2012年英国蛋白酶抑制剂治疗基因1型慢性丙型肝炎的共识指南

Chronic hepatitis C infection (HCV) affects around 200 million people worldwide. It is estimated that up to 30% of these patients will develop cirrhosis and around 5% per year will develop decompensated liver disease or hepatocellular carcinoma. Furthermore, chronic HCV infection remains one of the principal indications for liver transplantation, with an increasing incidence in the Western world. Therefore, HCV infection already represents a major health burden, which is predicted to increase several fold in the next two decades. Currently, there are six HCV genotypes recognised with several subtypes identified. Genotype 1 infection (subtypes 1a and 1b) represents the commonest cause of chronic infection in the world.

The advent of dual therapy with pegylated interferon-a (IFN-a) and ribavirin resulted in a vast improvement in the treatment for chronic HCV infection. The current measure of successful therapy is to achieve a sustained virological response (SVR), defined as an undetectable serum HCV RNA level, 24 weeks after cessation of treatment. An SVR is typically associated with resolution of liver disease and improved quality of life in noncirrhotic patients, although cirrhotic patients may still be at risk of liver-related complications. The current standard of care (SoC) treatment for genotype 1 infected patients, with pegylated IFN-a and ribavirin for 48 weeks, is associated with an SVR rate of between 40% and 50% in most clinical trials. Although this is a significant advance over single-agent therapy, there remains a large number of patients who will not achieve an SVR. Furthermore, there have been very limi ted options for those patients who fail to clear the virus with initial dual therapy, retreatment with Peg IFN-a and ribavirin, giving overall SV R rates of only between 10% and 20% in published studies. Given the global scale of HCV infection, this remains a significant health problem, and novel therapies are required.

As the life cycle of the HCV virus has become known, novel therapeutic targets have been identified, enabling the development of directly acting anti-viral (DAA) drugs that are more specific than standard treatment regimes. The nonstructural 3 serine protease inhibitors (PIs), telaprevir (Incivo, Janssen-Cilag SpA, Borgo San Michele, Italy) and boceprevir (Victrelis, MSD, Hoddeston, UK), directly inhibit viral replication and may also restore the natural innate immune response of hepatocytes. 14 Large phase 3 trials of both these PIs in patients with chronic infection with genotype 1 HCV have shown highly significant increases in the proportion of patients who obtain an SVR. These drugs have been recognised as a major advance in the treatment of patients infected with genotype 1 hepatitis C virus, and therefore, have been approved for use by the FDA, EMA and Scottish Medicines Consortium (SMC).

These guidelines for the use of boceprevir and telaprevir have been formulated following extensive review of the current literature, are based on the consensus opinion of a panel of national experts, and have been openly discussed at a national meeting of HCV care providers. They aim to concisely summarise the current evidence and to suggest current best practice, for the use of telaprevir and boceprevir in the management of chronic genotype 1 HCV infection.