NICE Guidelines on the Use of Ribavirin and

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

Hepatitis C - Transmission l l l 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

Hepatitis C - Risks l 20% develop acute hepatitis – – l 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 - 50 y to develop – 20% develop cirrhosis in <20 y l 33%do not progress ( or do after 50 y )

Hepatitis - Prevalence in England Wales l 200 - 400, 000 l 0. 04% blood donors l 0. 4% antenatal attenders (in London) l 1% GU clinic attenders l 50% IV drug l

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

Treatments l Interferon – Mode of action ? – Dose = 3 million units s/c 3 times a week l Ribavirin – Nucleoside analogue with a broad spectrum of antiviral activity (esp RNA V) – 500 mg (for<75 kg) or 600 mg (for>75 kg) PO bd l Combination therapy – SE’s as for IFN include - Flu, Thyroid, Haematology, Psychiatric, GI, Dermatology

Trial Evidence 19 published RCTs involving 3765 patients a l First presentation with Hepatitis C l – Sustained virology responses were seen in – Monotherapy = 6 % (24/52) and 16% (48/52) – Combination = 33% and 41% l For those who responded to IFN alone but r – Monotherapy = 5% (24/52) – Combination = 49% (24/52)

Treatments l 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

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

Additional Information 10 -20% of combination therapy in the trials l Eradication is more likely if the patient is <4 l Unknown l – Benefits of Combo in non-responders to monoth – Treatment in <18 y, or in mild hepatitis

Costs l 18 million per year However increasing numbers are being diagnosed l Advances l – 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 nonresponders and early responders respectively.

Summary l 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 l Contraindications – Continuing IV drug use (excluding methadone) – alcoholics – decompensated liver disease