Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon α2a

Zeuzem, Stefan; Lee, Jung‐Hun; Herrmann, Eva; Fricke, Jens; Neumann, Avidan U.; Modi, Marlene; Colucci, Giuseppe; Roth, W. Kurt

doi:10.1053/gast.2001.24006

Cited by 259 publications

(278 citation statements)

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“…[15][16][17]23,25,26 Here, viral kinetics in 20 patients with chronic hepatitis C and persistently normal ALT levels and 19 patients with elevated ALT levels were analyzed. The first-phase decline of the viral load is mainly determined by the clearance rate of free viral particles c and the effectiveness of blocking virus production ⑀.…”

Section: Discussionmentioning

confidence: 99%

“…To include data below the detection limit, the Tobit approach was used as described previously. 17 Numeric minimization and solution of the differential equations was performed using Matlab software (Math Works Inc., Natick, MA).…”

Section: Methodsmentioning

confidence: 99%

“…[15][16][17] Therefore, in the present study, viral kinetics were analyzed in patients with chronic hepatitis C and persistently normal ALT levels to obtain information about the efficacy of combination therapy in blocking viral production (⑀), the clearance rate (c), the pretreatment infected cell loss (␦), and the infected cell loss during therapy (m␦). 15 Viral kinetic parameters were compared with data obtained from patients with chronic hepatitis C and elevated ALT levels.…”

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confidence: 99%

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Viral Kinetics During Antiviral Therapy in Patients With Chronic Hepatitis C and Persistently Normal Alt Levels

et al. 2004

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The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n ‫؍‬ 20) and elevated (n ‫؍‬ 19) ALT levels before and during treatment with 180 g pegylated interferon ␣-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pretreatment infected cell loss (␦) (P ‫؍‬ .13) but no differences in efficacy of blocking virus production (⑀) and infected cell loss during treatment (m␦) compared with patients with elevated ALT levels. Differences were significant for ⑀ (P ‫؍‬ .02) and ␦ (P ‫؍‬ .04) when applying updated "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters ⑀, ␦, and m␦ was observed in patients with elevated ␥-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P ‫؍‬ .02, P ‫؍‬ .005, and P ‫؍‬ .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Viral Kinetics During Antiviral Therapy in Patients With Chronic Hepatitis C and Persistently Normal Alt Levels

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“…[4][5][6][7][8][9][10][11] The rationale for this so-called induction strategy is that high-dose interferon may improve SVR by inducing a more rapid initial decline in HCV RNA. The relationships between interferon dose and early phase HCV kinetics, including phase I and II slope and time to undetectable HCV RNA, 12,13 and early virological responses and SVR support such a rationale. 1,[14][15][16] Studies utilizing induction therapy with (peg)interferon in patients with genotype 1 CHC have yielded mixed results, with some patients demonstrating an enhanced SVR 4,5 and others not.…”

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confidence: 92%

Impact of High-Dose Peginterferon Alfa-2A on Virological Response Rates in Patients with Hepatitis C Genotype 1: a Randomized Controlled Trial† ‡

Roberts¹,

Weltman²,

Crawford³

et al. 2009

Hepatology

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This study tested the hypothesis that high-dose peginterferon alfa-2a (PEG-IFN␣-2a) for the first 12 weeks would increase early and sustained virological response (SVR) rates in patients with chronic hepatitis C genotype 1. Eight hundred ninety-six patients were randomized 1:1 to 360 g (n ‫؍‬ 448) or 180 g (n ‫؍‬ 448) PEG-IFN␣-2a weekly plus ribavirin at 1000-1200 mg/day for 12 weeks, followed by 36 weeks of 180 g PEG-IFN␣-2a weekly plus ribavirin at 1000-1200 mg/day with 871 patients evaluable for the intention-to-treat analysis. Virological responses were assessed by TaqMan (limit of detection 15 IU/mL) at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (SVR). Undetectable hepatitis C virus RNA rates were significantly higher among patients receiving high-dose induction therapy at week 4 (36% versus 26%, P < 0.005), week 8 (61% versus 50%, P < 0.005), and week 12 (74% versus 62%, P < 0.005). However, SVR was not significantly different between patients receiving high-dose (53%) and standard (50%) therapy. Significant baseline prognostic factors for SVR included age, sex, race, histological stage, and viral load. SVR was considerably higher among patients with no or minimal fibrosis (64% and 60%, respectively) compared to those with severe fibrosis/cirrhosis (28% and 24%, respectively). The frequency of serious adverse events and drug discontinuations were similar in both groups, whereas PEG-IFN dose modification, weight and appetite reduction, and grade IV neutropenia were significantly higher in the induction arm.

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“…15,16 The addition of a polyethylene glycol moiety to interferon-a has also been developed, and may be administered alone or in combination with ribavirin. 17,18 During the first 3 months of therapy, HCV viral loads usually fall to undetectable levels in response to interferon-a. However, in a small proportion of patients (nonresponders) HCV viral loads persist at or near pretreatment levels.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR

et al. 2003

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Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position À88 in the MxA gene promoter in self-limiting HCV infection (OR ¼ 0.56; 95% CI: 0.35-0.8; P ¼ 0.010) and in nonresponders to therapy (OR ¼ 0.49; 95% CI: 0.25-0.95; P ¼ 0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR ¼ 0.22 95% CI: 0.07-0.67; P ¼ 0.002). A polymorphism in the 3 0 -untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR ¼ 0.43; 95% CI: 0.21-0.86; P ¼ 0.010). A polymorphism at position À168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR ¼ 2.75; 95% CI: 1.45-5.24; P ¼ 0.002). Further associations were found with a CGG trinucleotide repeat in the 5 0 UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.

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Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon α2a

Cited by 259 publications

References 20 publications

Viral Kinetics During Antiviral Therapy in Patients With Chronic Hepatitis C and Persistently Normal Alt Levels

Viral Kinetics During Antiviral Therapy in Patients With Chronic Hepatitis C and Persistently Normal Alt Levels

Impact of High-Dose Peginterferon Alfa-2A on Virological Response Rates in Patients with Hepatitis C Genotype 1: a Randomized Controlled Trial† ‡

Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR

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