title: Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.
abstract: The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Ming V
authors.initials: MV
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Sise
authors.affiliation: Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Martha
authors.initials: M
authors.lastname: Pavlakis
authors.affiliation: Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Beth M
authors.initials: BM
authors.lastname: Amundsen
authors.affiliation: Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Donald
authors.initials: D
authors.lastname: Chute
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Rutherford
authors.affiliation: Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Hanifi
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Gabardi
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Anil
authors.initials: A
authors.lastname: Chandraker
authors.affiliation: Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.|Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Eliot C
authors.initials: EC
authors.lastname: Heher
authors.affiliation: Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Nahel
authors.initials: N
authors.lastname: Elias
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Leonardo V
authors.initials: LV
authors.lastname: Riella
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery; D016030:Kidney Transplantation; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069616:Simeprevir / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir