Hep C treatment, EASL 2016 Update and Dr. John Farley

Merck Pharmaceuticals was terrific to organize with Dr. G. Horvath and Dr. John Farley, Gasterenterologist to provide us a much needed presentation on Hepatitis at the lovely LaTerrazza  Italian Restaurant in Yaletown. I work with a half dozen other doctors at Doc Side Medical providing treatment to a wide variety of patients with IV drug use and alcoholism. Many have Hepatitis C and we identify their disease and the state of their liver disease on our intake history, physical and laboratory assessments. 
These are the rough notes that I took which don’t do justice to the topic.  The take home message though was that Hep C is treatable now thanks to the newer medications that are more directly anti viral, with better tolerance from a side effect profile and  now approved for a wider group of patients.  Merck has been at the forefront of research in the  area of Hepatitis so it’s not surprising that they were hosting the dinner.  The sooner treatment is begun the better the results but this is at variance right now with the existing protocols for public funding of treatment.
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Dr John Farley
Merck

EASL2016 Update
- Hep C is curable disease
- moving away from interferon to oral more effective treatment using lessons learned from tx of HIV
- newer medications are direct acting anti vitals

Difficult cases
- advanced liver disease
dAA's
Interferon failures

Eg
Ledipasavir
Simeprevir
are a Couple of newer meds

New anti viral are protease inhibitors, polymerase inhibitors
Used in combination  (lesson learned from successful treatment of HIV)

Fewer side effects, better tolerance

Concern with medications which cost hundreds and thousands of dollars / with methadone patients they are getting daily witnessed ingestion so can do the same 
For others 3 and 7 day dispense not monthly

Expert guidance with decompressed cirrhosis
- avoid interferon
- be careful with protease inhibitors

3 large pop based studies
Hepa- C registry
SVR, safety and deaths HCV Tx

Death rate higher for cp B/C versus CP A

Data saying we should treat earlier

(Presently government doesn't fund early tx)

HCC Risk persists after DAA tx in puts with HCV- related cirrhosis
- hepacellular carcinoma risk is still 7.6% risk
HCC screening guidelines every 6 month in this population

EBR/GZR combination tx most effective in randomized studies and superior to interferon based tx

HCV reinfect ion rate 8.4 per 100 person years

SVR12 is endpoint = sustained virologic response for 12 months

Undetectable virus is outcome

Efficacy and safety obv/ptv/rtv with or without DSV or RBV
German Hep C restructuring cohort
Israel cohort 
Studies

Merck product better response in studies  

Hepatitis C in Addiction

Hepatitis C in Addiction

Sept 28, 2013

Mark Hull MHSc FRCPC

Lecture given at the Canadian Society of Addiction Medicine, Vancouver, 2013

My poor rough notes just give a slice of the wealth of information presented by this cutting edge researcher, clinician and remarkably fine communicator. I trust this will help someone appreciate the depth and breadth of information available and the extraordinary work and advances being made.  

Hepatitis C Overview

HCV is a RNA virus

single strang Rna 3000 amino acid

North Amer - 1 a and 1 b dominant straints

Overlapping Global HCV and HIV

• 8 million co infection
• 33 mill HIV
• 170 million Hep C

BC Chronic HCV rates

• gradual decrease since 2002
• increasing number of women
• originally male
• baby boomers with increased elderly

High Prevalance of HCV among PWID Worldwide

Injection drug users in canada make up 60% of HCV

HIV in BC PWID

VIDUS Youth   

CEDAR Youth/youth/young adults

Miller C CAn J. Public Health 2005

Spittal P BMC Public Health 2012

Risk for acquiring HCV rises dramatically after 2 years of IV drugs

Harm Reduction and HCV

-number of syringes - associated with decrease in HCV - free needle programs

Harm Reduction and HCV

effect of opiate subtitution treatment on HCV incident

-80% reduction in risk of HepC with OAT

Turn, K et al Addiction 2011

HCV Surveillance - Corrections Canada

Seroprevalence people entering jail fairly high compared to general population but very flat over years

