Ratio Of Hepatocellular Carcinoma Research Articles

Defining ablative radiotherapy in patients with hepatocellular carcinoma: An expert consensus.

485 Background: External beam radiotherapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, there are many types of EBRT described in the literature with no formal definition of what constitutes “ablative.” Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. Methods: A Steering Committee was convened to generate a series of Key Criteria (KC) that could be used to define ablative EBRT for HCC. KC were based on factors related to dose, fractionation, radiobiology, target identification, and delivery technique. An international panel of experts participated in a modified Delphi (mDelphi) process to independently answer questions for each KC. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥ 70% was used to define consensus for answers to each KC. Results: Invitations were sent to 40 individuals and 35 (88%) returned responses. In the first round of the mDelphi, 3 of 7 KC reached consensus. In the second round, 100% of participants returned responses and consensus was reached in 3 of the remaining 4 KC. Based on this mDelphi analysis, there was expert agreement that ablative EBRT for HCC should be defined as 1) a BED10 ≥ 80 Gy, 2) daily imaging and multi-phasic contrast used for target delineation should be used, 3) treatment breaks (e.g., for adaptive EBRT) are allowed, but the total treatment time should be ≤ 6 weeks, 4) the equivalent dose when treating with protons should use a conversion factor of 1.1, and 5) there is no single conversion factor for carbon ions. In one KC, which questioned the expert’s opinion on the α/β ratio of HCC, consensus was not achieved. Conclusions: Using an mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empiric data are required to define the α/β of HCC.

Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus

External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy.

The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.

Measurement of the Tumor-to-Normal Ratio for Radioembolization of Hepatocellular Carcinoma: A Prospective Study Comparing 2-Dimensional Perfusion Angiography, Technetium-99m Macroaggregated Albumin, and Yttrium-90 SPECT/CT

PurposeTo calculate the preradioembolic tumor-to-normal (T:N) ratio in hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography and compare it with that calculated using technetium-99m macroaggregated albumin (99mTc MAA) single-photon emission computed tomography (SPECT)/computed tomography (CT). Materials and MethodsThis prospective single-arm study enrolled 15 participants with HCC who underwent 2D perfusion angiography immediately before the enrollment and with the microcatheter located at the same location as 99mTc MAA injection, after which SPECT/CT was performed. Quantitative digital subtraction angiography was used to calculate the area under the curve for the tumor and normal hepatic parenchyma and subsequently calculate the T:N ratio. The T:N ratio was calculated from the 99mTc MAA SPECT/CT and post–yttrium-90 bremsstrahlung SPECT/CT using dosimetry software. ResultsThe mean participant age was 64.1 years ± 9.8, and the study included 14 (93%) men and 1 (7%) woman. The mean tumor size was 4.1 cm (SD ± 2.4), and all participants received segmental treatments with glass microspheres. The mean T:N ratio calculated by 99mTc MAA SPECT/CT was 2.28 (SD ± 0.89) vs 2.25 (SD ± 0.99) calculated by 2D perfusion angiography (P = .45). For the 13 participants who underwent selective internal radiation therapy (transarterial radioembolization), there was no significant difference between the T:N ratios calculated by 2D perfusion angiography and post-90Y SPECT/CT (2.25 [SD ± 1.05] vs 1.91 [SD ± 0.39]; P = .12). ConclusionsThe T:N ratio calculated by 2D perfusion angiography correlated well with that calculated by 99mTc MAA SPECT/CT.

Diagnostic accuracy of alpha-fetoprotein combined with neutrophil-to-lymphocyte ratio for hepatocellular carcinoma

Diagnostic accuracy of alpha-fetoprotein combined with neutrophil-to-lymphocyte ratio for hepatocellular carcinoma

PO-1344 Prognostic significance of platelet-to-lymphocyte ratio in hepatocellular carcinoma

PO-1344 Prognostic significance of platelet-to-lymphocyte ratio in hepatocellular carcinoma

The prognostic role of the AST/ALT ratio in hepatocellular carcinoma patients receiving thermal ablation combined with simultaneous TACE

BackgroundTo evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE.MethodsThe data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram.ResultsThe AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600–0.748).ConclusionsThe preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.

