Ferroelectric-defined reconfigurable homojunctions for in-memory sensing and computing.

Recently, the increasing demand for data-centric applications is driving the elimination of image sensing, memory and computing unit interface, thus promising for latency- and energy-strict applications. Although dedicated electronic hardware has inspired the development of in-memory computing and in-sensor computing, folding the entire signal chain into one device remains challenging. Here an in-memory sensing and computing architecture is demonstrated using ferroelectric-defined reconfigurable two-dimensional photodiode arrays. High-level cognitive computing is realized based on the multiplications of light power and photoresponsivity through the photocurrent generation process and Kirchhoff's law. The weight is stored and programmed locally by the ferroelectric domains, enabling 51 (>5 bit) distinguishable weight states with linear, symmetric and reversible manipulation characteristics. Image recognition can be performed without any external memory and computing units. The three-in-one paradigm, integrating high-level computing, weight memorization and high-performance sensing, paves the way for a computing architecture with low energy consumption, low latency and reduced hardware overhead.

The Effect of Microvascular Invasion on Hepatocellular Carcinoma With Portal Vein Tumor Thrombus After Hepatectomy: A Retrospective Study.

BACKGROUND: There is no report resolving whether microvascular invasion (MVI) affects the prognosis of hepatectomy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). The present study aimed to investigate the effect of MVI on HCC with PVTT after hepatectomy. METHODS: 362 HCC patients with PVTT were included in this retrospective study. Diagnostic criteria of PVTT in HCC patients were based on typical preoperative radiological features on imaging studies. The log-rank test was utilized to differentiate overall survival (OS) and recurrence-free survival (RFS) rates between the two groups. Univariate and multivariate Cox proportional hazard regression was utilized to detect independent factors. RESULTS: PVTT without MVI accounted for 12.2% (n = 44). PVTT without MVI groups was significantly superior to PVTT with MVI groups in OS (the median survival = 27.1 months vs 13.7 months) and RFS (the median survival = 6.4 months vs 4.1 months). The 1-, 3-, and 5-year OS rates (65.5%, 36.8%, 21.7% vs 53.5%, 18.7%, 10.1%, P = .014) and RFS rates (47.0%, 29.7%, 19.2% vs 28.7%, 12.2%, 6.9%, P = .005) were significant different between two groups. Multivariate analysis showed that MVI was an independent risk factor for OS (hazard ratio (HR) = 1.482; P-value = .045) and RFS (HR = 1.601; P-value = .009). CONCLUSIONS: MVI was an independent prognostic factor closely linked to tumor recurrence and poorer clinical outcomes for HCC patients with PVTT after hepatectomy. MVI should be included in current PVTT systems to supplement to the PVTT type.

2D materials-based photodetectors combined with ferroelectrics.

Photodetectors are essential optoelectronic devices that play a critical role in modern technology by converting optical signals into electrical signals, which are one of the most important sensors of the informational devices in current 'Internet of Things' era. Two-dimensional (2D) material-based photodetectors have excellent performance, simple design and effortless fabrication processes, as well as enormous potential for fabricating highly integrated and efficient optoelectronic devices, which has attracted extensive research attention in recent years. The introduction of spontaneous polarization ferroelectric materials further enhances the performance of 2D photodetectors, moreover, companying with the reduction of power consumption. This article reviews the recent advances of materials, devices in ferroelectric-modulated photodetectors. This review starts with the introduce of the basic terms and concepts of the photodetector and various ferroelectric materials applied in 2D photodetectors, then presents a variety of typical device structures, fundamental mechanisms and potential applications under ferroelectric polarization modulation. Finally, we summarize the leading challenges currently confronting ferroelectric-modulated photodetectors and outline their future perspectives.

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification.

BACKGROUND: There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma (HCC) recurrence. Recent studies suggest that postoperative adjuvant transarterial chemoembolization (PA-TACE) is beneficial for patients at high risk of tumor recurrence. However, it is difficult to select the patients. The present study aimed to develop an easy-to-use score to identify these patients. METHODS: A total of 4530 patients undergoing liver resection were recruited. Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization (PDTE) scoring system was established. RESULTS: The scoring system was composed of ten risk factors including alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, operative bleeding loss, resection margin, tumor capsular, satellite nodules, tumor size and number, and microvascular and macrovascular invasion. Using 5 points as risk stratification, the patients with PA-TACE had higher recurrence-free survival (RFS) compared with non-TACE in > 5 points group (P < 0.001), whereas PA-TACE patients had lower RFS compared with non-TACE in ≤ 5 points group (P = 0.013). In the training and validation cohorts, the C-indexes of PDTE scoring system were 0.714 [standard errors (SE) = 0.010] and 0.716 (SE = 0.018), respectively. CONCLUSIONS: The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance. Patients with > 5 points may benefit from PA-TACE.

