Search

To investigate the influencing factors of in-hospital acute heart failure (AHF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to construct and validate a risk prediction nomogram model. Three Hundred Thirty patients with AECOPD admitted to our hospital from June 2020 to June 2023 were retrospectively analyzed as a training set for the construction of the model. Three Hundred Twenty-five AECOPD patients admitted to the Second People's Hospital of Hefei from 2006 to June 2023 were also collected as the validation set for the validation of the model. A nomogram model was constructed to predict the risk of nosocomial AHF in patients with AECOPD, and C-index and receiver operating characteristic curve were drawn to assess the predictive predictive efficacy of the model. Model fit was evaluated by Hosmer-Lemeshow test, calibration curve was drawn to evaluate the calibration of the model; decision curve was drawn to analyze the net benefit rate of this nomogram model. Multivariate logistic regression analysis indicated that body mass index, mmRC grade, neutrophils, lymphocytes, hemoglobin, creatinine, PO2, PCO2, and Homocysteine were independent risk factors for in-hospital AHF in patients with AECOPD. To construct a nomogram model for risk prediction of in-hospital AHF in patients with AECOPD. The C-index of the training set was 0.949 (95% CI: 0.91-0.961); the C-index of the validation set was 0.936 (95% CI: 0.911-0.961) suggesting good model discrimination. The receiver operating characteristic curve calculated area under curve for the training set was 0.949 (95% CI: 0.928-0.97); area under curve for the validation set was 0.936 (95% CI: 0.91-0.961) suggesting good model accuracy. The results of Hosmer-Lemeshoe goodness-of-fit test and calibration curve analysis showed that the calibration curve of this nomogram model was close to the ideal curve. The clinical decision curve also showed good clinical net benefit of the nomogram model. Body mass index, mmRC grade, neutrophils, lymphocytes, hemoglobin, creatinine, PO2, PCO2, and Homocysteine are risk factors for in-hospital AHF in AECOPD patients, and nomogram models constructed based on the above factors have some predictive value for in-hospital AHF in AECOPD patients. It is also vital for nursing staff to strengthen nursing care., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Ex vivo liver resection combined with autotransplantation is an effective therapeutic strategy for unresectable end-stage hepatic alveolar echinococcosis (HAE). However, ex vivo liver resection combined with autotransplantation is a technically demanding and time-consuming procedure associated with significant morbidity and mortality. The authors aimed to present our novel remnant liver-first strategy of in vivo liver resection combined with autotransplantation (IRAT) technique for treating patients with end-stage HAE., Methods: This retrospective study included patients who underwent IRAT between January 2014 and December 2020 at two institutions. Patients with end-stage HAE were carefully assessed for IRAT by a multidisciplinary team. The safety, feasibility, and outcomes of this novel technique were analyzed., Results: IRAT was successfully performed in six patients, with no perioperative deaths. The median operative time was 537.5 min (range, 501.3-580.0), the median anhepatic time was 59.0 min (range, 54.0-65.5), and the median cold ischemia time was 165.0 min (range, 153.8-201.5). The median intraoperative blood loss was 700.0 ml (range, 475.0-950.0). In-hospital complications occurred in two patients. No Clavien-Dindo grade III or higher complications were observed. At a median follow-up of 18.6 months (range, 15.4-76.0) , all patients were alive. No recurrence of HAE was observed., Conclusion: The remnant liver-first strategy of IRAT is feasible and safe for selected patients with end-stage HAE. The widespread adoption of this novel technique requires further studies to standardize the operative procedure and identify patients who are most likely to benefit from it., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Vaccines have been considered the most promising solution for ending the coronavirus disease 2019 (COVID-19) pandemic. Information regarding neutralizing antibodies (NAbs) and T-cell immune response in inactivated SARS-CoV-2 vaccine-immunized COVID-19 convalescent patients were either only available for a short time after illness recovered or not available at all (T-cell immunity). We evaluated SARS-CoV-2 NAbs and cellular immune responses to the SARS-CoV-2 inactivated vaccine in convalescent patients who recovered from infection for about one and a half years. We found that compared to before vaccination, SARS-CoV-2 NAbs and specific T-cell responses were significantly boosted by the inactivated vaccine in convalescent patients, which confirmed the pre-existing adaptive immunity in SARS-CoV-2 infected people. We observed that NAbs and IFN-γ-secreting T-cell response elicited by a single vaccine dose in subjects with prior COVID-19 infection were higher than after two doses of vaccine in SARS-CoV-2 naïve subjects. Both humoral and cellular immune responses elicited by one and two doses of inactivated vaccine were comparable in COVID-19-recovered persons. In conclusion, inactivated COVID-19 vaccine induced robust NAbs and T-cell responses to SARS-CoV-2 in COVID-19 convalescent patients and immune responses after one dose were equal to that after receiving two doses, which highlighted that robust humoral and cellular immune response can be reactivated by the inactivated vaccine in SARS-CoV-2 convalescent patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine., Methods: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China., Results: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type., Conclusion: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.

