Patient's age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin

Elefsiniotis, Ioannis; Pavlidis, Christos; Ketikoglou, I.; Koutsounas, Sotirios; Scarmeas, Nikolaos; Pantazis, Konstantinos; Moulakakis, Antonios; Tsianos, Epameinondas V.

doi:10.1016/j.ejim.2007.06.014

Cited by 8 publications

(7 citation statements)

References 17 publications

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“…Eighty-four studies were closely evaluated for eligibility[10–16, 18, 26–101]. Fourteen studies did not have extractable treatment outcomes data[26, 29, 36, 47, 50, 58, 61, 64, 74, 86, 87, 92, 100, 101]. Six were redundant[49, 51, 57, 68, 89, 99] and four were not relevant[30, 43, 60, 94].…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis

Yee

Nguyen

Zhang

et al. 2014

European Journal of Gastroenterology &Amp; Hepatology

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Background The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ~20–70%. However, many of these studies are limited by different study designs and small sample sizes. Aim Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative fashion. Methods A comprehensive literature search in MEDLINE and EMBASE for ‘genotype 4’ was conducted in November 2013. Abstracts from AASLD, APASL, DDW, and EASL in 2012/2013 were reviewed. Inclusion criteria were original studies with ≥25 treatment-naïve HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were co-infection with HIV, HBV, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (p-value <0.05) and I-squared statistic (>50%). Results We included 51 studies (11,102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% (95% CI: 50–55%) (Q-statistic = 269.20, p<0.05; I2 = 81.43). On sub-group analyses, SVR was significantly associated with lower viral load, OR 3.05 (CI 1.80–5.17, p<0.001); mild fibrosis, OR 3.17 (CI 2.19–4.59, p<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI 2.87–7.69, p<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI 2.31–11.73, p<0.001). Conclusions HCV-4 patients treated with PEG IFN+RBV may expect SVR rate of ~50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

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Section: Resultsmentioning

confidence: 99%

Meta-analysis

Yee

Nguyen

Zhang

et al. 2014

European Journal of Gastroenterology &Amp; Hepatology

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“…Here, baseline IL-18 levels did not predict treatment outcome but high levels were observed in patients with advanced fibrosis (F4, cirrhosis). High IL-18 levels were similarly associated with disease progression in patients with alcoholic-induced cirrhosis [8] or cirrhosis due to different etiologies [16].…”

Section: Discussionmentioning

confidence: 96%

“…Whilst they noted that age affected response to treatment, it was not in their model. A study focusing on patient age showed the effect of genotype was restricted to patients aged 35-55 years [5].…”

Section: Discussionmentioning

confidence: 99%

Decreased IP-10 and Elevated TGFβ1 Levels are Associated with Viral Clearance Following Therapy in Patients with Hepatitis C Virus

et al. 2010

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The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNα) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Rα2), total and active transforming growth factor-beta 1 (TGFβ1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p = 0.045), but optimal prediction was achieved with an algorithm (“TIPscore”) based on TGFβ1 (total), IP-10, age, sex and HCV genotype (p = 0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p = 0.07), it associates high TGFβ1 and low IP-10 levels with a failure of therapy.

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“…In a study by Elefsiniotis et al [10], genotype was not found as a predictor of SVR in patients younger than 35 years, and age was not a significant predictor of SVR in the overall cohort. However, in their analysis, age was used as a continuous variable.…”

Section: Discussionmentioning

confidence: 96%

“…While several controlled clinical trials have evaluated effectiveness of treatment with peginterferon and ribavirin in HCV infected patients, the effectiveness of treatment in a routine clinical setting is less well shown [10,25], except for one retrospective, observational cohort study by Backus et al with SVR rates of 20%, 52% and 43% in genotypes 1, 2 and 3, respectively, although the patients included in this study were mainly men [12]. However, the present study demonstrated that the effectiveness of treatment, with SVR rates of 44-72%, is comparable to the SVR rates reported in controlled, clinical trials of genotype 1-3 patients [1,2].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study

et al. 2011

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BackgroundThe effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment.MethodsWe determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis.ResultsThe majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin.ConclusionsThe effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.

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Patient's age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin

Cited by 8 publications

References 17 publications

Meta-analysis

Meta-analysis

Decreased IP-10 and Elevated TGFβ1 Levels are Associated with Viral Clearance Following Therapy in Patients with Hepatitis C Virus

Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study

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