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Meccanismi patogenetici dell'anemia in corso di terapia antivirale in pazienti con epatite cronica HCV correlata
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The clinical impact of a 24-week treatment course of peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia
No full textComparative trials of peginterferon α2a and peginterferon α2b for chronic hepatitis C
No full textStandard of care for patients with chronic hepatitis C is pegylated interferon (pegIFN) combined with ribavirin (Rbv). It results in persistent viral eradication and prevents the progression of liver disease and the associated complications in about 50% of treated patients. Currently, two PegIFNs are available that differ significantly in terms of pharmacokinetic and pharmacodynamic profiles as a consequence of different pegylation chemistries. While the registration trials of the two therapeutic regimens demonstrated the superiority of each PegIFN vs the native IFN α2b, the superiority of one regimen over the other in terms of treatment efficacy remains unknown. Retrospective cohort studies and randomized prospective head-to-head trials have attempted to resolve the considerable controversy over this issue and support evidence-based treatment decision
Lack of rapid virological response predicts interferon-alpha2b/ribavirin therapy failure in HCV genotype 2 patients : a single-centre study
No full textBackground: A minority of patients with HCV-2 chronic hepatitis does not attain a sustained virological response to interferon-based therapies. Registration trials have failed to identify the real proportion of HCV-2 non-responders, and predictors of non-response. The analysis of 'real-life' HCV-2 patients might help define the effectiveness of anti-HCV therapy and the role of response moderators.
Methods: A re-analysis of all treatment-naive HCV-2 patients who consecutively received weight-dosed ribavirin with either 3 MU three times a week standard interferon-alpha 2b or 1.5 mu g/kg/week pegylated interferon-alpha 2b.
Results: The 94 interferon-treated patients and the 136 pegylated-interferon-treated patients were comparable for demography, prevalence of cirrhosis (25%) and adherence to therapy (74%). By intention-to-treat analysis, the overall sustained virological response rate was 80% (82% interferon versus 78% pegylated interferon). Overall, sustained virological rates were 83% for the 182 patients who cleared HCV RNA at week 4 (rapid virological response) and 52% for the 48 who did not (P<0.001). The corresponding week 12 figures of HCV RNA clearance were 90% and 32%, respectively (P<0.001). Sustained response was independent of gender, age, body mass index, modality of infection, duration and severity of liver disease, adherence to therapy and interferon type. After stratification for interferon type, the only treatment failure predictor was persistence of HCV RNA at week 4 and 12.
Conclusions: Despite the prevalence of moderators of treatment outcome, HCV-2 patients showed as high sustained virological response rates as those reported in registration trials for HCV-2 and HCV-3 pooled patients; pegylated interferon therapy failure was predicted by lack of rapid virological response
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Donor/recipient match of IL28B to predict interferon response in recurrent hepatitis C
No full textBackground & Aims: The role of pre-treatment predictors of
Interferon (IFN) response has been overshadowed by the strong
predictive power of on-treatment viral kinetics. However, in
recurrent hepatitis C (HCV) following liver transplantation, a
strong negative pre-treatment predictor of IFN response would
have the benefit of further optimizing response-guided therapy
treatment algorithms while also positively impacting on patient
selection to reduce IFN related risks. Methods: Consecutive
patients with recurrent HCV treated with Ribavirin (Rbv) in combination
with PegIFN or IFN, were tested for the IL28B
rs12979860 SNP in DNA extracted from recipients blood sample
and paraffin-embedded donor liver graft. Results: Out of the
110 HCV patients transplanted from 2000 to 2010, 54 (49%)
received anti-HCV treatment and 48 completed post-treatment
follow-up (37 males, median age 54 years, median donor age
57 years, 65% Cyclosporine A, 85% HCV 1-4, median HCVRNA
3.5 x106 UI/ml, 29% S≥4 by Ishak, median interval to
treatment of 19 months, median treatment duration 45 weeks).
The remaining 56 patients were not treated due to non progressive
hepatitis (n=30), contraindications or severe co-morbidities
(n=26). Overall an SVR was achieved in 56% of
patients (49% genotype 1-4 vs. 100% genotype 2-3, p=0.01).
The CC IL28B genotype was less common in recipient blood
than in donor liver (24% vs 58%, p=0.001). In the 41 patients
with genotype1-4, the donor CC IL-28B genotype had more
SVR than CT/TT genotype (62% vs. 29%, p= 0.058), whereas
this was not true for recipient IL-28B genotype (70% vs. 42%,
p=0.15). Interestingly, when matching donor/recipient IL28B
genotype, patients with either donor or recipient CC genotype
had higher SVR rates than those without a CC (75% vs 20%,
p=0.009). By multivariate logistic regression analysis in genotype
1-4, the presence of an IL28B CC genotype either in the
donor or recipient (p=0.006; OR 11.7; 95% CI 2.05 - 66.55)
and Cyclosporine A (p=0.03; OR 5.83; 95% CI 1.13 - 30)
were independently associated with a SVR. Conclusion:
Although the combination of donor/recipient IL28B genotype
emerged as the strongest baseline predictor of treatment outcome
its added value to the existing therapeutic algorithm is
questionable in virtue of its unsatisfactory negative predictive
power
Effect of the PNPLA3 I148M polymorphism on the outcome of peg-interferon plus ribavirin treatment in chronic hepatitis C
No full textBackground & Aims : Homozygosity for the Patatin-like phospholipase
domain-containing 3 (PNPLA3) p.I148M polymorphism (p.148M/M) has been associated with steatosis, fibrosis
progression, and hepatocellular carcinoma in chronic hepatitis
C (CHC) patients, but the effect on treatment outcome is still controversial. Aim of this study was to evaluate the effect of p.148M/M on the rate of sustained virological response (SVR) and viral kinetics in CHC patients who underwent standard of
care (SOC) antiviral therapy with peg-interferon and ribavirin,
stratified according to viral genotype (genotype 2 (gen2) vs. others), and severity of fibrosis (Metavir 2). Patients: 602 naïve consecutive patients from two tertiary referral centers in Milan and one in Vienna, for whom DNA samples and liver biopsy were available. Mean age 50.8±12 years, 39% were females, 61% gen1, 17% gen2, 6% gen3, 16% gen4, 30% had advanced fibrosis, 33% were IL28B rs12979860 CC.
Results: p.148M/M was detected in 49 patients (8%), and was associated with advanced fibrosis (21/49, 43% vs. 158/553, 28%; p=0.049), but not with demographic, anthropometric, and virological parameters. The p.148M/M genotype was not significantly associated with SVR in the whole series (25/49, 51% vs. 326/553, 59%; p=0.29), but it was associated with a lower SVR rate in non-gen2 patients with advanced fibrosis (4/18, 22% vs. 64/135, 48%; p=0.047). In these subjects, p.148M/M was also associated with a lower rate of complete early viral response (5/18, 28% vs. 80/135, 59%; p=0.021).
SVR was not influenced by p.148M/M in gen2 patients and in patients without advanced fibrosis. In non-gen2 patients, SVR was independently associated with younger age, absence of
advanced fibrosis, IL28B CC genotype, completion of adequate dose treatment (≥80/80/80%), and p.148M/M (OR 0.70, 95% c.i 0.46-1.0). Conclusions: PNPLA3 genotype seems to represent a negative prognostic factor for antiviral
treatment outcome independently of the effect on fibrosis progression,
but only in a very selected subgroup of difficult-to-cure CHC patients (3% in this series). However, whether it also influences the outcome of triple therapies with direct antiviral agents
needs to be evaluated in future studie
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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