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Hepatitis C: treatment challenges

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Lee Copley, BSc (Hons), RN.

Service Improvement Manager and Clinical Nurse Specialist, St George's Hospital, London

Hepatitis C is an increasing cause of liver disease. An estimated 200 000 people in the UK are infected with the virus (Donaldson, 2001). Over the next 10-20 years, chronic hepatitis C virus (HCV) infection is predicted to become a burden on the health-care system as patients who are currently asymptomatic with mild disease progress to end-stage liver disease and develop hepatocellular carcinoma (Figure 1). Yet transmission can be prevented and the infection is treatable.

Hepatitis C is an increasing cause of liver disease. An estimated 200 000 people in the UK are infected with the virus (Donaldson, 2001). Over the next 10-20 years, chronic hepatitis C virus (HCV) infection is predicted to become a burden on the health-care system as patients who are currently asymptomatic with mild disease progress to end-stage liver disease and develop hepatocellular carcinoma (Figure 1). Yet transmission can be prevented and the infection is treatable.

There is widespread misunderstanding about hepatitis C, with respect to how it is transmitted, risk groups, treatment of the condition and prognosis. This confusion, together with inconsistent service provision for disenfranchised and stigmatised patients, presents a challenge for multidisciplinary team members. Specialist nurses fill a pivotal role in managing side-effects of treatment, providing advice and education, and making a difference to treatment outcomes. See panel, right, for transmission routes and symptoms.

Diagnosis of HCV infection
Diagnosis is not straightforward. Antibodies can take from eight to 12 weeks to six months or more to appear after exposure to the virus, rendering serum HCV tests inconclusive. An anti-HCV-positive result indicates exposure to the virus but does not prove active infection, as about 20% of people who become infected clear the virus at the acute stage.

Liver function tests (LFTs) provide an indication of the liver damage associated with chronic HCV infection, such as necrosis or inflammation. However, levels can fluctuate throughout the course of the disease and can remain normal in the presence of liver damage. In general, a positive HCV test and elevated LFTs in the setting of risk factors for transmission is usually sufficient to diagnose HCV infection.

To distinguish between those with antibody alone and viral carriers, the polymerase chain reaction (PCR) test or HCV ribonucleic acid (RNA) test are used. Both detect very low levels of virus in the blood. There are at least six major genotypes or strains of HCV, and each affects the detection of the virus, disease progression and effectiveness of antiviral treatment. Genotype 1 is the most common in the UK, found in 40-50% of cases. Genotypes 2 and 3 account for a further 40-50% and genotypes 4, 5 and 6 constitute about 5%. The PCR test is also used to determine the genotype of the circulating virus and the viral load.

A liver biopsy is needed to determine the extent of liver scarring and necro-inflammation, which in turn determines severity of disease and guides decisions regarding treatment.

Testing for HCV infection
Counselling and support of patients before and after testing is crucial. Patients need to understand the implications of positive and negative results. They should be given their test results personally whenever possible. If appropriate, patients with a negative antibody test result should be counselled on the continued possibility of infection with risk-taking behaviour. A repeat test should be offered to those recently exposed to the virus, as HCV antibodies can take up to six months to develop.

Management of chronic HCV infection
The goals of treatment of HCV infection are to achieve long-term sustained virological response (SVR) as determined by a persistent negative HCV RNA.

The standard treatment approach for chronic HCV recommended by the National Institute for Clinical Excellence (NICE) is the combination of interferon alpha and ribavirin. An average of 33% of patients achieve a SVR after 24 weeks and 41% at 48 weeks (Shepherd et al, 2000).

Antiviral therapy with a combination of interferon alpha and ribavirin provides an opportunity to change the natural progression of the disease. Recent developments in this combination approach, the addition of polyethylene glycol groups (PEG) to interferon, mean that therapeutic drug levels are maintained over a longer period. This allows treatment to be administered once-weekly. It also appears to have enhanced antiviral effects (Dusheiko et al, 2000).

Overall efficacy rates of 61% with pegylated interferon alfa2b and ribavirin in combination (Cohen, 1999) and significant benefits of pegylated interferon have been seen in the genotype 1 HCV patients, where 48% achieved an SVR compared to previous findings of 29-33% (Manns et al, 2001).

Who to treat
Treatment is not suitable for everyone (see panel, left). Patient age and gender, HCV genotype, duration of infection, degree of liver damage and presence of cirrhosis all impact on its effectiveness. Additional factors include contraindications to therapy, compliance issues and the possibility of re-infection with continued injecting-drug use.

