immune stimulation within the central nervous system (CNS) is involved in the pathogenesis of neurologic HIV-1 disease.
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| 12. |
- Gisslén, Magnus, 1962, et al.
(author)
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Elevated cerebrospinal fluid sulfatide concentrations as a sign of increased metabolic turnover of myelin in HIV type I infection
- 1996
-
In: AIDS Res Hum Retroviruses. ; 12:2, s. 149-55
-
Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) sulfatide concentrations were analyzed in 18 patients with asymptomatic HIV-1 infection, in 16 patients with AIDS who were free from opportunistic infections in the central nervous system (CNS), in 12 HIV-1-infected patients with opportunistic CNS infections or lymphoma, and in 19 HIV-negative controls, by thin-layer chromatography overlay technique using an antisulfatide antibody to estimate the metabolic turnover of myelin. The majority of asymptomatic HIV-1-infected patients had normal CSF sulfatide concentrations, but the mean CSF sulfatide concentration was still elevated compared to that in HIV-negative controls (152 compared to 99 nmol/liter, p < 0.05). The CSF sulfatide concentrations in the AIDS group (mean 395 nmol/liter) were significantly increased compared to those in asymptomatic HIV-1-infected patients (p < 0.01) and in HIV-negative controls (p < 0.001), but did not differ significantly between patients with and without dementia. Increased CSF sulfatide concentrations were also found in patients with opportunistic infection or lymphoma in the CNS. In the entire study population, the sulfatide levels were associated with blood-brain barrier function, but not with intrathecal immunoglobulin production or with positive HIV isolations from CSF. Thus, signs of white matter changes, measured as increased CSF sulfatide concentrations, could be found in some asymptomatic HIV-1-infected patients, but the highest levels were seen in patients with AIDS.
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| 13. |
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| 14. |
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| 15. |
- Gisslén, Magnus, 1962, et al.
(author)
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Increased cerebrospinal fluid ganglioside GM1 concentrations indicating neuronal involvement in all stages of HIV-1 infection
- 1997
-
In: J Neurovirol. ; 3:2, s. 148-52
-
Journal article (peer-reviewed)abstract
- Measurements of cerebrospinal fluid (CSF) concentrations of gangliosides can be used as markers of central nervous system (CNS) neuronal involvement. We have analysed the CSF concentrations of the four major brain gangliosides GM1, GD1a, GD1b, and GT1b at different stages of HIV-1 infection. CSF samples were collected from 44 HIV-1-infected patients and from 24 HIV-negative, healthy controls. A significantly higher mean CSF concentration of the ganglioside GM1 was found in HIV-1-infected patients than in HIV-negative controls (27 and 19 nmol/l, respectively, P<0.01). The HIV-infected patients also had a higher mean GM1 proportion of the total ganglioside concentration (11% compared with 8.5%, P < 0.01). Nine out of 27 patients with asymptomatic HIV-1 infection, three of ten with AIDS without neurological complications, and three of seven with AIDS dementia complex had CSF GM1 concentrations above the mean+2SD in the HIV-negative control group. Conclusion: Biochemical signs of ongoing neuronal involvement could be found in about one third of HIV-1-infected patients. The same frequency was found regardless of stage, although the highest levels of CSF gangliosides were found in patients with AIDS.
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| 16. |
- Gisslén, Magnus, 1962, et al.
