John Bartlett's Game Changers in Infectious Disease: 2011

John G. Bartlett, MD


October 26, 2011

In This Article

Curing Hepatitis C

With a combination of a nucleoside and a polymerase inhibitor, Gane and colleagues[6] have shown a high rate of success in suppressing hepatitis C virus (HCV) to undetectable levels in 14 days without the need for peginterferon and ribavirin. Although based on limited sample size and long-term follow-up, these findings represent enormous progress in the field of hepatitis C treatment.

The standard treatment for the most common and difficult to treat form of HCV infection, genotype 1, has been peginterferon plus ribavirin. Cure was achieved in only 30%-40%, and toxicity was often severe, but this combination represented the state of the art for many years until telaprevir and boceprevir were approved by the FDA in May 2011.[7,8,9] These protease inhibitors substantially augmented the probability of achieving "sustained viral response" (indicating cure) when added to peginterferon plus ribavirin. The INFORM-1 trial suggests that we will be able to achieve this goal with greater success and far less toxicity within 1-2 years with the avalanche of these and other new drugs that are currently being tested.[7]

Why Is This a Game Changer?

Unlike antibacterials, drug development for HCV is exploding. At present, new drugs for HCV include 4 agents in phase 3 and 2 agents in phase 2 FDA testing. Although these new drugs are clearly "game changers" for patients with hepatitis C, their use is restricted to specialists as a result of the complexity of the regimens, toxicity, resistance issues, drug interactions, and cost.

In contrast to treatment of HIV or hepatitis B, the goal of hepatitis C treatment is a cure. With the 2 recently approved protease inhibitors, a cure is likely to be achieved in more than 70% of patients, and in almost all patients when the new drugs in the pipeline become available. Nevertheless, economics will be an issue because current costs of treatment are $50,000-$70,000/patient.

What Does This Mean to the Practitioner?

  • About 1% of people in the United States (approximately 3 million individuals) are infected with hepatitis C, and 70% of these people do not know they are infected. It will be important to screen patients with HCV antibody serology and evaluate those who are positive with liver function tests, genotyping, and HCV viral load, all tests that are readily available.

  • The decision for treatment depends on results of baseline tests and confounding issues such as substance abuse, mental health, and other comorbidities. These issues can be resolved at the primary care or specialty level.

  • Decisions about who to treat must take into account the stage of the patient's disease because it is likely that the newer drugs that are anticipated for 2012-2013 will more effective, less toxic, and possibly less expensive. The urgency of treatment typically depends on the liver fibrosis score, which predicts the consequences of a delay in treatment. It is probably wise to urge patients who can delay therapy for 1-2 years to wait.