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
- 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?)
- 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.”)
- 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?)
- 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.)
- 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..)
- …the accumulated data showed that HCV residing in immune cells fully retains biological competence, including infectivity…(No identity confusion in these monsters.)
- …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.)
- 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?)
- 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!