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

Kronenberger, Bernd; Herrmann, Eva; Micol, Florence; Wagner, Michael; Zeuzem, Stefan

doi:10.1002/hep.20487

Cited by 28 publications

(20 citation statements)

References 35 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates a non-significant association between ALT levels and SVR in univariate and multivariate analyses without GGT levels, but a significant association between ALT and SVR in multivariate analysis including GGT levels. These data are in accordance with findings of reduced efficacy of blocking virus production and lower infected cell loss in patients with elevated GGT levels showing only slight differences in viral kinetics depending on ALT values [22].…”

Section: Discussionsupporting

confidence: 93%

The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, the GGT quotient tended to be higher in the non-responder group in agreement with other studies [12], [23]; higher GGT levels have been related to advanced fibrosis, steatosis and insuline resistance, which are more common among non-responders [24]. The body weight tended to be higher in non-responder patients; in fact, it has been suggested that obese subjects have an increased expression of the IFN-α signalling inhibitor factor SOCS-3 [25].…”

Section: Discussionsupporting

confidence: 89%

Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors

et al. 2010

View full text Add to dashboard Cite

BackgroundCurrent treatment of chronic hepatitis C virus (HCV) infection has limited efficacy −especially among genotype 1 infected patients−, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline.MethodologyForty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1–E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A “leave-one-out” cross-validation method was used to assess the reliability of the discriminant models.Principal FindingsLower alanine transaminase levels (ALT, p = 0.009), a higher number of quasispecies variants in the E1–E2 region (number of haplotypes, nHap_E1–E2) (p = 0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p = 0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1–E2, and gamma-glutamyl transferase and ALT levels.Conclusions and SignificanceDiscriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this study led to accurate predictions in our population of Spanish HCV-1b treatment naïve patients.

show abstract

“…This correlation was explained by IFN use, that acts by establish a non-virus-specific antiviral state[15], ultimately leading to a progressive clearance of serum HCV-RNA mediated by both clearance of circulating virions (first-phase) and, afterwards, by the death or clearance of productively-infected hepatocytes (second-phase)[1], eventually leading to serum ALT increase. Indeed, previous kinetics studies in IFN-treated patients showed a positive correlation between lower infected-cell death (δ) and persistently normal ALT values [16]. …”

Section: Discussionmentioning

confidence: 99%

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

et al. 2017

View full text Add to dashboard Cite

BackgroundIntracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR.Study designMathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization.ResultsHCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted δ and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted λ, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR.ConclusionsOur data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of “cell-cure” by DAAs, leading to a fast improvement of liver homeostasis.

show abstract

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

Cited by 28 publications

References 35 publications

The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection

The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection

Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Contact Info

Product

Resources

About