The danger signal interferon-induced protein 35 (IFP35) mediates acetaminophen-induced liver injury.

Acute liver injury caused by overdose usage of acetaminophen (APAP) is an intractable clinical problem. Necrotic hepatocytes release large amounts of intracellular components including damage-associated molecular patterns (DAMPs) which contribute to liver failure and may serve as therapeutic targets. However, the pathogenic mechanisms of DAMPs in APAP-induced liver injury (AILI) are remain largely uncovered. Here, we found that a recently identified DAMP, interferon-induced protein 35 (IFP35), is involved in the early phase of AILI. Our data demonstrated that although the expression level of IFP35 is not significantly increased in either patients or mice with AILI, it is released from necrotic hepatocytes. Within 24 h post APAP injection, mice lacking Ifp35 are resistant to APAP-induced toxicity, and induce less inflammatory response than that of wild-type mice, including reduced AST/ALT level, pro-inflammatory cytokines production and neutrophils infiltration. More importantly, antibody of IFP35 reduces the expression level of inflammatory factors and chemokines. This study brings new knowledge into the pathogenic mechanism of AILI.

Deubiquitinating enzyme JOSD2 promotes hepatocellular carcinoma progression through interacting with and inhibiting CTNNB1 degradation.

Although a variety of molecular targets have been identified, hepatocellular carcinoma (HCC) remains among the leading causes of death. As functions of they deubiquitinating enzyme Josephin domain containing 2 (JOSD2) in cancers are still poorly understood, we investigated its function and molecular mechanism in the regulation of HCC progression. Here, we indicated that JOSD2 expression is elevated in patient samples with HCC and positively associated with poor prognosis. Moreover, the promoting roles of JOSD2 in HCC cell survival, migration, and invasion were determined using in vitro models. Importantly, a mechanistic study revealed that JOSD2 binds to and decreases the ubiquitination level of catenin beta 1 (CTNNB1), a key component of Wnt signaling, thereby augmenting Wnt pathway transduction. Furthermore, a series of rescue experiments confirmed the significance of CTNNB1 in the modulation of HCC progression by JOSD2. Our study uncovered JOSD2 as a novel prognostic marker for patients with HCC and identified CTNNB1 as a pivotal partner and downstream target protein of JOSD2, which may aid in the development of JOSD2 as a promising molecular target for HCC treatment.

Antiviral Therapy Improves Survival in Hepatocellular Carcinoma with Microvascular Invasion: A Propensity Score Analysis.

BACKGROUND AND AIMS: To investigate the effect of postoperative adjuvant antiviral therapy (AVT) on hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after R0 liver resection. METHODS: A total of 1008 patients with HBV-related HCC with MVI were recruited, which comprises 378 non-AVT groups and 630 AVT groups. Propensity score matching (PSM) was developed to reduce any bias in patient selection. Independent risk factors were identified by Cox regression analysis. RESULTS: After PSM, the 1-, 3-, and 5-year overall survival rates in the AVT group and non-AVT group were 89.2%, 62.4%, 42.1%, and 73.3%, 46.3%, 22.1%, (p < 0.01), respectively. The 1-, 3-, and 5-year recurrence-free survival rates in the AVT group and non-AVT group were 52.5%, 30.4%, 22.1%, and 46.3%, 26.8%, 13.2% (p = 0.02), respectively. Multivariate Cox analysis revealed that postoperative adjuvant AVT was the independent protective factor associated with mortality (HR = 0.55, 95%CI = 0.46-0.67, p < 0.01) and tumor recurrence (HR = 0.81, 95%CI = 0.69-0.96, p = 0.01). CONCLUSIONS: Among patients who underwent curative hepatectomy for HBV-related HCC with MVI, postoperative adjuvant AVT was the independent protective factor associated with mortality and tumor recurrence. Given the high rate of postoperative recurrence and poor prognosis of HBV-related HCC with MVI, our findings may have useful clinical significance in the prevention of tumor recurrence in these patients.

Development of pre and post-operative nomograms to predict individual survival for ideal liver resection candidates with hepatocellular carcinoma.

