Department of Internal Medicine, Soon Chun Hyang University Hospital Bucheon, Soon Chun Hyang University College of Medicine, Bucheon, Korea.
Clin Mol Hepatol. 2013 Jun;19(2):120-30. doi: 10.3350/cmh.2013.19.2.120. Epub 2013 Jun 27.
BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.
One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.
According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.
Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.
背景/目的：本研究的目的是：（1）确定用于区分非酒精性脂肪性肝炎（NASH）与非酒精性脂肪性肝病（NAFLD）的非侵入性方法的有用临床参数；（2）确定鉴定参数的水平是否与 NASH 患者肝损伤的严重程度相关。
本前瞻性研究纳入了韩国 10 个参与中心的 108 例经活检证实的 NAFLD 患者（年龄 39.8±13.5 岁，均值±标准差；男性占 67.6%）。
根据 NAFLD 亚型的原始标准，67 例（62.0%）患者患有 NASH（定义为存在肝细胞气球样变和/或 Mallory-Denk 小体或纤维化≥2 级的脂肪变性）。在 NAFLD 亚型 3 或 4 的患者中，无患者的 NAFLD 组织学活动评分（NAS）低于 3 分，40.3%的患者为 3 或 4 分，59.7%的患者为>4 分。片段化细胞角蛋白-18（CK-18）水平与 NAS（r=0.401）呈正相关，与 NAS 成分（如小叶炎症[r=0.387]和气球样变[r=0.231]）也呈正相关。片段化 CK-18 还与天冬氨酸氨基转移酶（r=0.609）、丙氨酸氨基转移酶（r=0.588）、血清铁蛋白（r=0.432）和纤维化分期（r=0.314）相关。片段化 CK-18 的截断值为 235.5 U/L 时，诊断 NASH 的敏感性、特异性、阳性预测值和阴性预测值分别为 69.0%、64.9%、75.5%（95%CI 62.4-85.1）和 57.1%（95%CI 42.2-70.9）。
血清片段化 CK-18 水平可用于区分 NASH 和 NAFL。需要进一步评估是否联合检测血清 CK-18 和铁蛋白水平可以提高这种区分的诊断性能。
