Higher Barcelona Clinic Liver Cancer Research Articles

The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma.

BackgroundAdvanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis.MethodsA total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model.ResultsDuring a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P<0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669–0.751) than BCLC stage.ConclusionAIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.

Abstract No. 550 Comparison of efficacy of primary Yttrium-90 radiation segmentectomy versus percutaneous microwave ablation in patients with ≤4-cm hepatocellular carcinoma

Current guidelines including Barcelona Clinic Liver Cancer (BCLC) criteria recommend thermal ablation for patients with 3 or fewer, <3-cm hepatocellular carcinoma (HCC) who are not surgical candidates. The objective of this study was to compare the tumor response and overall survival (OS) in patients with solitary, small (<4 cm) HCC treated with primary percutaneous microwave ablation (MWA) vs. Yttrium-90 (Y90) radioembolization radiation segmentectomy (RS). From March 2014 to March 2017, 118 consecutive treatment naïve patients with solitary HCC ≤4 cm were included. Baseline characteristics including patient age, gender, MELD score, BCLC stage and Child-Pugh (CP) scores were compared between the two groups using t-test and chi-square. Tumor response at 3 months post therapy was evaluated using modified Response Evaluation Criteria in Solid Tumors (m-RECIST). Survival from initial treatment was calculated using Kaplan-Meier estimation. Statistical analysis was performed using SPSS v25 (IBM, Armonk, NY) with significance set at 0.05. Overall, 118 consecutive patients were included of whom 75 patients were treated with MWA and 43 patients were treated with Y90 RS. Five of 75 patients (6.7%) in the MWA group and 2 of 43 patients in the RS were lost to follow-up. Median follow-up for the entire cohort was 30.2 months. The MWA group had smaller lesions diameter compared (1.7 cm) vs. those with RS (2.7 cm, P = 0.001). The MWA group had more patients who were ≤65 years (53.9% of patients) vs. RS group (37.2%, P = 0.079). While the MWA group had larger proportion of higher CP score (30.7% of CP B for MWA vs. 11.6% of CP B RS, P = 0.05), the RS group had higher BCLC B stage (76.7%) vs. 60.0% for MWA (P = 0.01). The incidence of favorable tumor response (partial or complete response) was similar for the two groups; 85.8% for MWA vs. 87.8% for RS (P = 0.49). There was no difference in OS from first procedure in the MWA group (46.4 months) vs. RS (43.7 months; P = 0.907). Our data suggests Y90 RS is noninferior to percutaneous MWA in the management of HCC lesions ≤4 cm with similar medium-term OS outcomes.Tabled 1MWAY90RSImaging Response (mRESIST) Complete Response57(76.0%)32(74.4%) Partial Response3(2.67%)4(9.30%) Stable Disease4(5.33%)2(4.65%)P=0.487 Progression of Disease6(8.0%)3(6.98%)Overall Survival (months)95% Confidence Interval46.3843.68P=0.907(41.47-51.286)(36.72-50.64) Open table in a new tab

Risk factors of mortality in the patients with hepatocellular carcinoma: A multicenter study in Indonesia

Background and AimsHepatocellular carcinoma (HCC) is considered a significant burden, and its associated rate of mortality is increasing. Therefore, a population-based cancer registry is considered an essential element in the baseline and comprehensive analysis of the risk factors associated with HCC. We present a multicenter analysis of HCC registry from 2 hospitals in Indonesia. MethodsWe performed a follow-up on patients with HCC who were admitted between January 2015 and November 2017 in Cipto Mangunkusumo National General Hospital and Dharmais Hospital, Jakarta, Indonesia. Patient's death was considered the primary outcome of the study. A multivariate analysis was conducted using logistic regression, and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. ResultsA total of 282 patients with HCC included. At the last follow-up, 136 (48.2%) patients had died. Mortality rate was not significantly affected by sex, age, etiology, the presence of cirrhosis, nor surveillance of HCC. Based on the Child-Pugh (CP) classification, the OR increased progressively in CP C patients (OR 1.95; 95% CI 1.08-3.53; P = 0.026). The progressive increase was also found in patients with a higher Barcelona Clinic Liver Cancer stage, and the OR for CP C and D patients were 3.50 (95% CI 1.18-10.38; P = 0.024) and 3.41 (95% CI 1.02-11.41; P = 0.047), respectively. Supportive treatment was the most common treatment modality with an OR of 2.17 (95% CI 1.14-4.16; P = 0.019), and it was associated with the mortality rate of HCC. ConclusionsThe CP classification, Barcelona Clinic Liver Cancer staging system, and treatment modality might predict mortality in patients with HCC. Moreover, other parameters must be further evaluated.