BACKGROUND: Liver resection is currently the only recommended treatment option for solitary hepatocellular carcinoma (HCC) at an early stage, with well-preserved liver function and no clinically significant portal hypertension. However, this population is heterogeneous, rendering it crucial to develop a risk stratification tool. Therefore, this study aimed to develop preoperative and post-operative nomograms to predict individual survival and stratify patient risk in the ideal candidates for liver resection. METHODS: A total of 1405 ideal liver resection candidates were recruited. Independent risk factors were identified by Cox regression model and used to establish two ideal liver resection for overall survival (IROS) nomograms in training cohort. Model performance was assessed by discrimination, calibration, clinical usefulness. The two model also compared with six other prognostic nomograms and six other staging systems. RESULTS: Multivariate COX analysis revealed that ALP, ln(AFP), NrLR, PNI, ln(tumor size), microvascular invasion, Edmondson-Steiner grade and tumour capsular were the independent risk factors associated with mortality. 5 preoperative variables were incorporated to construct IROS-pre model; All eight available variables were used to draw IROS-post model. The C-index, K-index, time-dependent AUC and DCA of the two models showed significantly better predictive performances than other models. The models could stratify patients into three different risk groups. The web-based tools are convenient for clinical practice. CONCLUSIONS: These two nomograms were developed to estimate survival probability and stratify three strata with significantly different outcomes, outperforming other models in training and validation cohorts, as well as different subgroups. Both IROS models will help guide individualized follow-up.

Transforming growth factor ß1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation.

BACKGROUND: Long-term survival of patients following liver transplantation can be achieved by application of genetically modified, immune tolerogenic immature dendritic cells (imDCs) to overcome allograft-induced acute cellular rejection, a major cause of death. In this study, using a rat model of liver transplantation, we determined whether cotransfection of transforming growth factor ß1 (TGF-ß1) and Fas ligand (FasL) in imDCs synergistically enhances immune tolerance. MATERIALS AND METHODS: We first determined the immune tolerogenic effects of TGF-ß1 and FasL independently or together in imDCs by measuring the levels of CD86 and CD80 and by assessing T-cell proliferation using mixed lymphocyte reaction tests. Next, a rat model of liver transplantation, in which dark agouti and Lewis rats treated with DCs exogenously expressing TGF-ß1 and/or FasL served as donors and recipients, respectively, was used to examine TGF-ß1/FasL-induced immune tolerance. Specifically, we assessed the Banff rejection activity index (RAI), liver functions (alanine transaminase and total bilirubin levels), serum levels of interleukin (IL)-1, IL-10, and IL-12, apoptosis by TUNEL, and posttransplant survival. RESULTS: TGF-ß1/FasL cotransfection of imDCs resulted in greater reduction of CD85 and CD80 expression and T-cell proliferation than a monotransfection. Cotransfected imDCs also showed reduced RAI scores, decreased plasma alanine transaminase and total bilirubin, altered cytokine levels, increased apoptosis, and prolonged survival than monotransfected imDCs in liver-allografted rats. CONCLUSIONS: By enhancing immune tolerance, reducing liver damage, and achieving long-term postsurgery survival, TGF-ß1/FasL cotransfection of imDCs may prove more beneficial for patients undergoing liver transplantation.

Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma.

Recurrence, invasion, and metastasis are the major reasons of the low 5-year survival of hepatocellular carcinoma. However, the mechanisms of recurrence, invasion, and metastasis are still poll understood. Long noncoding RNAs (LncRNAs, >200 nt) have been demonstrated to play important roles in both tumor suppressive and oncogenic signaling pathways. Here, we employed the LncRNAs microarray technology to study the LncRNAs expression profiles at genome-wide in hepatocellular carcinoma (HCC) tissue samples with early recurrence (less than 1 year, with invasion and metastasis out of liver) and late recurrence (longer than 2 years, without invasion and metastasis out of liver), which had different recurrent/metastatic potentials, by using normal liver tissue as control to screen the dysregulated LncRNAs which are potentially involved in the recurrence, invasion, and metastasis process of HCC. Overall, 1170 LncRNAs were identified to differentially expressed between the early and late recurrence samples. These differentially expressed LncRNAs were further characterized by integrating examination of genomic context, co-expression network analysis, and gene ontology (GO) enrichment of their associated protein-coding genes. Furthermore, 15 LncRNAs selected randomly from top 50 differentially expressed LncRNAs were validated by quantitative PCR (qPCR) in cell lines MHCC97H and MHCC97L, which have exactly the same genetic background but with different invasion potentials. Meanwhile, the prognostic potential of three verified LncRNAs at cell line level was further validated in 59 HCC samples. Therefore, our results demonstrated that the aberrant expression of LncRNAs might be responsible for the HCC invasion and metastasis and provide fundamental information for further study the LncRNAs involved molecular mechanisms of the invasion and metastasis of HCC.

