In 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.
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
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.
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
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
Labels: Genotype, predictors of response, Subtype