HepatitisC 1998

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Curing Hepatitis C Individualized Approach and
New Therapies
Lorenzo Rossaro, MD Gastroenterology and
Hepatology University of California Davis
Medical Center
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c/o ? Liver Cancer (HCC)
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HCV History Outcome Factors
POSITIVE
NEGATIVE
Male, Age,
Interferon Ribavirin
ETOH HBV HIV
Transplant
3.6
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HCV Screening Who is at risk ()

• Blood product for clotting problems
  produced ? 1987 (i.e.hemophilia) 90
• Injected illegal drugs (IVDU) 80
  
• Long-term kidney dialysis 10
• Blood transfusion or solid organ transplant ??
  July, 1992 6
• Born from HCV mother 5
• Tattoos, cocaine, body piercing ?

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HCV diagnosis and staging

• Proposed Algorithm
• 1 Screening (ALT) and HCV Antibody
• 2 Confirmation HCV-RNA (not RIBA)
• 3 Predict success HCV-Genotype
• 4 Refer to Liver Clinic and/or Request
• Liver Biopsy (if appropriate)

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Hepatitis C Genotype in U.S. Predict Response
to Treatment
BEST RESPONSE Type 2 INTERMEDIATE RESPONSE Type 3
and 4 LOWEST RESPONSE Type 1
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HCV Severity of Liver Disease

• Symptoms and Liver Function Tests usually in
  late stages
• ALT levels often normal
• Ultrasound Examination not sensitive for
  fibrosis/staging
• Liver Biopsy gold standard
• Consider fibrosis markers or elastography

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Fibrospect?

• Low values (lt20) indicative of mild disease
• High values (gt80) indicative of advanced disease
• Between 20 and 80 can be anything

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Assessing the Severity of Liver Disease

• LIVER BIOPSY
• The most accurate method of determining disease
  severity and activity
• Disease severity Fibrosis (stage 1-4)
• Indicator of prognosis
• Helpful in guiding treatment options

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Liver Biopsy by Stage
Mild Fibrosis
Cirrhosis
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Treatment Response by Genotype and Duration of
Therapy
2002-2011
1998-2001
1987-1997
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Hepatitis CThe Goals of Treatment

1. Virus eradication negative HCV-RNA six months
   after the end of treatment CURE
2. Decrease progression of disease
3. from hepatitis to cirrhosis (or reverse ?)
4. risk of cancer (Hepato Cellular Carcinoma)
5. need for liver transplant or retransplant

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HCV Who should be treated ?

• Whoever is affected in some way by the chronic
  disease
• AND
• fully understands the risks and benefits of
  therapy

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Side effects of Interferons

• FLU-like symptoms (Tylenol)
• Behavioral changes
• Depression, Irritability
• Myelosuppression
• Neutropenia
• Thrombocytopenia
• Skin, GI, Thyroid, Hair loss

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RibavirinRisk of Treatment

• Hemolytic anemia
• Reversible
• May require dose reduction or erythropoietin in
  selected patients
• Pregnancy Risks
• Contrtraception required

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C Complete EVR P Partial EVR
P
C
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SVR with 48 wks PEGRIBAand Patterns of
Virological Response(RRapid 4w, EEarly 12w,
Nnone, ccomplete, ppartial)
RVR
NVR
pEVR
cEVR
Marcellin P. AASLD 2007
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Factors Associated with Cure

• Viral
• Non-1 Genotype (2,3)
• Lower Viral Load
• Rapid/Early response
• Disease related
• No fibrosis/cirrhosis
• Higher ALT
• Lack of steatosis
• Ribavirin dosage (15 mg/kg)

• Adherence
• More than 80 of intended treatment for gt 80 of
  intended duration
• Host Factors
• Lower body weight
• Younger age
• Female gender
• Race (non-AA, non-Latino)

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January 15, 2009
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January 15, 2009
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, Plt0.001).
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New Studies for Hepatitis C at UC-Davis Fully
enrolled
Drug Patient Population Phase Sponsor
Protease PEGRBV Naïve genotype 1 And Non Respond. 3 Schering
Protease PEGRBV Naïve geno 1 3 Vertex
Polymerase PEGRBV Naïve geno 1 2b Roche/ Pharmassett
Protease PEGRBV Naïve geno 1 2b Roche/ Intermune
New IMRBV No PEG Relapsers 2b Sciclone
Cyclophillin PEG Non Responders 1 Novartis
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NEW drugs for Hepatitis C

• Will not be approved until 2011-2012 ?
• Improved efficacy with TRIPLE Rx (70)
• Ribavirin and IFN still platform 3-5 yrs
• Added side effects neutropenia, lymphopenia,
  skin toxicities
• Breakthrough and resistance concerns
• How many will pass phase 2 and 3 ?

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Education for Health Choices

• Moving Mountains
• Train Providers for Hands on management of
  liver disease
• Leslie Benson [phone]

HCV University

• http//www.hcvu.org
• HCV University is a project of OASIS, a
  not-for-profit community-based clinic located in
  Oakland, CA (Diana Sylvestre)

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Summary

• Hepatitis C is a serious disease
• Ask about risk factors and ? HCV Ab
• Confirm HCV-RNA and Genotype
• Consider treatment to cure and to halt
  progression to cirrhosis and cancer
• Standard therapy Pegylated Interferons and
  Ribavirin
• Refer for Clinical Trials with New Rx

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GI and Hepatology Clinical Research GroupThank
you

• Thomas Amankonah
• Chris Bowlus
• Juan Carlos Garcia
• Valentina Medici
• Thomas Prindiville
• Lorenzo Rossaro
• Natalie Torok
• Shiro Urayama
• Mark Zern

• Laura Lester (Supervisor)
• Annika Bryant
• Sandeep Dhaliwal
• Nicole Ekedahl
• Mia Minoletti
• Emanuel Obanor
• Nina Parks
• Elizabeth Pickett
• Monica Ruiz
• Ann Sanchez
• Yihey Yuk

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How to refer for GI and Hep studies

• Laura Lester, NP
• Phone [phone]
• Fax [phone]
• E-mail laura.lester_at_ucdmc.ucdavis.edu

• Nina Willis, MA
• Phone [phone]
• Fax [phone]
• E-mail nina.willis_at_ucdmc.ucdavis.edu