Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Nishicho 86, Yonago, Tottori, 683-8503, Japan,
Hepatol Int. 2008 Jun;2(2):213-21. doi: 10.1007/s12072-008-9053-6. Epub 2008 Apr 9.
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).
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.
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.
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.
我们之前报道过,使用定量、一步、实时 RT-PCR 测量血清端粒酶逆转录酶 (hTERT) mRNA 对于肝癌和肺癌比传统肿瘤标志物更具优势。在这里,我们研究了血清再生相关 mRNA 检测作为暴发性肝炎 (FH) 的生物标志物。
在 53 例患者中,包括 17 例急性肝炎 (AH)、7 例重型肝炎 (SH)、4 例迟发性肝衰竭 (LOHF) 和 25 例 FH,我们测量了 hTERT、肝细胞生长因子 (HGF)、肝细胞生长因子受体 (c-met)、表皮生长因子受体 (EGFR) 和转化生长因子-α (TGF-α) 的血清 mRNA 水平。我们检查了该技术在 FH 诊断中的灵敏度和特异性,以及与其他临床和预后测试相比的临床和预后意义。
FH 患者入院时血清 TGF-α mRNA 的拷贝数明显低于 AH 和 SH。在 FH 中,存活者的 TGF-α mRNA 水平比死亡或接受肝移植的患者高 10 倍(P = 0.034),尽管这些患者不能通过其他临床参数区分。TGF-α mRNA 对 FH 预后的灵敏度/特异性为 74.3%/65.5%。在四个预后评分系统中,只有对数似然比对于预后评估有用。
TGF-α mRNA 是 FH 预后的早期预测指标,也是再生肝脏能力较低的敏感生物标志物。该检测方法有助于促进早期治疗选择,例如肝移植。