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| 2. |
- 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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| 3. |
- Lagging, Martin, 1965, et al.
(författare)
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Randomized comparison of 12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection.
- 2008
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 47:6, s. 1837-45
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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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| 4. |
- 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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| 5. |
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| 6. |
- Leutscher, Peter Derek Christian, et al.
(författare)
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Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C.
- 2010
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 52:2, s. 430-435
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Rembeck, Karolina, et al.
(författare)
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Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3.
- 2012
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
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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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| 8. |
- Rembeck, Karolina, et al.
(författare)
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PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection.
- 2012
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Ingår i: BMC medical genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. METHODS: Three hundred and eighty-two treatment naive HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. RESULTS: In HCV genotype 2 infected patients carrying the PNPLA3 148 M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. CONCLUSIONS: Our results suggest a possible association between the PNPLA3 148 M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.
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| 9. |
- Rembeck, Karolina, et al.
(författare)
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Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2/3.
- 2014
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 59:6, s. 2131-2139
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Tidskriftsartikel (refereegranskat)abstract
- The present study evaluated the impact of variations in the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) on treatment outcome in patients with hepatitis C virus (HCV) genotype 2/3 infection receiving peginterferon-α2a and lower, conventional 800 mg daily dose of ribavirin. Previous studies using higher, weight-based ribavirin dosing report that patients carrying polymorphisms encoding reduced predicted ITPase activity show decreased risk of ribavirin-induced anemia but increased risk of thrombocytopenia, with no impact on elimination of virus. Three hundred fifty-four treatment naïve HCV genotype 2/3 infected patients, enrolled in a phase III trial (NORDynamIC), were genotyped for ITPA (rs1127354 and rs7270101). Homo- or heterozygosity at Ars1127354 or Crs7270101, entailing reduced ITPase activity, was observed in 37% of patients and was associated with increased likelihood of achieving sustained virological response (SVR) (P=0.0003 in univariate and multivariate analyses) accompanied by a reduced risk of relapse among treatment-adherent patients. The association between ITPA variants and SVR remained significant when patients were subdivided by the 12- and 24-week treatment duration arms, HCV genotype, fibrosis stage and IL28B genotype, and was not secondary to improved adherence to therapy or less pronounced anemia. Gene variants predicting reduced predicted ITPase activity also were associated with decreased risk of anemia (P<0.0001), increased risk of thrombocytopenia (P=0.007), and lower ribavirin concentrations (P=0.02). Conclusion: These findings demonstrate a novel ribavirin-like association between polymorphisms at ITPA and treatment efficacy in chronic hepatitis C mediated by reduced relapse risk. We hypothesize that patients (63%) being homozygous for both major alleles, leading to normal ITPase activity, may benefit more from the addition of ribavirin to present and future treatment regimens for HCV in spite of concomitant increased risk of anemia.
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