infohep is no longer being updated. Visit for HIV and hepatitis news.

Persistence of very low levels of virus increase risk of relapse after hepatitis C therapy

Michael Carter
04 November 2011

The persistence of a low viral load during the first twelve weeks of hepatitis C therapy is associated with an increased risk of relapse after the completion of treatment, investigators report in the December 1st edition of Clinical Infectious Diseases.

Even with complete viral suppression, a high baseline viral load also increased the risk of relapse. The German study involved patients with hepatitis C mono-infection.

“Our study links the presence of minimal residual viremia to the risk of suffering a relapse,” comment the investigators.



An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.

Standard hepatitis C therapy consists of up to 48 weeks of treatment with pegylated interferon and a weight-based dose of ribavirin. The aim of this treatment is a cure, defined as an undetectable viral load six months after the completion of treatment (a sustained virological response).

Early responses to treatment – at weeks four, eight and twelve – are predictive of longer-term outcomes. These can also be affected by hepatitis C genotype and patient characteristics. For example, poorer response rates are seen in patients who are co-infected with HIV.

Investigators wished to see if the persistence of very low levels of virus during early therapy was associated with poorer treatment response rates.

They therefore analysed the outcomes of 255 patients with hepatitis C genotype-1 infection. All received standard therapy.

Levels of hepatitis C were measured by two different methods. The first was a branched DNA assay which had a lower limit of detection of 615 iu/ml. The second method was significantly more sensitive. Called a transcription-mediated amplification (TMA) assay, it was capable of detecting levels of virus as low as 5.3 iu/ml.

The investigators also wanted to determine the impact of baseline viral load on treatment outcomes. Therefore the patients were categorised according to whether their viral load was above or below 800,000 iu/ml. Presence of the IL28B gene has been associated with improved treatment responses, so patients were tested for its presence and analysis was conducted to see if it affected response rates.

Using the less sensitive branched DNA test, a response to treatment was seen in 34% of patients at week four, increasing to 76% at week twelve.

However, use of the more sensitive TMA assay revealed the presence of minimal levels of hepatitis C replication in 59% of these individuals at week four and 26% at week twelve.

The presence of very low levels of virus at week four was associated with a 21% risk of relapse, and a 55% risk at week twelve.

Much lower rates of relapse were observed in patients who had an undetectable hepatitis C viral load using the TMA assay (week four = 0%; week twelve = 9%).

Baseline viral load also affected the risk of relapse. There were no cases of relapse among patients with a viral load below 800,000 iu/ml at baseline an undetectable viral load in the first twelve weeks of therapy.

However, a higher viral load at the start of treatment was associated with higher rates of relapse, even if the TMA assay showed undetectable levels of virus (p < 0.005).

The presence of the IL28B gene did not affect treatment response rates in patients whose viral load was below the TMA assay limit of detection. In these patients, only a baseline viral load above 800,000 iu/ml affected outcomes (p = 0.016).

Two hepatitis C protease inhibitors have recently been approved, and several other drugs are currently in development. The investigators believe their results could help determine how these new drugs should be used, and call for “individualised treatment strategies.” These should include a consideration of “all available parameters such as baseline viral load, early viral kinetics, IL28B genotype, and histological staging.”

Moreover, “only highly sensitive HCV RNA assays should be used to adequately monitor viral kinetics and predict the risk of relapse.” To ensure that cases of late relapse are not missed, the investigators also recommend that the follow-up period should be extended beyond the current six months after the completion of treatment.


Wiegand J et al. Importance of minimal residual viremia for relapse prediction in patients with chronic hepatitis C genotype 1 infection. Clin Infect Dis, online edition: doi: 10.1093/cid/cir670, 2011 (click here for the free abstract).