Predictors of DAA Treatment Failure

There are many questions that come to mind when preparing to start hepatitis C treatment. A common concern is whether the drug will work. Scientists have determined predictors of direct-acting antivirals (DAA) therapy success.  While going through the list below, it is important to keep in mind that DAA success rates are generally high: over 90% of people achieve sustained virologic response (SVR). SVR is the measure of treatment success.

HCV genotype and subtype

HCV genotype is the most important factor in DAA selection. Some DAAs are genotype-specific and have poor activity against other genotypes. Nowadays, there are more pan-genotypic regimens available, meaning that they work against all genotypes.

Genotype 3 is the most significant predictor of a poor treatment response, especially if prior treatment failure and cirrhosis are also present. Out of the two genotype 1 subtypes, subtype 1a is typically more difficult to treat than 1b. However, this should not be considered in isolation. Unless other negative predictors exist, high SVR rates can be achieved in all genotypes when the right drug and regimen are used.

Prior treatment failure

Failure of interferon-based therapy alone does not indicate poor outcomes to DAA therapy. The type of prior treatment makes a difference on future therapy outcomes. Examples of treatments that are poor predictors of future DAA therapy success include: peginterferon plus ribavirin or peginterferon plus ribavirin plus DAA.

Compensated cirrhosis

SVR rates in compensated cirrhosis are comparable to people without cirrhosis. Genotype 3 is the exception. Cirrhosis is the main feature associated with a poorer response in Genotype 3. It’s unclear why this occurs; it could be linked to the breakdown and delivery of the drug.

Decompensated cirrhosis

Decompensated cirrhosis describes the complications of late-stage liver disease, such as ascites, hepatic encephalopathy, and gastroesophageal variceal hemorrhage. People with decompensated cirrhosis have a poorer response to HCV therapy compared to those with compensated cirrhosis.

Baseline HCV RNA level

The baseline HCV RNA level has little overall impact on treatment response with DAA therapy.

Overall, DAAs are extremely potent and often result in high SVRs. One negative predictor alone has limited impact on treatment outcomes. However, the combination of negative predictors, for example, decompensated cirrhosis and previous treatment failure, has more bearing.

A study conducted in 2014 assessed the effect of multiple negative predictors on SVR rates. 800 people with various genotypes were recruited for the study. Some negative predictors identified are prior unsuccessful treatment, cirrhosis, male gender, weight above 75 kg, and HCV RNA level above 800,000 IU/mL. The study highlighted that DAA SVR rates does not dip below 90% until 4 negative predictors were present!¹ If you are concerned about failing treatment, speak to your physician. With the right drug and regimen, SVR can be achieved for most people.