The pandemic COVID-19 is certainly one of the most severe infectious diseases in human history. In the last 2 years, the COVID-19 pandemic has caused over 418.6 million confirmed cases and 5.8 million deaths worldwide. Young people make up the majority of all infected COVID-19 cases, but the mortality rate is relatively lower compared to older age groups. Currently, about 55.04% individuals have been fully vaccinated rapidly approaching to herd immunity globally. The challenge is that new SARS-CoV-2 variants with potential to evade immunity from natural infection or vaccine continue to emerge. Breakthrough infections have occurred in both SARS-CoV-2 naturally infected and vaccinated individuals, but breakthrough infections tended to exhibit mild or asymptomatic symptoms and lower mortality rates. Therefore, immunity from natural infection or vaccination can reduce SARS-CoV-2 pathogenicity, but neither can completely prevent SARS-CoV-2 infection/reinfection. Fortunately, the morbidity and mortality of COVID-19 continue to decline. The 7-day average cumulative case fatality of COVID-19 has decreased from 12.3% on the February 25, 2020, to 0.27% on January 09, 2022, which could be related to a decreased SARS-CoV-2 variant virulence, vaccine immunization, and/or better treatment of patients. In conclusion, elimination of SARS-CoV-2 in the world could be impossible or at least an arduous task with a long way to go. The best strategy to prevent COVID-19 pandemic is to expand inoculation rate of effective vaccines. As the population reaches herd immunity, the mortality rate of COVID-19 may continue to decrease, and COVID-19 could eventually become another common cold., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population., Methods: We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients' sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays., Results: We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10-11 months) and one and a half years (17-18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age., Conclusions: We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Liu, Li, Zhou, Li, Wang, Shen, Lu, Long, Xiao, Wang, Li, Han, Yu, Zhou, Lv and Yu.)

The emerging coronavirus diseases such as COVID-19, MERS, and SARS indicated that animal coronaviruses (CoVs) spillover to humans are a huge threat to public health. Therefore, we needed to understand the CoVs carried by various animals. Wild hedgehogs were collected from rural areas in Wuhan and Xianning cities in Hubei Province for analysis of CoVs. PCR results showed that 5 out of 51 (9.8%) hedgehogs ( Erinaceus amurensis ) were positive to CoVs in Hubei Province with 3 samples from Wuhan City and 2 samples from Xianning City. Phylogenetic analysis based on the partial sequence of RNA-dependent RNA polymerase showed that the CoVs from hedgehogs are classified into Merbecovirus of the genus Betacoronavirus ; the hedgehog CoVs formed a phylogenetic sister cluster with human MERS-CoVs and bat MERS-related CoVs. Among the 12 most critical residues of receptor binding domain in MERS-CoV for binding human Dipeptidyl peptidase 4, 3 residuals were conserved between the hedgehog MERS-related CoV obtained in this study and the human MERS-CoV. We concluded that hedgehogs from Hubei Province carried MERS-related CoVs, indicating that hedgehogs might be important in the evolution and transmission of MERS-CoVs, and continuous surveillance of CoVs in hedgehogs was important., Competing Interests: All authors declare no conflict of interest., (© 2021 The Authors.)

