| 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
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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. |
- Jerkeman, Anna, et al.
(författare)
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Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy-Factors associated with advanced fibrosis
- 2014
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 46, s. 340-347
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Jerkeman, A., et al.
(författare)
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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
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Ingår i: European Journal of Gastroenterology & Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0954-691X. ; 26:5, s. 523-531
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Tidskriftsartikel (refereegranskat)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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| 9. |
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| 10. |
- Lagging, Martin, 1965, et al.
(författare)
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Reply.
- 2014
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 60:6, s. 2130-1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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