 -about 30% - higher than community

-jail amplifier - New infections acquired in jail

-new infections with tattooing and Intravenous drug use

HCV prevalence by birth cohort in USA

-prevalence in baby boomer 5x higher than others 

-amstrong , G An. Int Med 2010

-most don’t know - may have got young and may have been victim of poor blood transfusion, or very young , or other ways

HCV Natural History

-75 to 85% patient develop chronic infection

20% develop cirrhosis after 20 years

Estimated reduction in morbity by birth cohort

-recommending routine screening if baby boomer - birth 1945 to 1955

Ontario Burden of Infectious Disease Study 2010

-Hep C the most burdensom infectious disease - loss of life and disability - HIV far less

Mortality in Canadian HIV/HCV Co Infection Cohort Study

-rate of death due to liver disease extremely high

-escallates liver disease

-Klein, M

Baseline Assessment

-All PWID (Persons with Injection Drug Use) should be screened for HCV 

-HCV antibody

-if negative, re screen every 6 months if still at risk

-if HCV Antibody positive

--HCV RNA PCR/genotype

--vacinate for Hepatitis A, B if non-immune

-pneumoccocal vacine

-alcohol cessation treatment

Staging of Liver Disease

-all patients should undergo staging of liver disease - cirrhosis - (clinical, laboratory, radiography)

Use of non invasive techniques - fibroscan (transient elastography 

alternative to Biopsy

Stebbing, J et al, J Clin Gastro 2010

biopsy is still used occasional

Evaluation of HCV treatment

Absolute contraindication to treatment

-pregnancy

Strong contraindication

• active autoimmune
• hepatic decompensation

Relative contraindication

-major depression

-major psychosis

-renal failure

Ideal study - Peg IFN alfa -2a vs Peg IFN alfa-2b 

Serious side effects

 -Neuropsychiatric symptons

20-30 % severe depression

Benefits of successful treatment

• Van der mer, Jama 2012
• all-cause mortality reduce- increases long term survival, regeneration of liver

Pegylated Interferon and ribavirine for genotype 2/3

24 weeks if RVR

48 week

Boceprevir - SPRINT2 overal SVR Rates - doubling of response

Telaprevir - 75% cure rate - revolutionary over last 2 years

These drugs also have this effect with those who have relapsed after previous response

There is a very minor subgroup of non responders that are still a tricky problem but hopefully will respond to new drugs.

Now responses to 6 month of treatment excellent

Integrate Models of Care

-Community based multidisciplinary team - grebel, Eur J Gastroenterology Hep

HIV treatment as prevention BC

Patients currently on HAART

HIV engagement in care

HCV Engagement in CAre 

Decreased mortality and morbidity

decrease sero prevalence

Hepatalogy - Martin, n et al 2013 -

Conclusions

PWID have high burden of HCV disease and should be screened routinely 

Treatment uptake is low among PWID

Use of HCV DAA’s have substantially altered treatentn paradigms and success rates will continue to improve

Treatment as PRevention models suggest populations level benefits to improved therapy 

Q&A Periods

1)System failing - British Columbia - restriction on treatment meaning that our patients aren’t being treated.

Reduces morbidity and mortality for individual but also stops spread at population level

Pharmacare is recognising fibroscan - it’s as acceptable as biopsy

Cost effectiveness of dx and treatment to health care system

1. Viremia - clear and negative tests - might have negative test this month but negative 6 months - want 4 negative tests over 3 years q 6 months
2. Fatty liver - first nations - seems almost all my patients have - aboriginal care giver gave - results in poorer response to treatment, mortality worsened, 

some treatment programs in us are treating metabolic syndrome as well as liver

4) lady with seizure disorder, socially unstable, on methadone, continues to inject cocaine and heroin - should I treat hep c early - or should I just continue to work at treatment of her addiction - if you waited a year unstable - and stabilize for this year then treat -