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Curing Hepatitis C: Individualized Approach and New Therapies Lorenzo Rossaro, MD Gastroenterology and Hepatology Universi...
c/o    Liver Cancer (HCC)
HCV History: Outcome Factors Male, Age, 3.6% POSITIVE ETOH HBV HIV  Interferon + Ribavirin Transplant NEGATIVE
HCV Screening:  Who is at risk (%) <ul><li>Blood product for clotting problems  produced    1987 (i.e.hemophilia)    ~90 ...
HCV: diagnosis and staging <ul><li>Proposed  Algorithm </li></ul><ul><li>1   Screening: (ALT) and HCV Antibody </li></ul><...
Hepatitis C Genotype in U.S.:   Predict Response to Treatment BEST RESPONSE Type 2 INTERMEDIATE RESPONSE Type 3 and 4 LOWE...
HCV: Severity of Liver Disease <ul><li>Symptoms and Liver “Function” Tests:  usually in late stages </li></ul><ul><li>ALT ...
Fibrospect  <ul><li>Low values (<20) indicative of mild disease </li></ul><ul><li>High values (>80) indicative of advance...
Assessing the Severity of Liver Disease <ul><li>LIVER BIOPSY </li></ul><ul><li>The most accurate method of determining dis...
Liver Biopsy by Stage Cirrhosis Mild  Fibrosis
Treatment Response by Genotype and Duration of Therapy 1987-1997 2002-2011 1998-2001
Hepatitis C The Goals of Treatment <ul><li>Virus eradication = negative HCV-RNA  six months after the end of treatment = C...
HCV: Who should be treated ? <ul><li>Whoever is affected in some way by the chronic disease  </li></ul><ul><li>AND  </li><...
Side effects of Interferons <ul><li>FLU-like symptoms (®Tylenol) </li></ul><ul><li>Behavioral changes: </li></ul><ul><ul><...
Ribavirin: Risk of Treatment <ul><li>Hemolytic anemia </li></ul><ul><ul><li>Reversible </li></ul></ul><ul><ul><li>May requ...
C P C = Complete EVR;  P = Partial EVR
SVR with 48 wks PEG+RIBA and Patterns of Virological Response (R=Rapid 4w, E=Early 12w, N=none, c=complete, p=partial)   R...
 
Factors Associated with Cure <ul><li>Viral </li></ul><ul><ul><li>Non-1 Genotype (2,3) </li></ul></ul><ul><ul><li>Lower Vir...
January 15, 2009
We evaluated the effect of Latino ethnic background on the response to treatment with peginterferon alfa-2a and ribavirin ...
New Studies for Hepatitis C at UC-Davis  Fully enrolled* Roche/ Intermune 2b Naïve geno 1 Protease PEG+RBV Roche/ Pharmass...
NEW drugs for Hepatitis C <ul><li>Will  not  be approved until 2011-2012 ? </li></ul><ul><li>Improved efficacy with TRIPLE...
 
Education for Health Choices <ul><li>Moving Mountains </li></ul><ul><ul><li>Train Providers for “Hands on” management of l...
 
Summary <ul><li>Hepatitis C is a serious disease </li></ul><ul><li>Ask about risk factors and    HCV Ab </li></ul><ul><li...
GI and Hepatology Clinical Research Group Thank you <ul><li>Thomas Amankonah </li></ul><ul><li>Chris Bowlus </li></ul><ul>...
How to refer for GI and Hep studies <ul><li>Laura Lester, NP </li></ul><ul><li>Phone (916) 734-8696  </li></ul><ul><li>Fax...
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Curing Hepatitis C: Individualized Approach and New Therapies

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Curing Hepatitis C: Individualized Approach and New Therapies