Epithelial-mesenchymal transition (EMT) plays an important role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We hypothesized that germline variants in the major EMT regulatory genes ( SNAIL1 , ZEB1 , ZEB2 , TWIST1 ) may influence the development of HBV-related HCC. We included 421 cases of HBsAg-positive patients with HCC, 1371 cases of HBsAg-positive subjects without HCC [patients with chronic hepatitis B (CHB) or liver cirrhosis (LC)] and 618 cases of healthy controls in the case-control study. Genotype, allele, and haplotype associations in the major EMT regulatory genes were tested. Environment-gene and gene-gene interactions were analysed using the non-parametric model-free multifactor dimensionality reduction (MDR) method. The SNAIL1 rs4647958T>C was associated with a significantly increased risk of both HCC (CT+CC vs . TT: OR =1.559; 95% confidence interval [ CI ], 1.073-2.264; P =0.020) and CHB+LC (CT+CC vs . TT: OR =1.509; 95% CI , 1.145-1.988; P =0.003). Carriers of the TWIST1 rs2285681G>C (genotypes CT+CC) had an increased risk of HCC (CG+CC vs . GG: OR =1.407; 95% CI , 1.065-1.858; P =0.016). The ZEB2 rs3806475T>C was associated with significantly increased risk of both HCC ( P recessive =0.001) and CHB+LC ( P recessive <0.001). The CG haplotype of the rs4647958/rs1543442 haplotype block was associated with significant differences between healthy subjects and HCC patients ( P =0.0347). Meanwhile, the CT haplotype of the rs2285681/rs2285682 haplotype block was associated with significant differences between CHB+LC and HCC patients ( P =0.0123). In MDR analysis, the combination of TWIST1 rs2285681, ZEB2 rs3806475, SNAIL1 rs4647958 exhibited the most significant association with CHB+LC and Health control in the three-locus model. Our results suggest significant single-gene associations and environment-gene/gene-gene interactions of EMT-related genes with HBV-related HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yang, Yan, Yan, Zhang, Ma, Tang, Gao and Liu.)

Aims: Sepsis is a systemic inflammatory complication, which is the common cause of death in critical patients. This study aimed to evaluate the potential regulatory mechanisms of miR-150 in lipopolysaccharide (LPS)-challenged HUVECs and cecal ligation and puncture (CLP)-induced septic mice., Materials and Methods: Human umbilical vein endothelial cells (HUVECs) were challenged with LPS. Pulmonary arterial endothelial cells (PAECs) were isolated from CLP-induced septic mice. The mRNA and protein levels of target molecules were detected by RT-qPCR and Western blotting. Apoptosis of HUVECs was determined by Annexin V/PI staining on a flow cytometry. The interaction between miR-150 and MALAT1 was assessed by luciferase reporter assay, RIP and RNA pull-down assay., Key Findings: MiR-150 was downregulated in LPS-induced HUVECs. MiR-150 mimics restrained LPS-induced inflammatory response by reducing TNF-α and IL-6 levels, but increasing IL-10 level. Moreover, miR-150 mimics downregulated endoplasmic reticulum (ER) stress-related proteins, GRP78 and CHOP levels in LPS-exposed HUVECs. Additionally, LPS-induced apoptosis was suppressed by miR-150 mimics via decreasing cleaved caspase-3 and Bax levels, while enhancing Bcl-2 level. Mechanistically, MALAT1 could competitively bind to miR-150. LPS-induced apoptosis, ER stress and inflammation were promoted by MALAT1 overexpression, but reversed by siMALAT1. Furthermore, miR-150 inhibitor strengthened LPS-induced apoptosis, ER stress and inflammation, which could be attenuated by siMALAT1 via regulating NF-κB pathway. Finally, agomiR-150 repressed ER stress and inflammatory response in PAECs isolated from septic mice via decreasing MALAT1 level., Significance: Our findings suggest that miR-150 affects sepsis-induced endothelial injury by regulating ER stress and inflammation via MALAT1-mediated NF-κB pathway., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To apply artificial intelligence technology in clinical real-world data of patients with primary hepatocellular carcinoma, explore the precise treatment of disease and build up artificial intelligence-based clinical decision support system. Methods: A total of 5 642 patients with primary hepatocellular carcinoma admitted to West China Hospital from July 2004 to June 2016 with complete follow-up records were included in the study. A merged model composed of multiple sub-classifiers was adopted to calculate therapy recommendation coefficient, and receiver operator characteristic curve was analyzed. Survival risk and recurrence risk were predicted by DeepSurv algorithm, and Kaplan-Meier survival curves were further compared among low, middle and high risk groups. Siamese-Net was applied to find similar patients. Results: The Top-1 and Top-2 accuracy of therapy recommendation coefficient reached 82.36% and 94.13% respectively. In internal verification of West China Hospital, the above-mentioned value reached 95.10% in accordance with multi-disciplinary team results. The C-index derived from survival risk model was 0.735 (95 %CI: 0.70-0.77), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test ( P< 0.001). Meanwhile, the C-index derived from recurrence risk model was 0.705 (95 %CI: 0.68-0.73), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test ( P< 0.001). Conclusions: The artificial intelligence-based clinical decision support system for primary hepatocellular carcinoma has can accurately make therapy recommendation and prognosis prediction for primary hepatocellular carcinoma.