Serum Protein Kinase C Delta: New Kid on the Block for Early Detection of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths in the world.1 Age-standardized incidence rates of HCC are highest in Asia and Africa; however, both incidence and mortality are rapidly rising in the United States and Europe due to a shift in epidemiology of HCC from viral hepatitis to nonalcoholic fatty liver disease–related cancer.2 Given the dual clinical challenges of detection at late stages and the high incidence-to-mortality ratio of HCC,3 major hepatology societies have recommended abdominal ultrasound with or without alpha fetoprotein (AFP) as the primary HCC surveillance strategy for at-risk patients.

Prior ablation and progression of disease correlate with higher tumor-to-normal liver 99mTc-MAA uptake ratio in hepatocellular carcinoma.

Factors affecting tumor-to-normal tissue ratio (T:N) have implications for patient selection, dosimetry, and outcomes when considering radioembolization for HCC. This study sought to evaluate patient, disease specific, and technical parameters that predict T:N as measured on planning pre-90Y radioembolization 99mTc-MAA scintigraphy for hepatocellular carcinoma (HCC). 99mTc-MAA hepatic angiography procedures with SPECT/CT over a 4-year period were reviewed. Data recorded included patient demographics, details of underlying liver disease, tumor size, history of prior treatments for HCC and technical parameters from angiography. Anatomic-based segmentation was performed in 93 cases for measurement of tumor and perfused liver volumes and SPECT counts. T:N were calculated and correlated with collected variables. Mean calculated T:N was 2.52. History of prior ablation was significantly correlated with higher T:N (mean 3.39 vs 2.24, p = 0.003). Cases in which mapping was being performed for treatment of disease progression was significantly correlated with higher T:N (mean 3.35 vs 2.14, p = 0.001). Larger tumor size trended toward lower T:N (p = 0.052). Patients with history of ablation and those undergoing treatment for disease progression have higher T:N and, therefore, could be considered for radioembolization preferentially over alternative treatments.

Prognostic prediction of the platelet-to-lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis

Platelet-to-lymphocyte ratio (PLR) has been used to predict the prognosis of patients with hepatocellular carcinoma (HCC) with inconsistent results. This meta-analysis aimed to clarify the prognostic value of PLR in patients with HCC. We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to November 20, 2021. The primary outcomes were the hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS), and secondary study outcomes were recurrence-free survival (RFS), disease-free survival (DFS), progression-free survival (PFS). All statistical analyses were conducted by Review Manager 5.4.1 and STATA 16.0 software. A total of 21 studies comprising 8,779 patients were included in this meta-analysis. Pooled results suggested that a high PLR was significantly associated with poor OS (HR: 1.34, 95% CI: 1.18-1.52, P<0.00001; I2=59%, P=0.0005), RFS or DFS (HR: 1.35, 95% CI: 1.13-1.63, P=0.001; I2=69%, P=0.002), and PFS (HR: 1.55, 95% CI: 1.09-2.22, P=0.02; I2=73%, P=0.02). The subgroup analysis for OS showed, when the PLR cutoff value was greater than 150, the heterogeneity decreased to 0 (HR: 1.48, 95% CI: 1.33-1.68, P<0.00001; I2=0%, P=0.56); when the HBsAg positive population was increased to 100%, the heterogeneity decreased to 0 (HR: 1.46, 95% CI: 1.22-1.73, P<0.0001; I2=0%, P=0.45); compared with other regions in the world, it was more significant in China (HR: 1.43, 95% CI: 1.26-1.62, P<0.00001; I2=52%, P=0.01). In addition, scatter plot showed that the HR was negatively correlated with the proportion of patients with liver cirrhosis. This meta-analysis suggests that PLR is a negative correlation prognostic biomarker for HCC, high PLR values indicate poor OS, RFS, DFS and PFS, especially in hepatitis B virus (HBV) related patients.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Hepatocellular Carcinoma Treated with Stereotactic Body Radiotherapy.