(author)
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Markers of immune stimulation in the cerebrospinal fluid during HIV infection: a longitudinal study
- 1994
-
In: Scand J Infect Dis. - : Informa UK Limited. ; 26:5, s. 523-33
-
Journal article (peer-reviewed)abstract
- Markers of immune stimulation were studied in 76 sequential cerebrospinal fluid (CSF) samples from 19 patients infected with HIV-1 without antiretroviral treatment during observation periods ranging from 22 months to 6 years. Eight of these patients were further followed with 14 CSF samples for 3-24 months of zidovudine treatment. During the course of HIV-1 infection, the mean CSF neopterin and beta 2-microglobulin (beta 2M) concentrations increased from 12.7 to 20.4 nmol/l (p < 0.01) and from 1.93 to 2.17 mg/l (p < 0.05), respectively, while the mean peripheral CD4 + T cell count decreased from 624 to 320 cells x 10(6)/l (p < 0.001). The IgG index, reflecting intrathecal immunoglobulin production, increased from 0.72 to 0.92 (p = 0.08). The number of patients with CSF pleocytosis did not change significantly during follow-up (8/19 at baseline, 7/19 at endpoint). In the 8 patients followed up during antiretroviral treatment, a significant reduction in mean CSF levels of neopterin and beta 2M (-48% and -32%, respectively, p < 0.01) was seen after 3-12 months on zidovudine. We suggest that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.
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| 17. |
- Gisslén, Magnus, 1962, et al.
(author)
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The effect on human immunodeficiency virus type 1 RNA levels in cerebrospinal fluid after initiation of zidovudine or didanosine
- 1997
-
In: J Infect Dis. ; 175:2, s. 434-7
-
Journal article (peer-reviewed)abstract
- Human immunodeficiency virus type 1 (HIV-1) RNA, neopterin, and beta2-microglobulin levels were analyzed in cerebrospinal fluid (CSF) and serum before and 3-13 months after initiation of antiretroviral monotherapy in 16 HIV-1-infected persons. Twenty-one treatment periods, 13 after initiation of zidovudine and 8 after initiation of didanosine, were studied. During zidovudine treatment, CSF HIV RNA levels decreased by a mean of 1.05 log10 (-91%, P < .01), and CSF neopterin and beta2-microglobulin levels by 57% and 33%, respectively (P < .01). No reduction was seen during didanosine treatment in CSF HIV RNA (+0.13 log10, not significant), CSF neopterin, or beta2-microglobulin levels. Changes in CSF HIV RNA levels correlated with changes in CSF neopterin and beta2-microglobulin (r(s) = .81 and .83, respectively, P < .001). The decrease in HIV RNA was significantly larger in CSF than in serum following zidovudine treatment (P < .01). These data demonstrate that zidovudine is a potent reducer of central nervous system virus load, which may be important for long-term neuroprotection.
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| 18. |
- Gisslén, Magnus, 1962, et al.
(author)
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Tryptophan concentrations increase in cerebrospinal fluid and blood after zidovudine treatment in patients with HIV type 1 infection
- 1994
-
In: AIDS Res Hum Retroviruses. ; 10:8, s. 947-51
-
Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) and blood concentrations of indoleamines and catecholamines were analyzed in 14 HIV-1-seropositive individuals before antiviral treatment with zidovudine, after 3-14 months of treatment, and, in 8 of the patients, also after 14-30 months. The median pretreatment concentrations of tryptophan in CSF and blood were low (224 ng/ml and 6.0 micrograms/ml, respectively), but an increase in these values by an average of 40% in CSF and 23% in blood was seen after 3-14 months of zidovudine treatment (p < 0.01) and remained undiminished after 14-30 months of treatment. No significant change was observed in the 5-hydroxytryptamine (5-HT, serotonin) level in blood or in the CSF concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite homovanillic acid (HVA). The CSF concentrations of the noradrenalin metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) had decreased by 12% on average (p < 0.01) by the time of the second follow-up, that is, after 14-30 months of zidovudine treatment. A decrease in neopterin during antiretroviral treatment correlated with an increase in tryptophan (p < 0.01). The data suggest that an association between decreased immune stimulation and reduced tryptophan degradation in patients treated with zidovudine.
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| 19. |
- Hagberg, Lars, 1951, et al.
