Successful HCV Treatment May Not Eliminate Risk of Transmission

Successful HCV Treatment May Not Eliminate Risk of Transmission

By Michael Smith, North American Correspondent, MedPage Today
Published: May 05, 2009

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit
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TORONTO, May 5 -- Even after successful treatment for hepatitis C, patients may have low levels of virus that could be infectious, Canadian researchers said.
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■Note that this study -- using highly sensitive research tests -- found that viral RNA remains in some successfully treated patients and can be infectious in vitro.
Highly sensitive research tests can detect traces of the virus in patients months and even years after the conventional tests used to assess recovery come up negative, according to Tomasz Michalak, M.D., Ph.D., of Memorial University in St. John's, Newfoundland, and colleagues.


Plasma or supernatants from cultured peripheral blood mononuclear cells from such patients can then infect lymphoid cells in vitro, Dr. Michalak and colleagues reported in the May issue of Hepatology.


The findings "can be interpreted as a strong indication of potential virus infectivity in vivo," the researchers argued.


The conventional definition of successful treatment for chronic hepatitis C -- the so-called "sustained virological response" -- is lack of evidence of viral RNA in the serum for at least six months after therapy is complete.


But the tests used for that measurement have a lower limit of detection of between about 52 and 1,000 "virus genome equivalents" per milliliter of serum, Dr. Michalak and colleagues said.


In contrast, the tests they used for this study can detect fewer than 10 such virus genome equivalents per milliliter.


The researchers looked at nine patients who had a sustained virological response for between 24 and 72 months based on a commercial test able to detect 1,000 virus genome equivalents.


But, the patients had occult virus detectable by the more sensitive test at levels between 40 and 400 virus genome equivalents, the researchers reported, although one patient had a markedly higher level.


Dr. Michalak and colleagues cultured lymphoid cells from healthy donors and exposed them to plasma or to supernatants from the patients.


The exposed cells were analyzed for positive and negative strands of viral RNA, where the positive strand simply indicates the presence of the virus and the negative strand is an indication of reactive replications.


Analysis showed that 11 of the 12 cell cultures showed evidence of the positive strand hepatitis C RNA, the researchers said.


The cultures also showed the negative strand hepatitis C RNA -- evidence of active viral replication -- in three cases, they found.


"These findings provide in vitro evidence that trace quantities of (hepatitis C virus) persisting in the circulation for a long time after therapeutically induced resolution of CHC (chronic hepatitis C) can remain infectious," the authors said.


Interestingly, replication could be prevented by treating plasma from a patient with a monoclonal antibody to hepatitis C, or by treating the recipient cells with interferon-alpha, Dr. Michalak and colleagues said.