Hepatitis C

• HCV is blood-borne and, based upon differences in molecular structure, a number of different strains (genotypes) have been described.
• The incubation period of acute hepatitis C is usually between 6 and 9 weeks, with specific antibody usually present by 3 months from infection, although in some cases it may take up to 6 months before antibody is detected.
• HCV infection may be acute or chronic. Acute hepatitis C is usually asymptomatic and often does not come to light until some years after infection. Hepatitis C is often diagnosed after routine blood testing, with the onset of hepatic impairment, or when screening a person at risk or a blood donor.
• Individuals who do recover from acute infection are not at risk of long term sequelae and do not need treatment, but only about 20% of those with acute infection will resolve viraemia spontaneously.¹

Hepatitis C is transmitted via:

• Parenteral, especially by intravenous drug use, but also blood transfusion received before September 1991 (since 1991 all blood used in the UK has been screened for HCV)
• Haemodialysis
• Sexual contact with an infected individual
• Needlestick injury
• Perinatal transmission from an infected mother.

• In the UK, 0.3-0.7% of the population have the HCV.
• In 2006, the number of confirmed hepatitis C infections reported from laboratories in England rose to 8,346; 10% higher than in 2005.
• Deaths, transplants and hospital admissions for hepatitis-related end stage liver disease continue to rise.
• Worldwide, 170 million people (3% of the world's population) are infected.
• However there are a very large number of undiagnosed cases and estimates of true prevalence are much higher.
• Surveillance suggests that almost 90% of individuals in England have genotype 1 or 3 infections, with genotype 3a being the single most common genotype. Patients can be infected by more than one genotype.

Risk factors²

• Injecting drug use remains the single most important reported risk factor for acquiring hepatitis C infection.
• In 2006, the prevalence of hepatitis C infection amongst those who have recently started injecting drugs within the last 3 years remained high at 22%.
• In Northern Europe, about 70% of infected patients have been intravenous drug users.³
• The major route of HCV transmission in the UK is by sharing equipment for injecting drug use, usually via blood-contaminated needles and syringes. Other drug injecting equipment (e.g. spoons and filters) may also transmit the infection if it is contaminated with infected blood.
• Receiving a blood transfusion before September 1991. It has since been shown to account for the majority of cases of post-transfusion non-A, non-B hepatitis.
• Mother to baby (before or during birth); transmission rate from mother to child is about 6%. However, this is increased to around 14 -17% when there is co-infection with HIV. Breast feeding is considered safe.
• Sexual transmission of HCV is possible but uncommon.⁴ Less than 5% of the regular sexual partners of people with HCV infection will become infected. Studies have shown that individuals with multiple sexual partners have a slightly increased prevalence of hepatitis C compared to the general population.
• Needle-stick injury is a significant risk for healthcare workers and other groups such as police, prison staff and social workers. There is a 3% infection rate following needle-stick injury with an HCV positive source.⁵
• The use of medical and dental treatment with unsterile equipment.
• Tattooing, ear piercing, body piercing or acupuncture when performed with unsterile equipment.
• Sharing razors or toothbrushes which are contaminated with blood.
• Certain factors are associated with more rapid progression to severe liver disease. These include:
  • Being over 40 years old at the time of infection
  • Alcohol consumption
  • Male gender
  • Co-infection with HIV or hepatitis B
  • Immuno-suppressive therapy

May be confused with common GP presentations of chronic fatigue, depression and lethargy.

Acute HCV infection

• The majority are asymptomatic. 20-30% present with jaundice or deranged liver enzymes (ALT); and 20-30% have non-specific symptoms such as anorexia, lethargy or abdominal pain.
• Average time from exposure to onset of symptoms is 6-7 weeks, and to seroconversion is 8-9 weeks (can take up to 9 months).
• 15%-25% of patients appear to clear the virus without sequelae (no detectable virus and normal LFTs), but remainder develop chronic infection.

Chronic HCV infection

• 75-85% of patients.
• It is indicated by persistently elevated or fluctuating liver enzyme levels.
• Chronic infection often goes unrecognised for 10-20 years unless identified when a patient volunteers for blood donation or has LFTs performed (AST, gamma GT).
• Cirrhosis develops in 10-20% after 20-30 years, and some develop hepatocellular carcinoma.

• FBC, LFT, GGT, Glucose, INR, serum ferritin (to exclude haemochromatosis), autoantibodies/immunoglobulins, hepatitis B serology and USS liver.
• Patients with suspected HCV infection should be tested for anti-HCV by an up-to-date (currently third generation) ELISA test. These have a sensitivity of over 97% but are unable to distinguish acute, chronic or resolved infection. As with any screening test, it has poor positive predictive value in populations with a low prevalence of infection (HCV <10%).
• Patients with positive antibody tests (and those patients at risk of HCV infection with negative or equivocal tests) should have PCR testing of the serum:
  • A positive result confirms current viraemia.
  • 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.
• Patients with positive ELISA but negative PCR should therefore be tested with recombinant immunoblot assay to confirm antibody status.
• Liver biopsy:
  • Is valuable to provide an histological assessment of the severity of liver inflammation, potential progression of fibrosis, and the presence or absence of cirrhosis (LFTs correlate poorly with both necro-inflammatory and fibrosis scores found on liver biopsy).
  • It may also be used to assess suitability for treatment (but the need for biopsy as a guide to treatment has been questioned).
  • 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 quantitative 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.

