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Sökning: WFRF:(Westin Johan 1965)

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1.
  • Alsiö, Åsa, 1965, et al. (författare)
  • Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection
  • 2012
  • Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 31:7, s. 1631-1635
  • 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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3.
  • Alsiö, Åsa, 1965, et al. (författare)
  • Nonresponder patients with hepatitis C virus genotype 2/3 infection: a question of low systemic interferon concentrations?
  • 2010
  • Ingår i: Clinical infectious diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 50:4, s. e22-e25
  • 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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4.
  • Askarieh, Galia, 1983, et al. (författare)
  • 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
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
  • 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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5.
  • Lagging, Martin, 1965, et al. (författare)
  • Randomized comparison of 12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection.
  • 2008
  • Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 47:6, s. 1837-45
  • Tidskriftsartikel (refereegranskat)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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7.
  • Pedersen, C., et al. (författare)
  • Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection
  • 2011
  • Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:4, s. 245-51
  • Tidskriftsartikel (refereegranskat)abstract
    • In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 μg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.
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8.
  • Rembeck, Karolina, et al. (författare)
  • Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3.
  • 2012
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver histology in the context of a phase III treatment trial (NORDynamIC) for treatment-naïve patients with chronic HCV genotype 2 or 3 infection, where pretreatment liver biopsies were mandatory.
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9.
  • Waldenström, Jesper, 1985, et al. (författare)
  • Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience
  • 2016
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:3, s. 337-343
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. Material and methods: The impact of established response predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12-16 weeks in accordance with national guidelines. Results: In the NORDynamIC trial, age <40 years or achieving HCV RNA<1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12-16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. Conclusions: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation.
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10.
  • Westin, Johan, 1965, et al. (författare)
  • A non-invasive fibrosis score predicts treatment outcome in chronic hepatitis C virus infection.
  • 2008
  • Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 43:1, s. 73-80
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The results of a previous study suggest that an index calculated according to the formula (normalized ASAT x PK-INR) x 100/thrombocyte count (x 10(9)/L; GUCI) may reflect liver fibrosis in patients with chronic hepatitis C virus (HCV) infection. The aims of the present study were (i) to validate the association between the Göteborg University Cirrhosis Index (GUCI) score and liver fibrosis and (ii) to evaluate the utility of this index in predicting the outcome of antiviral treatment. MATERIAL AND METHODS: A total of 269 patients with chronic HCV infection, stratified according to HCV genotype (1/4 versus 2/3) participated in a phase III trial using pegylated interferon alpha-2a and ribavirin (DITTO study). Retrospective analyses of the baseline GUCI scores and assessments of pretreatment liver biopsies using the Ishak protocol were performed. Cut-off GUCI scores were calculated to distinguish patients with a high or low probability of sustained viral response (SVR). RESULTS: Striking associations between GUCI and Ishak fibrosis stages (stages 0-2 versus stages 3-4, p = 0.0002, stages 3-4 versus stages 5-6, p = 0.002) were observed. In patients with genotype 1 or 4, a GUCI score below 0.33 was associated with a rapid viral response to antiviral treatment and an SVR rate of 80%. Ninety-two percent of patients (92/101) with a SVR had a pretreatment GUCI score below 1.11. CONCLUSIONS: Our results suggest that the GUCI score appropriately reflects the stage of liver fibrosis in HCV-infected patients, and predicts initial viral kinetics as well as treatment outcome in patients infected with HCV genotype 1 or 4.
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