Transcatheter embolization of hepatocellular carcinoma with epirubicin-loaded DC beads in Chinese patients

Background: This study evaluated the safety and efficacy of transcatheter chemoembolization with drug eluting beads (DEB-TACE) and compared it to the conventional TACE (cTACE) therapy method for hepatocellular carcinoma (HCC) in Chinese patients. Methods: Seventy-four patients were treated with DEB-TACE using the DC bead, and 80 patients were treated with cTACE for HCC. The modified response evaluation criteria in solid tumors (mRECIST) criteria were used to evaluate clinical response, with adverse events assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Post-TACE, 9 patients (12.2%) achieved complete response (CR) and 44 (59.5%) achieved partial response (PR), with an overall tumor response rate (ORR) of 71.6% in the DEB-TACE group. Twelve patients (15%) achieved CR, and 38 (47.5%) achieved PR, with an ORR of 62.5% in the cTACE group. However, there was no significant difference in ORR between the two groups (P=0.229). Univariate logistic regression analysis determined that more than 3 nodules, higher Barcelona clinic liver cancer (BCLC) stage, portal vein invasion, previous chemotherapy (cTACE), and previous surgery were correlated with a worse ORR. Most common adverse events were not severe. Conclusions: DEB-TACE by DC bead was efficient and well-tolerated compared to cTACE in Chinese HCC patients. However, the present study showed no significant difference in ORR between the DEB-TACE and cTACE in the patient group with HCC. The BCLC stage, number of nodules, portal vein invasion, cTACE, and surgery history could possibly be a predictive factor for HCC treatment response.

Transcatheter embolization of hepatocellular carcinoma with epirubicin-loaded DC beads in Chinese patients.

BackgroundThis study evaluated the safety and efficacy of transcatheter chemoembolization with drug eluting beads (DEB-TACE) and compared it to the conventional TACE (cTACE) therapy method for hepatocellular carcinoma (HCC) in Chinese patients.MethodsSeventy-four patients were treated with DEB-TACE using the DC bead, and 80 patients were treated with cTACE for HCC. The modified response evaluation criteria in solid tumors (mRECIST) criteria were used to evaluate clinical response, with adverse events assessed according to the Common Terminology Criteria for Adverse Events (CTCAE).ResultsPost-TACE, 9 patients (12.2%) achieved complete response (CR) and 44 (59.5%) achieved partial response (PR), with an overall tumor response rate (ORR) of 71.6% in the DEB-TACE group. Twelve patients (15%) achieved CR, and 38 (47.5%) achieved PR, with an ORR of 62.5% in the cTACE group. However, there was no significant difference in ORR between the two groups (P=0.229). Univariate logistic regression analysis determined that more than 3 nodules, higher Barcelona clinic liver cancer (BCLC) stage, portal vein invasion, previous chemotherapy (cTACE), and previous surgery were correlated with a worse ORR. Most common adverse events were not severe.ConclusionsDEB-TACE by DC bead was efficient and well-tolerated compared to cTACE in Chinese HCC patients. However, the present study showed no significant difference in ORR between the DEB-TACE and cTACE in the patient group with HCC. The BCLC stage, number of nodules, portal vein invasion, cTACE, and surgery history could possibly be a predictive factor for HCC treatment response.

Complete genome sequencing and clinical analysis of intrahepatic hepatitis B virus cccDNA from HCC

More than half of hepatocellular carcinomas (HCCs) are etiologically attributed to hepatitis B virus (HBV) infection, but it remains unclear whether HBV mutations are virological factors that contribute to formation of HCC or instead reflect accumulation during the progression of HBV-related disease. Rolling-cycle amplification and PCR sequencing were used to characterize covalently closed circular DNA (cccDNA) mutations in tumor tissues. Paired non-tumor tissues were used as controls. High frequencies of C1653T, T1753V, and A1762T/G1764A cccDNA mutations were observed in both tumor and non-tumor tissues. T1719G, C1329A, and T3098C mutations were related to the overall survival of HCC patients. Patients with G1719 tended to be in the high Barcelona Clinic Liver Cancer stage and had lower levels of total DNA and cccDNA per cell than patients with T1719. Additionally, invitro analysis revealed that T1719G mutation reduced viral replication efficacy. Finally, significantly higher levels of preoperative alpha-fetoprotein were observed in patients harboring the G1078T, C1653T, G1727A, C1913A, T1978C, or C3116T mutations at the cccDNA level. We speculated that HBV cccDNA mutations accumulated over the course of HBV-related disease development, and that some key mutations had prognostic value for patients with HBV-related HCC.

Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.

As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p=0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.

Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma.

BackgroundSeveral hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC.MethodsWe retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups.ResultsDuring a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05). GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival.ConclusionThe GPR is an effective preoperative predictor for outcomes in hepatitis B-associated HCC.

King's score as a novel prognostic model for patients with hepatitis B-associated hepatocellular carcinoma.

