future research agenda for latin americaregist2.virology-education.com/2013/2la/docs/02_silva.pdf•...

Future Research agenda for Latin America

Marcelo Silva MDHead of Liver and Transplant Units, Hospital Universitario Austral

Board Member of the Clinical Research Unit, School of Biomedical SciencesUniversidad Austral

Future Research agenda for Latin America

Liver Research Fields:1. Viral Hepatitis

• (HAV, HBV, HCV, HDV, HEV)

2. NAFLD3. Alcohol‐induced liver disease4. Drug‐induced liver injury5. Autoimmune diseases6. Metabolic diseases7. Fibrosis and Cirrhosis8. Portal Hypertension9. Hepatocellular carcinoma10. Liver Transplantation

Types of Liver Research:1. Epidemiological2. Basic:

• Virology• Pathology• Immunology• Molecular biology• Fibrosis• Oncology

3. Translational4. Clinical5. Cost effectiveness

Where do we stand in Latin American Region ?

1. Good individual (KOL) efforts2. Low rate of collaborative studies within each country,

even less among different countries3. Lack of interdisciplinary research approaches4. Scanty federal budgets for basic scientists, few

translational research if any5. Most Government Health Offices don´t allocate funds

for clinical nor epidemiological research, and ususallyhave no “interest” to raise the field

6. Scientific Societies do not handle adequate budgets to support research and do not have professional organizations to help fund raising

Pharma companies like physicians, scientific societies and policy makers also have an opportunity to improve:

• They have prioritized: their own drug pipelines short term revenues Focused on battling for market share more than

it’s growth (strong marketing orientation with low research and awareness investment in the region)

• University Centers and their P.I./ opinion leaders, as key players, have been out of the game in this region



There is a great need for: enhance awarenessmultiply medical education expand research and develop local scientific data

Bottle neck: Low federal and private research resources Lack of tax deduction benefits to benefactors

A Research Network: Is it a reasonable tool to improve

Liver Regional Research ?

Hep‐Net: a German Liver Foundation initiative as an example to follow

M Manns RC3 Conqueror Coalition, Panama 2010

12.06.2013

1. INCREASE PUBLIC AWARENESS and EDUCATION : Increase prevention, early identification of patients with hepatitis and optimization of therapies

2. Horizontal and vertical networking to optimize diagnosis and therapy of viral hepatitis

3. Transfer of knowledge: Fast transfer from “Bench to Bedside“

Aims of the Network

11M Manns RC3 Conqueror Coalition, Panama 2010

Areas of Intervention

12.06.2013

HEALTHY LIVER

INFLAMMATION

CIRRHOSIS

HCC

InformationVaccination

Early diagnosisTreatment


Website German Liver Foundation • Information for Patients, e.g. Flyers

• Liver Tests

• Information for Health Care

Professionals

• Intranet for Associate Members

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12.000

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Information

Home Page: Visits per month


6/12/2013

Information Information for patients and physicians

Telefone hotline

Homepage


6/12/2013

Information Public Awareness Campaigns„Hepatitis B vaccination of German Olympic Team 2008“

Oliver Roggisch (World Champignon Handball 2007)„Vaccination is important“

Eike Onnen (German Champignon High Jump)„Now I feel safe“


www.hep‐net.de

2007

Cornberg et al, Z. Gastroenterol. 2007; J Viral. Hep, 2008 51M Manns RC3 Conqueror Coalition, Panama 2010

advanced liver fibrosisliver cirrhosis

testing of HBV‐DNA and ALT

every 3‐6 monthstherapy indication

HBV‐DNA ≥ 104 cop/ml (2x103 IU/ml)

no yes

detectable HBV‐DNA (PCR)

yes no

ALT > 2xtimes ULN or

histology >A1/F1

yes

no yes

Risk factors for HCCother indications

(i.e. extrahepatic manifestations)

no yes

testing of HBV‐DNA and ALT

every 3 (ALT elevated) otherwise

every 6 months

no

Cornberg et al., Z Gastroenterol. 2007 Jun;45(6):525‐74. Cornberg et al., Z Gastroenterol. 2007 Jun;45(6):525‐74.

German Guidelines: Chronic HBV TherapyChronic Hepatitis B


Implementation of Guidelines

6/12/2013

Conferences, Seminars Short versions of the Guideline

Telephone Hotline, E‐Mail consulting, Homepage etc…


12.06.2013

1. INCREASE PUBLIC AWARENESS : Increase prevention, early identification of patients with hepatitis and optimization of therapies


3. Transfer of knowledge: Fast transfer from „Bench to Bedside“

Aims of the Network


12.06.2013

Vertical Networking

> 12

00 associate m

embe

rs

Horizontal Networking (26 Universities, Research sites)

Municipal Hospitals

Private Practitioners

Patients (Advocacy Groups)

Universities

Public (i.e. pupils)


12.06.2013

• Acute Hepatitis B and C• Co‐infections (i.e. HBV/HCV, Delta Hepatitis)• Special patient groups

