Early detection of hepatocellular carcinoma in patients with diabetes mellitus

Abstract

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.

The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma

“…These results are comparable to the data of mixed etiologies and viral HCC detection [ 4 – 6 ]. This model is different from the findings of Nouso K (FIB4A model: AST + ALT + platelets + age + AFP) [ 7 ], Best J (GALAD model: age + gender + AFP + AFP-L3 + PIVKA-II) [ 9 ], Caviglia GP (age + gender + PIVKA-II + glypican-3 + adiponectin) [ 10 ], and Guan MC (AFP + PIVKA-II) [ 11 ]. It is easy to see that subjects of these studies (diabetes, NAFLD, and NASH) are different from our populations (chronic hepatitis, simple hepatic cyst, necrosis, hyperplasia, dysplastic nodules…), which may lead to distinct observations.…”

“…It is more arduous when most cases do not have any signs or symptoms before detecting HCC at the advanced stages [ 14 ]. AFP, AFP-L3, and PIVKA-II are important biomarkers (low-cost, non-invasiveness, rapid and easy implementation, standardization, and accepted performance) that have been globally recognized and applied for many years, but few studies dealt with the NBNC-HCC group [ 7 – 12 ]. We investigated and showed that the AFP + PIVKA-II model combined with AST and patients’ age exhibited good diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values in classifying NBNC-HCC (Additional file 3: Table S3 ).…”

“…However, this referred information is for the mixed etiology or viral hepatitis. A few studies assessed the diagnostic role of these markers in those without hepatitis B and C viruses (non-B non-C HCC, NBNC-HCC) [ 7 – 12 ], which tends to rise in current years [ 13 , 14 ]. We aim to clarify the role of AFP, AFP-L3, PIVKA-II, and other markers in the surveillance of NBNC-HCC by real-world data.…”

Potential role of Fibrosis‐4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study

“…The FIB‐4 score was used to define the risk of advanced fibrosis as follows: <1.30 (“low risk”), 1.30–2.67 (“intermediate risk”), and ≥2.67 (“high‐risk”) 33 . Additionally, based on previous research findings of enhanced HCC diagnostic performance with increasing FIB‐4 scores, we conducted an investigation to assess the results based on varying FIB‐4 score cutoff values 34–37 …”

“…33 Additionally, based on previous research findings of enhanced HCC diagnostic performance with increasing FIB-4 scores, we conducted an investigation to assess the results based on varying FIB-4 score cutoff values. [34][35][36][37]…”