Significance of Transient HCV Viral Load Blips during Interferon-based Therapy

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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, 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."