• … registration trials in these fields are not pushed by the industry

Investigators initiated trials only possible with a structure such as HEP‐NET

Unmet Need for Investigator initiated trials (IIT)

More than20 clinical trials since 2002


Acute Hepatitis C

12.06.2013 29M Manns RC3 Conqueror Coalition, Panama 2010

20

HEP‐NET Acute HCV‐II Study

P. Strohbach, C. Gartung, S. Matern (Aachen), U. Welter, H. Knechten (Aachen), K. Striepeke, M. Schüller (Bad Driburg), M. Seifert, E. Pape (Bad Driburg), J. Kröninger (Bad Sachsa), Dr. Zboril, H.J. Weis (Bamberg), A. See (Battenberg); A. Bergk, V. Weich, B. Wiedenmann (Berlin), A. Jansen, M. Zeitz (Berlin), U. Gottschalk (Berlin), C. John (Berlin), B. Hintsche (Berlin), A. Baumgarten (Berlin), B. Muckelbauer, M. Vogt (Breitengüßbach), B. Rühlmann (Bremen), B. Kohler (Bruchsal), H. Wietholtz(Darmstadt), U. Müller, J. Epping (Dortmund), E. Zehnter (Dortmund), H. Kinkel, PD Dr. Pauletzki (Düren), K. Koop, S. Bein, G. Gerken (Essen), B. Dürr, K. Haag (Frankfurt‐Höchst), L. Schneider (Fürth), P. Geyer (Fulda), J. Stadick, M. Keles, T. Schneider (Fürth), T. Heidenreich (Gevelsberg), R.D. Hanrath (Hagen), W.E. Fleig (Halle), B. Seegers, K. Wursthorn, H. Greten(Hamburg), K. Borchert, K. Deterding, A. Potthoff, H.L. Tillmann, C. Trautwein (Hannover), C.Maass, A. Tromm (Hattingen), W. Stremmel (Heidelberg), D. Hüppe (Herne), A. Wolf (Herrenberg), Dr. Becker (Herrenberg), M. v. Wagner, U. Mihm, J. Fischinger (Homburg), M. Wiese (Leipzig), C. Bernsmeier, H. Hinrichsen, U.R. Fölsch (Kiel), N. Hoffmann, T. Göser (Köln), W. Tekolf (Lemgo), A. Bühl, J.F. Riemann (Ludwigshafen), T. Hütteroth (Lübeck), H. Hillenbrand, F. Tieringer, P. Galle (Mainz), L. Kurtsiefer (Mönchengladbach), K. Zemke, R. Götz (Moers), H. Schuppan (Moers), O. Oehm (Niederwerrn), H. Gröpel, H. Schönekäs (Nürnberg), C. Niederau (Oberhausen), Dr. Endemann, Dr. Friedrich, Dr. Rockmann, J. Schölmerich (Regensburg), H. Pernice (Riedlingen), H. Burghardt (Rockenhausen), M. Lafrenz, E.C. Reisinger (Rostock), H. Schiel (Schwäbisch Hall), P. Steinbach, W. Koch (Schweinfurt), C. Meibaum (Schwelm), I. Rimbach (Schwerte), U. Tappe, R. Müller (Siegburg), E. Schnaitmann, A. Trein (Stuttgart), H. Ruppin (Tauberbischofsheim), S. Kaiser, M. Gregor (Tübingen), M. Fuchs, G. Adler (Ulm), J. Schmidt, W. Holtkamp (Westerstede), D. Schaps (Wilhelmshaven), C. Genters, P. Herzog (Wilhelmshaven), H. Klinker, K. Wilms (Würzburg), W. Stimming (Wuppertal)

89 Patients in 53 centers

18 Universities26 Community hospitals09 Private Practices


Al‐Eryani (Arnsberg), Allescher (Garmisch Part.), Arbter (Mutlangen), Bästlein (Köln) Berthold (Wetzlar), Bey/Thießen (Lemgo), Böcher (Mainz), Buggisch (Hamburg), Cordes (Frankfurt), Dikopoulos (Ulm), Doberauer (Gelsenkirchen), Feyerabend (Hagen), Fleig (Halle), Frank

(Marburg), Franke (Hamminkeln), Frieling/Kreysel (Krefeld), Gerken (Essen), Geyer (Fulda), Göbel/Lößner (Cottbus), Günther/Kataev (Kiel), Gutberlet (Bremen), Haas (Frankfurt/Main), Hackenberg (Bergisch Gladbach), Haßkamp (Osterholz), Herzog (Wilhelmshaven), Heyer/Triller

(Düren), Hoffmann (Köln Kalk), Höhler (Recklinghausen), Hüppe (Herne), John (Berlin), Kaiser/Bissinger (Tübingen), Kehl (Wesel), Kern (München), Kirsch/Lehmann (Dresden), König

(Bautzen), Kordes (Emden), Krichbaum (Wittlich), Kröger (Bünde), Lippert (Hamburg), Lochs/Berg/Weich (Berlin), Lohnstein (Augsburg), Malfertheiner/Csepregi(Magdeburg),