There is an increased risk of developing diabetes mellitus in patients with HCV infection.⁶ There is also an increased risk of developing the following conditions:

• Sjogren's Syndrome
• Essential mixed cryoglobulinaemia
• Polyarteritis nodosa
• Autoimmune hepatitis
• Thyroiditis
• Membranous glomerulonephritis
• Porphyria cutanea tarda
• Lichen planus
• Idiopathic thrombocytopenic purpura

• Early diagnosis is essential for effective patient care; HCV testing in specialist drug services has increased nearly ten-fold between 2002 and 2006; testing via GP surgeries also remains high.²
• Refer to a specialist with a particular interest in HCV. All patients should have access to the appropriate diagnostic and therapeutic options available in the management of HCV infection.
• Arrange counselling from a health carer with knowledge and experience of chronic HCV infection - on the implications of HCV positivity, the risks of passing on the infection and risk reduction.
• They should not donate blood, organs, tissues or semen.
• The risk of sexual transmission is small - maximum of 5%, but possibly much less. 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.
• Patients should be advised that excess alcohol consumption appears to hasten the progression of disease. Abstinence from alcohol is advisable.
• Consideration should be given to entering patients with established cirrhosis into surveillance programmes for hepatocellular carcinoma (provided their general health is good enough that emerging cancers could be appropriately treated).
• Peginterferon alfa-2a (or alfa-2b) and ribavirin can be prescribed in line with current NICE guidelines:⁷
  • Combination therapy with peginterferon alfa-2a (or alfa-2b) and ribavirin is recommended for the treatment of mild chronic hepatitis C.
  • Monotherapy with peginterferon alfa-2a or peginterferon alfa-2b is recommended for the treatment of mild chronic hepatitis C for people who are unable to tolerate ribavirin, or for whom ribavirin is contraindicated.
  • A person with mild chronic hepatitis C can be treated immediately or wait until the disease has reached a moderate stage ("watchful waiting") depending on the views of the patient following a fully informed consultation with the responsible clinician.
  • The duration of treatment should vary according to the licensed indications of the chosen drug, the genotype of the virus, the initial viral load, the response to treatment, and the treatment regimen chosen.
  • Second or subsequent courses of treatment are not recommended for people who have been treated with a first course of either combination therapy or monotherapy with peginterferon alfa if they have not had an early response (as indicated by reduction in viral load at 12 weeks).
  • There is insufficient evidence to recommend combination therapy or monotherapy with peginterferon alfa for people with mild chronic hepatitis C who are under the age of 18 years, or those who have had a liver transplant.

• Cirrhosis develops in about 20-30% of patients over a period of 20 to 30 years.¹
• Patients who develop cirrhosis are at increased risk of hepatocellular carcinoma. Between 1% and 5% of those infected with HCV will develop primary liver cancer. Hepatocellular carcinoma is suggested by weight loss and raised alpha fetoprotein level.

• The natural history is slowly progressive. 90% will progress to chronic liver disease (median time to cirrhosis is 28-32 years).
• Co-infection with both hepatitis B and alcohol seem to have an additional effect.

• No vaccine is currently available.
• Patients and at risk groups should be counselled to minimise transmission.
• Prevention strategies target those groups at greatest risk of infection (e.g. intravenous drug users and in prisons), and include:²
  • Improving drugs education
  • Reducing initiation of injecting drug use
  • Helping intravenous drug users to quit injecting
  • Minimising harm for those who continue to inject

• Risk of transmission is estimated at 3%.¹
• No post exposure vaccine is currently available and neither immunoglobulin nor antiviral agents have been shown to be effective.
• For health care workers exposed to a source known to be positive for anti-HCV or HCV RNA (or a source whose hepatitis C status is unknown but who is assessed to be at high risk), serum should be obtained from the health care worker at baseline, 6, 12, and 24 weeks after exposure.
• Serum should be tested for HCV RNA at six and 12 weeks and for anti-HCV at 12 weeks and 24 weeks.
• Early testing of the serum of the health care worker for HCV RNA will, if negative, give some reassurance at this stage.
• If the care worker seroconverts, they should be referred for specialist care.

• As many as a third of patients with HIV also have HCV.⁸
• With increased survival in patients with HIV, the major burden of disease is becoming end-stage liver disease secondary to HCV infection with rapidly progressive fibrosis and cirrhosis.
• Co-infection leads to earlier and more severe liver disease.