Clinical impact of serum transforming growth factor-alpha mRNA as a predictive biomarker for the prognosis of fulminant hepatitis.
OBJECTIVE
We previously reported that measuring serum telomerase reverse transcriptase (hTERT) mRNA with a quantitative, one-step, real-time RT-PCR was superior to conventional tumor markers for hepatocellular carcinoma and lung cancer. Here, we examined serum regeneration-related mRNA detection as a biomarker for fulminant hepatitis (FH).


METHODS
In 53 patients, including 17 patients with acute hepatitis (AH), seven with severe hepatitis (SH), four with late-onset hepatic failure (LOHF), and 25 with FH, we measured serum mRNA levels of hTERT, hepatocyte growth factor (HGF), hepatocyte growth factor receptor (c-met), epidermal growth factor receptor (EGFR), and transforming growth factor-alpha (TGF-alpha). We examined the sensitivity and specificity of the technique in FH diagnosis as well as its clinical and prognostic significance compared with other clinical and prognostic tests.


RESULTS
Serum copy number of TGF-alpha mRNA in FH on admission was significantly smaller than in AH and SH. In FH, TGF-alpha mRNA level was 10(6)-fold higher in survivors than in patients who died or received liver transplants (P = 0.034), although these patients were not discriminated by other clinical parameters. The sensitivity/specificity for prognosis in FH was 74.3/65.5% for TGF-alpha mRNA. Of four prognostic scoring systems, only logit-lambda was useful for prognosis assessment.


CONCLUSIONS
TGF-alpha mRNA is an early predictor of FH outcome and a sensitive biomarker of lower regenerative liver capacity. This assay could help facilitate early therapy choice, such as liver transplantation.
Miura
Norimasa
N
Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Nishicho 86, Yonago, Tottori, 683-8503, Japan, mnmiura@grape.med.tottori-u.ac.jp.
Kabashima
Hiroko
H
Shimizu
Mika
M
Sato
Reina
R
Tsukamoto
Tomoe
T
Harada
Tomomi
T
Takahashi
Shunsaku
S
Endo
Ryujin
R
Nakayama
Nobuaki
N
Takikawa
Yasuhiro
Y
Mochida
Satoshi
S
Suzuki
Kazuyuki
K
Hasegawa
Junichi
J
Shiota
Goshi
G