Note from the Scottish Intercollegiate Guidelines Network (SIGN) and National Guideline Clearinghouse (NGC): In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the full-text guideline document.
The grades of recommendations (A–D) and levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) are defined at the end of the "Major Recommendations" field.
Testing
Clinical and Cost-Effective Testing for Hepatitis C Virus (HCV)
D - The following groups should be tested for HCV:
- Blood/tissue donors
- Patients on haemodialysis
- Healthcare workers who intend to pursue a specialty that requires them to perform exposure prone procedures
D - The following groups should be offered an HCV test:
- Patients with an otherwise unexplained persistently elevated alanine aminotransferase
- People with a history of injecting drug use
- People who are human immunodeficiency virus (HIV) positive
- Recipients of blood clotting factor concentrates prior to 1987
- Recipients of blood and blood components before September 1991 and organ/tissue transplants in the UK before 1992
- Children whose mother is known to be infected with HCV
- Healthcare workers following percutaneous or mucous membrane exposure to blood which is, or is suspected to be, infected with HCV
- People who have received medical or dental treatment in countries where HCV is common and infection control may be poor
- People who have had tattoos or body piercing in circumstances where infection control procedure is, or is suspected to be, suboptimal
- People who have had a sexual partner/household contact who is HCV infected.
HCV Diagnostic Testing
B - Diagnostic testing for HCV should be performed on serum or plasma where possible.
D - HCV genotyping should be undertaken if antiviral therapy is being considered.
D - Following an isolated acute percutaneous exposure to blood infected, or strongly suspected of being infected, with HCV, healthcare workers should be offered HCV RNA testing at six, 12 and 24 weeks and anti-HCV testing at 12 and 24 weeks.
Prevention of Secondary Transmission
Transmission Through Sexual and Household Contact
D - Individuals co-infected with HIV/HCV should be advised always to practise safe sex and use condoms.
D - Individuals infected with HCV should be advised to avoid activities which could result in percutaneous or mucous membrane exposure to their infected blood, such as the sharing of razors and toothbrushes.
Transmission Through Injecting Drug Use
D - Injecting drug users known to be infected with HCV should be given advice on how they can prevent transmission of infection to other injecting drug users.
Transmission Between Healthcare Workers and Patients
Risk of Healthcare Worker Infection
D - Healthcare workers who are aware they are HCV RNA positive should not undertake exposure prone procedures.
Referral
D - Individuals, including injecting drug users, diagnosed with chronic HCV should be offered integrated multidisciplinary care as it can maximise their uptake of, and retention in, services.
A - Patients with acute HCV infection should be referred to specialist care immediately.
Children and Hepatitis C
Mother to Child Transmission
B - In pregnant women knowledge of HCV RNA positive status should not influence obstetric management or standard advice regarding breast feeding.
HCV in Children and Infants
B - Infants born to women who are HCV antibody positive and HCV RNA negative do no need to be tested.
B - In children born to women infected with HCV, an HCV antibody test should be performed at 12 months of age or thereafter to identify the majority of children who are not infected.
B - In children whose mothers are co-infected with HIV, and in infants found to be HCV antibody positive after 12 months, an HCV RNA test should be performed, and if positive, confirmed on a second sample.
B - If information regarding the risk of HCV infection in an individual child is required before 12 months of age, an HCV RNA test and retest can be performed after two months of age. Further testing is still required to make a definitive diagnosis.
Natural History of HCV Infection in Children
D - Children infected with HCV should be monitored to identify the minority who are at risk of progressive fibrosis during childhood, and who may be candidates for treatment.
Treatment of Children with Hepatitis C
D - Children with evidence of moderate or severe liver disease should be considered for treatment with pegylated IFN and ribavirin.
D - In children who are asymptomatic with mild or no liver disease, benefits of treatment need to be weighed against the risk of side effects.
Acute Hepatitis C
Natural History
D - Patients with acute hepatitis C virus infection require clinical and laboratory monitoring (looking for spontaneous viral clearance) for the initial three months following diagnosis as they will often have a self limiting illness.
Treatment of Patients with Acute Hepatitis C
Timing of Treatment
D - Treatment should start between three and six months after diagnosis of acute hepatitis C, if the infection has not resolved spontaneously.
Choice and Duration of Treatment
A - Patients with acute HCV infection should be treated with interferon (IFN) therapy if the infection does not resolve spontaneously.
D - Patients can be treated with either pegylated IFN or non-pegylated IFN.
D - Patients with acute HCV infection should be treated with IFN therapy for 24 weeks irrespective of genotype.
Assessment of Liver Disease
Fibrosis Markers
B - Biochemical markers should not be used as an alternative to liver biopsy for staging of intermediate grades of fibrosis.