Manns/Wedemeyer(Hannover), Muthwill (Düsseldorf), Pape/Grüner (München), Petrasch (Duisburg), Pfäffl (Nürnberg), Polzien (Braunschweig), Probst (Augsburg), Reiser (Bochum), Restrepo (Marburg), Rösch (Würzburg), Schäfer (Xanten), Schmidt/Schlenker (Heidelberg), Schubert/Göser (Köln), Schuppert/Krautheim (Bad Oeynhausen), Settele (Zirndorf), Singer (Mannheim), Spelter (Wuppertal), Spengler (Bonn), Sprung (Brühl), Stadick (Fürth), Stalter

(Landau), Stich (Würzburg), Theis (Witten), Tillmann/Wiegand (Leipzig), Többe (Ankum), Wehr (Coburg), Wiedmann (Regensburg), Witthöft (Lübeck), Zehnter (Dortmund),

Zeuzem/Kronenberger (Frankfurt M.)

Hep‐Net Acute HCV‐III Study

12.06.2013

72 centers in Germany recruited 108 patients from 2004 to 2008


HBV/HCV CoinfectionSofar limited studies for therapy of HBV / HCV coinfection


12.06.2013

The Hep‐Net/International Delta Hepatitis Intervention Trial (HIDIT‐1)

91 patients in 6 monthsWedemeyer, Yurdaydin, …….Manns, EASL 2007 45

M Manns RC3 Conqueror Coalition, Panama 2010

Hep ‐ Net Research´s output

12.06.2013

National and International Recommendations for Therapy of

- Acute Hepatitis C- Hepatitis B/Hepatitis C Coinfection- Hepatitis Delta- Chronic Hepatitis C

Are based on Hep-Net Study results

Worldwide largest Study on the efficacy of Amantadin in chronic hepatitis C results in recommendation not to use Amantadin in HCV(PRAMA Study, von Wagner et al., Hepatology 2008)


12.06.2013

1. INCREASE PUBLIC AWARENESS : Increase prevention, early identification of patients with hepatitis and optimization of therapies


3. Transfer of knowledge: Fast transfer from “Bench to Bedside“

Aims of the Network


From Bench to Bedside Translational Research

12.06.2013

Nature Biotechnology 26, 335 - 341 (2008)

Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope proteinJoerg Petersen1,7, Maura Dandri1,7, Walter Mier2, Marc Lütgehetmann1, Tassilo Volz1, Fritz von Weizsäcker3,6, Uwe Haberkorn2, Lutz Fischer4, Joerg-Matthias Pollok4, Berit Erbes5, Stefan Seitz5 & Stephan Urban5

Journal of Virology, February 2005, p. 1613-1622, Vol. 79, No. 3Efficient Inhibition of Hepatitis B Virus Infection by Acylated Peptides Derived from the Large Viral Surface ProteinPhilippe Gripon,1 Isabelle Cannie,1 and Stephan Urban2*

Phase I‐Study 2010

Hep-NetStart-Up Fund

Journal of Hepatology 2005, Volume 42, Issue 1, Pages 54-60Chronic infection with hepatitis B viruses and antiviral drug evaluation in uPA mice after liver repopulation with tupaia hepatocytesMaura Dandria†, Martin R. Burdaa†, David M. Zuckermanb, Karsten Wursthorna, Urte Matschla, Joerg M. Pollokc, Xavier Rogiersc, Andreas Gochtd, Josef Köcke, Hubert E. Blume, Fritz von Weizsäcker, Joerg Petersen


The Research Network Virtuous Cycle: Integrated Research

Basic Research

Epidemilogic and Clinical Research

Development

Patient Care Medicine Medical Education

Community Applied Research

Why such a network should be developed in the Region ?

• Public policy makers in most of Latin American countries demonstrated at least lack of interest in the impact of chronic liver diseases

• Pharmaceutical industry “messages” are usually not well taken nor understood due to their bias

• An academic network has a “neutral” profile which favors acting as bridge among different health‐care players: policy makers, community physicians, scientists, patients, general population and pharma companies

• Locally produced data published in peer review journals have greater upon policy makers and colleagues

• Need for local data, eg: 1) prevalence data adjusted to local risk factors,

gender and age2) cost effectiveness of different treatments strategies3) local host genetic resistance factors: genomics &

proteomics

Why such a network should be developed in the Region ?

Liver Latin American Research Education and Awareness Network

Processes

Supportive Systems

AgreementsDesired Results Guideliness

Resources Accountability Consequences

Relationships

CharacterIntegrity maturity Abundance Mentality

Key players and the five dimensions of win‐win

Health Policy Makers

Who should come on board ?

A strong and committed group of KOL and researchers with the same strategic vision:

• “ Integrated, Clinical & Epidemiological Research is associated to a better health related system”

• A network which shall:

– Improve medical education– Enhance awareness of liver diseases– Expand access to therapy– Serve as a bridge between patients, health care policy

makers, physicians, pharmaceutical industry and non profit organizations

Austral University Hospital: University Campus Scientific & Biotechnology Park

Thanks for you attention !!!

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