Clinical guidelines on the management of hepatitis C - British Society of Gastroenterology (April 2001)

These guidelines were published in GUT (2001) Volume 49, supplement 1. They were compiled on behalf of the Royal College of Physicians of London and the British Society of Gastroenterology by J C L Booth, J O'Grady, & J Neuberger.

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Summary of recommendations Patients infected with hepatitis C virus (HCV) should be referred to a clinician with a particular interest in the infection. Patients must have access to adequate counselling from a health carer with knowledge and experience of chronic HCV infection. All patients must have access to the appropriate diagnostic and therapeutic options available in the management of HCV infection. Where possible a judgement is made on the quality of information used to generate the guidelines. Categories of evidence are classified: (A) - randomised control trials (RCT's), meta-analyses or systematic reviews (B) - prospective, retrospective or cross-sectional studies (C) - expert opinion This classification is used throughout the text.	Guideline recommendations: Diagnosis part 1 Patients with suspected HCV infection should be tested for anti-HCV by an up-to-date (currently third generation) ELISA test (C). All patients with positive antibody tests and those patients thought to be at risk of HCV infection despite negative or indeterminate serological tests should undergo PCR testing of the serum. A positive result confirms current viraemia whereas a negative test suggests non-viraemic infection, transient absence of viraemia or recovered infection, a level of viraemia below the detection limit of the assay or may reflect a non-specific ELISA result (B). Patients with positive ELISA but negative PCR should therefore be tested with recombinant immunoblot assay to confirm antibody status (B). A qualitative PCR test is recommended in immunodeficient patients with suspected HCV infection (B).	Guideline recommendations: Diagnosis part 2 The results of routine liver tests correlate poorly with both necro-inflammatory and fibrosis scores found on liver biopsy (B). Liver biopsy is valuable for assessing status of liver inflammation, potential progression of fibrosis and the presence or absence of cirrhosis. To clarify these, and to assess suitability for treatment, liver biopsy is recommended for patients found to be viraemic, whether or not liver function tests are abnormal. Standard histological scoring systems by a suitably experienced pathologist, should be used to encourage uniformity of histological reports. The risks and benefits of liver biopsies must be fully discussed with the patient (B). The measurement of HCV RNA concentrations in serum and the determination of HCV genotype are recommended and should be used to determine the duration of treatment (see later) (A).
Guideline recommendations: Counselling regarding transmission ,,, Patients should be counselled on the implications of HCV positivity and advised on the risks of infectivity. the natural history is slowly progressive (median time to cirrhosis = 28-32 years) (A). HCV positive patients should not donate blood, organs, tissues or semen (C). the risk of sexual transmission is small - maximum of 5%, but possibly much less (B). There is insufficient evidence firmly to recommend barrier contraception in stable monogamous relationships but is strongly advised for HCV infected patients with multiple sexual partners (C). transmission from mother to child is rare - maximum of 6%, but transmission rates are higher in HIV positive mothers (B). breast feeding is not contraindicated (C). household contacts should avoid third party contact with blood by not sharing toothbrushes and razors, and by covering open wounds (C). standard precautions for the prevention of transmission to medical personnel and patients is mandatory in health care settings (C). needle exchange programs in drug addicts may help reduce parenterally transmitted infection (C). Current IVDUs should not be treated although in selected cases ex-IVDUs taking regular oral methadone may be considered for treatment (C).	Guideline recommendations: Treatment - General measures Patients should be advised that excess alcohol consumption (> 50 g/day) appears to hasten the progression of disease (B). Consideration should be given to entering patients with established cirrhosis into surveillance programmes for hepatocellular cancer, if their general state of health is sufficiently good that emerging cancers could be appropriately treated (C). Patients must be screened for their suitability to receive Interferon and Ribavirin, with criteria which includes proven viraemia and abnormal liver histology (C). Interferon (IFN) and Ribavirin are currently the only licensed treatments for HCV in the United Kingdom. IFN/Ribavirin combination is the treatment of choice for IFN naive patients (A). IFN/Ribavirin combination is also recommended for those patients relapsing after IFN monotherapy (A). IFN monotherapy should be considered for those patients in whom ribavirin is contraindicated (C).	Guideline recommendations: Treatment - Interferon monotherapy We recommend IFN monotherapy should be initiated at a dose of 3MU three times per week by injection (B). IFN monotherapy should be continued for 12 months unless there is evidence of failure to respond (see below) (B). There is no evidence to suggest that one type of ?-interferon is superior to another (alfa-2b, alfa-2a, alfa-n1 and consensus interferon (CIFN) (B).
Guideline recommendations: Treatment - Interferon/Ribavirin combination therapy part 1 ,,, Recent results of large randomised controlled studies have shown improved response rates for IFN/Ribavirin combination therapy in IFN naive and relapsers when compared to IFN monotherapy (A). Combination therapy consists of IFN at standard doses (usually 3MU three times per week) with Ribavirin 1000mg/day for patients weighing 75kg or less and 1200mg for those weighing more than 75kg. (A) In viraemic patients, the decision to offer treatment should be influenced by the histological findings (B): treatment can be reasonably withheld in patients with mild disease (see text) but they should be followed to see if there is evidence of progressive liver disease by the use of repeated biopsy after an interval (C). treatment should be offered to those patients shown to have moderate disease (C). cirrhotic patients respond less well to IFN monotherapy but sustained responses have improved with IFN/Ribavirin combination treatment. There is no conclusive evidence that treatment in this group of patients delays progression of liver disease or the development of hepatocellular carcinoma (B). Treatment should not be withheld on the basis of genotype analysis or the measurement of HCV RNA levels (B). The duration of combination depends of the genotype and level of viraemia (A). Patients infected with non-HCV 1 ( mostly genotype 2 or 3) should be treated for 6 months irrespective of the level of viraemia (A).	Guideline recommendations: Treatment - Interferon/Ribavirin combination therapy part 2 Patients infected with genotype 1 and low level viraemia ( < 2 million copies per ml) should be treated for 6 months whereas 12 months treatment is recommended for those infected with genotype 1 and high level viraemia ( > 2 million copies per ml) (A). If HCV quantitation is not available treatment is recommended for 12 months in HCV 1 infected patients (A). Patients unlikely to respond to IFN monotherapy can be identified at 3 months by persistent elevation of serum transaminase levels and the persisting presence of HCV RNA by PCR in serum (B). If ALT levels are normal or HCV RNA negative (or both) at 3 months, treatment should be continued for the full duration (12 months) (B). In patients with initially normal ALT levels, failure to become RNA negative at 3 months suggests longer treatment will be ineffective (B). The recommendation that early treatment response can be used to predict sustained response does not apply to patients receiving combination therapy (A). In those patients receiving 12 months IFN/Ribavirin combination therapy a positive PCR at 6 months is an indication to stop treatment (C).	Guideline recommendations: Treatment - Interferon/Ribavirin combination therapy part 3 Although transient or mild side-effects are common during IFN monotherapy, serious toxicity requiring reduction in dose or cessation of treatment occurs in 5-10% of patients during treatment (A). Withdrawal from IFN/Ribavirin combination therapy occurs more often with 10-20% of patients requiring a reduction in dose or cessation of combination therapy (A). Patients with a combined biochemical and virological response at the end of IFN monotherapy, who relapse in follow-up over the next year, have a significant chance of a sustained response after further treatment with IFN/Ribavirin (A). Patients with a biochemical but not virological response during initial treatment with IFN monotherapy are unlikely to have a sustained response to further treatment with IFN/Ribavirin (A). There is continuing development in the treatment of patients with HCV infection. The guidelines will need regular and frequent review (C).
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