Maximising the benefits of treatment
NICE recently published draft interim clinical guidance (2003) on the use of pegylated interferon alpha-2b as monotherapy and in combination, advocating that 'pegylated combination therapy is a very cost-effective intervention' in the management of chronic HCV infection. However, these clinical and cost benefits can only be realised if the many people with asymptomatic HCV infection are identified and treated. Greater awareness of hepatitis C and how it is transmitted is needed; availability, accessibility and acceptability of testing need to be addressed; and self-identification encouraged. Underpinning all this is a need for the education of more nurses to equip them for their role at all stages of the care pathway.

ROUTES OF TRANSMISSION
- The most common route of transmission in the UK is through sharing equipment for injecting drugs. HCV is transmitted in unsterile, blood-contaminated paraphernalia including syringes, needles, spoons, water and filters.

Other routes of transmission include:

- Receipt of unscreened blood products (pre-1986)

- Medical and dental procedures with inadequately cleaned equipment, particularly in poorly developed countries

- Unsterile tattooing or body piercing

- Needlestick injuries among health-care and laboratory workers

- Transmission between mother and child (2-5%)

- Sexual contact (considered to be extremely rare).

SYMPTOMS
Around 10% of people infected with HCV are acutely ill for several weeks or months soon after infection. The most common symptoms include:

- Nausea

- Abdominal discomfort

- Jaundice.

Other symptoms include:

- Aching muscles and high temperature

- Mild to severe fatigue

- Loss of appetite and weight loss

- Depression or anxiety

- Poor memory or concentration

- Alcohol intolerance.

However, one in five never experience any symptoms and make a full recovery, while others develop chronic disease but stay seemingly healthy for many years without any outward signs or symptoms.

FACTORS AFFECTING TREATMENT SUCCESS
- Treatment side-effects

Typical side-effects include flu-like symptoms, headaches and anaemia. Most are dose-related, so dose reduction and occasionally discontinuation have shown to reverse most adverse effects. This can result in decreased levels of treatment and influence efficacy. Nursing strategies to maximise adherence play a large part in improving efficacy of treatment. Educating patients about expectations of treatment, particularly the likelihood of experiencing one or more adverse effects, together with advice about lifestyle in monthly follow-up visits in a supportive environment, all facilitate early detection of adverse events likely to impact on compliance.

- Weight-based dosing

Weight is a significant predictive factor for response during fixed-dose regimens. When both ribavirin and interferon were administered in a weight-based dose, as in Manns et al's study (2001), SVR was achieved in 61% of patients.

- The 12-week rule

A lack of virological response at week 12 provides an accurate indication of whether the patient will achieve an SVR with the full 48-week treatment. Patients who did not achieve an early virological response (EVR) did not become sustained responders in 100% of all cases (Davis et al, 2003). This 100% negative predictive value allows clinicians to predict where treatment will succeed, and it can act as an incentive to patients responding to treatment at week 12 to continue with their treatment regimen, aiding concordance.

DISCUSSION POINTS IN EARLY MANAGEMENT
- Stopping or reducing alcohol consumption, as this is the most likely predictor of disease progression

- Not donating blood or carrying an organ donor card

- Never sharing injecting equipment

- Using condoms to minimise the risk of sexual transmission, even though rare

- Never sharing razors or toothbrushes or any toiletry equipment that could have been contaminated with blood

- Details of tests and treatment where appropriate

- Suitability for treatment.

Cohen, J. (1999)The scientific challenge of hepatitis C. Science 285: 26-30.

Davis, G.L., Wong, J.B., McHutchison, J.G. et al. (2003)Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 38: 3, 645-652.

Department of Health. (2003)Communicable Disease and Blood: Hepatitis C - information for professionals. Available at: www.doh.gov.uk/ hepatitisc/briefing.htm

Donaldson, L. (2001)The Annual Report of the Chief Medical Officer. London: Department of Health.

Dusheiko, G., Barnes, E., Webster, G. et al. (2000)The science, economics and effectiveness of combination therapy for hepatitis C. Gut 47: 159-161.

Manns, M.P., McHutchison, J.G., Gordon, S.C. et al. (2001)Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358: 958-965.

NICE. (2003)Interferon Alpha (Pegylated and Non-pegylated) and Ribavirin in the Treatment of Chronic Hepatitis C (Appraisal consultation document). London: NICE. www.nice.org.uk/article.asp?a=82254

Shepherd, J., Waugh, N., Hewitson, P. (2000)Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review. Health Technology Assessment 4: 33

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