Treatment and care for hepatitis C

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Treatment and care for hepatitis C

• 7th UK Hepatitis C Mentoring Conference 2009
• Earl J Williams
• Consultant Gastroenterologist
• Royal Bournemouth Hospital

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Overview

• HCV in Dorset
• Patient selection and testing
• Current standard practice
• Evidence for
• -Varying length and dose of treatment
• -Retreatment
• -Maintenance
• Outcomes with current approach
• Future developments in HCV

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HCV in Dorset

• UK prevalence gt0.4
• Genotype 1 predominates
• County of 700,000
• Implies gt28000 affected
• True prevalence?

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HCV services in Dorset

• Referrals come from several sources
• Network of 3 sites
• Underpinned by 3 nurse specialists
• Funding for 120 patients/year
• 148 patients on treatment in 2008-2009
• (88 newly commenced)
• Service expanding to include prison clinics

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Patient Selection

• Planned treatment better than rushed treatment
• Risks of Interferon and ribavirin reviewed
• Important considerations include
• - Previous treatment
• - Liver failure and other medical problems
• - Domestic issues (housing, children, job)
• - Mental health
• - Alcohol and drug use

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Initial tests

• If HCV antibody positive
• RNA testing confirms active infection
• Genotyping to plan treatment
• Ultrasound to look for cirrhosis
• Hepatitis B and HIV testing
• Blood tests to exclude other liver diseases
• Liver biopsy not routine but still important

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Antiviral treatment
SIDE EFFECTS Anaemia
SIDE EFFECTS Flu Altered mood Changes in blood
counts
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Current Standard Practice
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Aims of treatment

• SHORT TERM
• - Undetectable HCV 6 months after treatment
• - Known as sustained viral response (SVR)
• - Occurs in
• 40-50 of genotype 1 patients
• 80 of genotype 2/3 patients
• LONG TERM
• - Avoid cirrhosis (occurs up to 30 of CHC)
• - Avoid liver cancer (3-5 per year once
  cirrhosis)
• - Treat extra-hepatic complications (rare)

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Factors determining SVR

• Genotype
• Missed or reduced treatment
• Important, particularly at start
• Support with side effects therefore important
• Obesity
• Rapid response to treatment (RVR)
• Length of treatment

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Shorter treatment Genotype 1

• 24 weeks treatment may be possible if
• Initial viral load low
• Virus undetectable after 4 weeks treatment

Good outcomes with RVR regardless of genotype
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Shorter treatment Genotype 2/3

• Is 16 weeks treatment enough if
• Initial viral load low
• Rapid Viral Response occurs

16 weeks possible but not recommended
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Extended treatment Genotype 1

• Evidence of benefit for Slow Responders
• low levels of virus at week 12
• undetectable virus at week 24

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Extended treatment Genotype 2/3

• Evidence lacking
• HIV and cirrhotic patients treated for 48 weeks
• More studies needed on
• G 2/3 patients with high viral load
• G2/3 patients without RVR

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Audit of Sustained Viral Response 2003-2007
SVR
Vergara M et al. Gastro y Hepa 2008 31(5)
274-279 Hadziyannis SJ, et al. Ann Intern Med
2004, 140(5) 346-357
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Partial and Non-responders G2/3

• All but 1 partial responders had advanced
  fibrosis /- other adverse factors (retreatment,
  dose reductions, obesity)
• Of 4 non-responders 2 were on re-treatment, 1 was
  obese and 1 had adverse markers

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Re-treatment

• Consider if
• - previous dose reduction
• - 1st treated with monotherapy
• Pegylated IFN following standard IFN
• - SVR 4-26 (41-59 if relapsed)
• REPEAT study supports longer treatment but not
  higher dosing

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Maintenance Treatment

• Is long term treatment beneficial?
• HALT-C study LFTs improved BUT
• No evidence of effect on
• liver failure
• liver cancer
• At present not generally recommended

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Future developments
A lot of exciting possibilities! (but a lot of
dead ends as well)
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Telaprevir

• Protease inhibitor
• Used alone problems with resistance
• Used with IFN and RBV
• - SVR 61-68 for genotype 1
• SE more common (13 drop out)

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Summary

• Standard treatment works for 50-80
• Side effects are common but usually manageable
• Length of treatment should be tailored to the
  individual
• New drugs are on the horizon but only work in
  combination with interferon