(author)
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Intrathecal immunoactivation in patients with HIV-1 infection is reduced by zidovudine but not by didanosine
- 1996
-
In: Scand J Infect Dis. - : Informa UK Limited. ; 28:4, s. 329-33
-
Journal article (peer-reviewed)abstract
- The effect of zidovudine and didanosine on the cerebrospinal fluid (CSF) concentrations of neopterin was studied in 12 patients with human immunodeficiency virus type-1 (HIV-1) infection 3-12 months after initiation of antiretroviral therapy. Ten treatment periods on zidovudine and 7 on didanosine were analysed. The CSF concentrations of neopterin decreased by 63% (from 29.6 to 12.9 nmol/l, p < 0.01) during zidovudine but increased by 15% (from 22.6 to 25.9 nmol/l, not significant during didanosine treatment. The CSF monocytic cell count decreased during zidovudine but increased during didanosine treatment. The results suggest that zidovudine but not didanosine reduces intrathecal immunoactivation during HIV-1 infection.
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| 20. |
- Hagberg, Lars, 1951, et al.
(author)
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Kinetics of HIV-1 in cerebrospinal fluid and serum after zidovudine treatment
- 1999
-
In: J NeuroAIDS. ; 2:2, s. 29-35
-
Journal article (peer-reviewed)abstract
- Two patients with HIV-1 infection associated with neurological complications were repeatedly followed with cerebrospinal fluid (CSF) and serum analyses before, and 1 to 2.5 years after single zidovudine treatment. Retrospectively, HIV-RNA levels were analyzed with quantitative PCR assay. The number of HIV-RNA copies in CSF was decreased already 1 week after initiation of zidovudine, and continued to decrease during 5 months of follow up, while the serum levels increased during the same period. The difference between HIV levels in CSF and serum compartments following zidovudine treatment indicates that the CSF viral load does not merely reflect blood levels. Single zidovudine treatment did not reduce the viral load in CSF to non-detectable levels but had a better and more long-lasting anti-HIV effect in CSF than in peripheral blood.
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| 21. |
- Hannoun, Charles, 1967, et al.
(author)
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Phylogeny of African complete genomes reveals a West African genotype A subtype of hepatitis B virus and relatedness between Somali and Asian A1 sequences.
- 2005
-
In: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 86:Pt 8, s. 2163-7
-
Journal article (peer-reviewed)abstract
- Hepatitis B virus (HBV) is a major cause worldwide of liver disease, including hepatocellular carcinoma. There are eight known genotypes (A-H), of which genotype A has been divided into two subtypes: A2, prevalent in Europe, and A1, which is prevalent in sub-Saharan Africa, but also occurs in southern Asia. In this study, which includes 14 new complete genomes of non-European genotype A HBV, it was found that West African strains seem to constitute a new subgroup, A3. The high degree of genetic diversity within Africa indicates that genotype A originates from Africa. Based on a 2 % genetic distance between Asian and Somali sequences, it seems that the A1 subtype has spread from East Africa to southern Asia during the last 1000-2000 years. Moreover, it is proposed here that the A2 subtype originates from southern Africa and was imported to Europe around 500 years ago or later. The finding of T-1809/1812 close to the precore start codon and T-1862 and A-1888 in the precore region in HBV e antigen-positive children with signs of a mimimal immune response indicates that these substitutions are stable variants, rather than mutations emerging during infection in individual carriers.
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| 22. |
- Hansen, J. F., et al.
(author)
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PRO-C3: a new and more precise collagen marker for liver fibrosis in patients with chronic hepatitis C
- 2018
-
In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:1, s. 83-87
-
Journal article (peer-reviewed)abstract
- Objective: Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score3) and cirrhosis (Ishak score5) both as a single test and as a part of algorithms.Materials and methods: PRO-C3 was assessed in baseline samples from the NORDynamIC trial. 270 patients were stratified into groups according to baseline biopsy. Baseline APRI, FIB-4 and GUCI scores were available for comparison in 232 patients.Results: PRO-C3 increased with Ishak scores (p=.001). Area under the curve (AUC) for significant fibrosis was 0.75 (95% CI 0.68-0.81) and 0.76 (95% CI 0.68-0.84) for cirrhosis. FIB-4, APRI and GUCI had similar AUCs. In a PRO-C3 algorithm including age, platelet count, body mass index (BMI) and international normalised ratio (INR), the diagnostic efficacy improved to 0.85 (CI 0.80-0.89) and 0.90 (IQR 0.84-0.96) for significant fibrosis and cirrhosis, respectively.Conclusions: In our study, PRO-C3 was an independent predictor of fibrosis stage, and may play an important role in managing CHC patients.