B - Biochemical tests may be used as an alternative to liver biopsy to diagnose cirrhosis or to direct screening for complications of fibrosis.
Liver Biopsy
When to Biopsy
D - Liver biopsy should be performed if there is concern about additional causes of liver disease.
D - Repeat liver biopsies should be considered in patients with mild disease who remain untreated, if progression of liver fibrosis would influence the decision to opt for antiviral therapy.
Biopsy and Genotype
D - Liver biopsy should not be considered an essential test prior to using antiviral therapy, especially in patients with genotype 2 and 3 disease.
Progression of Untreated Disease
Age, Gender and Ethnicity
D - When estimating the likely rate of progression of liver disease age at infection, gender and ethnicity should be considered.
Tobacco Smoking
D - Patients with chronic hepatitis C (CHC) should be advised that smoking tobacco can accelerate progression of liver disease.
Alcohol
B - Patients with CHC should be advised that drinking alcohol (even in moderation) can accelerate progression of liver disease.
Alanine Aminotransferase
D - When defining persistently normal serum alanine aminotransferase (PNALT) serum transaminases (ALT) measurement should be undertaken every two to three months to ensure that flares in ALT are not missed.
HIV Co-Infection
B - The increased rate of progression to decompensated liver disease in patients with HCV and HIV co-infection should prompt early consideration of antiviral therapy.
Co-Infection with Hepatitis A or B Viruses
D - Vaccination against hepatitis A and B should be considered for patients infected with hepatitis C.
D - When estimating the likely rate of progression of liver disease as a result of hepatitis C infection, active or previous hepatitis B virus (HBV) infection should be considered.
Iron Status
D - Modest iron loading does not justify specific intervention prior to antiviral therapy as it is unlikely to be of clinical importance.
D - Patients with significant iron retention require further investigation for additional conditions known to result in iron overload.
Treatment of Chronic Hepatitis C
Antiviral Therapy
A - A combination of pegylated IFN and ribavirin is the treatment of choice for patients with hepatitis C.
Sustained Viral Response
B - Sustained viral response should be used as a marker for viral clearance.
Genotype and Duration of Treatment
B - The duration of treatment with a combination of pegylated IFN with ribavirin, should be 12-24 weeks for patients with genotype 2 or 3 and 48 weeks for patients with genotype 1 or 4.
A - Patients with genotype 1 infection should be tested for an early viral response at 12 weeks.
A - Patients with genotype 1 infection who fail to achieve an early viral response (EVR) at 12 weeks should be considered for cessation of treatment.
A - Patients with genotype 1 infection with an EVR at 12 weeks should continue treatment for 48 weeks. Those who are still HCV RNA positive at 24 weeks should be considered for cessation of treatment.
B - Patients with genotype 2 or 3 infection should have an HCV RNA test performed four weeks after starting antiviral therapy, and if this is negative, may be considered for a reduced duration of therapy of 12 or 16 weeks.
Patient Subgroups
Patients With Mild Chronic Hepatitis
B - Patients with mild CHC should be considered for treatment with a combination of pegylated IFN with ribavirin.
Patients With Persistently Normal ALT Levels
A - Patients with chronic hepatitis C and normal ALT should be considered for treatment with pegylated IFN and ribavirin.
Patients With HIV Co-Infection
A - Patients with CHC and HIV should be considered for treatment with a combination of pegylated IFN and ribavirin for 48 weeks irrespective of genotype.
A - For patients with HCV genotype 1 infection and HIV, the lack of an early viral response at week 12 predicts those who are unlikely to obtain an sustained viral response (SVR), and treatment can be stopped.
Patients With Hepatitis B Co-Infection
C - Patients with chronic hepatitis B and C co-infection should be considered for combination treatment with pegylated IFN and ribavirin.
Patients in Drug Treatment Programmes
C - Patients with CHC who are on a drug treatment programme can be considered for treatment with a combination of pegylated IFN and ribavirin.
Factors Influencing Effectiveness
Age, Gender and Ethnicity
A - Patients should be advised that older age at the time of treatment leads to a lower sustained viral response.
B - Patients should be advised about the likelihood of sustained viral response according to their ethnic origin.
Contraindications
Patients with Renal Failure
D - Patients with CHC and renal failure may be treated with IFN monotherapy, with careful monitoring required.
Patients with Mental Health Problems
B - Patients with stable mental health problems should not be excluded from treatment for CHC.
B - Patients with mental health problems should have their psychiatric symptoms monitored prior to and throughout IFN treatment.
Management of Adverse Effects
Flu-Like Symptoms
D - Patients experiencing flu-like side effects from pegylated IFN and ribavirin can be advised to use paracetamol within manufacturers' guidelines.
D - Patients should be advised to maintain an adequate fluid intake throughout treatment with pegylated IFN and ribavirin.
