Alan FranciscusIn the past, there were many factors that predicted successful treatment outcome.  Today, that list is much longer and is somewhat dependent on the particular HCV inhibitor used to treat hepatitis C.

This article is about the negative predictors of treatment response—genotype, subtype, cirrhosis, prior treatment response and viral load.

Genotype
The most dramatic current negative predictor of treatment response is genotype 3.  The current standard of care for treating HCV genotype 3, a combination of sofosbuvir (Sovaldi) plus ribavirin for 24 weeks, has an overall cure rate of 93%. Among those in the group who had never been treated (treatment naïve), the cure rate was 93% for those without cirrhosis compared to 92% for those with cirrhosis. Among treatment experienced patients in this test group, the cure rate was 85% for those without cirrhosis compared to only 60% for those with cirrhosis.   Future treatments are needed for people with genotype 3 that have higher cure rates with shorter treatment durations, and which work in cirrhotic patients who have not responded to prior treat­ment.  

Subtype
Subtype has long been known to affect treatment outcome.  In regards to genotype 1, subtype 1a is generally harder to treat.  If we look at VIEKIRA PAK to treat HCV genotype 1a without cirrhosis, adding ribavirin is indicated.  There is no recommendation to add ribavirin to VIEKIRA PAK for treatment of genotype 1b without cirrhosis. 

Cirrhosis
People with cirrhosis have always been harder to cure than those without it, although now it is not as difficult as in the past. The recommended treatment duration for genotype 1a patients with cirrhosis is 24 weeks with VIEKIRA PAK plus ribavirin.  There is a note that 12 weeks can be considered for some patients based on prior treatment history.

Treatment-Experienced
Patients without cirrhosis can be treated with HARVONI for 12 weeks. Treatment experienced (but not cured) patients with cirrhosis can be harder to cure, so 24 weeks treatment with HAR­VONI is recommended.  

HCV RNA or Viral Load
In the Full Prescribing Information for HARVONI for genotype 1, there is a footnote about the recommended treatment duration saying that “HARVONI for 8 weeks can be considered in treatment-naïve patients without cirrhosis who have pre-treatment HCV RNA less than 6 million IU/mL.”  This consideration is based on the ION-3 study of 123 patients with baseline viral loads under 6 million IU/mL who were treated for eight weeks.  The cure rates were 97% (119 of 123 patients).   This is only true with HARVONI.  The viral load thresholds need to be studied in all of the newer therapies.Even now, matching a person’s characteristics to the specifics of the HCV drugs can help cure most people.  The future of hepatitis C treatment holds the promise that, when matched with all of a patient’s characteristics, new medicines or combinations of medications will be able to treat and cure everyone with HCV.

This article is reprinted from the February 2015 HCV Advocate. Copyright 2015 with permission from the HCV Advocate and Alan Franciscus.