Science

Infectious HCV persists despite apparent sustained virological response

Last Updated: 2009-05-15 9:40:46 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Hepatitis C virus (HCV) persisting after a clinically apparent sustained virological response to antiviral therapy can retain infectivity in vitro, according to a report in the May issue of Hepatology.

"Given that the identification of low-level (occult) HCV infection was only made possible by employing research tests of a much greater sensitivity than that of those applied for clinical use, it is not surprising that low levels of HCV RNA are frequently escaping detection in clinical situations, giving conflicting results on the occurrence and infectivity of HCV persisting at trace levels," Dr. Tomasz I. Michalak told Reuters Health.

Dr. Michalak from Memorial University, St. John's, Newfoundland, Canada and colleagues used an cell culture system to assess the potential infectivity of HCV persisting at trace quantities for years in nine patients who achieved a sustained virological response after completion of interferon alpha therapy with or without ribavirin.

HCV RNA negative strands, indicative of active virus replication, were seen in 3 of 7 cell cultures from individuals with clinically apparent sustained virological response, the authors report. Estimated HCV loads ranged from 1000 to 50,000 virus genome equivalents per 10 million cells.

Virus infectivity could be neutralized by preincubation of HCV with anti-HCV E2 monoclonal antibody, but not with an isotype control, the researchers note.

Unique HCV variants were present in the peripheral blood mononuclear cells, the investigators say, and these same variants emerged in T cells exposed to the plasma.

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

"In general," Dr. Michalak said, "the existence of occult HCV infection should not be an unexpected situation, considering other infections with noncytopathic viruses which with a high frequency tend to establish chronicity and where the host's immune system plays a main role in limiting virus spread and in more or less successful resolution of virally induced inflammation."

Hepatology 2009;49:1431-1441.