To investigate the prognostic value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). The medical records of HCC patients treated with SBRT between 2008 and 2019 were reviewed retrospectively. The NLR and PLR were calculated from the serum complete blood count before and after SBRT, and the prognostic values of the NLR and PLR for the treatment outcomes were evaluated. Thirty-nine patients with 49 HCC lesions were included. After a median follow-up of 26.8 months (range, 8.4-80.0 months), three-year local control, overall survival (OS), and progression-free survival (PFS) rate were 97.4%, 78.3%, and 35.2%, respectively. Both NLR and PLR increased significantly after SBRT and decreased slowly to the pre-SBRT value at 6 months. Univariable analysis showed that gross tumor volume (GTV) >14 cc, post-SBRT PLR >90, and PLR change >30 were associated with a poorer OS (p=0.002, p=0.011, and p=0.001, respectively), and the PLR change was significant in multivariable analysis (hazard ratio [HR], 10.09; 95% CI, 1.15-88.40; p=0.037). For PFS, GTV >14 cc, post-SBRT NLR >2.5 and post-SBRT PLR >90 were predictive of a poorer PFS in univariable analysis (p=0.011, p=0.004 and p=0.041, respectively) and only post-SBRT NLR >2.5 remained significant in multivariable analysis (HR, 2.44; 95% CI, 1.03-5.76; p=0.042, respectively). The NLR and PLR increased transiently after SBRT, and the post-SBRT NLR and PLR were associated with the clinical outcomes of HCC patients.

Prognostic value of neutrophil-to-lymphocyte ratio in hepatocellular carcinoma after major hepatectomy

Prognostic value of neutrophil-to-lymphocyte ratio in hepatocellular carcinoma after major hepatectomy

Differentiation between combined hepatocellular cholangiocarcinoma and hepatocellular carcinoma: comparison of diagnostic performance between ultrasomics-based model and CEUS LI-RADS v2017

BackgroundThe imaging findings of combined hepatocellular cholangiocarcinoma (CHC) may be similar to those of hepatocellular carcinoma (HCC). CEUS LI-RADS may not perform well in distinguishing CHC from HCC. Studies have shown that radiomics has an excellent imaging analysis ability. This study aimed to establish and confirm an ultrasomics model for differentiating CHC from HCC.MethodsBetween 2004 and 2016, we retrospectively identified 53 eligible CHC patients and randomly included 106 eligible HCC patients with a ratio of HCC:CHC = 2:1, all of whom were categorized according to Contrast-Enhanced (CE) ultrasonography (US) Liver Imaging Reporting and Data System (LI-RADS) version 2017. The model based on ultrasomics features of CE US was developed in 74 HCC and 37 CHC and confirmed in 32 HCC and 16 CHC. The diagnostic performance of the LI-RADS or ultrasomics model was assessed by the area under the curve (AUC), accuracy, sensitivity and specificity.ResultsIn the entire and validation cohorts, 67.0% and 81.3% of HCC cases were correctly assigned to LR-5 or LR-TIV contiguous with LR-5, and 73.6% and 87.5% of CHC cases were assigned to LR-M correctly. Up to 33.0% of HCC and 26.4% of CHC were misclassified by CE US LI-RADS. A total of 90.6% of HCC as well as 87.5% of CHC correctly diagnosed by the ultrasomics model in the validation cohort. The AUC, accuracy, sensitivity of the ultrasomics model were higher though without significant difference than those of CE US LI-RADS in the validation cohort.ConclusionThe proposed ultrasomics model showed higher ability though the difference was not significantly different for differentiating CHC from HCC, which may be helpful in clinical diagnosis.

LDH and GGT/ALT Ratio as Novel Prognostic Biomarkers in Hepatocellular Carcinoma Patients after Liver Transplantation.