Background: To investigate the effects of valproic acid (VPA) on autophagic flux in multiple myeloma (MM) cells., Methods and Results: Cell proliferation was assayed by the Cell Counting Kit-8 assay. The qRT-PCR was used to measure the expressions of LC3-II at mRNA level. Autophagic flux was measured by LC3-II turnover using western blot analysis and flow cytometry using the fluorescent dye Cyto-ID. An assay using the RFP-GFP-LC3 tandem construct was performed to monitor autophagic flux. Cell proliferation assay showed that VPA could inhibit the proliferation of MM cells and the inhibitory effects were enhanced with the extension of time. The qRT-PCR and western blot showed that the expression level of LC3-II in the VPA plus CQ group was significantly higher than that in CQ group. Cyto-ID autophagy test showed that the intracellular average fluorescence intensity in VPA plus CQ group was significantly higher than that in control and VPA group (all p < 0.001). The results of RFP-GFP-LC3 tandem construct showed that the numbers of yellow puncta and red puncta in VPA group was higher than that in control group., Conclusions: VPA could inhibit the proliferation of MM cells and the inhibitory effects were enhanced with the extension of time. VPA could enhance autophagic flux in MM cells, and the increase of autophagosomes was caused by autophagy enhancement rather than inhibition. These findings provided rationale for the treatment of MM with VPA., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Worldwide, hepatocellular carcinoma (HCC) remains a crucial medical problem. Precise and concise prognostic models are urgently needed because of the intricate gene variations among liver cancer cells. We conducted this study to identify a prognostic gene signature with biological significance. We applied two algorithms to generate differentially expressed genes (DEGs) between HCC and normal specimens in The Cancer Genome Atlas cohort (training set included) and performed enrichment analyses to expound on their biological significance. A protein-protein interactions network was established based on the STRING online tool. We then used Cytoscape to screen hub genes in crucial modules. A multigene signature was constructed by Cox regression analysis of hub genes to stratify the prognoses of HCC patients in the training set. The prognostic value of the multigene signature was externally validated in two other sets from Gene Expression Omnibus (GSE14520 and GSE76427), and its role in recurrence prediction was also investigated. A total of 2000 DEGs were obtained, including 1542 upregulated genes and 458 downregulated genes. Subsequently, we constructed a 14-gene signature on the basis of 56 hub genes, which was a good predictor of overall survival. The prognostic signature could be replicated in GSE14520 and GSE76427. Moreover, the 14-gene signature could be applied for recurrence prediction in the training set and GSE14520. In summary, the 14-gene signature extracted from hub genes was involved in some of the HCC-related signalling pathways; it not only served as a predictive signature for HCC outcome but could also be used to predict HCC recurrence., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sensitive, novel, and accurate biomarkers for the detection of physiological changes in type 2 diabetes (T2DM) at an early stage are urgently needed., Aim: To build a multi-parameter diagnostic model for the early detection of T2DM., Methods: MiR-148b, miR-223, miR-130a, and miR-19a levels were detected by real-time polymerase