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| 23. |
- Jerkeman, Anna, et al.
(author)
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Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy-Factors associated with advanced fibrosis
- 2014
-
In: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 46, s. 340-347
-
Journal article (peer-reviewed)abstract
- Background: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. Methods: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. Results: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). Conclusions: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs. © 2014 Informa Healthcare.
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| 24. |
- Jerkeman, A., et al.
(author)
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Treatment for chronic hepatitis C in a cohort of opiate substitution therapy recipients in three Swedish cities - completion rates and efficacy
- 2014
-
In: European Journal of Gastroenterology & Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0954-691X. ; 26:5, s. 523-531
-
Journal article (peer-reviewed)abstract
- Objectives Opiate substitution treatment (OST) programs could provide opportunities for management of comorbidities, such as hepatitis C virus (HCV) infection, in people who inject drugs. We aimed to prospectively evaluate the real-life feasibility of interferon/ribavirin-based HCV treatment in OST recipients, with a special focus on psychiatric status and health-related quality of life. Patients from a cohort of OST recipients from three cities in Sweden were selected for HCV treatment on the basis of structured investigation for HCV-related liver disease. Therapy was delivered in collaboration between infectious disease and OST clinics, with monitoring for completion and adherence, treatment response, adverse events, health-related quality of life (HRQoL) (SF-36) and signs of depression (MADRS-S), or relapse into drug abuse. The primary endpoint was completion of prescribed treatment; the secondary endpoints were sustained virological response (SVR), adherence, and incidence of depression. Among 69 patients with an indication for antiviral therapy, 41 initiated treatment; 34/41 (83%) completed treatment and 19/41 (46%) achieved SVR. Adequate adherence was observed in 29/41 patients (71%). Two serious adverse events occurred, including one death because of liver failure. Baseline scores for self-assessed health were low, with a significant reduction during treatment. Seventy-one percent of patients (29/41) fulfilled the criteria for clinically significant depression at some time point during treatment. Baseline scores for HRQoL/MADRS-S were associated with treatment completion, SVR, and depression during treatment. Despite the low HRQoL and the high occurrence of depression, HCV treatment was feasible and showed satisfactory rates of completion in this cohort of unselected OST recipients.
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| 25. |
- Lagging, Martin, 1965, et al.
(author)
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IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection
- 2006
-
In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 44:6, s. 1617-25
-
Journal article (peer-reviewed)abstract
- Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-alpha-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > or = 25 kg/m2 (P = .004) and with baseline viral load > or = 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.
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| 26. |
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| 27. |
- Lagging, Martin, 1965, et al.
(author)
-
Randomized comparison of 12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection.
- 2008
-
In: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 47:6, s. 1837-45
-
Journal article (peer-reviewed)abstract
- Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator-initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short-term therapy. Three hundred eighty-two genotype 2/3-infected patients [intention-to-treat (ITT) population] at 31 centers in Denmark, Finland, Norway, and Sweden were randomized to 12 or 24 weeks of peginterferon alpha-2a (180 microg/week) plus ribavirin (800 mg/day). Twelve weeks of therapy was inferior to 24 weeks in the ITT population (sustained viral response [SVR] rates: 59% versus 78%, P < 0.0001) and in the subgroups of patients infected with genotype 2 (56% versus 82%, P = 0.006) or 3 (58% versus 78%, P = 0.0015). These differences were observed regardless of the fibrosis stage. Age and HCV-RNA levels on days 7 and 29 were independent predictors of SVR. Short-term treatment was useful in patients < 40 years old, especially if HCV-RNA was undetectable on day 29, and also in patients > or = 40 years old, provided that HCV-RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29. If neither of these two criteria were met for patients > or = 40 years old, 24 weeks of therapy was superior (P < 0.0001). CONCLUSION: Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus.
