Aa
A
A
A
Close
Hepatitis C Community
13.4k Members
Avatar universal

New tests help pinpoint who will SVR before tx.

As I mentioned in a previous post concerning mortality and HCV tests such as the one below can determine with good accuracy who is likely to proceed to cirrhosis. There are other studies on this topic,using different means to accomplish the same goal, especially with G1. These types of diagnostic tests could greatly influence who should or shouldn't pursue treatment at this time. Elimination of the scattershot approach used now for treating to a more targeted one would have profound effects on many aspects of treatment . Most importantly it would result in fewer patients exposed needlessly to IFN/Riba. Anyone who has ever been on tx , or just read about it, can see the great benefit this can have for those with HCV. As an example if we can identify through genetic markers before tx those who could benefit from a longer course it would eliminate the risk and suffering which is inherent in any re-treatment scenario.  -- ML

Science News Share    Blog    Cite Print    Email    BookmarkHepatitis C Patients Who Are At High Risk Of Developing Cirrhosis Can Now Be Reliably Identified
ScienceDaily (Apr. 30, 2007) — A researcher at the Stanford University School of Medicine has helped confirm the reliability of a new test for liver disease that is ushering in the long-promised era of personalized medicine based on each individual's genetic makeup.

The Stanford group was one of the five sites that helped determine that the genetic test can identify patients who are at high risk of developing cirrhosis from chronic hepatitis C infection. That means high-risk patients could be directed toward a long course of expensive, debilitating drug therapy, while low-risk patients might be better off delaying treatment.

"Management of cirrhosis patients is challenging," said Ramsey Cheung, MD, associate professor of medicine at the school and chief of hepatology at the Palo Alto Veterans Affairs Health Care System, who led the Stanford arm of the study. "This test is the first of its kind to use the genetic makeup of each patient to determine who is likely to develop cirrhosis. High-risk patients should be targeted for early treatment."

The test looks at variations of seven genes, and was developed by Celera, headquartered in Rockville, Md. Cheung is the senior author of the study, which will be published in the journal Hepatology. Cheung is a paid consultant for Celera, which also funded the study.

"Current therapy for hepatitis C unfortunately is very expensive, has multiple side effects and a suboptimal response rate for most patients," said Cheung. Treatment includes weekly injections of alpha interferon along with the drug ribavirin, which can cost more than $30,000 per year and can cause flu-like symptoms, nausea, depression and other side effects. And only half of patients undergoing this therapy will be cured of the infection.

Nearly 4 million Americans are infected with the hepatitis C virus, of which nearly 80 percent have a chronic infection, according to the American Liver Foundation. Chronic infection can lead to the severe scarring known as cirrhosis, which in turn may result in liver cancer or liver failure. Hepatitis C infection is the most common reason people need a liver transplant in the United States and is responsible for between 8,000 and 10,000 U.S. deaths annually.

But in the majority of people chronically infected with hepatitis C, the virus causes either no symptoms or vague, nonspecific ones. In around one-third of people chronically infected with the virus, the disease progression is slow and they may never develop cirrhosis, even after decades of infection.

The dilemma physicians face, explained Cheung, is deciding who to treat and who can wait for better therapies to come along. The key is being able to determine which patients are likely to see the infection progress to cirrhosis. Doctors consider such factors as age, gender and alcohol consumption to predict such risk, but because of individual variability, these factors don't yield a very accurate prediction. A liver biopsy can indicate the amount of damage to the liver up until the time of the biopsy, but can't reveal how much future damage will occur. The new test assessed by Cheung and his colleagues is a way to hedge the bets.

The lead author of the paper is Hongjin Huang, PhD, associate director of liver diseases at Celera in Alameda, Calif. Huang and her Celera colleagues developed the test by initially scanning the DNA of more than 1,000 people who had hepatitis C. Out of 25,000 genetic variations tested, the researchers discovered seven that could be used together as a "signature" for predicting progression to cirrhosis in Caucasians.

The resulting gene signature - the Cirrhosis Risk Score - was then independently validated on 154 hepatitis C patients at Stanford, the University of Illinois-Chicago and California Pacific Medical Center. Among patients with early-stage liver disease, the researchers were able to divide them into a high-risk category based on their gene pattern, compared with those who had low-risk gene patterns. "The Cirrhosis Risk Score was superior to the known clinical factors, such as alcohol consumption, in predicting the risk of developing cirrhosis," said Cheung.

"This test allows both physicians and patients to make an intelligent decision about the urgency of beginning antiviral therapy," he said. "If a patient turns out to be low-risk, we might advise the patient to consider deferring treatment, avoiding unnecessary side effects and expense of current therapy."

Last June, Celera licensed Specialty Laboratories of Valencia, Calif., to perform the genetic test. The test currently costs about $500.

In addition to Cheung and Huang, the other 12 authors of the study are from Celera, Virginia Commonwealth University, Mount Sinai School of Medicine, California Pacific Medical Center, the University of Illinois-Chicago and the University of California-San Francisco.
12 Responses
Avatar universal
Among patients with early-stage liver disease, the researchers were able to divide them into a high-risk category based on their gene pattern, compared with those who had low-risk gene patterns. "The Cirrhosis Risk Score was superior to the known clinical factors, such as alcohol consumption, in predicting the risk of developing cirrhosis," said Cheung.

