Aim Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus‐related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha‐fetoprotein (AFP‐L3) in the process of nonalcoholic fatty liver (NAFL) disease development. Methods Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP‐L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH). Results Trace amounts of AFP‐L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP‐L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77–25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP‐L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort. Conclusion Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.

Objectives Diabetes mellitus is a risk factor for non-B, non-C hepatocellular carcinoma (NBNC-HCC); however, the number of diabetes mellitus patients is too large to examine tumor occurrence with periodic imaging modalities. Thus, the aim of this study was to develop a novel strategy for early detection of NBNC-HCC in diabetes mellitus patients. Patients and methods Ninety-three diabetes mellitus patients who had a single NBNC-HCC tumor less than 2 cm in diameter were selected from 6789 HCC patients. As controls, 172 tumor-free diabetes mellitus patients were enrolled. Characteristics were compared between groups. Furthermore, the efficacy of FIB4A, a new integrated score with FIB4 and alpha-fetoprotein, was analyzed as a marker for the early diagnosis of NBNC-HCC. Results Age, percentage of males, alcohol consumption, total bilirubin, transaminases, γ-glutamyl transpeptidase, FIB4 index, alpha-fetoprotein, and des-gamma-carboxy-prothrombin were higher in NBNC-HCC patients, whereas albumin and platelet counts were higher in the diabetes mellitus control group. Among these factors, the FIB4 index showed the highest odds ratio [OR: 20.0, 95% confidence interval (CI): 9.60–41.7] followed by alpha-fetoprotein (OR: 12.8, 95% CI: 6.53–25.4). A newly developed score, FIB4A, showed the highest area under the receiver operating characteristic curve (0.959) among the factors examined. The sensitivity was 86.2% at a Youden index cutoff (3.5) and it increased to 95.4%, while keeping high specificity (70.9%) when a cutoff of 2.5 was used. Conclusion FIB4A is a potential marker for early detection of NBNC-HCC in patients with diabetes mellitus. However, further studies are needed to confirm these findings.

Aim: The incidence of non-virus-related nonB-nonC hepatocellular carcinoma (NBNC-HCC) is on the rise. However, screening at-risk individuals using imaging methods is complicated by the large size of the at-risk patient pool. The aim of this study is to develop an effective simple screening method, using blood tests. Methods: The diagnostic value of aspartate aminotransferase (AST), alpha-fetoprotein (AFP), and des-gammacarboxy prothrombin (DCP) was analyzed using sera from 203 NBNB-HCC patients and 106 diabetes mellitus patients. Results: Areas under receiver operating characteristic curves for AST, AFP, and DCP were 0.844, 0.901, and 0.914, respectively. The optimal cutoffs for diagnosing NBNC-HCC based on Youden indices were 30 IU/L, 3.6 ng/mL, and 25 mAU/mL, respectively. On selecting patients who were positive at least one parameter (AST, AFP, or DCP), the sensitivity was 97.5%. This high sensitivity was preserved (98.0%) even in cases of nonadvanced HCC (≤ 3 cm, ≤ 3 nodules). Specificity was 72.6%. Conclusion: This simple triple screen for AST, AFP, and DCP appears to have diagnostic value in NBNC-HCC and could be used to select candidates for further testing using imaging.