Utility of FIB4-T as a Prognostic Factor for Hepatocellular Carcinoma

Abstract

Background: Most integrated scores for predicting the prognosis of patients with hepatocellular carcinoma (HCC) comprise tumor progression factors and liver function variables. The FIB4 index is an indicator of hepatic fibrosis calculated on the basis of age, aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels, and platelet count, but it does not include variables directly related to liver function. We propose a new staging system, referred to as "FIB4-T," comprising the FIB4 index as well as tumor progression factors, and examine its usefulness.

Method: Subjects included 3800 cases of HCC registered in multiple research centers. We defined grades 1, 2, and 3 as a Fibrosis-4 (FIB4) index of <3.25, 3.26⁻6.70, and >6.70 as FIB4, respectively, and calculated the FIB4-T in the same manner in which the JIS (Japan Integrated Staging Score) scores and albumin-bilirubin tumor node metastasis (ALBI-T) were calculated. We compared the prognostic prediction ability of FIB4-T with that of the JIS score and ALBI-T.

Results: Mean observation period was 37 months. The 5-year survival rates (%) of JIS score (0/1/2/3/4/5), ALBI-T (0/1/2/3/4/5) and FIB4-T (0/1/2/3/4/5) were 74/60/36/16/0, 82/66/45/22/5/0 and 88/75/65/58/32/10, respectively. Comparisons of the Akaike information criteria among JIS scores, ALBI-T, and FIB4-T indicated that stratification using the FIB4-T system was comparable to those using ALBI-T and JIS score. The risk of mortality significantly increased (1.3⁻2.8 times/step) with an increase in FIB4-T, and clear stratification was possible regardless of the treatment.

Conclusion: FIB4-T is useful in predicting the prognosis of patients with HCC from a new perspective.

Keywords: ALBI-T; FIB4 index; FIB4-T; JIS score.

Figure 1

Kaplan–Meier curves according to (a) FIB4 grade and (b) Tumor, Node, Metastases (TNM) stage (data obtained from the Liver Cancer Study Group of Japan (n = 3800)). Statistically significant differences were observed among survival curves on the basis of FIB4 grade and TNM stage (log-rank test, p < 0.0001).

Figure 2

Overall survival rate according to (a) JIS score, (b) ALBI-T, and (c) FIB4-T (n = 3800) and Distribution of FIB4-T in (d) JIS score and (e) ALBI-T. The difference in survival between FIB4-T (0) and (1) was small compared with those in JIS score and ALBI-T, but prognosis of FIB4-T (0) was significantly better than prognosis of FIB4-T (1) (p = 0.048). The p-value for each group was FIB 4-T 0–1: 0.048, 1–2: <0.001, 2–3: <0.001, 3–4: <0.001, and 4–5: <0.001 (log-rank test). All p-values for each group in JIS score, ALBI-T were <0.001 (log-rank test). As prognostic models, good stratification was possible for all three systems (p < 0.0001). Distribution of FIB4-T in JIS score and ALBI-T were as shown in (d) and (e).

Figure 3

Survival curves stratified with FIB4-T for different treatments. Stratification was possible regardless of treatment type (surgery, p < 0.0001; RFA, p < 0.0001; TACE, p < 0.0001). Abbreviations: RFA, radiofrequency ablation; TACE, transcatheter arterial chemoembolization.

Figure 4

Survival curve stratified by treatment type (Surgery, RFA and TACE) for each Figure 4. grade. Abbreviations: RFA, radiofrequency ablation; TACE, transcatheter arterial chemoembolization.