Early detection of hepatocellular carcinoma in patients with diabetes mellitus.

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.

Treatment of Intermediate-Stage Hepatocellular Carcinoma in Japan: Position of Curative Therapies.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is the standard therapy for intermediate-stage (IM) hepatocellular carcinoma (HCC). However, IM-HCC includes various clinical conditions, and various therapies were conducted in practice. In this study, we retrospectively analyzed the actually conducted treatments for IM-HCC and their efficacies to elucidate the treatment strategies suitable for IM-HCC. METHODS: This study included 627 IM-HCC of 5,260 HCC from 9 hospitals. We examined the treatment strategies of these patients and analyzed the efficacy of each therapy with the Cox proportional hazard model and propensity score-matched analysis. RESULTS: Liver resection, radiofrequency ablation (RFA), and TACE were performed in 165, 108, and 351 patients, respectively. Liver resection and RFA were preferably selected in cases of Barcelona Clinic Liver Cancer (BCLC)-B1/B2, and patient survival was significantly longer than in those treated with TACE (p< 0.0001). However, no beneficial effect of these active therapies was observed in cases of BCLC-B3/B4. Multivariate analysis revealed that surgical resection (hazard ratio = 0.384) and RFA (hazard ratio = 0.597) were negative risk factors for survival. Propensity score-matching analysis revealed that -survival of RFA-treated patients was longer than that of TACE-treated patients (p = 0.036). CONCLUSION: RFA and surgical resection were effective for IM-HCC, particularly in BCLC-B1/B2 cases.

EZ-ALBI Score for Predicting Hepatocellular Carcinoma Prognosis.

INTRODUCTION: The ALBI score is acknowledged as the gold standard for the assessment of liver function in patients with hepatocellular carcinoma (HCC). Unlike the Child-Pugh score, the ALBI score uses only objective parameters, albumin (Alb) and total bilirubin (T.Bil), enabling a better evaluation. However, the complex calculation of the ALBI score limits its applicability. Therefore, we developed a simplified ALBI score, based on data from a large-scale HCC database. We used the data of 5,249 naïve HCC cases registered in eight collaborating hospitals. METHODS: We developed a new score, the EZ (Easy)-ALBI score, based on regression coefficients of Alb and T.Bil for survival risk in a multivariate Cox proportional hazard model. We also developed the EZ-ALBI grade and EZ-ALBI-T grade as alternative options for the ALBI grade and ALBI-T grade and evaluated their stratifying ability. RESULTS: The equation used to calculate the EZ-ALBI score was simple {[T.Bil (mg/dL)] - [9 × Alb (g/dL)]}; this value highly correlated with the ALBI score (correlation coefficient, 0.981; p < 0.0001). The correlation was preserved across different Barcelona clinic liver cancer grade scores (regression coefficient, 0.93-0.98) and across different hospitals (regression coefficient, 0.98-0.99), indicating good generalizability. Although a good agreement was observed between ALBI and EZ-ALBI, discrepancies were observed in patients with poor liver function (T.Bil, ≥3 mg/dL; regression coefficient, 0.877). The stratifying ability of EZ-ALBI grade and EZ-ALBI-T grade were good and their Akaike's information criterion values (35,897 and 34,812, respectively) were comparable with those of ALBI grade and ALBI-T grade (35,914 and 34,816, respectively). CONCLUSIONS: The EZ-ALBI score, EZ-ALBI grade, and EZ-ALBI-T grade are useful, simple scores, which might replace the conventional ALBI score in the future.

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

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.

Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma.

BACKGROUND AND AIM: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC. METHODS: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching. RESULTS: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (>30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (>100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group. CONCLUSIONS: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

Modified radiofrequency ablation for the treatment of hepatocellular carcinoma.

AIM: Radiofrequency ablation is commonly used for the treatment of early hepatocellular carcinoma. However, it requires time to ablate sufficient areas, resulting in increased burden for the patients and operators. We introduce a novel and simple method to overcome this problem. METHODS: We placed the grounding pad on the back (Back group) instead of the thigh of the patient (Thigh group). To assess the effect of this method, we randomly assigned the patients into two groups, based on the location of the grounding pad, and compared the outcomes. RESULTS: The ablation time until two roll-offs was shorter in the Back group than in the Thigh group (median, 2.5 min vs 3.4 min; P = 0.01). The ablated area was larger in the Back group than that in the Thigh group (P = 0.01) and pain was less in the Back group (P = 0.02). No severe side-effects were observed in either group. CONCLUSION: This new method is useful in that it achieved shorter ablation times, expansion of the ablated areas, and reduction of pain during the ablation.

Percutaneous Radiofrequency Ablation for Intermediate-Stage Hepatocellular Carcinoma.

OBJECTIVES: Radiofrequency ablation plays a key role in the treatment of early-stage hepatocellular carcinoma. However, it is not recommended for intermediate-stage hepatocellular carcinoma. The objective of this study was to clarify the efficacy and safety of radiofrequency ablation for treating intermediate-stage hepatocellular carcinoma. METHODS: We examined the outcome of 65 consecutive patients who were treated with radiofrequency ablation with or without transarterial chemoembolization for intermediate-stage hepatocellular carcinoma. RESULTS: With a median follow-up of 37 months, overall survival rates of 65 cases at 1, 3, 5, and 7 years were 90, 70, 51, and 36%, respectively. Multivariate analysis of clinical parameters revealed that the multicentric occurrence (MC)/intrahepatic metastasis (IM) was the only significant prognostic factor for overall survival (hazard ratio, 4.9; 95% confidence intervals, 2.1-11.4). Tumor size and tumor number were not significant factors for survival. The overall survival rates of patients with MC (n = 33) at 1, 3, 5, and 7 years were 97, 90, 80, and 59%, respectively; those for patients with IM (n = 32) were 86, 55, 14, and 8%, respectively (p < 0.0001). Two cases (4.9%) had complications of hemothorax and diaphragmatic burn; however, no major complications were observed. CONCLUSION: Radiofrequency ablation is safe and effective for the treatment of intermediate-stage hepatocellular carcinoma, especially for patients with MC.