Galectin-4 serves as a prognostic biomarker for the early recurrence / metastasis of hepatocellular carcinoma.

Galectin-4 is a multifunctional lectin found at both intracellular and extracellular sites. It could serve as a tumor suppressor intracellularly and promote tumor metastases extracellularly during colorectal cancer development. However, galectin-4 expression and its prognostic value for patients with hepatocellular carcinoma (HCC) have not been well investigated. Here we report that galectin-4 was significantly downregulated in early recurrent/metastatic HCC patients, when compared to non-recurrent/metastatic HCC patients. Low expression of gelectin-4 was well associated with larger tumor size, microvascular invasion, malignant differentiation, more advanced TNM stage, and poor prognosis. Cancer cell migration and invasion could be significantly reduced through overexpression of galectin-4, but upregulated by knocking down of galectin-4 in vitro. Moreover, the serum galectin-4 level could be significantly elevated solely by hepatitis B virus infection. Combined with clinicopathological features, the higher serologic level of galectin-4 was well associated with more aggressive characteristics of HCC. Taken together, galectin-4 expression closely associates with HCC progression and might have potential use as a prognostic biomarker for HCC patients.

Quantitative proteomics analysis of early recurrence/metastasis of huge hepatocellular carcinoma following radical resection.

BACKGROUND: Hepatic resection is the preferred treatment for huge hepatocellular carcinoma (>10 cm in diameter; H-HCC). However, the patients with H-HCC suffer from poor prognosis due to the early recurrence/metastasis. The underlying mechanism of H-HCC's early recurrence/metastasis is currently not well understood. RESULTS: Here, we describe an Isobaric Tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach to analyze the early recurrence/metastasis related proteins of H-HCC after radical resection through multidimensional chromatography coupled with tandem mass spectrometry (2DLC-MS/MS). The different protein expression profiles between the early recurrence/metastasis within 6 months(R/M≤6months) and late recurrence/metastasis within 6-12 months after surgery (R/M6-12months) were confirmed and might reveal different underlying molecular mechanisms. We identified 44 and 49 significantly differentially expressed proteins in the R/M≤6months group and the R/M6-12months group compared to the group who had no recurrence within 2 years post surgery (the NR/M group), respectively. Moreover, among those proteins, S100A12 and AMACR were down regulated in the R/M≤6months group but up-regulated in the R/M6-12months group; and this regulation was further confirmed in mRNA and protein level by Q-PCR, Western-Blot and Immunohistochemistry (IHC). CONCLUSIONS: This current study presents the first proteomic profile of the early recurrence/metastasis of H-HCC. The results suggest that S100A12 and AMACR might be potential prognostic markers for predicting the early recurrence/metastasis of H-HCC after hepatectomy.

Binding of dihydromyricetin and its metal ion complexes with bovine serum albumin.

The binding mechanisms of the interaction of three dihydromyricetin (DMY)-metal complexes (DMY-Cu (II) complex, DMY-Mn (II) complex, DMY-Zn (II) complex) and DMY with bovine serum albumin (BSA) were investigated using fluorescence and ultraviolet spectroscopy at different temperatures. The results indicated some differences in the binding process between different DMY-metal complexes and BSA compared with that of free DMY. All of the complexes and DMY quenched the fluorescence of BSA based on static mode combined with radiationless energy transfer, yet having different binding distance based on the Förster theory. Different DMY-metal complexes can change the binding constants. The binding constants increase for DMY-Cu (II) and DMY-Mn (II) complexes, whereas the opposite is true for the DMY-Zn (II) complex compared to the one with free DMY. The DMY-metal complexes can also affect the types of the interaction. The van der Waals forces and hydrogen bonding may play a major role in the interaction of free DMY with BSA, while for the three complexes, the nature of the binding forces lies in hydrophobic forces and hydrogen bonding based on the thermodynamic parameters.

Huaier granule improves liver inflammation and fibrosis and prevents recurrence in hepatitis B virus related hepatocellular carcinoma.

