Eradication of hepatitis C virus genotype 1 after liver transplantation by interferon therapy before surgery: Report of three patients with analysis of interleukin-28 polymorphism, hepatitis C virus core region and interferon-sensitivity determining region.
The achievement of sustained viral response (SVR) with interferon (IFN) therapy before liver transplantation (LT) is difficult due to liver dysfunction, pancytopenia and frequent side-effects. Here, we report eradication of hepatitis C virus (HCV) genotype 1 after LT in three patients by IFN therapy before surgery. All three patients achieved virological response (VR), namely, fall in serum HCV RNA titer below the detection limit of real-time polymerase chain reaction (PCR) during IFN administration. However, HCV RNA rebound after cessation of treatment in all three patients; namely, they could not achieve SVR despite treatment with pegylated (PEG) IFN plus ribavirin. All three patients had wild-type amino acids (a.a.) at either aa70 or aa91 in the core region. Genotyping of IL-28 single nucleotide polymorphisms (rs8099917) showed TT genotype in two patients and TG genotype in one. All three patients developed multiple hepatocellular carcinomas during the clinical course, and requested living donor LT using liver grafts from their relatives. The patients were treated with IFN to immediately before LT, at which time they remained negative for HCV RNA in serum by real-time PCR. The three patients were followed-up for 14-15 months after LT, during which they remained negative for HCV RNA despite no further IFN therapy. In conclusion, it is possible to eradicate HCV after LT by inducing VR with continuous IFN therapy to before LT in spite of viral and host evidences reflecting low susceptibility to IFN treatment.
Department of Medicine and Molecular Science, Division of Frontier Medical Science             Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University             Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan.
Tomokazu
T
Kawaoka
Hiroshi
H
Aikata
Daisuke
D
Miyaki
Eisuke
E
Murakami
Takahiro
T
Azakami
Shintaro
S
Takaki
Yuko
Y
Nagaoki
Yoshimasa
Y
Hashimoto
Yoshio
Y
Katamura
Akira
A
Hiramatsu
Koji
K
Waki
Nobuhiko
N
Hiraga
Daiki
D
Miki
Masataka
M
Tsuge
Michio
M
Imamura
Yoshiiku
Y
Kawakami
Shoichi
S
Takahashi
Hidenori
H
Ochi
Hirotaka
H
Tashiro
Hideki
H
Ohdan
Kazuaki
K
Chayama