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| 28. |
- Lagging, Martin, 1965, et al.
(author)
-
Reply.
- 2014
-
In: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 60:6, s. 2130-1
-
Journal article (other academic/artistic)
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| 29. |
- Lagging, Martin, 1965, et al.
(author)
-
Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse
- 2013
-
In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 48:7, s. 839-847
-
Journal article (peer-reviewed)abstract
- Objectives. Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy. Materials and methods. Seventy-one patients with chronic HCV genotype 2/3 with prior relapse were enrolled in a phase III multicenter study. Patients were retreated with peg-IFN alpha-2a 180 mu g per week and ribavirin 1000/1200 mg daily. Patients having received previous therapy for 24 weeks were retreated for 48 weeks (Group A), whereas patients having received at least 12 weeks but less than 24 weeks of treatment were allocated to either 48 (Group B) or 24 weeks (Group C) on the basis of whether they had achieved rapid virological response (RVR). Results. Sustained virological response (SVR) rates of 53%, 81% and 75% were achieved in groups A, B and C, respectively. Patients with favorable baseline characteristics, e. g., less advanced liver fibrosis, age < 40 years, duration of infection < 20 years, or BMI < 25 kg/m(2), tended to have more favorable outcomes. All patients achieving HCV RNA below 1000 IU/mL day 6 achieved SVR in contrast to none of the patients with detectable HCV RNA at week 12. Conclusions. Retreatment with peg-IFN and ribavirin for 24-48 weeks entails SVR among the majority of HCV genotype 2/3 infected patients with prior relapse. However, in light of the prolonged treatment duration, moderate effect and considerable side effects, deterring therapy until new options are available may be preferential, particularly in patients previously treated for 24 weeks.
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| 30. |
- Lagging, Martin, 1965, et al.
(author)
-
Treatment of hepatitis C virus infection for adults and children: Updated Swedish consensus recommendations.
- 2016
-
In: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 48:4, s. 251-261
-
Journal article (other academic/artistic)abstract
- In a recent expert meeting, Swedish recommendations for the treatment of HCV infection were updated. An interferon-free combination of direct-acting antiviral agents was recommended as the first line standard-of-care treatment for chronic HCV infection. Interferon-based therapy should be considered as a second line option after an individual benefit-risk assessment. Treatment is strongly recommended for HCV infected patients with bridging fibrosis or cirrhosis (Metavir stages F3-4), before and after liver transplantation, and in the presence of extra-hepatic manifestations. Additionally, patients with moderate liver fibrosis (stage F2) as well as women in need of in vitro fertilisation should be prioritised for therapeutic intervention. Treatment indications for people who inject drugs, children, chronic kidney disease and HIV co-infection are also discussed.
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| 31. |
- Lagging, Martin, 1965, et al.
(author)
-
Treatment of hepatitis C virus infection: updated Swedish Guidelines 2016.
- 2017
-
In: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:8, s. 561-575
-
Journal article (peer-reviewed)abstract
- In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed.
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| 32. |
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| 33. |
- Larsson, Simon B., et al.
(author)
-
HBsAg quantification for identification of liver disease in chronic hepatitis B virus carriers
- 2014
-
In: Liver International. - : Wiley. - 1478-3223. ; 34:7
-
Journal article (peer-reviewed)abstract
- Background & Aims: Quantification of hepatitis B surface antigen (HBsAg) has been proposed as a useful diagnostic marker for clinical staging (identification of inactive carrier state) and prognosis of chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the correlation between HBsAg levels in serum and histological liver damage in patients with chronic infection. Methods: HBsAg levels in serum (by Abbott Architect) were related to HBV DNA, ALT and histological score (n = 160) and covalently closed circular DNA (cccDNA) (n = 84). Results: HBsAg levels correlated with cccDNA, serum HBV DNA, ALT and high inflammation scores (P < 0.001). Among HBeAg-negative patients, an HBsAg level below 3.0 log(10) IU/ml identified minimal liver damage (normal ALT and mild inflammation) with a predictive value of 92% (alone) or 96% (in combination with HBV DNA <4.0 log(10) copies/ml), whereas an HBsAg level above 3.5 log(10) IU/ml identified severe inflammation with a predictive value of 16% (alone) or 33% (in combination with HBV DNA >5.0 log(10) copies/ml). Conclusions: HBsAg levels reflect clinical stage and liver disease, and a combined quantification of HBsAg and HBV DNA may improve clinical staging.
