Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels

Zeuzem, Stefan; Diago, M.; Gane, Edward; Reddy, K. Rajender; Pockros, Paul J.; Prati, Daniele; Shiffman, Mitchell L.; Farci, Patrizia; Gitlin, Norman; O’Brien, Christopher B.; Lamour, François; Lardelli, Pilar

doi:10.1053/j.gastro.2004.09.050

Cited by 224 publications

(261 citation statements)

References 14 publications

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“…A prior study has shown no relationship between normal or elevated ALT levels at baseline and the response to standard therapy with peginterferon and ribavirin. 13 Analysis of the HCV NS3 protease domain sequence from patients in a previous clinical study of telaprevir monotherapy showed that viral rebound during the 14-day treatment period was associated with the presence of viral variants with reduced sensitivity to telaprevir. 4 Consistent with these findings, the viral rebound observed in patients who received telaprevir alone in the present study was associated with the selection of similar variants.…”

Section: Discussionmentioning

confidence: 99%

Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

et al. 2007

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“…9 However, a recent large international randomized trial in patients with chronic hepatitis C and persistently normal ALT levels showed that PEG IFN-␣2a plus ribavirin has a similar efficacy, tolerability, and safety profile as in patients with elevated ALT levels. 10 Patients with chronic hepatitis C and persistently normal ALT levels have lower rates of hepatocyte apoptosis and hepatocyte proliferation, 11 less intrahepatic CD4 ϩ T-lymphocytes, a reduced antigen-specific CD4 ϩ T-cell proliferation, a lower in vitro T-helper 1 (interferon ␥) cytokine production, 12 and a lower HCV quasispecies heterogeneity than patients with elevated ALT levels. 13,14 Together, these studies indicate that patients with chronic hepatitis C and persistently normal ALT levels have an altered immunoreactivity against HCV associated with a lower hepatocellular turnover.…”

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confidence: 99%

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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“…Nevertheless, several studies described significant histological liver lesions and increased ALT levels over time in these patients [36][37][38][39][40], indicating that this specific cohort may develop Immunoblot analysis from representative patient samples (P1-P5) and healthy controls (H1-H5) as well as Huh7 dilution series (D1-D3). Enrichment of soluble CD81 had been standardized before sample processing, and a standardized volume of 1 mL serum was used for CD81 enrichment and quantification in all study samples analyzed.…”

Section: Discussionmentioning

confidence: 97%

876 Soluble Serum Cd81 Is Elevated in Patients With Chronic Hepatitis C and Correlates With Alanine Aminotransferase Serum Activity

Welker¹,

Reichert²,

Susser³

et al. 2012

Journal of Hepatology

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Aim: Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.Patients and Methods: Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.Results: Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p.0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).Conclusion: CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis.

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Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels

Cited by 224 publications

References 14 publications

Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels

876 Soluble Serum Cd81 Is Elevated in Patients With Chronic Hepatitis C and Correlates With Alanine Aminotransferase Serum Activity

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