1. NICE Guidelines on the Use of Ribavirin and Interferon Alpha for Hepatitis C Matt Johnson and Dr. Hunt / Asante / Jenkins

2. Hepatitis C - Transmission There are 6 major types 40% are type 1, the rest are mainly type 2 + 3 Parenteral transmission ( IV drugs, blood transfusion, tattooing, electrolysis, ear piercing, acupuncture) 6% Vertical transmission HIV increases transmission

3. Hepatitis C - Risks 20% develop acute hepatitis –Jaundice and RUQ pain –Flu like illness with muscle aches –Decreased appetite and nausea –generalized weakness 85% of those exposed will develop chronic hepatitis C (15% clear virus) –can take between 20 - 50y to develop –20% develop cirrhosis in <20y 33%do not progress ( or do after 50y )

4. Hepatitis - Prevalence Prevalence in England and Wales 200 - 400,000 0.04% blood donors 0.4% antenatal attenders (in London) 1% GU clinic attenders 50% IV drug

5. Treatments Interferon –47% respond to monotherapy within 3-4/12 but some had to continue for 12/12 PEGulated IFN Ribavirin –Licenced for use in combination therapy Combination Therapy (>1744 )

6. Treatments Interferon –Mode of action ? –Dose = 3 million units s/c 3 times a week Ribavirin –Nucleoside analogue with a broad spectrum of antiviral activity (esp RNA V) –500mg (for 75kg) PO bd Combination therapy –SE’s as for IFN include - Flu, Thyroid, Haematology, Psychiatric, GI, Dermatology

7. Trial Evidence 19 published RCTs involving 3765 patients and 2 meta analysis First presentation with Hepatitis C –Sustained virology responses were seen in –Monotherapy = 6 % (24/52) and 16% (48/52) –Combination = 33% and 41% For those who responded to IFN alone but relapsed within < 6/12 –Monotherapy = 5% (24/52) –Combination = 49% (24/52)

8. Treatments Combination Therapy (>1744 ) –Type 1 = 17% sustained response after 24/52 – = 28% (approx 1/3) after 48/52 –Others = 67% (approx 2/3) after 24/52 – = no further benefit with another 24/52

9. Follow Up PCR, LBx, Genotype testing, Viral load Type 1 are treated for 12/12 Types 2 - 6 treated for 6/12 6/12 Combination therapy costs £4800 Tests cost a further £200 Weekly for 1/12 Then 1/12 OPA FBC and TFT

10. Additional Information 10-20% of combination therapy in the trials was discontinued due to SE’s (usually haematological) Eradication is more likely if the patient is <40y, female, viral load <3.5milli/ml, minimal portal fibrosis Unknown –Benefits of Combo in non-responders to monotherapy –Treatment in <18y, or in mild hepatitis

11. Costs 18 million per year However increasing numbers are being diagnosed Advances –Pegylated Interferon = longer acting version of IFN alpha ( more effective ) –Prognostic and cost implications in monitoring at the 1 and 3 month stage. This enables stopping or reduced lengths of therapy in non- responders and early responders respectively.

12. Summary Indications –histologically proven, previously untreated Hep C, without liver decompensation –adult patients who have previously responded to monotherapy but relapsed within <6/12 –cirrhosis with increased risks of HCC Contraindications –Continuing IV drug use (excluding methadone) –alcoholics –decompensated liver disease