2 Clinical need and practice
2.1 Hepatitis C is an infectious disease of the liver caused by the hepatitis C virus (HCV). The virus is acquired primarily through percutaneous exposure to contaminated blood. People infected with HCV are often asymptomatic, but about 20% develop acute hepatitis. In approximately 80% of people who are infected, the virus is not cleared and they go on to develop chronic hepatitis C. Chronic hepatitis C is categorised as mild, moderate or severe depending on the extent of liver damage. The rate of progression from mild to severe disease is slow but variable, taking about 20 to 50 years from the time of infection. About 30% of infected people develop cirrhosis within 20 to 30 years, and some of these develop hepatocellular carcinoma. Some people with end-stage liver disease or hepatocellular carcinoma may require liver transplantation.
2.2 Estimates from the Health Protection Agency suggest that approximately 142,000 people between the ages of 15 and 59 years had chronic HCV infection in England and Wales in 2003, a prevalence of 0.44% in this age group. The prevalence of chronic HCV infection varies by sex and age, and it is most common in men and in people aged 25 to 44 years. In 2007, the number of confirmed new HCV infections in England and Wales was 7540.
2.3 Six genetic types of HCV, known as genotypes, have been found. Genotype 1 is the most common in the UK, accounting for about 40% to 50% of those infected with HCV. Genotypes 2 and 3 together contribute another 40% to 50%, while genotypes 4, 5 and 6 account for the remaining infections. In England and Wales, genotypes 1 and 3 represent more than 90% of all diagnosed HCV infections.
2.4 The primary aim of treatment is to clear the virus from the blood. Successful treatment is usually indicated by a sustained virological response, which is defined as undetectable serum HCV RNA 6 months after the end of treatment. A sustained virological response is considered to indicate permanent resolution of infection, although relapse may occur in approximately 5% of people after 5 years.
2.5 Previous NICE guidance (TA106 and TA75) recommends combination therapy with ribavirin and either peginterferon alfa-2a or peginterferon alfa-2b for adults with chronic hepatitis C. The previous guidance also recommends that monotherapy with peginterferon alfa-2a or peginterferon alfa-2b should be used only by people who are unable to tolerate ribavirin or for whom ribavirin is contraindicated. The recommended duration of treatment is 24 or 48 weeks depending on a combination of factors, including the HCV genotype, the viral load at the start of treatment and whether a person has a rapid virological response to treatment. For people with mild HCV infection, the person and their clinician should decide whether to treat immediately or adopt an approach of 'watchful waiting' (see TA106). The use of peginterferon alfa and ribavirin combination therapy is also considered suitable for people who are co-infected with HCV and HIV, unless it is contraindicated.
2.6 Approximately 75% to 85% of people with moderate or severe infection with HCV genotype 2 or 3 have a sustained virological response 6 months after finishing a course of treatment with peginterferon alfa plus ribavirin. The proportion of people with HCV genotype 1 who show a sustained virological response after the end of treatment is about 40% to 50%, while for the other genotypes (4, 5 and 6) the proportion is generally reported to be between 50% and 75%. Clinical advice indicates that a substantial proportion of people treated in specialist clinics in England and Wales have had previous treatment, but their condition has not responded or has relapsed.