Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

• Published in: Clinical and molecular hepatology Vol. 19; no. 2; pp. 120 - 130
• Main Authors: Kim, Young Seok, Jung, Eun Sun, Hur, Wonhee, Bae, Si Hyun, Choi, Jong Young, Song, Myeong Jun, Kim, Chang Wook, Jo, Se Hyun, Lee, Chang Don, Lee, Young Sok, Choi, Sang Wook, Yang, Jin Mo, Jang, Jeong Won, Kim, Sang Gyune, Jung, Seung Won, Kim, Hee Kyung, Chae, Hee Bok, Yoon, Seung Kew
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Association for the Study of the Liver 01.06.2013; The Korean Association for the Study of the Liver; 대한간학회
• Subjects: Adult; Aged; Aged, 80 and over; Alanine Transaminase - blood; Apoptosis; Asian Continental Ancestry Group; Aspartate Aminotransferases - blood; Biomarkers; Biomarkers - blood; Biopsy; Blood pressure; Body mass index; Cholesterol; Correlation analysis; Cytokeratin-18; Data analysis; Diabetes; Fatty Liver - classification; Fatty Liver - metabolism; Fatty Liver - pathology; Female; Ferritin; Ferritins - blood; Fibrosis - complications; Gastrointestinal surgery; Glucose; High density lipoprotein; Hospitals; Humans; Hypertension; Inflammation; Insulin resistance; Keratin-18 - analysis; Laboratories; Liver diseases; Male; Metabolic syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Nonalcoholic fatty liver disease; Obesity; Original; Predictive Value of Tests; Prospective Studies; Republic of Korea; Severity of Illness Index; Young Adult; 내과학; Republic of Korea; Cytokeratin-18; Nonalcoholic fatty liver disease; Ferritin
• ISSN: 2287-2728; 2287-285X; 2287-285X
• DOI: 10.3350/cmh.2013.19.2.120

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.