  1. 1. Curing Hepatitis C: Individualized Approach and New Therapies Lorenzo Rossaro, MD Gastroenterology and Hepatology University of California Davis Medical Center
  2. 2. c/o  Liver Cancer (HCC)
  3. 3. HCV History: Outcome Factors Male, Age, 3.6% POSITIVE ETOH HBV HIV Interferon + Ribavirin Transplant NEGATIVE
  4. 4. HCV Screening: Who is at risk (%) <ul><li>Blood product for clotting problems produced  1987 (i.e.hemophilia) ~90 </li></ul><ul><li>Injected illegal drugs (IVDU) 80 </li></ul><ul><li>Long-term kidney dialysis 10 </li></ul><ul><li>Blood transfusion or solid organ transplant  July, 1992 6 </li></ul><ul><li>Born from HCV+ mother 5 </li></ul><ul><li>Tattoos, cocaine, body piercing ? </li></ul>
  5. 5. HCV: diagnosis and staging <ul><li>Proposed Algorithm </li></ul><ul><li>1 Screening: (ALT) and HCV Antibody </li></ul><ul><li>2 Confirmation: HCV-RNA ( not RIBA) </li></ul><ul><li>3 Predict success: HCV-Genotype </li></ul><ul><li>4 Refer to Liver Clinic and/or Request </li></ul><ul><li>Liver Biopsy (if appropriate) </li></ul>
  6. 6. Hepatitis C Genotype in U.S.: Predict Response to Treatment BEST RESPONSE Type 2 INTERMEDIATE RESPONSE Type 3 and 4 LOWEST RESPONSE Type 1
  7. 7. HCV: Severity of Liver Disease <ul><li>Symptoms and Liver “Function” Tests: usually in late stages </li></ul><ul><li>ALT levels: often normal </li></ul><ul><li>Ultrasound Examination: not sensitive for fibrosis/staging </li></ul><ul><li>Liver Biopsy: gold standard </li></ul><ul><li>Consider fibrosis markers or elastography </li></ul>
  8. 8. Fibrospect  <ul><li>Low values (<20) indicative of mild disease </li></ul><ul><li>High values (>80) indicative of advanced disease </li></ul><ul><li>Between 20 and 80: can be anything </li></ul>
  9. 9. Assessing the Severity of Liver Disease <ul><li>LIVER BIOPSY </li></ul><ul><li>The most accurate method of determining disease severity and activity </li></ul><ul><li>Disease severity = Fibrosis ( stage: 1-4 ) </li></ul><ul><li>Indicator of prognosis </li></ul><ul><li>Helpful in guiding treatment options </li></ul>
  10. 10. Liver Biopsy by Stage Cirrhosis Mild Fibrosis
  11. 11. Treatment Response by Genotype and Duration of Therapy 1987-1997 2002-2011 1998-2001
  12. 12. Hepatitis C The Goals of Treatment <ul><li>Virus eradication = negative HCV-RNA six months after the end of treatment = CURE </li></ul><ul><li>Decrease progression of disease: </li></ul><ul><ul><li>from hepatitis to cirrhosis (or reverse ?) </li></ul></ul><ul><ul><li>risk of cancer (Hepato Cellular Carcinoma) </li></ul></ul><ul><ul><li>need for liver transplant or retransplant </li></ul></ul>
  13. 13. HCV: Who should be treated ? <ul><li>Whoever is affected in some way by the chronic disease </li></ul><ul><li>AND </li></ul><ul><li>fully understands the risks and benefits of therapy </li></ul>
  14. 14. Side effects of Interferons <ul><li>FLU-like symptoms (®Tylenol) </li></ul><ul><li>Behavioral changes: </li></ul><ul><ul><li>Depression, Irritability </li></ul></ul><ul><li>Myelosuppression: </li></ul><ul><ul><li>Neutropenia </li></ul></ul><ul><ul><li>Thrombocytopenia </li></ul></ul><ul><li>Skin, GI, Thyroid, Hair loss </li></ul>
  15. 15. Ribavirin: Risk of Treatment <ul><li>Hemolytic anemia </li></ul><ul><ul><li>Reversible </li></ul></ul><ul><ul><li>May require dose reduction or erythropoietin in selected patients </li></ul></ul><ul><li>Pregnancy Risks </li></ul><ul><ul><li>Contrtraception required </li></ul></ul>
  16. 16. C P C = Complete EVR; P = Partial EVR
  17. 17. SVR with 48 wks PEG+RIBA and Patterns of Virological Response (R=Rapid 4w, E=Early 12w, N=none, c=complete, p=partial) RVR cEVR pEVR NVR Marcellin P. AASLD 2007
