To treat or not to treat – Dr. Marc van der Valk discusses treatment of HCV infection
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Dr. Marc van der Valk works as an internist-infectiologist at the department of Infectious Diseases and at the department of Hepatology of the Academic Medical Center (AMC), University of Amsterdam. At his outpatient clinic, he is responsible for the clinical care of a large cohort of individuals infected with viral hepatitis. Furthermore, he has extensive clinical and research experience in HIV care. He agreed to talk to us about his knowledge and experience in treating hepatitis C virus (HCV) infection. |
 Photo: Ben Balster |
Can you please describe the current treatment for HCV infection?
Current treatment is a combination of pegylated interferon alpha (peginterferon) and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on the HCV genotype. For HCV genotype 2 and 3, treatment is generally 24 weeks and for genotypes 1 and 4, treatment is generally for a period of 48 weeks.
What is the response to treatment?
That also varies depending on genotype. For HCV genotypes 2 and 3 the chance of success is around 80% whereas for genotypes 1 and 4 it is much lower at 40 to 50%. The amount of liver damage, that is fibrosis or cirrhosis, is also an important determinant for treatment success.
It’s important to note that even when the virus has been cleared, individuals can become re-infected with the same or another genotype of HCV. Unfortunately, the body doesn’t seem to develop protective immunity to the virus.
How do you decide if and when to start treatment?
I believe that dialogue with the patient is key. It is definitely a two way decision. Treatment with peginterferon and ribavirin leads to many unpleasant side effects and it is important that the patient is fully aware of these before deciding if or when to start treatment. As some new medications are shortly coming onto the market, I try to delay the start of treatment until these are available, depending on the amount of liver damage. If liver fibrosis is moderate to severe I usually recommend treatment. Fibrosis is usually measured by taking a liver biopsy, but now at the AMC we have a fibroscan. This machine can measure the amount of fibrosis without the need for a liver biopsy. It’s an easier, less invasive method that doesn’t cause any pain.
I’d just like to point out that a person can have HCV for years and be completely unaware of it, including what is happening to their liver. Liver damage may not show any symptoms. So I strongly recommend that anybody that was or still is at risk be tested for HCV. The majority of HCV infections occur through coming into contact with infected blood. This could be from experimental drug use back in the 1970’s when heroin was a popular drug, or may be from having a tattoo or blood transfusion. (Editor’s Note: The Netherlands first started screening blood stocks for HCV in 1991-1992, so people who received transfusions prior to 1992 may be at risk. Also, some countries still do not screen for HCV due to the cost.) Sharing razors or toothbrushes can also transmit HCV as these items could be contaminated with blood.
What are the side effects of peginterferon and ribavirin?
The most common side effects from taking peginterferon and ribavirin are flu-like symptoms such as fever, chills, muscle pain and headaches, psychological changes such as depression, irritability and anxiety, insomnia, anaemia, extreme tiredness, skin rashes, nausea and vomiting.
New medications are now becoming available such as direct acting agents (DAA’s) boceprevir and telaprevir. Could you explain how these new agents will be used to treat HCV?
I’m very happy that these new compounds are going to be available. They are a big step forward in treating HCV. Boceprevir and telaprevir are protease inhibitors (PIs), similar to medications used in treating HIV. PIs work on the virus to interrupt the life cycle of HCV, which is in contrast to peginterferon which boosts the hosts immune system helping to eliminate the virus. Boceprevir and/or telaprevir are used in combination with peginterferon and ribavirin, and they work specifically on HCV genotype 1. For this genotype they increase the chance of treatment success from 40 to 50% up to 70 to 80%, which is a huge improvement. They also decrease the treatment duration so that two thirds of patients can be treated for half a year instead of a full year. Unfortunately they don’t work for HCV genotype 4, which currently has low response rates to treatment, but there are some very promising compounds in development that will work on all genotypes if they become available. In fact, there is a huge pipeline of HCV medications in phase II or phase III clinical trials, and they should hopefully become available in four to five years time.
Whether patients have previously been treated unsuccessfully for HCV with peginterferon and ribivirine has an effect on treatment response to boceprevir and/or telaprevir . Those patients that had a poor response to previous treatment (a null-responder or partial responder) have a poorer response again to treatment with boceprevir and/or telaprevir. For patients in whom the virus relapsed after finishing previous treatment with peginterferon and ribavirine treatment success with these new compounds are very good.
Are there many side effects for boceprevir and telaprevir?
The most common side effect for telaprevir is a frequently seen skin rash. If this is aggressively treated by the physician this isn’t usually severe enough to stop treatment. For boceprevir, patients often experience a change in taste and usually have a metallic taste in their mouth when they eat.
One of the difficulties in taking these medications is that they must be taken three times a day, eight hours apart, with food. This kind of routine is difficult to maintain and I’ve found that adherence to taking the drug can be a problem. The key target for new medications in development is that they can be taken in one tablet, once a day and have little side effects. That would dramatically improve how HCV infection is treated.