Case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis C after liver retransplantation

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA.
Liver Transplantation (Impact Factor: 3.79). 09/2012; 18(9):1053-9. DOI: 10.1002/lt.23482
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Liver transplantation (LT) is an accepted mode of treatment for patients with chronic liver disease. Historically, patients with HIV were excluded from LT programs, but with the introduction of highly effective antiretroviral regimens, HIV is no longer a contraindication. LT outcomes for some liver diseases in HIV-positive patients are equivalent to those observed in non-HIV-positive patients. This is not the case for patients coinfected with HIV and HCV, however, where results at 5 years have led to suggestions that LT for coinfection should be abandoned. This article examines the role of LT for HIV/HCV and identifies groups of patients where transplantation is associated with good outcomes. We believe that the application of existing knowledge to patient selection and organ allocation could improve outcomes further, and with the advent of directly acting antivirals for HCV, LT for HIV/HCV coinfection will no longer be controversial.
    Future Virology 07/2013; 8(7):639-648. DOI:10.2217/fvl.13.51 · 1.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Complications of cirrhosis due to hepatitis C virus (HCV) are increasing and liver transplantation (LT) is the most effective treatment for those with liver decompensation or small hepatocellular carcinoma. However, for patients with human immunodeficiency virus (HIV) coinfection, barriers to LT exist. This is related to the poorer survival rates post LT (55% at 5 years) and, up until this year, the limited options for treating those coinfected LT recipients with progressive recurrent HCV disease, the commonest reason for reduced survival. The newly approved antiviral therapies, sofosbuvir and simeprevir, with significantly improved efficacy and markedly better safety and tolerability in HIV and transplant patients, offer the opportunity to transform the outcomes of HIV-HCV patients with liver complications. Additional new therapies, anticipated within the year, are expected to further simplify the management of coinfected patients in the transplant setting.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interferon-based treatments have a poor safety profile and limited efficacy in patients with advanced liver disease and in patients with hepatitis C (HCV) recurrence after liver transplantation (LT). Despite the recent approval of the first interferon-free regimen, which will be followed by several other interferon-free combinations in 2014 and 2015, data in patients with advanced cirrhosis and hepatitis C after LT are still limited. One study has already proven the concept that graft HCV infection can be prevented in a significant proportion of patients by treating them with sofosbuvir and ribavirin while awaiting LT. Two interferon-free regimens have also demonstrated a high efficacy in patients with hepatitis C recurrence after transplantation. Before these treatment strategies can be implemented in clinical practice, a few issues need to be addressed: (1) safety and efficacy of new antivirals in patients with decompensated cirrhosis, (2) the impact of viral clearance on liver function, (3) the potential consequences of virological failure (and the selection of multi-drug resistant HCV strains) in patients with decompensated cirrhosis or with severe hepatitis C recurrence after LT, and (4) drug-drug interactions (DDI) profiles. Finally, in the transplant setting it is also relevant to learn which strategy is most cost-effective in minimizing the negative impact of hepatitis C: preventing graft infection by treating patients before transplantation or treating hepatitis C recurrence after LT.
    Journal of Hepatology 11/2014; 61(1). DOI:10.1016/j.jhep.2014.07.020 · 10.40 Impact Factor

Full-text (2 Sources)

Available from
May 27, 2014