  18. 19. Factors Associated with Cure <ul><li>Viral </li></ul><ul><ul><li>Non-1 Genotype (2,3) </li></ul></ul><ul><ul><li>Lower Viral Load </li></ul></ul><ul><ul><li>Rapid /Early response </li></ul></ul><ul><li>Disease related </li></ul><ul><ul><li>No fibrosis/cirrhosis </li></ul></ul><ul><ul><li>Higher ALT </li></ul></ul><ul><ul><li>Lack of steatosis </li></ul></ul><ul><li>Ribavirin dosage (~15 mg/kg) </li></ul><ul><li>Adherence </li></ul><ul><ul><li>More than 80% of intended treatment for > 80% of intended duration </li></ul></ul><ul><li>Host Factors </li></ul><ul><ul><li>Lower body weight </li></ul></ul><ul><ul><li>Younger age </li></ul></ul><ul><ul><li>Female gender </li></ul></ul><ul><ul><li>Race (non-AA, non-Latino) </li></ul></ul>
  19. 20. January 15, 2009
  20. 21. We evaluated the effect of Latino ethnic background on the response to treatment with peginterferon alfa-2a and ribavirin in patients infected with HCV genotype 1 who had not been treated previously The rate of sustained virologic response was higher among non-Latino whites than among Latinos (49% vs. 34%, P<0.001). January 15, 2009
  21. 22. New Studies for Hepatitis C at UC-Davis Fully enrolled* Roche/ Intermune 2b Naïve geno 1 Protease PEG+RBV Roche/ Pharmassett 2b Naïve geno 1 Polymerase PEG+RBV Sciclone 2b Relapsers New IM+RBV No PEG Novartis 1 Non Responders Cyclophillin + * PEG Schering 3 Naïve genotype 1 And Non Respond. Protease * PEG+RBV Drug Patient Population Phase Sponsor Protease * PEG+RBV Naïve geno 1 3 Vertex
  22. 23. NEW drugs for Hepatitis C <ul><li>Will not be approved until 2011-2012 ? </li></ul><ul><li>Improved efficacy with TRIPLE Rx (~70%) </li></ul><ul><li>Ribavirin and IFN still platform 3-5 yrs </li></ul><ul><li>Added side effects: neutropenia, lymphopenia, skin toxicities </li></ul><ul><li>Breakthrough and resistance concerns </li></ul><ul><li>How many will pass phase 2 and 3 ? </li></ul>
  23. 25. Education for Health Choices <ul><li>Moving Mountains </li></ul><ul><ul><li>Train Providers for “Hands on” management of liver disease </li></ul></ul><ul><li>Leslie Benson (916) 717-5722 </li></ul>HCV University <ul><li>http://www.hcvu.org </li></ul><ul><li>HCV University is a project of OASIS, a not-for-profit community-based clinic located in Oakland, CA (Diana Sylvestre) </li></ul>
  24. 27. Summary <ul><li>Hepatitis C is a serious disease </li></ul><ul><li>Ask about risk factors and  HCV Ab </li></ul><ul><li>Confirm HCV-RNA and Genotype </li></ul><ul><li>Consider treatment to cure and to halt progression to cirrhosis and cancer </li></ul><ul><li>Standard therapy: Pegylated Interferons and Ribavirin </li></ul><ul><li>Refer for Clinical Trials with New Rx </li></ul>
  25. 28. GI and Hepatology Clinical Research Group Thank you <ul><li>Thomas Amankonah </li></ul><ul><li>Chris Bowlus </li></ul><ul><li>Juan Carlos Garcia </li></ul><ul><li>Valentina Medici </li></ul><ul><li>Thomas Prindiville </li></ul><ul><li>Lorenzo Rossaro </li></ul><ul><li>Natalie Torok </li></ul><ul><li>Shiro Urayama </li></ul><ul><li>Mark Zern </li></ul><ul><li>Laura Lester (Supervisor) </li></ul><ul><li>Annika Bryant </li></ul><ul><li>Sandeep Dhaliwal </li></ul><ul><li>Nicole Ekedahl </li></ul><ul><li>Mia Minoletti </li></ul><ul><li>Emanuel Obanor </li></ul><ul><li>Nina Parks </li></ul><ul><li>Elizabeth Pickett </li></ul><ul><li>Monica Ruiz </li></ul><ul><li>Ann Sanchez </li></ul><ul><li>Yihey Yuk </li></ul>
  26. 29. How to refer for GI and Hep studies <ul><li>Laura Lester, NP </li></ul><ul><li>Phone (916) 734-8696 </li></ul><ul><li>Fax (916) 734-8666 </li></ul><ul><li>E-mail: laura.lester@ucdmc.ucdavis.edu </li></ul><ul><li>Nina Willis, MA </li></ul><ul><li>Phone (916) 734-8942 </li></ul><ul><li>Fax (916) 734-8850 </li></ul><ul><li>E-mail: nina.willis@ucdmc.ucdavis.edu </li></ul>

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