Background: There is basic research suggesting that Huaier granule can inhibit liver cirrhosis and hepatocellular carcinoma (HCC), but this conclusion has not been clinically verified. We analyzed the distant cancer tissue of two groups of hepatitis B virus (HBV) related HCC with/without Huaier granule, to clarify the effect of Huaier granule on liver inflammation, liver fibrosis, and postoperative recurrence. Methods: We collected clinicopathological data of HCC patients who received two surgery procedures at Mengchao Hepatobiliary Hospital of Fujian Medical University in China from January 2014 to December 2020. Patients according to taking/not taking Huaier granule after the first hepatectomy were divided into two groups, 51 patients with Huaier granule for more than 6 months after operation (Group A); 56 patients without Huaier granule (Group B). The effects on liver inflammation, fibrosis grade, and postoperative recurrence were compared between two groups. Results: The results showed that liver inflammation improved significantly in the Group A [19 (37.3%) cases improved, 31 (60.8%) cases remained unchanged, and 1 (2.0%) case deteriorated] was significantly more than that in the Group B [7 (12.5%) cases improved, 32 (57.1%) cases remained unchanged, and 17 (30.4%) cases deteriorated] (P<0.001). The liver fibrosis in the Group A [17 (33.3%) cases improved, 32 (62.7%) cases remained unchanged, and 2 (3.9%) cases deteriorated] was significantly improved in the Group B [5 (8.9%) cases improved, 45 (80.4%) cases remained unchanged, and 6 (10.7%) cases deteriorated] (P=0.005). The recurrence interval (27.0±21.2 months) in the Group A was significantly longer than that in the Group B (19.0±14.2 months) (P=0.026). Conclusions: Huaier granule can improve liver inflammation, fibrosis, and liver function and prolong the time to recurrence in HBV-related HCC. Given the high rate of postoperative recurrence and poor prognosis of HBV-related HCC, our findings may have useful clinical significance in the prevention of tumor recurrence in these patients.

ARHGEF39 targeted by E2F1 fosters hepatocellular carcinoma metastasis by mediating fatty acid metabolism.

BACKGROUND: Hepatocellular carcinoma (HCC) stands as the prevailing manifestation of primary liver cancer. Previous studies have implicated ARHGEF39 in various cancer progression processes, but its impact on HCC metastasis remains unclear. METHODS: Bioinformatics analysis and qRT-PCR were employed to test ARHGEF39 expression in HCC tissues and cells, identified enriched pathways associated with ARHGEF39, and investigated its regulatory relationship with E2F1. The impact of ARHGEF39 overexpression or knockdown on cellular phenotypes in HCC was assessed through the implementation of CCK-8 and Transwell assays. Accumulation of neutral lipids was determined by BODIPY 493/503 staining, while levels of triglycerides and phospholipids were measured using specific assay kits. Expression of E-cadherin, Vimentin, MMP-2, MMP-9, and FASN were analyzed by Western blot. The interaction between ARHGEF39 and E2F1 was validated through ChIP and dual-luciferase reporter assays. RESULTS: Our study demonstrated upregulated expression of both ARHGEF39 and E2F1 in HCC, with ARHGEF39 being associated with fatty acid metabolism (FAM) pathways. Additionally, ARHGEF39 was identified as a downstream target gene of E2F1. Cell-based experiments unmasked that high expression of ARHGEF39 mediated the promotion of HCC cell viability, migration, and invasion via enhanced FAM. Moreover, rescue assays demonstrated that the promotion of HCC cell metastasis by high ARHGEF39 expression was attenuated upon treatment with Orlistat. Conversely, the knockdown of E2F1 suppressed HCC cell metastasis and FAM, while the upregulation of ARHGEF39 counteracted the repressive effects of E2F1 downregulation on the metastatic potential of HCC cells. CONCLUSION: Our findings confirmed the critical role of ARHGEF39 in HCC metastasis and unmasked potential molecular mechanisms through which ARHGEF39 fostered HCC metastasis via FAM, providing a theoretical basis for exploring novel molecular markers and preventive strategies for HCC metastasis.

NMI Functions as Immuno-regulatory Molecule in Sepsis by Regulating Multiple Signaling Pathways.