"This test allows both physicians and patients to make an intelligent decision about the urgency of beginning antiviral therapy," he said. "If a patient turns out to be low-risk, we might advise the patient to consider deferring treatment, avoiding unnecessary side effects and expense of current therapy."
______________________________________________________________________

On the other hand what about those that are high risk even with early stage liver disease?  What does that say about the "watch and wait" approach?  I'm not a proponet of watch and wait even if the damage is staged at 2.  To tell someone to wait until their damage advances past stage 2 is ludicuious to me with or without and cirrhosis marker test.
Avatar universal
My spell check is wacked so here is proponent and ludicrous spelled correctly.

And just to clarify, I'm not saying those with stage 2 should not wait for the PI's if indeed they arrive in 2011.   I'm saying once the best available treatment is on the market and the odds for SVR have increased significantly, watchful waiting at stage 2 or even stage 1 with a genetic marker for cirrhosis does not make any sense to me.
Avatar universal
Ditto, from me... Susan400
96938 tn?1189803458
I don't get the title of this thread as "New tests help pinpoint who will SVR before tx". It should be  "Celera Needs Money, Comes Up With Cirrhosis Guessing Tool".

Based on what I'm reading and to the extent that I understand, I don't see how the test can be validated.  It seems that they looks at the 7 genes to arrive at a signature.  I don't see where they have completed multi-year follow-up to see if the gene guessing is correct.  Even if they did follow speed of progression all the way to cirrrhosis how would they know the point of infection when most patients don't know.

I don't know about this one. I admit that I don't get the whole concept of genes or even planet formation.
Avatar universal
I don't have enough info to comment on the Celera product, but here's another tack on genetic analysis.
Vertex have sequenced the HCV RNA for every subject in each of their Telaprevir trials. Now, several years after the first trials, they know which subjects achieved SVR and which did not and can now attempt to isolate genetic markers that characterize those that failed treatment. I can't comment on their progress with this analysis, but if it turns out that there are unique genetic markers that predict successful tx, surely that would be a major therapeutic advance. The only caveat is that [initially at least] such markers may only be reliable for the tx protocol of the trials - PI + SOC for n weeks.

Its really hard to see how anyone could even approach this problem without an extensive library of genetic samples from a large cohort of subjects both pre and post tx.
Avatar universal
I think it is a sound idea.  I just wish that they had done it 10 years earlier.  Part of my issue with it is that for many people this may be arriving too late.  They have already treated when they could have waited.  Conversely, I'm of the opinion that this is going to become a very curable disease in 5 years; perhaps not 100% mind you but many people will be cured or curable.  The issue may be whether some can wait further for prices to come down more, or whether they could wait even longer for shorter and shorter (or less toxic, problematic) forms of TX.  It has been pointed out that the drugs are coming, but it remains unknown what they will cost, who will get them, etc.

What is also unknown is about what will happen with all these various drugs in development when they get approved.  My feeling is that the price will come down, even for what seems like a good treatment for us now; triple therapy w/ a PI.  When STAT C drugs get approved in 4 -5 years this will virtually become discarded treatment.

My point remains though, that I don't think that many of us will have to decide whether to wait a lifetime to treat.  

My question is how accurate will these tests be?

My presumption is that they are to be used at predicting the efficacy of current SOC on patients based on genetics.  Isn't that about to be changed, perhaps discarded with the addition of PI's to the mix?

When STAT-C combination PI's are used in the future there may still be a profile of people more/less likely to succeed but in general, the drugs will tend to work on more people, perhaps everyone, since they stop viral replication.  Further, since there may be few sides there may not be an issue of broadcasting.....giving the drugs combo to anybody.  
There may not be a need for such a test in 5 years if one were to assume that the cost of TX were to be accessible- a big IF perhaps.

Willy
Have an Answer?
Top Hepatitis Answerers
317787 tn?1473362051
DC
683231 tn?1467326617
Auburn, WA
Learn About Top Answerers
Didn't find the answer you were looking for?
Ask a question
Answer a few simple questions about your Hep C treatment journey.

Those who qualify may receive up to $100 for their time.
Explore More In Our Hep C Learning Center
image description
Learn about this treatable virus.
image description
Getting tested for this viral infection.
image description
3 key steps to getting on treatment.
image description
4 steps to getting on therapy.
image description
What you need to know about Hep C drugs.
image description
How the drugs might affect you.
image description
These tips may up your chances of a cure.
Popular Resources
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Here’s how your baby’s growing in your body each week.
These common ADD/ADHD myths could already be hurting your child
This article will tell you more about strength training at home, giving you some options that require little to no equipment.
In You Can Prevent a Stroke, Dr. Joshua Yamamoto and Dr. Kristin Thomas help us understand what we can do to prevent a stroke.
Smoking substitute may not provide such a healthy swap, after all.