IFNL4 Genotype for Predicting Response to Ledipasvir/Sofosbuvir
IFNL4 Genotype for Predicting Response to Ledipasvir/Sofosbuvir
Background:

 Hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma and
 end-stage liver disease. Ledipasvir/sofosbuvir is used to treat chronic HCV. The drug name
 for it is Harvoni. It is a very effective treatment, but it is expensive. Researchers have
 found a genetic variation that predicts how people will respond to this treatment. They want
 to learn more about this genetic link. It could help develop better treatments for HCV.

 Objective:

 To study if certain inherited genetic differences and other factors affect the different ways
 patients respond to treatment with Harvoni.

 Eligibility:

 Adults ages 18 who are members of the Kaiser Health Plan and have recently been treated for
 hepatitis C with Harvoni

 Design:

 Researchers will review medical records to identify a group of people who could be in the
 study.

 Participants will provide a saliva sample at home. They will get instructions and kit to
 collect it in.

 Participants will spit into a funnel until it reaches a mark on the funnel. It will be about
 1 teaspoon of saliva with no bubbles.

 They will return the sample in a prepaid mailer.

 Researchers will do genetic tests on the samples. The participant data will be kept
 confidential. It will not be given to insurance companies.

 Participants will not be given any test results.

 ...
Hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC) and
 end stage liver disease - successful treatment markedly reduces those risks.
 Ledipasvir/sofosbuvir is a highly effective, but expensive, treatment for chronic hepatitis
 C. Previously, we demonstrated that genetic variation in IFNL4 predicts response to this
 regimen. We now propose to examine the association between genotype for the functional
 IFNL4-DeltaG/TT polymorphism and treatment response among patients enrolled in a large
 managed care organization. In a two-stage design, limited demographic and clinical data for
 patients who have been treated with ledipasvir/sofosbuvir will be ascertained from an
 electronic database. In the second stage, additional demographic and clinical data will be
 extracted from medical records and consented patients will provide a specimen for IFNL4
 genotyping. These data will be combined to examine associations of IFNL4-DeltaG/TT genotype
 and other variables with response to ledipasvir/sofosbuvir. We will also develop a clinical
 prediction model for response to ledipasvir/sofosbuvir treatment. These results could inform
 more efficient treatment of HCV in the United States and globally.
-  INCLUSION CRITERIA:

 Subject Inclusion Criteria:

 -  At least 18 years of age

 -  Chronic HCV VGT-1 infection

 -  Completed treatment with ledipasvir/sofosbuvir (with or without ribavirin) for either
 8, 12 or 24 weeks at a participating KP-NC clinical site

 -  Data available to determine virological relapse and SVR12

 EXCLUSION CRITERIA:

 Subject Exclusion Criteria:

 -  Otherwise eligible subjects who have left KPNC will not be included in the study

 -  Otherwise eligible subjects who cannot provide informed consent in English will not be
 included in the study