Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 after liver transplant.
Treatment with an all-oral interferon-free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non-liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3-F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV-based regimens) received treatment and were followed for a median of 30 weeks (range 12-53 weeks). The median time from LT to treatment was 32 months (range 2-317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%-96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3-F4 (71%) compared to those with F0-F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug-induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention.


CONCLUSIONS
An all-oral interferon-free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection.
Department of Transplantation, Mayo Clinic, Jacksonville, FL.|Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL.
Surakit
S
Pungpapong
Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.
Bashar
B
Aqel
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Michael
M
Leise
Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.
K Tuesday
KT
Werner
Department of Transplantation, Mayo Clinic, Jacksonville, FL.
Jennifer L
JL
Murphy
Department of Transplantation, Mayo Clinic, Jacksonville, FL.
Tanisha M
TM
Henry
Department of Transplantation, Mayo Clinic, Jacksonville, FL.
Kristen
K
Ryland
Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.
Amy E
AE
Chervenak
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Kymberly D
KD
Watt
Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.
Hugo E
HE
Vargas
Department of Transplantation, Mayo Clinic, Jacksonville, FL.|Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL.
Andrew P
AP
Keaveny
D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D007165:Immunosuppression Therapy; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir; D000069474:Sofosbuvir; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000627:therapeutic use
D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D013449:Sulfonamides; D012254:Ribavirin; D000069616:Simeprevir; D014542:Uridine Monophosphate; D000069474:Sofosbuvir