Background Liver inflammation indices reflect its inflammatory microenvironment, which may play a role in the proliferation, invasion, and migration of carcinoma. This study is aimed at exploring the prognostic significance of serum lactate dehydrogenase (LDH) levels and gamma-glutamyl transferase (GGT)/alanine aminotransferase (ALT) ratio in hepatocellular carcinoma after liver transplant (LT). Methods We retrospectively analyzed data from 155 patients with a pathologically confirmed diagnosis of hepatocellular carcinoma who received LT between January 2013 and September 2017. We used receiver operating characteristics (ROC) curves to determine the optimal LDH and GGT/ALT ratio cut-off values. The Kaplan–Meier method and the logarithmic rank test were used to compare the survival curves without recurrence (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify factors associated with survival. Results Serum LDH levels were significantly associated with the Child-Pugh score (P = 0.037), largest tumor size (<50 vs. ≥50 mm) (P = 0.017), tumor count (<3 vs. ≥3) (P = 0.009), microvascular invasion (P = 0.006), and the Milan criteria (P ≤ 0.001). The serum GGT/ALT ratio was significantly correlated with alpha-fetoprotein (AFP) levels (of <400 vs. ≥400 ng/ml) (P ≤ 0.001), largest tumor size (of <50 vs. ≥50 mm) (P ≤ 0.001), the Edmondson grade (I-II vs. III-IV) (P = 0.028), microvascular invasion (P ≤ 0.001), and the Milan (P = 0.002) and Hangzhou criteria (P = 0.018). The survival curves showed that the patients with high LDH and the GGT/ALT ratio were associated with poor RFS and OS (P < 0.05). Univariate and multivariate analyses showed that AFP levels of ≥400 ng/ml, largest tumor size of ≥50 mm, microvascular invasion, LDH levels of ≥213.5 U/l, and the GGT/ALT ratio of ≥3.1338 were factors independently associated with RFS. Conclusion Elevated LDH levels and the GGT/ALT ratio before LT were associated with poor OS and RFS in the present study. These factors could be used in the prognostication of patients with hepatocellular carcinoma undergoing LT.

Racial Differences in Hepatocellular Carcinoma Incidence and Risk Factors among a Low Socioeconomic Population.

Simple SummaryLiver cancer incidence in the United States is higher among African Americans compared to White Americans. The determinants of racial disparities in liver cancer incidence are not clear. Using data from White and African Americans from low socioeconomic backgrounds, we compared the prevalence of known liver cancer risk factors by race and assessed factors associated with liver cancer incidence. Understanding liver cancer risk differences can assist prevention strategies that target people at high risk, potentially based on risk factors that differ by race.The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1–1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58–35.00) and diabetes (aHR = 3.55, 95%CI: 1.96–6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71–10.47 and aHR = 1.48, 95%CI: 1.06–2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87–4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19–2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.

The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

BackgroundThe neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC).MethodsIn this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis.ResultsOn entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage.ConclusionNLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

NT157 Inhibits HCC Migration via Downregulating the STAT3/Jab1 Signaling Pathway.

Purpose:The high fatality-to-case ratio of hepatocellular carcinoma is directly related to metastasis. The signal transducer and activator of transcription-3 is a key mediator of the cytokine and growth factor signaling pathways and drives the transcription of genes responsible for cancer-associated phenotypes. However, so far, no specific inhibitor for signal transducer and activator of transcription-3 has been used in clinical practice. Therefore, targeting the signal transducer and activator of transcription-3 for cancer therapy is highly desired to improve outcomes in patients with hepatocellular carcinoma.Experimental Design:Using the small-molecule inhibitor NT157, the effect of signal transducer and activator of transcription-3 inhibition on cell migration was tested in hepatocellular carcinoma cell lines and a lung metastasis model of the disease.Results:NT157 significantly inhibited the migration of hepatocellular carcinoma cell lines in vitro and lung metastasis of hepatocellular carcinoma in vivo. Mechanistically, it inhibited the phospho-signal transducer and activator of transcription-3 in a dose- and time-dependent manner. Furthermore, NT157 treatment suppressed the c-Jun activation domain-binding protein-1 levels in the nucleus but no significant decrease was observed in its expression in the cytoplasm. Finally, high mRNA expression levels of signal transducer and activator of transcription-3 and c-Jun activation domain-binding protein-1 in hepatocellular carcinoma were associated with significantly low survival rates.Conclusion:NT157 inhibits hepatocellular carcinoma migration and metastasis by downregulating the signal transducer and activator of transcription-3/c-Jun activation domain-binding protein-1 signaling pathway and targeting it may serve as a novel therapeutic strategy for the clinical management of hepatocellular carcinoma in the future.

