NICE Guidelines on the NICE Guidelines on the Use of Ribavirin and Interferon Use of Ribavirin and Interferon Alpha for Hepatitis CAlpha for Hepatitis C

Matt Johnson

and Dr. Hunt / Asante / Jenkins

Hepatitis C - TransmissionHepatitis 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

Hepatitis C - RisksHepatitis 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 )

Hepatitis - PrevalenceHepatitis - 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

TreatmentsTreatments

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 )

TreatmentsTreatments

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) or 600mg (for>75kg) PO bd

Combination therapy– SE’s as for IFN include - Flu, Thyroid,

Haematology, Psychiatric, GI, Dermatology

Trial EvidenceTrial 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)

TreatmentsTreatments

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 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

Additional InformationAdditional 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

CostsCosts

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.

SummarySummary

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