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Polymorphism Associated With Good Antiviral Response But Also Depression in HCV

November 3, 2010 (San Antonio, Texas) — Researchers say they have identified a genetic polymorphism in the promoter region of interferon alpha/beta receptor 1 (IFNAR1), which increases the risk for major depression in patients with hepatitis C virus (HCV) being treated with pegylated interferon and ribavirin.

The study involved 170 treatment-naive patients with HCV infection who were genotyped for polymorphism –408 in the promoter regions of IFNAR1 (C/C C/T T/T) and treated with pegylated interferon and ribavirin. The results indicate that those carrying the C/C allele had a greater risk of developing major depression, but also had an increased likelihood of HCV viral clearance.

Previous research has shown that as much as 20% to 30% of hepatitis C patients receiving antiviral treatment experience major depression, which can result in dose reductions and a shorter duration of treatment. The need to identify patients at risk is therefore exceptionally pressing, according to the study's lead author, Muhamad Aly Rifai, MD, from the Lehigh Valley Health Network in Bethlehem, Pennsylvania.

"The identification of patients with this polymorphism may be useful in helping us determine who is at a greater risk of depression and tailor preventive treatment strategies to prevent discontinuation or adverse effects during their treatment," Dr. Rifai told attendees here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.

In addition to genotyping, patients were assessed using the Center for Epidemiological Studies Depression Scale. Patients completed visual analog self-report questionnaires before HCV antiviral treatment, and at weeks 0, 2, 4, 6, 8, 12, 16, 20, and 24 of treatment. Kaplan–Meier analyses were used to compare the incidence of major depression between different genetic profiles.

As is consistent with previous research, the results indicated that 28% of patients receiving the antiviral treatment developed major depression (47 of 170).

According to the Mantel–Cox rank test, the C/C allele was associated with an increased rate of developing major depression (P < .05) and an increased rate of HCV viral clearance (P = .0081).

Dr. Rifai noted that previous research has also suggested an improved HCV clearance rate with the C/C allele. "There have been multiple reports from Japanese researchers that this allele is associated with an improved likelihood of HCV viral clearance; however, the numbers were low."

The C/T and T/T alleles, meanwhile, appeared protective regarding the risk of developing major depression (P = .012).

The differences in the genetic groups were significant in a Cox regression analysis that was adjusted for age, sex, response to interferon alpha treatment, viral genotype, and previous psychiatric history (χ2, 8.02; df, 1; P = .005).

"The findings suggest that incorporating genomic predictors in a treatment strategy may help guide the process of determining whether or not to initiate antiviral treatment in patients with hepatitis C," Dr. Rifai said.

The risk of depression among hepatitis C patients using antiviral medications represents a substantial concern for physicians, and the findings could represent valuable information to help address that concern, said session moderator Paul Pockros, MD, head of the Division of Gastroenterology/Hepatology and director of the Scripps Clinic Liver Research Consortium at The Scripps Clinic in La Jolla, California.

"The presentation was provocative because treatment-related depression is extremely common and is probably the single biggest reason patients fear [pegylated interferon and ribavirin] therapy and are poorly adherent to treatment," said Dr. Pockros.

"If this test were validated, it would offer another genomic pretreatment test that would be useful, just as [interleukin] 28B testing, and likely ITPA deficiency testing, will be."

The study received no funding. Dr. Rifai has disclosed no relevant financial relationships. Dr. Pockros reports being a consultant, speaker, and/or on the advisory board for Genentech, Vertex, Merck, Gilead, BMS, Abbott, Phenomix, Tibotec, Pharmasset, Pfizer, Conatus, 3RT, Novartis, J&J, Achillion, and Regulus; and receiving grants or contracts from Genentech, Vertex, Gilead, BMS, Abbott, Quest, Conatus, Tibotec, Pfizer, Globeimmune, Debio, Novartis, and Mochida.

American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 32. Presented October 19, 2010.

http://www.medscape.com/viewarticle/731841?src=mp&spon=3&uac=39980BG
Best Answer
Avatar universal
It would be so helpful if doctors could know in advance which patients were most likely to develop treatment related depression.  IThat information could be a big factor in the decision to prescribe ADs with treatment or not.  

My doctor wanted me to start on ADs a few weeks before I started tx, "just in case."  I said "just in case what?"  He explained about the depression side effect but I didn't want to take them unnecessarily, and asked why not wait and see if I get depression or not.  We had a protracted argument about it but I was pretty adamant about not taking any more meds unless I was sure I needed them. ADs come with a whole lot of risks of their own and I really didn't want them.  I decided to wait and see.  I'm really glad I did because I did not have depression during treatment and it was one less drug for my poor liver to process.

Thanks for posting an interesting article.  Information is power and anything that gives me power over Hep C has to be a good thing.


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Avatar universal
Interesting,
They never offered my son AD's...., till say week four of
his first tx.  He denied them.  Fearing it would hurt his liver more.
He seemed OK...at that time.
Helpful - 0
476246 tn?1418870914
Interesting, Mike.  

I was sure that I would not get any depression.

But two weeks into treatment it hit me real bad. Fortunately I had been reading about it on this forum and called my hepatologist right away. She prescribed AD's and I staggered through the first week until they started working.
Helpful - 0
315996 tn?1429054229
I'm depressed just reading this stuff.
Helpful - 0
548668 tn?1394187222
I had a negative reaction to an AD mid-way through tx and ended up with the resident psychiatrist to see if I needed another brand.

He discussed the 4 major reactions to stress; (which I can't remember), and asked me my reactions to the different types of scenarios.   His diagnosis of my ability to copy was that I reacted 'in a manner of coping' in three out of the four areas, so, he said, I could probably manage without AD's but he gave me his number and said he'd be on standby if I needed anything.

I was so grateful to him, and wondered why this 'stress test' wasn't done to all pre-tx patients.   Suggest that if anyone's in doubt pre-tx, ask if you can see a psychiatrist to discuss.    There may not be SOC around anymore by the time there is funding to look at the biochemical predictors!!  (But really nice they're thinking about us).  Thanks Mike!!
Helpful - 0
Avatar universal
I am surprised that you read the article. I found it thought provoking even if it does seem to be a modest cohort.

Mr. Jones, the good news is you have a greater likelihood of clearing the virus. The bad news is you're also likely to suffer major depression. So, what do you say - do you wanna take a shot?

Mike
Helpful - 0
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