King's score (KS) has been developed to predict the presence of cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic liver diseases. We aimed to investigate the prognostic significance of the KS in hepatitis B-associated HCC. We retrospectively analyzed 319 hepatitis B-associated HCC patients. Preoperative data were collected to calculate the KS (age × aspartate aminotransferase × international normalized ratio/platelet count). The primary outcomes were overall survival (OS) and disease-free survival (DFS), which was estimated using the Kaplan-Meier method. Then, we carried out a multivariate Cox analysis to assess the independent significance of the KS. Additional analyses were carried out after patients were stratified on the basis of cirrhosis status and therapy methods to investigate the significance of KS in different subgroups. During a median follow-up period of 44 months, 199 (62.4%) patients died and 144 (45.1%) experienced recurrence. The cut-off value for the KS was determined to be 33.31 with 56.8% sensitivity and 66.7% specificity. Compared with patients with low KS, the high group showed a higher probability of cirrhosis and worse Child-Pugh class (both P<0.05). Multivariate analysis identified older age, tumor size 5 or more, palliative therapy, high Barcelona Clinic Liver Cancer stage, and high KS as significant factors for predicting poor OS and DFS. A combination of the KS and tumor size showed better discrimination ability for survival than Barcelona Clinic Liver Cancer stage. The KS is an effective index for predicting OS and DFS in hepatitis B-associated HCC. Larger cohorts are needed to validate our finding.

The Prognostic Role of Mitotic Index in Hepatocellular Carcinoma Patients after Curative Hepatectomy.

PurposeHigh proliferation rate is a hallmark of cancer. The mitotic index is a useful and simple method for analysis of cell proliferation. However, the practical utility of mitotic index as a predictor of prognosis in patients with hepatocellular carcinoma (HCC) has not been determined. Therefore, we examined mitotic index as a prognostic marker in HCC patients.Materials and MethodsWe counted the number of mitotic cells in 10 high-power fields of the tumor area on hematoxylin and eosin–stained slides representing 282 surgically resected HCCs. The highest number of mitotic cells was defined as the mitotic index.ResultsHigh mitotic index was observed in 127 of 282 HCCs. High mitotic index showed significant association with younger age, larger tumor size, higher Edmondson grade, microvascular invasion, major portal vein invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T-stage, higher Barcelona Clinic Liver Cancer (BCLC) stage, higher alpha-fetoprotein level, hepatitis B virus etiology, and liver cirrhosis. Patients with high mitotic index had shorter disease-specific survival (DSS) (p < 0.001) and tended to have shorter recurrence-free survival (p=0.112). In subgroup analysis among patients with a larger tumor size, microvascular invasion, intrahepatic metastasis, higher AJCC T-stage, and higher BLCL stage, high mitotic index showed unfavorable influences on DSS (p=0.001, p=0.008, p=0.003, p=0.012, and p < 0.001, respectively). In addition, high mitotic index was an independent predictor of shorter DSS (p=0.004).ConclusionHigh mitotic index may be a novel predictor of DSS in patients with HCC and may have utility as an auxiliary prognostic factor in HCC.

DNA Methylation Profiling Identifies EYA4 Gene as a Prognostic Molecular Marker in Hepatocellular Carcinoma

DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values. DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene. Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P<0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P<0.050). EYA4 expression was inversely related to tumor size (P<0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P<0.050). EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.

Metadherin is a prognostic predictor of hepatocellular carcinoma after curative hepatectomy.

Background/AimsThe prognosis after surgical resection of hepatocellular carcinoma (HCC) remains poor because of a high rate of recurrence. Thus, it is crucial to identify patients with a high risk of recurrence after curative hepatectomy and to develop more effective and targeted treatment strategies to improve disease outcomes. In this study, we investigated the roles of metadherin (MTDH) in the prognosis of HCC.MethodsWe investigated MTDH expression using immunohistochemistry in tumor tissue microarrays of 288 primary HCC patients who underwent curative surgical resection.ResultsHigh MTDH expression was observed in 138 of the 288 HCC cases (47.9%). High MTDH expression was associated with a younger age (p<0.001), higher Edmondson grade (p<0.001), microvascular invasion (p<0.001), higher American Joint Committee on Cancer T stage (p=0.001), and higher α-fetoprotein level (p=0.003). Multivariate analyses revealed that high MTDH expression (p=0.014), higher Barcelona-Clinic Liver Cancer (BCLC) stage (p<0.001), and Edmondson grade III (p=0.042) were independent predictors of shorter disease-free survival (DFS). Higher BCLC stage (p<0.001) and Edmondson grade III (p=0.047) were also independent predictors of shorter disease-specific survival.ConclusionsHigh MTDH expression may be a prognostic predictor of shorter DFS in HCC patients after curative hepatectomy.

CHD1L Is a Marker for Poor Prognosis of Hepatocellular Carcinoma after Surgical Resection

BackgroundThe gene for chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC.MethodsWe investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months.ResultsCHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher α-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival.ConclusionsCHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.

Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma

BackgroundBCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients.MethodsWe evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months.ResultsNuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078).ConclusionsBCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.