Case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis C after liver retransplantation.
A recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) can lead to accelerated allograft injury and fibrosis. The aim of this article is to report the first ever use of daclatasvir (DCV; also known as BMS-790052), a potent orally administered nonstructural 5A replication complex inhibitor, in combination with peginterferon α (PEG-IFNα) and ribavirin in an LT recipient. A 49-year-old female developed a severe recurrent HCV genotype 1b infection 4 months after transplantation with severe cholestasis on biopsy, an HCV RNA level of 10,000,000 IU/mL, an alkaline phosphatase level of 1525 IU/mL, and a total bilirubin level of 8.4 mg/dL. Despite partial virological suppression with PEG-IFNα and ribavirin, progressive allograft failure ensued and culminated in retransplantation at 9 months. Three months after the second transplant, DCV (20 mg/day), PEG-IFNα2a (180 μg/week), and ribavirin (800 mg/day) were prescribed for early recurrent cholestatic HCV. Serum HCV RNA became undetectable at week 3 of treatment and remained undetectable during 24 weeks of triple therapy and during the posttreatment follow-up. DCV was well tolerated, and the trough drug levels were within the targeted range throughout the treatment. The cyclosporine trough levels were also stable during and after therapy. In conclusion, the lack of anticipated drug-drug interactions between DCV and calcineurin inhibitors and the potent antiviral efficacy of DCV make this agent (in combination with PEG-IFN and ribavirin) an attractive antiviral regimen worthy of further study in LT recipients with recurrent HCV.
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA. rfontana@med.umich.edu
Robert J
RJ
Fontana
Eric A
EA
Hughes
Henry
H
Appelman
Robert
R
Hindes
Dessislava
D
Dimitrova
Marc
M
Bifano
D000469:Alkaline Phosphatase / Q000097:blood; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002219:Carbamates; D002779:Cholestasis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use*; D017093:Liver Failure / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012086:Reoperation; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D002219:Carbamates; D007093:Imidazoles; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D011759:Pyrrolidines; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000469:Alkaline Phosphatase; D014633:Valine; C549273:daclatasvir; C100416:peginterferon alfa-2a; D001663:Bilirubin