August 29, 2013

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

Original Article

B. Baran1, M. Gulluoglu2, O. M. Soyer1, A. C. Ormeci1, S. Gokturk1, S. Evirgen1, S. Yesil2, F. Akyuz1, C. Karaca1, K. Demir1, S. Kaymakoglu1, F. Besisik1,*

Article first published online: 27 AUG 2013

DOI: 10.1111/jvh.12127

© 2013 John Wiley & Sons Ltd

Abstract

Keywords: fibrosis progression; gamma-glutamyl transferase; hepatitis C; nonresponder; treatment failure

Summary

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon-based therapy. We aimed to investigate long-term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty-three patients had TF, and 62 patients were treatment-naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow-up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma-glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01–1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81–19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon-based CHC treatment may lead to accelerated FPR in the long-term compared with the natural course.

Source

Journal of Hepatology

Article in Press

M. Patrizia Carrieri, Caroline Lions,Philippe Sogni, Maria Winnock,  Perrine Rouxm Marion Moram Philippe Bonnard, Dominique Salmon, François Dabis, Bruno Spire, ANRS CO13 HEPAVIH Study Group

Received 12 March 2013; received in revised form 6 August 2013; accepted 16 August 2013. published online 26 August 2013.
Accepted Manuscript

Abstract

Background & aims

We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV coinfected individuals to investigate whether polyphenol rich foods intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels.

Methods

Longitudinal data collection included self-administered questionnaires and medical data (ASpartate aminoTransferase (AST) and ALanine aminoTransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (> or equal to 3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5x upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on Generalised Estimating Equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio.

Results

After adjustment, elevated coffee consumption and daily chocolate intake were independently associated with normal ALT (OR = 0.65; p = 0.04 and OR = 0.57; p=0.04, for coffee and chocolate respectively), while only elevated coffee consumption was positively associated with normal AST values (p = 0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with a 40-50% reduced risk of abnormal liver enzymes (p = 0.003 for AST; p = 0.002 for ALT).

Conclusions

Elevated coffee consumption and daily chocolate intake appear to be associated with reduced level of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.

Abbreviations: ANRS, Agency for Research on Aids and Viral Hepatitis, ALT, ALanine aminoTransferase, ART, Antiretroviral Treatment, AST, ASpartate aminoTransferase, AU, Alcohol Units, AUDIT-C, Alcohol Use Disorders Identification Test, BMI, Body Mass Index, CDC, Centers for Disease Control and Prevention, CD4, Cluster of Differentiation 4, GEE, Generalized Estimating Equations, HCV, Hepatitis C Virus, HIV, Human Immunodeficiency Virus, IDU, Intravenous Drug Users, IQR, Interquartile Range, kPa, kilopascal, OR, Odds Ratio, PEG-IFN, Pegylated Interferon, RNA, RiboNucleic Acid, TGF-Beta, Transforming Growth Factor Beta, TRIPS, Trade-Related Aspects of Intellectual Property Rights

Keywords: Polyphenol, Coffee, Chocolate, Cocoa, Liver enzyme, Hepatitis C HIV

PII: S0168-8278(13)00608-9

doi:10.1016/j.jhep.2013.08.014

© 2013 Published by Elsevier Inc.

Source

FDA, academia and industry team up to end hepatitis C

Provided by the University of Florida

Published: August 29th, 2013

GAINESVILLE, Fla. — As doctors prepare to manage an influx of new hepatitis C patients and treatment options, a collaboration among academia, industry and the U.S. Food and Drug Administration is poised to deliver real-world data that can help doctors and patients optimize their treatment experience.

A research consortium known as the Hepatitis C Therapeutic Registry and Research Network, or HCV-TARGET, has joined forces with the FDA to share national data on how newly approved therapies for hepatitis C are used and managed in routine practice. HCV-TARGET is led jointly by investigators at the University of Florida and the University of North Carolina at Chapel Hill and is sponsored in part by multiple pharmaceutical companies.

The new partnership’s goal is to establish research collaborations using the HCV-TARGET database to better inform patients and clinicians about hepatitis C therapies.

“This collaboration will not only strengthen our ongoing efforts to monitor the safety and effectiveness of existing hepatitis C treatment regimens,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, “it will also provide opportunities for FDA scientists to apply their research expertise in studying existing data held by HCV-TARGET to identify areas for improvement in clinical trial design that may help improve the future of HCV drug development programs.”

Hepatitis C is a viral liver disease that can lead to liver damage, cirrhosis, liver failure or liver cancer. It is transmitted through contact with infected blood. Because a person with chronic hepatitis C can live symptom-free for decades, many people do not know they are infected.

Two factors increase the significance of this collaboration:

  • More patients to be screened and treated — Within the last year, both the Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommended all baby boomers be tested for hepatitis C. The CDC estimates baby boomers represent three-quarters of the more than 3 million Americans believed to be infected with hepatitis C. Among those at highest risk are individuals who received blood transfusions before 1992, when screening donated blood for the virus began.
  • New treatments on the horizon — The first all-oral hepatitis C treatment is moving through the final stages of FDA approval. If approved, it would be the first of a new generation of hepatitis C drugs that will improve what for many has been a grueling treatment regimen that can take up to 48 weeks and requires injections of interferon, a drug that can be difficult to tolerate. The introduction of new drugs will bring new questions about managing side effects, drug combinations and other clinical considerations.

“Leading liver doctors across the country have joined HCV-TARGET to study and navigate rapidly evolving treatment paradigms for hepatitis C. We see a healthier future for patients battling this virus and formed HCV-TARGET to help guide the way,” said Dr. David R. Nelson, co-principal investigator, director of the UF Clinical and Translational Science Institute and a professor of medicine at UF Health, which serves as the clinical coordinating center for HCV-TARGET.

Following close to 2,500 patients in North America who have agreed to participate in its study to date, HCV-TARGET includes populations underrepresented in clinical trials such as patients with cirrhosis, patients age 65 and older and African-Americans. The initial focus of the network’s observational study has been treatment with boceprevir and telaprevir, drugs newly approved by the FDA when HCV-TARGET launched in 2011. HCV-TARGET will expand its study this year to include the entire spectrum of antiviral hepatitis C therapeutics.

“Real-world data about how drugs perform outside of restricted clinical trials are extremely important. HCV-TARGET allows us to capture this information using novel approaches to ensure the integrity and quality of the data. Through our partnership with the FDA, we hope this information can be used to help doctors and their patients more readily determine the most beneficial treatment options across a broad spectrum of patients,” said Dr. Michael W. Fried, co-principal investigator and professor of medicine at the UNC School of Medicine, which serves as the HCV-TARGET data coordinating center.

HCV-TARGET and the FDA signed in May a memorandum of understanding to promote scientific research in the area of hepatitis C drug development. In mid-July, HCV-TARGET held meetings with representatives from the FDA Center for Drug Evaluation and Research’s division of antiviral products and offices of computational science, clinical pharmacology and biostatistics. Attendees agreed one of the first priorities should be to align how data elements of common interest are defined so the clinical trial data collected by the FDA can be reasonably compared to the real-world observational data collected by HCV-TARGET, a critical step in developing research collaborations and pilot projects. In addition, the agreement allows an FDA representative to join HCV-TARGET’s advisory council.

HCV-TARGET includes 103 academic and community sites in 31 states, Puerto Rico, Canada and Europe. HCV-TARGET currently receives ongoing industry support from Merck, Genentech, Kadmon and Vertex. Fried receives research grant support from and serves as ad hoc consultant to Genentech, Vertex, Merck, Gilead, Bristol Myers Squibb, Janssen Pharmaceuticals and Abbott. Nelson receives grant support from Genentech, Kadmon, Merck, Vertex, Gilead, Boehringer Ingelheim and Abbott/Abbvie; and payment for the development of educational presentations from Clinical Care Options, Rush University Medical Center, Practice Point Communications and the Chronic Liver Disease Foundation.

Credits

Media Contact
Claire Baralt (UF), cbaralt@ufl.edu, 352-273-8211
Media Contact
Michelle Maclay (UNC), maclay@med.unc.edu, 919-843-5365

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