Significance
of Transient HCV Viral Load "Blips" during Interferon-based Therapy for Chronic
Hepatitis C By
Liz Highleyman  Response
to treatment for chronic hepatitis
C virus (HCV) infection is measured in terms of reduction in HCV RNA level,
or viral load. End-of-treatment response (ETR) is defined as undetectable HCV
RNA at the completion of therapy (24 or 48 weeks, depending on HCV genotype).
Sustained virological response (SVR) - typically considered a "cure"
- is continued undetectable viral load 24 weeks after completion of treatment.
In
clinical practice, virological response is usually assessed using a polymerase
chain reaction (PCR) assay. But a newer, more sensitive test -- known as transcription-mediated
amplification (TMA) -- can measure HCV RNA down to 5 IU/mL. Thus, some individuals
may be TMA positive despite being PCR negative for HCV RNA. Some
patients experience persistent virological breakthrough while on therapy or relapse
after completing treatment, which are both considered as treatment failure. However,
the significant of transient episodes of detectable HCV RNA - or "blips"
- on the TMA test while patients are PCR negative is unknown. As
reported at the Digestive Disease Week (DDW) 2008 conference
last week in San Diego, Christopher DiGiorno and colleagues retrospectively reviewed
the records of chronic hepatitis C patients (both treatment-naive and treatment-experienced)
who received therapy at their center between March 2002 (when the TMA test became
available) and July 2007. A
TMA "blip" was defined as a PCR negative/TMA positive result in a patient
with both a prior and a subsequent PCR negative/TMA negative result. Results
•
Of
412 included patients, 25 (6%) experienced a TMA blip.
•
Of
the 25 individuals with TMA blips:
•
10 (40%) achieved ETR but then relapsed;
•
9 (36%) achieved SVR;
•
o
4 (16%) were still undergoing follow-up at the time of abstract submission;
•
1 (4%) experienced subsequent PCR viral breakthrough;
•
1 (4%) was lost to follow-up.
•
2
of the 25 individuals experienced 2 separate blip episodes; both achieved ETR
but subsequently relapsed.
•
9
relapsers and 5 SVR patients with blips had HCV genotype 1, while 1 relapser and
4 SVR patients had genotypes 2 or 3.
•
Among
patients with blips, those who experienced relapse and those who achieved SVR
did not differ significantly with respect to time between start of therapy and
blips (41 vs 43 weeks).
•
Alanine
aminotransferase (ALT) levels at the time of blips were also similar in the relapsers
and SVR group (45 vs 32 IU).
•
The
interval from the first TMA negative result to the blip was shorter in relapsers
compared with SVR patients (15 vs 29 weeks).
•
Patients
with blips had a higher relapse rate than those with ETR and no blips for all
genotypes considered together (53% vs 21%; P=0.012) and for those with genotype
1 (64% vs 33%; P=0.016).
Conclusion "TMA
blips indicate an increased frequency of relapse," the researchers concluded.
"For blip [positive] patients, genotype 1 and shorter interval from first
TMA to blip is associated with relapse." They
added that, "Our data does not suggest that increasing duration of therapy
post-blip prevents relapse, but further study is needed." 5/23/08 Reference
C
DiGiorno, K Deng, A. Casellas, and others. The "TMA blip": clinical
significance of transient positivity of hepatitis C virus (HCV) transcription-mediated
amplification (TMA) during periods of polymerase chain reaction (PCR) negativity
on anti-viral therapy. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22,
2008. Abstract S1015.
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