&lt;p&gt;Prognostic Significance of Preoperative Gamma-Glutamyltransferase to Alkaline Phosphatase Ratio in Hepatocellular Carcinoma Patients with Curative Liver Resection: A Retrospective Cohort Study&lt;/p&gt;

PurposeGamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were involved in the development and progression of cancers. This study aimed to evaluate the prognostic value of a preoperative GGT:ALP ratio (GAR) in hepatocellular carcinoma (HCC) patients with curative liver resection.Patients and MethodsA total of 380 HCC patients underwent curative liver resection before December 2017 and from January to December 2018 were included and stratified into training set and validation set, respectively. Prediction accuracy was evaluated by the area under the receiver operating characteristic curve (AUC). Factors determined to be significant for overall survival (OS) and tumor-free survival (TFS) by using Cox regression analysis. The Kaplan–Meier method and Log rank test were utilized for survival analysis.ResultsThe AUC of GAR was 0.70 (P < 0.001). An optimal cut-off value of 0.91 yielded a sensitivity of 78.1% and a specificity of 60.4% for GAR (P < 0.001), which stratified the HCC patients into high-risk (>0.91) and low-risk (≤ 0.91) groups. Time-dependent ROC revealed that the AUCs for 1-, 3-, and 5-year OS predictions for GAR were 0.60, 0.69 and 0.62, respectively. In addition, GAR was identified as an independent risk factor for OS and TFS both in training and validation cohort by univariate and multivariate Cox regression analysis, as well as a good prognostic indicator for patients with Barcelona Clinic Liver Cancer stage C or without vascular invasion. Notably, the AUC of the GAR for survival was better than several potential prognostic indices (P < 0.05).ConclusionWe identified the GAR as a prognostic indicator in two independent cohorts of HCC patients with curative liver resection. The patients with decreased GAR score were significantly associated with better OS and TFS.

THU498 - The prognostic and diagnostic significance of the neutrophil to lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

THU498 - The prognostic and diagnostic significance of the neutrophil to lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

Genetic Polymorphisms Predisposing the Interleukin 6-Induced APOBEC3B-UNG Imbalance Increase HCC Risk via Promoting the Generation of APOBEC-Signature HBV Mutations.

APOBEC3-UNG imbalance contributes to hepatitis B virus (HBV) inhibition and somatic mutations. We aimed to explore the associations between hepatocellular carcinoma (HCC) risk and genetic polymorphisms predisposing the imbalance.Experimental Design: Genetic polymorphisms at APOBEC3 promoter and UNG enhancer regions were genotyped in 5,621 participants using quantitative PCR. HBV mutations (nt.1600-nt.1945, nt.2848-nt.155) were determined by Sanger sequencing. Dual-luciferase reporter assay was applied to detect the transcriptional activity. Effects of APOBEC3B/UNG SNPs and expression levels on HCC prognosis were evaluated with a cohort of 400 patients with HCC and public databases, respectively. APOBEC3B rs2267401-G allele and UNG rs3890995-C allele significantly increased HCC risk. rs2267401-G allele was significantly associated with the generation of APOBEC-signature HBV mutation whose frequency consecutively increased from asymptomatic HBV carriers to patients with HCC. Multiplicative interaction of rs2267401-G allele with rs3890995-C allele increased HCC risk, with an adjusted OR (95% confidence interval) of 1.90 (1.34-2.81). rs2267401 T-to-G and rs3890995 T-to-C conferred increased activities of APOBEC3B promoter and UNG enhancer, respectively. IL6 significantly increased APOBEC3B promoter activity and inhibited UNG enhancer activity, and these effects were more evident in those carrying rs2267401-G and rs3890995-C, respectively. APOBEC3B rs2267401-GG genotype, higher APOBEC3B expression, and higher APOBEC3B/UNG expression ratio in HCCs indicated poor prognosis. APOBEC-signature somatic mutation predicts poor prognosis in HBV-free HCCs rather than in HBV-positive ones. Polymorphic genotypes predisposing the APOBEC3B-UNG imbalance in IL6-presenting microenvironment promote HCC development, possibly via promoting the generation of high-risk HBV mutations. This can be transformed into specific prophylaxis of HBV-caused HCC.