Fang J W, Bird G L, Nakamura T, Davis G L, Lau J Y
Department of Medicine, University of Florida, Gainesville 32610.
Lancet. 1994 Apr 2;343(8901):820-3. doi: 10.1016/s0140-6736(94)92025-7.
To determine whether clinical outcome in patients with acute alcoholic hepatitis is related to the regenerative capability of the liver, liver biopsy specimens from 25 prospectively recruited patients with acute alcoholic hepatitis were studied for hepatic expression of mRNA for two proliferation markers, proliferating cell nuclear antigen and human histone, and for transforming growth factor alpha (TGF alpha) and TGF beta 1 and hepatocyte growth factor (HGF), which regulate hepatocyte proliferation. Proliferation markers were detected to varying degrees in 0-80% of hepatocytes and occasionally in sinusoidal cells and bile-duct epithelium in 19 patients (76%). Patients who survived for 6 months had greater expression of proliferation markers than those who did not survive (p < 0.01). TGF alpha was detected in hepatocytes and bile-duct epithelium, whereas TGF beta 1 was detected mainly in sinusoidal cells and was associated with perivenular fibrosis. Patients who survived for 6 months had greater expression of TGFs than non-survivors (p < 0.02). HGF was detected in sinusoidal cells in 7 patients and correlated with survival (p < 0.01). These data indicate that hepatocyte proliferation, which is possibly related to the pattern of hepatotrophic factor expression, is a good indicator of outcome in acute alcoholic hepatitis.
为了确定急性酒精性肝炎患者的临床结局是否与肝脏的再生能力有关,对25例前瞻性招募的急性酒精性肝炎患者的肝活检标本进行了研究,检测了两种增殖标志物(增殖细胞核抗原和人类组蛋白)的mRNA在肝脏中的表达,以及调节肝细胞增殖的转化生长因子α(TGFα)、TGFβ1和肝细胞生长因子(HGF)。在19例患者(76%)中,0 - 80%的肝细胞不同程度地检测到增殖标志物,偶尔在窦状隙细胞和胆管上皮中也能检测到。存活6个月的患者增殖标志物的表达高于未存活者(p < 0.01)。TGFα在肝细胞和胆管上皮中被检测到,而TGFβ1主要在窦状隙细胞中被检测到,并与中央静脉周围纤维化有关。存活6个月的患者TGFs的表达高于未存活者(p < 0.02)。7例患者的窦状隙细胞中检测到HGF,且HGF与生存相关(p < 0.01)。这些数据表明,肝细胞增殖可能与肝细胞生长因子的表达模式有关,是急性酒精性肝炎预后的一个良好指标。