Tests for diagnosis and monitoring
 

David Bernstein MD: Genotype testing is probably one of the most important tests that can be obtained in evaluating and treating someone with chronic hepatitis C.

Robert Brown MD: The simplest definition of genotype is a subtype of hepatitis C. These are based on molecular variability in the actual sequence of the hepatitis C virus and probably represent the equivalent of subspecies in mammalian phylogeny.

David Bernstein MD: The virus in general is an approximately 10,000 base-pair virus. If there's a more than 30% difference in the base pairs, it's termed a different genotype. There are numerous hepatitis C genotypes or subtypes of hepatitis C. They are named by number; so the genotypes are 1, 2, 3, 4, 5 and 6.

The most common hepatitis C genotypes in North America and Europe are genotypes 1 and 2, with genotype 1 being far and away the most common. In the United States, this is the case with approximately 75% of the people who have the disease.

Robert Brown MD: Genotypes 2 and 3 are more common in Europe. Genotype 4 is the most common genotype in Egypt.

David Bernstein MD: Genotype 5 is very common in South Africa and genotype 6 is very common in areas of Southeast Asia. The determination of genotype is very important and also very easy to obtain. It's a blood test, done in similar fashion to a PCR assay. It requires a little bit more virus to be present to be able to obtain it.

Hepatitis C genotype really isn't used for monitoring. It's a test that's obtained once, and it doesn't change. It's used in treatment, because it helps you determine what treatments you're going to use, how long you're going to treat the person for and what the medications are. In addition, it helps the patient very much, because patients with genotype 2 are far more likely to have a response and it's very helpful for them to know that.

Rajender Reddy MD: Time and again, the patients come in and say that they have the "bad" genotype. And when I ask them the definition of a "bad" genotype, they say it's genotype 1. In essence, what they're trying to say is that they have the more difficult-to-treat genotype, but not necessarily a type that is associated with more severe liver disease.

David Bernstein MD: Genotype testing is probably one of the most important tests that can be obtained in evaluating and treating someone with chronic hepatitis C. There are numerous genotypes that we see; most commonly in the United States, genotype 1, which makes up approximately 75% of the population who have hepatitis C. Genotypes 2 and 3 make up 99% of the remainder, with scattered pockets throughout the country of genotypes 4, 5 and 6.

The importance of genotype testing is that it enables us to determine what therapy to use and, in some newer studies, for how long. What I mean by that is that in the studies that looked at standard three-times-a-week interferon-alpha-2b plus ribavirin - patients could be treated for a six-month period of time with ribavirin, either a gram or 1200 mg, and had an approximate 65% sustained response rate with six months of therapy. That short a course of therapy with such improved response rate, which is actually equivalent to that seen at 12 months, lead the European Union at the time to recommend treatment of genotypes 2 and 3 patients for six months only.

Since those studies have been done and those recommendations have been made, newer studies have been done with the newer pegylated interferons. In a study published by Michael Manns in the Lancet, the pegylated interferon alpha-2b plus ribavirin in the treatment of those patients with genotypes 2 and 3, found that those patients had about an 80 to 82% sustained viral response rate when treated for a full year.

In a study that was published by Hatziyannis in abstract form and currently being submitted in paper form, the genotype 2 and 3 responses were equivalent whether interferon was used with ribavirin for six months or twelve months. And in fact, the lower dose of ribavirin was used, 800 mg, in some of the arms. At the end of the day, the sustained response rates were 78% in those patients treated for six months with low doses of ribavirin and those were equivalent to those patients who were treated with a year of higher-dose ribavirin.

So I think what we've learned as far as genotypes 2 and 3 is they're the most sensitive genotypes. Genotype testing is the most cost-effective treatment, because if you're genotypes 2 or 3, you can only be treated for six months. That means the cost-saving is tremendous. Patients are happier, because it's easier to take these medications with lots of side-effects for a shorter period of time. And the overall sustained response rates - 80 to 85% - are much greater than you see with genotype 1.