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| 34. |
- Larsson, Simon B., et al.
(author)
-
Integration of hepatitis B virus DNA in chronically infected patients assessed by Alu-PCR
- 2018
-
In: Journal of Medical Virology. - : Wiley. - 0146-6615. ; 90:10, s. 1568-1575
-
Journal article (peer-reviewed)abstract
- Hepatitis B virus (HBV) infection is the main risk factor for hepatocellular carcinoma (HCC) worldwide. Integration of HBV DNA into the human genome has been found in >80% of HBV-related HCC cases. Some studies have, however, found similar integration patterns in tumorous and nontumorous tissues. Thus, the role of integrations for the development of HCC as well as the rate of integration in different stages of infection remain unclear. The aim of this study was to investigate integrations in patients without HCC, representing different stages of chronic HBV (CHB) infection. Extracted DNA in liver biopsies from 74 patients (one with 2 available biopsies) with CHB infection was analyzed by Alu-PCR. Amplicons were further analyzed by Sanger sequencing. Integration was detected in 39 biopsies (52%) as an amplicon containing both human and HBV sequences by Alu-PCR with one primer targeting a region in the HBV genome. Integrations were found in patients representing the different stages of CHB infection. A majority of the HBV sequences were located upstream or downstream of nucleotide position 1820, which previously has been identified as a common breakpoint in the HBV genome in integrated sequences. Approximately 60% of the HBV integrations were found in noncoding regions of the human genome. Integrations of HBV DNA into the human genome is an event frequently found in mild phases of chronic hepatitis.
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| 35. |
- Larsson, Simon B., et al.
(author)
-
Mechanisms downstream of reverse transcription reduce serum levels of HBV DNA but not of HBsAg in chronic hepatitis B virus infection
- 2015
-
In: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 12
-
Journal article (peer-reviewed)abstract
- Background: Hepatitis B virus (HBV) DNA in serum of chronically infected patients declines by 3-4 log(10) units at loss of HBe antigen (HBeAg) from serum. The mechanisms behind this decline, and the much smaller decline of surface antigen (HBsAg) levels, are still not well known. The aim of this study was to get a better understanding of this process by analysing both serum and intrahepatic markers of HBV replication. Methods: Levels of HBV DNA and HBsAg in serum, and covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) and S-RNA and total intrahepatic HBV DNA (ihDNA) in liver biopsies from 84 chronically infected patients (16 positive and 68 negative for HBeAg) were analysed. Results: Lower HBV DNA levels within HBeAg-positive stage reflected lower levels of cccDNA and pgRNA with strong correlation. In HBeAg-negative patients, ihDNA levels were greater and HBV DNA levels in serum lower than expected from pgRNA levels. A lower HBV DNA/HBsAg ratio corresponded with lower pgRNA/cccDNA (p < 0.01) and higher S-RNA/cccDNA (p < 0.0001) ratios, suggesting that in HBeAg-negative patients transcription of pgRNA, but not of S-RNA, becomes suppressed. Conclusions: The marked reduction of HBV DNA in serum after loss of HBeAg appears to be due to combined reduction of cccDNA, pgRNA and yet unidentified mechanisms downstream of reverse transcription. Such mechanisms include faster clearance of circulating virus or blocked secretion of virions, the latter supported by the observed relative increase of ihDNA in HBeAg-negative patients. The smaller reduction of S-RNA than of pgRNA partly explains why HBsAg remain high in the HBeAg-negative stage, supporting the possibility of HBsAg synthesis from integrated HBV DNA.
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| 36. |
- Leutscher, Peter Derek Christian, et al.