Sepsis-induced tissue and organ damage is caused by an overactive inflammatory response, immune dysfunction, and coagulation dysfunction. Danger-associated molecular pattern (DAMP) molecules play a critical role in the excessive inflammation observed in sepsis. In our previous research, we identified NMI as a new type of DAMP molecule that promotes inflammation in sepsis by binding to toll-like receptor 4 (TLR4) on macrophage surfaces, activating the NF-κB pathway, and releasing pro-inflammatory cytokines. However, it is still unknown whether NMI plays a significant role in other pathways. Our analysis of bulk and single-cell transcriptome data from the GEO database revealed a significant increase in NMI expression in neutrophils and monocytes in sepsis patients. It is likely that NMI functions through multiple receptors in sepsis, including IFNAR1, IFNAR2, TNFR1, TLR3, TLR1, IL9R, IL10RB, and TLR4. Furthermore, the correlation between NMI expression and the activation of NF-κB, MAPK, and JAK pathways, as well as the up-regulation of their downstream pro-inflammatory factors, demonstrates that NMI may exacerbate the inflammatory response through these signaling pathways. Finally, we demonstrated that STAT1 phosphorylation was enhanced in RAW cells upon stimulation with NMI, supporting the activation of JAK signaling pathway by NMI. Collectively, these findings shed new light on the functional mechanism of NMI in sepsis.

A mathematical model to predict short-term recurrence and metastasis of primary hepatocellular carcinoma larger than 10 cm in diameter.

BACKGROUND/AIMS: To construct a mathematical model to predict short-term recurrence and metastasis of primary hepatocellular carcinoma (HCC) larger than 10 cm in diameter after radical resection and analyze the influencing factors. METHODOLOGY: A total of 166 patients with primary HCC larger than 10 cm were recruited from January 2002 to December 2010. Univariable and multivariable logistic regression analyses were performed and a mathematic model predicting the recurrence of HCC at different time points was constructed. RESULTS: Univariable analysis showed preoperative serum AFP of ≥1210 ng/mL (X4), intraoperative macroscopic tumor thrombus (X7) and postoperative pathological grade (X11) were related to the recurrence within 6 months after surgery. Preoperative serum AFP of ≥1210 ng/mL (X4) and microscopic tumor thrombus (X10) were associated with the recurrence within 6-12 months after surgery. Multivariable analysis revealed the risk factors of recurrence within 6 months and 6-12 months after surgery included preoperative serum AFP of ≥1210 ng/mL (X4) and intra-operative macroscopic tumor thrombus (X7); those within 6-12 months after surgery were preoperative serum AFP of ≥1210 ng/mL (X4) and microscopic tumor thrombus (X10). CONCLUSIONS: Preoperative serum AFP and blood vessel involvement are risk factors of short-term recurrence/metastasis of huge HCC after surgery. The equation for prediction of HCC recurrence at different time points varies.

Inflammation-Related Marker NrLR Predicts Prognosis in AFP-Negative HCC Patients After Curative Resection.

Background: The role of inflammation-related markers in alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) is not well known. This study aimed to investigate the clinical significance of inflammation-related markers in AFP-negative HCC patients after curative resection. Methods: One thousand one hundred and seventy-nine AFP-negative HCC patients after curative resection were included. Survival rate and prognostic analysis were performed using Kaplan-Meier and Cox regression analysis. Propensity score matching (PSM) was used for patient selection. Results: Multivariate Cox regression showed that neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NrLR) was the independent risk factor associated with OS (p = 0.002) and RFS (p = 0.017). Low NrLR groups (n = 628) had lower rates of albumin-bilirubin (ALBI) grade 2 (p < 0.001), lower rates of bleeding and blood transfusion (p < 0.001) than high NrLR groups. Considering tumor features, low NrLR groups had lower AFP levels (p < 0.001), smaller tumor size (p < 0.001), and lower rates of Edmondson grade III-IV (p = 0.024) than high NrLR groups. After PSM, the 1-year, 3 year-, and 5-year OS rates in the low NrLR and high NrLR groups were 96.3%, 86.9%, 64.9%, and 91.4%, 76.7%, 59.5% (p < 0.001), respectively. The 1-year, 3-year, and 5-year RFS rates in the low NrLR and high NrLR groups were 80.0%, 62.9%, 47.5%, and 71.7%, 52.6%, 39.5% (p < 0.001), respectively. Conclusion: NrLR was a poor prognostic factor for mortality and tumor recurrence in AFP-negative HCC patients after curative resection. The simple and low-cost marker could help physician to determine patients at high risk of tumor recurrence for frequent clinical surveillance.