chain reaction in serum of healthy controls, individuals with impaired glucose regulation, and T2DM patients. The diagnostic value of miR-148b, miR-223, miR-130a, and miR-19a, alone or in combination, was analyzed., Results: The area under the curve (AUC) of miR-223, which had the best diagnostic value for discriminating the impaired glucose regulation and T2DM groups, was 0.84, and the sensitivity and specificity were 73.37% and 81.37%, respectively. The AUC of the four-miRNA signature was 0.90, and the sensitivity and specificity were 78.82% and 88.23%, respectively. In the validation set, the AUC was 0.88, and the sensitivity and specificity were 78.36% and 87.63%, respectively., Conclusion: In summary, we have built a multi-parameter diagnostic model consisting of miR-148b, miR-223, miR-130a, and miR-19a for the detection of T2DM. It may be a potential tool for the early detection of T2DM., Competing Interests: Conflict-of-interest statement: We declare that we have no financial or personal relationships with other individuals or organizations that can inappropriately influence our work and that there is no professional or other personal interest of any nature in any product, service and/or company that could be construed as influencing the position presented in or the review of the manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To analyze the effect of down-regulating the CD59 gene expression by RNAi lentivirus as vector on Jurkat cell line of acute T-lineage leukemia., Methods: The expression of CD59 in Jurkat cell line of acute T-line leukemia was induced to decrease by RNAi lentivirus as vector. The transfection of RNA lentivirus and the localization of CD59 molecule were analyzed by laser confocal technique. The relative expression of CD59 gene in blank control, negative control and RNAi lentivirus transfected group was detected by real-time fluorescence quantitative PCR, and the enzyme-linked immunosorbent assay was used to detect the expression of TNF-β and IL-3 in supernatants of cultured cells in 3 groups. The expression levels of apoptosis-related molecules including Caspase-3, Survivin, BCL-2 and BCL-2-associated X protein (BAX) were measured by Western blot., Results: The transfection efficiency for Jurkat cells was higher than 90%. CD59 was mainly located on the cell membrane. Compared with the blank control group and the negative control group, the expression level of CD59 mRNA and protein in the RNAi lentivirus transfected group significantly decreased (P<0.05). Compared with the blank control group and the negative control group, the expression of TNF-β and IL-3 in the RNAi lentivirus transfected group were significantly higher and lower (P<0.05) respectively. The expression levels of Survivin and BCL-2 in the RNAi lentivirus transfected group were significantly lower than those in the blank control group and the negative control group, while the expression levels of Caspase-3 and BAX in the RNAi lentivirus transfected group were significantly higher than those in the blank control group and the negative control group (P< 0.05)., Conclusion: The down-regulation of CD59 gene expression induced by RNAi lenti-virus can decrease the expression of proliferation and differentiation-promoting molecule such as IL-3 and increase the expression of TNF-related factor in Jurkat cell line of acute T-lineage leukemia, which also can increase the expression of apoptosis-related proteins such as Caspase-3 and BAX, and decrease the expression of anti-apoptosis-related proteins such as Survivin and BCL-2.

