Practice Therapeutics

Protease inhibitors for treatment of genotype 1 hepatitis C virus infection

BMJ 2011; 343 doi: (Published 10 November 2011) Cite this as: BMJ 2011;343:d6972
  1. Ian A Rowe, medical research council clinical research training fellow and honorary specialist registrar12,
  2. David J Mutimer, reader in hepatology and honorary consultant hepatologist12
  1. 1Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK
  2. 2Hepatitis C Virus Research Group, NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham
  1. Correspondence to: D J Mutimer david.mutimer{at}

Case scenario

A 35 year old man is referred for further investigation of abnormal liver function tests. As a teenager, he used intravenous drugs, and now he is found to have genotype 1 hepatitis C virus infection. He is keen to have antiviral treatment but has heard from friends that the results of treatment are disappointing and that the drugs have substantial side effects.

What are protease inhibitors?

Among people with hepatitis C infection, 70-80% develop chronic hepatitis, which can progress to cirrhosis and liver cancer. In some patients, the infection can be eradicated by treatment of finite duration. The protease inhibitors, telaprevir and boceprevir, are the first directly acting, hepatitis C virus specific antivirals to be licensed for the treatment of chronic hepatitis C virus infection. They are peptidomimetic inhibitors of the hepatitis C virus serine protease.1 This protease is essential for viral replication through cleavage of the viral polyprotein2 and is implicated in viral evasion of the host inflammatory response.3 Targeting the protease inhibits viral replication and may augment the host response to infection.4

How well do protease inhibitors work?

Hepatitis C virus exists as multiple species or genotypes, with variation in its protease gene and protein. The efficacy of the protease inhibitors varies according to hepatitis C virus genotype, and telaprevir and boceprevir are principally active against genotype 1.1 In early studies of short term monotherapy, both drugs showed substantial antiviral activity, but with early emergence of viral resistance.5 6 Subsequent studies therefore investigated the efficacy of the drugs in combination with the current standard of care (pegylated interferon and ribavirin) as triple therapy.

Hepatitis C virus infection can be cured by treatment of finite duration with antiviral therapy. Curative treatment is defined by a sustained virological response—that is, undetectable hepatitis C RNA in the plasma, maintained for at least six months after …

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