Prolongation of interferon therapy for recurrent hepatitis C after living donor liver transplantation: analysis of predictive factors of sustained virological response, including amino acid sequence of the core and NS5A regions of hepatitis C virus.
OBJECTIVE
The aim of the present retrospective study was to evaluate the therapeutic efficacy and predictive factors of prolongation of treatment with peginterferon (PEGIFN) combined with ribavirin (RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT).


METHODS
Fifty-three patients underwent LDLT due to HCV-related end-stage liver disease. Sixteen patients were removed from the study as a result of early death (n=14), no recurrence of HCV (n=1) and refusal of antiviral therapy (n=1). Therapy is ongoing in another 10 patients. The remaining 27 patients were available to establish the efficacy of IFN therapy. HCV genotype was 1b in 24 patients. All patients with genotype 1b were treated with IFN therapy for at least 48 weeks after HCV RNA levels had become undetectable. Amino acid substitutions in the HCV core region and NS5A region were analyzed by direct sequencing before LDLT.


RESULTS
The rate of sustained virological response (SVR) was 37.0% (10/27). SVR rate in patients with genotype 1 was 29.2% (7/24) and 100% (3/3) in patients with genotype 2. Most patients with genotype 1b whose HCV RNA reached undetectable levels achieved SVR (87.5%; 7/8). However, mutation of the HCV core region and number of ISDR mutations were not associated with SVR rate in LDLT in our study.


CONCLUSIONS
Prolonged IFN therapy for more than 48 weeks after HCV RNA reached undetectable levels might prevent virological relapse of HCV.
Kawaoka
Tomokazu
T
Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Hiraga
Nobuhiko
N
Takahashi
Shoichi
S
Takaki
Shintaro
S
Mitsui
Fukiko
F
Tsuge
Masataka
M
Nagaoki
Yuko
Y
Kimura
Yuki
Y
Hashimoto
Yoshimasa
Y
Katamura
Yoshio
Y
Hiramatsu
Akira
A
Waki
Koji
K
Imamura
Michio
M
Kawakami
Yoshiiku
Y
Aikata
Hiroshi
H
Tashiro
Hirotaka
H
Ohdan
Hideki
H
Chayama
Kazuaki
K
D000595:Amino Acid Sequence / Q000187:drug effects; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b