Proof that HCV Sustained Virological Response (SVR) is a myth?


nih-imagebank-1481-150

Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor.

The HCV monster-machines are apparently craftier than we have been led to believe.  Even after IFN/R therapy, and non-reactive (not detectable) standard clinical testing, more sensitive tests prove that HCV RNA still resides in the human body in reservoirs.  The researchers of the small “first” study, Persistence of Hepatitis C Virus during and after Otherwise Clinically Successful Treatment of Chronic Hepatitis C with Standard Pegylated Interferon α-2b and Ribavirin  Therapy (published November 2013) are very confident in their experimental methods, results and conclusions. There is no waffling.  

The study is highly technical but I’ve pulled out some sentences, the gist of which, can be understood by this layperson (with footnotes removed). My remarks are in red.

New terms: occult HCV infection (OCI) which was discovered in 2004 but “rarely investigated.” peripheral blood mononuclear cells  (PBMC). Lymphoid cells

  1. HCV is infectious even in trace amounts, with approximately 10 virions or 20 copies of viral RNA capable of transmitting infection in chimpanzees and with 20 to 50 virions able to establish productive infection in human T cells in vitro. (How many zillions of virions can fit on the nozzle of a jet injection gun?)
  2. The long-term consequences of this essentially asymptomatic infection, termed as occult HCV infection (OCI), remains uncertain; however, OCI coincides with histologically evident protracted low grade liver inflammation and fibrosis in some patients for at least 10 years after completion of antiviral treatment. (My spouse was told he was completely cured.”)
  3. Also, clinically diagnosed sustained virological response (SVR) achieved due to IFN or PegIFN/R does not universally prevent progression to HCC, which develops in up to 3.9% of these individuals. (This is not a good number and how many primary doctors are even looking for HCC in SVR patients?)
  4. Contrary to prevailing opinion based on the currently available clinical testing for HCV RNA, clinical diagnosis of SVR does not reflect molecular eradication of HCV…(They drive this point home throughout the paper.)
  5. In addition to persistence of HCV in plasma during OCI, virus and its replicating genomes were uncovered in PBMC and liver biopsies in individuals for many years after having been considered to be clinically cured of hepatitis C. (Yes, they are still replicating..)
  6. …the accumulated data showed that HCV residing in immune cells fully retains biological competence, including infectivity…(No identity confusion in these monsters.)
  7.  …to fully recognize the sterilizing potency of new DAAs in the context of the extremely high mutagenic capacity of HCV and the virus’ resulting ability to generate drug resistant mutants, the DAA effects on virus replication at extrahepatic sites, particularly in immune cells, should be routinely assessed since these cells also are the site of virus active propagation.  (The expect some to relapse after DAAs who may then be offered INF/R.  Ugh.)
  8. These and other findings prove that immune cells, including T lymphocytes, are targets of naturally occurring virus, they are reservoirs of replicating HCV regardless of symptomatic or occult appearance of infection.  (Is this why HCV is linked to lymphomas?)
  9. Therefore, HCV is not completely cleared during ongoing administration of PegIFN/R otherwise capable of ceasing progression of CHC and virus commonly persists at levels not detectable by the current clinical testing. The findings suggest the need for continued evaluation even after patients achieve undetectable HCV RNA post-treatment. (The VA won’t test my spouse for HCV anymore…but they should.)

The authors are affiliated with the following institutions: Virology and Hepatology Research Group, Memorial University, Can. Center for the Study of Hepatitis C/Div. of Gastroenterology and Hepatology, Weill Cornell Medical College, New York City; Div. of Gastroenterology, Hepatology and Nutrition, Dept. of Medicine, SUNY-Buffalo.  The study has only been downloaded 212 times so far and cited only twice even though it has greatly added to the knowledge base on HCV.

A preview of the book, HCV Infection and Cryoglobulinemia by Franco Dammacco, is available in Google books.  It’s a good resource. Using the keywords, “occult HCV infection (OCI)” I was able to read a discussion about this issue. 

So the upshot for SVRers is to take care of your whole biological system as best you can. 

Editor’s note: To all of you who VA says are SVR, this is the smoking gun you need to rebut with. When they say you are pure as the driven snow, wave this one in their face. Take note Malcolm!

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8 Responses to Proof that HCV Sustained Virological Response (SVR) is a myth?