D - Patients should be advised to coordinate their injections of pegylated IFN and ribavirin with periods of reduced activity, such as weekends and holidays.
Anaemia and Neutropenia
B - Erythropoietin should be considered in CHC patients receiving pegylated IFN and ribavirin therapy who develop anaemia, to prevent curtailment or dose reduction of ribavirin.
D - Granulocyte-colony stimulating factor (G-CSF) should be considered on a case-by-case basis for patients who develop significant neutropenia while receiving treatment with pegylated IFN and ribavirin for CHC infection, to prevent curtailment or dose reduction of pegylated IFN.
Depression
B - All patients receiving pegylated IFN and ribavirin should be monitored for signs of depression before, during and immediately post-treatment.
B - Patients treated with pegylated IFN and ribavirin who experience depression should be considered for treatment with antidepressants and for referral to a specialist, if necessary.
Skin Reactions
D - All patients on pegylated IFN and ribavirin should be advised to ensure appropriate skin hygiene and hydration.
D - Patients should be advised to avoid overexposure to sun.
D - Patients should be advised to rotate injection sites.
D - The use of emollients and topical corticosteroids can be considered for non-specific rashes.
Thyroid Dysfunction
D - Thyroid function should be monitored at baseline before IFN therapy, at week 12 of treatment and at any time where there is a suspicion of thyroid dysfunction.
Dyspnoea
D - Patients treated with pegylated IFN or ribavirin who report dyspnoea that is not related to anaemia should be urgently assessed medically for cardiopulmonary problems.
Retinopathy
D - Patients with CHC and hypertension or diabetes should have an ophthalmic examination prior to commencing treatment, paying particular attention to cotton wool spots and retinal haemorrhage.
D - Any patient reporting visual disturbance during treatment should be examined further by an ophthalmologist.
D - IFN should be discontinued in any patient with visual disturbance until it has resolved or an ophthalmologist has confirmed there is no retinal injury.
Alopecia
D - Patients should be advised that treatment related hair loss is reversible on cessation of treatment.
Relapse or Failed Treatment
IFN and Ribavirin
D - Patients with CHC who have had unsuccessful treatment with non-pegylated IFN and ribavirin should be considered for pegylated IFN and ribavirin retreatment.
Other Therapies
C - The following therapies are not recommended for the treatment of patients infected with CHC, whether they are being treated for the first time, previously relapsed, or have never responded to treatment:
- Amantadine in addition to pegylated IFN alone or in combination with ribavirin
- Ribavirin monotherapy
- Interleukin 12
Treatment of Advanced Infection
Antiviral Therapy
Patients with Cirrhosis
A - Patients with compensated cirrhosis should be considered for therapy with pegylated IFN and ribavirin, unless contraindicated.
A - Patients with compensated HCV cirrhosis may benefit from IFN treatment to reduce the risk of development of HCC. The duration of therapy required to achieve this is not clear.
Patients Referred for Liver Transplant
D - Patients in whom transplant is planned should not receive antiviral therapy in the pretransplant or peri-transplant stages, except as part of clinical trials.
D - Patients should be considered for antiviral therapy post liver transplant to achieve HCV clearance in cases of recurrence of HCV related liver disease.
Liver Transplantation
C - Patients with hepatitis C virus and concurrent operable hepatocellular carcinoma should be offered liver transplantation.
C - Patients with HCV associated chronic liver failure should be offered liver transplantation.
Screening for Hepatocellular Carcinoma
A - The measurement of alpha fetoprotein should not be used in isolation for screening or surveillance of the development of HCC in patients with hepatitis C.
D - Surveillance using ultrasound should take place at six monthly intervals.
C - Surveillance should be confined to patients with cirrhosis.
Nutrition, Supportive Care and Complementary Therapies
Nutritional Interventions
Dietary Interventions
D - Nutritional care for people infected with hepatitis C should involve promotion of optimal nutrition and prevention or treatment of malnutrition or deficiencies of specific nutrients.
D - Patients should have a nutritional screen and if needed a nutritional assessment and appropriate advice by a dietitian.
D - Patients with advanced liver disease should be given nutritional support to minimize malnutrition.
Overweight
C - Patients who are overweight should be advised to lose weight, within a realistic weight loss target, as this may have a beneficial effect on the degree of liver damage associated with hepatitis C infection.
Exercise
D - Patients with hepatitis C should be encouraged to take mild to moderate exercise. Those on antiviral therapy should be advised that they may find their capacity for exercise reduced.
Definitions:
Grades of Recommendation
Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.
A: At least one meta-analysis, systematic review of randomized controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D: Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Good Practice Points: Recommended best practice based on the clinical experience of the guideline development group
Levels of Evidence
1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2++: High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+: Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3: Non-analytic studies (e.g. case reports, case series)
4: Expert opinion