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: To evaluate the dependability and accuracy of midkine (MK) in the diagnosis of hepatocellular carcinoma (HCC)., Methods: PubMed, EMBASE, Web of Science, China Biology Medicine disc and grey literature sources were searched from the date of database inception to January 2019. Two authors (B-H.Z. and B.L.) independently extracted the data and evaluated the study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were estimated using a bivariate model. Moreover, hierarchical summary receiver operating characteristic curves were generated. The diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled using a univariate model., Results: Nine articles (11 studies) were included (1941 participants). The bivariate analysis revealed that the sensitivity and specificity of MK for HCC diagnosis were 0.85 (95% CI 0.78-0.91) and 0.83 (95% CI 0.76-0.88), respectively. We also found a LR+ of 5.05 (95% CI 3.33-7.40), a LR- of 0.18 (95% CI 0.11-0.28), a DOR of 31.74 (95% CI 13.98-72.09) and an AUC of 0.91 (95% CI 0.84-0.99). Subgroup analyses showed that MK provided the best efficiency for HCC diagnosis when the cutoff value was greater than 0.5 ng/mL., Conclusions: MK has an excellent diagnostic value for hepatocellular carcinoma., Competing Interests: The authors have declared that no competing interests exist.

Posthepatectomy liver failure (PHLF) is the most leading cause of mortality following hepatectomy in patients with hepatocellular carcinoma (HCC). Platelet count was reported to be a simple but useful indicator of liver cirrhosis and function of spleen. Spleen stiffness (SS) was used to evaluate the morphological change of spleen and was reported to be related to liver cirrhosis and portal hypertension. However, the predictive value of platelet to spleen stiffness ratio (PSR) on PHLF remains unknown. A retrospective study was performed to analyze 158 patients with HCC following hepatectomy from August 2015 to February 2016. Univariate and multivariate analyses were performed to evaluate the value of each risk factor for predicting PHLF. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve. PHLF occured in 23 (14.6%) patients. PSR (P<0.001, odds ratio (OR) = 0.622, 95% confidence interval (CI) 0.493~0.784), hepatic inflow occlusion (HIO) (P = 0.003, OR = 1.044, 95% CI 1.015~1.075) and major hepatectomy (P = 0.019, OR = 5.967, 95% CI 1.346~26.443) were demonstrated to be the independent predictive factors for development of PHLF in a multivariate analysis. Results of the present study suggested PSR is a novel and non-invasive model for predicting PHLF in patients with HCC., Competing Interests: The authors have declared that no competing interests exist.

Aim: To investigate the impact of circadian rhythms on the outcomes of liver transplantation on patients suffering from hepatocellular carcinoma (HCC)., Methods: We retrospectively reviewed data of patients who underwent liver transplantation from 2012 to 2017 in our center. Based on the begin time of transplantation, these patients were separated into 2 groups: day group and night group. The intraoperative and postoperative clinical variables were analyzed to find out the impact of the circadian rhythms. Multivariate analysis was performed to examine strength associations between the begin time of operation and surgical outcomes., Results: A total of 147 patients were included in this study: 102 patients in the day group and 45 patients in the night group. Compared with the day group, patients in the night group had higher incidence of intraoperative massive hemorrhage (11.1% vs 2.0%, P = .048), more intraoperative blood loss (2168.00 ± 2324.20 mL vs 1405.88 ± 1037.69 mL, P = .040), and more requirement of red blood cells (RBC) suspension (8.59 ± 7.11 u vs 6.37 ± 5.78 u, P = .048). In addition, total operation time in the night group was longer than that in the day group (8.90 ± 1.65 hours vs 8.26 ± 1.69 hours, P = .034), as well as the cold ischemia time (9.35 ± 5.03 hours vs 7.21 ± 3.93 hours, P = .014). Furthermore, the night group had higher incidence of other intraoperative complications (13.3% vs 2.9%, P = .038), postoperative abdominal infection (20.0% vs 6.9%, P = .038), and more hospital cost (37,357.96 ± 6779.96 dollars vs 33,551.75 ± 11,683.38 dollars, P = .045). Moreover, patients in the night group needed longer time to restore hepatic function to normal (21.77 ± 10.91 days vs 17.54 ± 10.80 days, P = .033). Multivariate analysis showed that begin time of operation was the independent risk factor of longer operation time, more blood loss during operation, higher incidence of massive hemorrhage and other intraoperative complications, longer time for restoration of hepatic function to normal, higher incidence of abdominal infection at the early stage after transplantation, and more hospital cost (all P value ≤ .05)., Conclusion: Liver transplantation performed at night was associated with higher incidence of intraoperative and early postoperative complications, as well as higher hospital cost. And these worsened outcomes all could be explained by the influence that circadian rhythms had on patients or medical workers., (Copyright © 2019. Published by Elsevier Inc.)

The well-controlled structural motifs of zirconium metal-organic frameworks (Zr-MOFs) and their similarity to enzyme cofactors make them ideally suited for biomimetic catalysis. However, the activation methodologies for these motifs, the structural information about active conformations and the reaction mechanism during these biomimetic reactions, are largely unknown. Herein, we have explored the precise pH-controlled activation processes, active sites, and reaction mechanisms for a series of Zr-MOFs as alkaline phosphatase mimics. Activation of the Zr-MOFs with a broad range and precise changes of pH led to the discovery of the MOF-catalyzed volcano plot with activity versus pH changes. This unique response revealed the existence of the precisely pH-controlled active form of the material, which was confirmed with computational analysis using density functional theory and diffuse reflectance infrared Fourier transform spectroscopy. These results will open a window for state-of-the-art design of efficient MOF enzyme mimics in aqueous solution.