(author)
-
Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C.
- 2010
-
In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 52:2, s. 430-435
-
Journal article (peer-reviewed)abstract
- The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa-2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 19 patients (6%) had major depression at baseline. An additional 114 (37%) developed depression while on HCV combination therapy, with baseline MDI score and female sex independently predicting the emergence of major depression during treatment in a multivariate analysis. Only 36 (32%) of the 114 patients developing major depression according to MDI/DSM-IV criteria were correctly diagnosed during routine medical interviews. The emergence of major depression frequently led to premature discontinuation of peginterferon/ribavirin therapy, and an on-treatment MDI score increment exceeding 30 points (i.e., a validated marker of idiopathic DSM-IV major depression) was correlated with impaired outcome of HCV therapy (P = 0.02). This difference was even more pronounced among patients with an on-treatment increase in MDI score greater than 35 points (P = 0.003). Conclusion: We conclude that (1) depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in identifying patients at risk for treatment-induced depression.
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| 37. |
- Lindgren, A, et al.
(author)
-
Paracetamol-induced cholestatic and granulomatous liver injuries.
- 1997
-
In: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 241:5, s. 435-9
-
Journal article (peer-reviewed)abstract
- To describe uncommon (previously unreported) types of adverse liver reactions to paracetamol.In addition to describing patients, with uncommon types of liver reactions to paracetamol, admitted to our hospitals, we surveyed all the liver reactions to paracetamol reported to the Swedish Adverse Drug Reactions Advisory Committee from 1973 to 1993.The Swedish population of 8 million inhabitants.Extensive medical evaluation.We found one case with a cholestatic liver reaction and one with granulomatous hepatitis. The reactions were probably idiosyncratic and took several months to disappear.In addition to the well-known dose-related toxic liver damage paracetamol may rarely cause non-dose-related severe, prolonged cholestasis or granulomatous hepatitis with cirrhosis.
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| 38. |
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| 39. |
- Lindh, Magnus, 1960, et al.
(author)
-
Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers.
- 1999
-
In: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 179:4, s. 775-82
-
Journal article (peer-reviewed)abstract
- Virus load and liver damage, as measured by quantitative polymerase chain reaction and histology activity index, were related to genotype and core promoter mutations in 43 chronic hepatitis B virus (HBV) carriers of East Asian origin. T-1762 mutants were more frequent in genotype C strains and were associated with more inflammation (P=.0036) and fibrosis (P=.0088) of the liver but not with hepatitis B e antigen (HBeAg) status or virus load. Conversely, precore mutations were associated with less liver inflammation (P=. 08), which was linked to HBeAg negativity and lower viral replication. Carriers with genotype C were more often HBeAg positive (P=.03) with precore wild type strains and more-severe liver inflammation (P=.009) than were those with genotype B. These findings suggest that pathogenic differences between genotypes may exist and that the T-1762 mutation may be useful as a marker for progressive liver damage but seem to contradict that down-regulation of HBeAg production is the major effect of this mutation.
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| 40. |
- Lindh, Magnus, 1960, et al.
(author)
-
Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
-
In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
-
Journal article (peer-reviewed)abstract
- The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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| 41. |
- Lindh, Magnus, 1960, et al.
(author)
-
Hepatitis C treatment response kinetics and impact of baseline predictors.
- 2011
-
In: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:6, s. 400-407
-
Journal article (peer-reviewed)abstract
- Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48 weeks and 139 with genotype 2 or 3 treated for 24 weeks. The reduced SVR rates in patients older than 45 years, with severe liver fibrosis or pretreatment viraemia above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks.
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| 42. |
- Lindh, Magnus, 1960, et al.
(author)
-
IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
- 2011
-
In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:7
-
Journal article (peer-reviewed)abstract
- Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7days of therapy was more pronounced (P<0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' =1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P=0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.
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| 43. |
- Lindh, Magnus, 1960, et al.