  1. SPrice says:

    I got an answer from Dr Robert Gish that says, “3 months and 12 months post treatment end date pcr “

  2. SPrice says:

    I asked 2 of the top hepatologists what they recommend as follow up for patients with cirrhosis who obtain SVR. So far I got one answer from Dr Diana Sylvestre, fromn the University of California, San Francisco. She said, “Cancer surveillance in the form of biannual AFP and imaging. MRI is best, CT next, ultrasound the least sensitive. If the AFP is normal and suspicion for HCC is low, then an ultrasound is fine. Otherwise I try to get one of the others. Also, annual upper endoscopy for varices, the follow-up frequency to be determined by what is seen. I also double check on the SVR six and twelve months after treatment completion, probably overkill.”

    • Kiedove says:

      Sylvia–This is an excellent SVR with cirrhosis/liver cancer surveillance check list. Thank you for doing this additional research and adding to the conversation. This check list can help this category make sure they are getting these cancer screenings biannually as practised by Dr. Sylvestre.. I don’t know if this is the protocol at the VA. Probably lightweight like Dr. Gish’s practice. (I prefer female physicians for my own care because I find that they are generally more thorough and picky about dotting all the i’s and crossing all the t’s!)

      I think the main thing that we’ll be seeing a lot more of in the months to come is information about HCC causing changes in other cells besides liver cells. So specialists besides hepatologists are beginning to ask questions about their patients problems who have a history of HCV infection. The studies of extrahepatic conditions are going to be of great interest to veterans.

  3. david j murphy says:

    At SP Price thanks for the info

  4. SPrice says:

    David…if it was replicating, it would keep growing in number and eventually it would make people relapse. But that’s not happening. Even people who got SVR then had to have a liver transplant and are on immunosuppressants don’t relapse. People who got SVR then developed some type of cancer and haver to take chemotherapy and their immune system is depressed also don’t relapse. SVR is durable, that is a fact.

    Kiedove, Notice that on the study you quoted it says “plasma was acquired before, during and up to 12–88 weeks post-treatment” So of course there’s going to be virus before and during treatment.

    There is now newer information. A paper called “Sporadic reappearance of minute amounts of Hepatitis C RNA after successful therapy stimulates cellular immune responses” gives data on 117 patients followed up to 20 years after clearing the virus (either on their own or with treatment)..
    Here’s the full text.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399733/

    The results showed that there was no reappearance of virus in the patients who had cleared the virus on their own. On patients who had cleared with treatment, 15 of 98 (15%) tested positive for virus in the plasma and 3 of 76 (4%) tested positive for virus in Peripheral Blood Mononuclear Cells (immune cells). But the reappearance of virus was sporadic, meaning it appeared and dissapeared and it happened only in the first 8 years after treatment and dissapeared after that.

    During the time the virus reappeared in small amounts, it was noted that the immune system became more active.

    Out of all 117, only 1 African American man had relapsed (his viral load was in the millions). He was clear at 6 months and 1 year then didn’t check the viral load until 6 years after treatment. So somewhere between 1 year and 6 years he had relapsed and had no symptoms.

    Bottom line….small amounts of virus appear sporadically for up to 8 years after treatment, but the immune system becomes more active during those times and prevents relapse.

    So the question then became….are those small amounts of virus infectious? Can they transmit the infection to others if they get exposed to your blood when the small amounts of virus are present? A brand new paper called, “Trace amounts of sporadically reappearing HCV RNA can cause infection” says yes, but it was done with monkeys and even though we may sometimes behave like monkeys, our immune systems are different. Here’s the full text…

    http://www.jci.org/articles/view/73104

    Clearly, quoting any of this to the VA is not going to get you the care you need. They wouldn’t understand it anyway. I think you should just keep it simple. Tell them that their own guidelines (which are based on AASLD guidelines) specify that anybody who has cirrhosis caused by hepatitis C needs follow-up ultrasounds to check for cancer.(also recommended for those with fatty liver and autoimmune hepatitis).

  5. hepper74 says:

    Good information and will store it on my computer. Still trying to reach the SVR point and can then explore this information further.

  6. WGM says:

    Good information Kiedove. Thank You for supplying more ammo for Vet’s to use when vA starts trying to deprive us of service connected ratings.

  7. david j murphy says:

    As yet we have no information about speed of viral replication after treatment, do we. Most excellent find for all the vets who are SVR and in battle with VA for bennies

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