Tarantino G, Conca P, Coppola A, Vecchione R, Di Minno G
Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy.
Eur J Clin Invest. 2007 Jan;37(1):48-53. doi: 10.1111/j.1365-2362.2007.01745.x.
Liver histology is the gold standard for diagnosis of non-alcoholic fatty liver disease. Ethical considerations and patient choice often preclude performing a liver biopsy, especially considering the rare but potential risk. Searching for a good serological marker substitute for the invasive procedure was the aim of our study. Keratins, mainly 8 and 18, play not only a mere structural role providing mechanical stability to hepatocytes, but also represent a target via toxic stress ultimately inducing apoptosis/necrosis. Tissue polypeptide-specific antigen (TPS), a serological mirror of keratin 18, is widely used as a marker for various cancers. This antigen was assessed in three different groups who were overweight or obese.
In this cross-sectional case-control study, 48 cancer-free patients with non-alcoholic steatohepatitis (NASH, Group 1), 48 patients with pure fatty liver (FL, Group 2), and 47 volunteers (Group 3) were studied. All of them were referred to our metabolic unit for routine evaluation.
The median (range) TPS levels were 123 (56-286) ng mL(-1) in NASH patients. FL patients and volunteers had significantly lower TPS levels, 76 (38-98) ng mL(-1) and 64 (28-87) ng mL(-1), respectively (P = 0.0001). A value of 88 ng mL(-1) in patients with underlying bright liver was associated with a high probability of NASH (sensitivity and specificity = 92% and 96%, respectively). One patient (2.1%) with FL had a TPS value > 88 ng mL(-1), but in the same group, 29 FL patients (60.4%) had an alanine aminotransferase value > 40 U L(-1). Based on a recent classification of liver fibrosis, the median (range) TPS values were significantly different among the stages: F1 (n = 23) = 100 (76-264) ng mL(-1); F2 (n = 21) = 134 (56-276) ng mL(-1); and F3 (n = 4) = 199.5 (123-286) ng mL(-1), respectively (P = 0.014).
Our study shows that TPS is a better marker than alanine aminotransferase activity, ultrasonography or the combination of both parameters in differentiating NASH from FL.
肝脏组织学是诊断非酒精性脂肪性肝病的金标准。出于伦理考虑和患者选择，通常不进行肝活检，尤其是考虑到其罕见但潜在的风险。寻找一种用于替代侵入性检查的良好血清学标志物是我们研究的目的。角蛋白，主要是角蛋白8和18，不仅起到为肝细胞提供机械稳定性的单纯结构作用，还通过毒性应激成为最终诱导细胞凋亡/坏死的靶点。组织多肽特异性抗原（TPS），作为角蛋白18的血清学反映，被广泛用作各种癌症的标志物。在三组超重或肥胖人群中对该抗原进行了评估。
在这项横断面病例对照研究中，对48例无癌症的非酒精性脂肪性肝炎患者（NASH组，第1组）、48例单纯性脂肪肝患者（FL组，第2组）和47名志愿者（第3组）进行了研究。他们均被转至我们的代谢科进行常规评估。
NASH患者的TPS水平中位数（范围）为123（56 - 286）ng/mL。FL组患者和志愿者的TPS水平显著较低，分别为76（38 - 98）ng/mL和64（28 - 87）ng/mL（P = 0.0001）。肝脏回声增强的患者中，TPS值为88 ng/mL与NASH的高可能性相关（敏感性和特异性分别为92%和96%）。1例（2.1%）FL患者的TPS值>88 ng/mL，但在同一组中，29例（60.4%）FL患者的丙氨酸氨基转移酶值>40 U/L。根据最近的肝纤维化分类，不同阶段的TPS值中位数（范围）有显著差异：F1期（n = 23）为100（76 - 264）ng/mL；F2期（n = 21）为134（56 - 276）ng/mL；F3期（n = 4）为199.5（123 - 286）ng/mL，分别（P = 0.014）。
我们的研究表明，在区分NASH和FL方面，TPS是比丙氨酸氨基转移酶活性、超声检查或这两个参数联合使用更好的标志物。