(author)
-
Interleukin 28B Gene Variation at rs12979860 Determines Early Viral Kinetics During Treatment in Patients Carrying Genotypes 2 or 3 of Hepatitis C Virus
- 2011
-
In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:12, s. 1748-1752
-
Journal article (peer-reviewed)abstract
- Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon lambda 3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P < .001). In patients treated for 24 weeks, rs12979860 also predicted the rate of sustained virologic response (P = .02), especially among those with high baseline HCV RNA levels (P = .002) or older than 45 years (P = .01). Patients carrying CCrs12979860 had higher baseline HCV RNA levels (P < .001) and did not, when treated for 12 weeks, achieve sustained virologic response more often than those carrying CTrs1297986 or TTrs1297986. The results indicate that IL28B gene testing may identify patients carrying genotype 2 or 3 who could benefit from extended treatment.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Lindh, Magnus, 1960, et al.
(author)
-
Response prediction and treatment tailoring for chronic hepatitis C virus genotype 1 infection
- 2007
-
In: J Clin Microbiol. - 0095-1137. ; 45:8, s. 2439-45
-
Journal article (peer-reviewed)abstract
- We monitored early viral response during the treatment of hepatitis C virus (HCV) infection with the aim of identifying predictors of treatment outcome. We studied 53 patients with genotype 1 infection who received 180 microg/week pegylated interferon alfa-2a and 1,000 or 1,200 mg/day ribavirin depending on body weight and serially assessed HCV RNA in serum, using the Cobas TaqMan assay. Thirty-one patients (58%) achieved sustained viral response (SVR). SVR was obtained in 100% (10/10) of patients with pretreatment viremia concentrations below 400,000 IU/ml, in 100% (14/14) of patients with more than 1.5 log reduction of HCV RNA after 4 days of treatment, and in 95% (22/23) of patients with a rate of decline in viremia higher than 0.70 log units/week during the second phase. Non-SVR was seen in all patients with a second-phase decline rate lower than 0.35 log units/week. Patients with slopes between 0.50 and 0.80 log units/week achieved SVR (4/4) unless the treatment dose was modified (3/3). We conclude that the second-phase slope appears to be an accurate and useful predictor of treatment response. On the basis of these findings, we propose a model of tailored treatment which takes into account the second-phase slope and the amount of HCV RNA after 21 days of treatment.
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| 48. |
- Lindh, Magnus, 1960, et al.
(author)
-
Treatment of chronic hepatitis B infection : an update of Swedish recommendations
- 2008
-
In: Scandinavian Journal of Infectious Diseases. - London : Taylor & Francis. - 0036-5548 .- 1651-1980. ; 40:6-7, s. 436-450
-
Research review (peer-reviewed)abstract
- The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.
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| 49. |
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| 50. |
- Malmström, Sebastian, 1976, et al.
(author)
-
Genotype impact on long-term virological outcome of chronic hepatitis B virus infection
- 2012
-
In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 54:4, s. 321-326
-
Journal article (peer-reviewed)abstract
- Background: The importance of hepatitis B virus (HBV) genotype on the clinical course of chronic HBV infection is not yet clarified. Objectives: To investigate genotype impact on long- term virological outcome of chronic HBV infection. Study design: HBsAg, HBeAg, ALT and HBV DNA levels were determined after a median of 9.2 years of follow-up of 124 adults with chronic HBV infection, of whom 33 were HBeAg-positive at inclusion. Results: HBV DNA levels decreased significantly in patients carrying genotype A (n = 28), B (n = 21) or D (n = 63), but not in those with genotype C infection (n = 12). Loss of HBeAg was seen in 44% (4/9) of patients with genotype C, as compared with 92% (22/24) with non-C genotypes. Loss of HBsAg was seen in 36% (10/28) patients with genotype A, 5% (1/21) with B, 0% (0/12) with C, and 11% (7/63) with genotype D. Conclusions: HBV DNA levels decreased over time in patients infected with genotypes A, B or D. However, highly active genotype C or D infection often remained highly active, implying a risk for progressive liver damage. (c) 2012 Elsevier B.V. All rights reserved.
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