Background/aims: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study., Materials and Methods: In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets., Results: From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754-0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716-0.995, P = 0.033)., Conclusions: In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence., Competing Interests: None

Posthepatectomy liver failure (PHLF) is the main cause of perioperative death, and liver cirrhosis is one of the most important risk factors for PHLF. Spleen stiffness (SS) is a novel ultrasonic indicator for liver cirrhosis and portal hypertension, however, it is not clear that whether it has a significant influence on PHLF. Future remnant liver volume (FRLV) is a significant factor for liver regeneration after hepatectomy, spleen volume (SV) could also predict the degree of liver cirrhosis, and recent literatures reported that SV to FRLV ratio (SV/FRLV) could predict small for size syndrome (SFSS) in liver transplantation, however, the relationship between SV/FRLV and PHLF in patients receiving hepatectomy is not known. Systemic inflammatory response (SIR) plays a significant role in the pathogenesis and progression of liver cirrhosis, however, it is not very clear about the exact relationship between SIR and PHLF.We prospectively collected the medical data of consecutive patients diagnosed with hepatocellular carcinoma (HCC) who underwent hepatectomy from August 2015 to February 2016. Preoperative measurements of SS, liver stiffness (LS), SV, FRLV, and SIR were performed on all patients. A univariate analysis was performed to find the risk factors of PHLF and a multivariate analysis was used to identify independent risk factors. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve.Twenty three (23) (14.6%) patients developed PHLF. Univariate analysis found several variables significantly related to PHLF, they were as follows: tumor diameter (P = .01), cirrhosis (P = .001), neutrophil to lymphocyte ratio (NLR) (P = .018), LS (P = .001), SS (P = .001), SV/FRLV (P < .001), operation duration (P = .003), transfusion (P = .009), hepatic inflow occlusion (HIO) (P = .001). Finally, SV/FRLV (P < .001, hazard ratio (HR) = 26.356, 95% confidence interval (CI) 1.627-425.21), SS (P = .009, HR = 1.077, 95%CI 1.017-1.141), and HIO time (P = .002, HR = 1.043, 95%CI 1.014-1.072) were determined as the independent risk factors of PHLF by multivariate analysis.SS and SV/FRLV help to predict the development of PHLF in patients with hepatocellular carcinoma.

Background: Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive (HBcAb + ) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb + liver recipients, and there are few relevant reports in the population of mainland China. We hypothesized that the safety of HBcAb + liver grafts is not suboptimal., Aim: To evaluate the safety of using hepatitis B virus (HBV) core antibody-positive donors for liver transplantation in Chinese patients., Methods: We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study., Results: In the whole population, 230 patients received HBcAb + and 841 patients received HBcAb negative (HBcAb - ) liver grafts. The 1-, 3- and 5-year survival rates in patients and grafts between the two groups were similar (patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3- and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcAb + liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive (HBsAg + ) and HBsAg negative (HBsAg - ) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg - patients with HBcAb + liver grafts (13.23%), in which HBV naive recipients suffered most (31.82%), although this difference did not affect patient and graft survival ( P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody (anti-HBs) titer (more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks., Conclusion: HBcAb + liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb + grafts is rational and feasible., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.

Objective: To investigate the postoperative hemodynamics changes and their influence factors in the donors after right lobe living donor liver transplantation., Methods: A total of 53 consecutive living donors from Dec 2010 to Aug 2015 who underwent donor right lobe hepatectomy were retrospectively analyzed. We measured residual liver hemodynamics with color doppler ultrasound, detected liver stiffness by transient elastography, also analyzed postoperative liver function, hemodynamics, and the long term variation tendency of hepatocirrhosis and spleen., Results: One week after operation, transient liver damage was observed. Post-operative hemodynamics within the follow-up time showed:portal vein diameter was gradually increasing, the velocity decreased gradually;Hepatic vein diameter increased, and the velocity decreased gradually. There was a negative correlation between portal vein diameter and portal vein velocity ( P =0.012, r =-3.11). Liver stiffness ( Kpa value) decreased gradually with time, while spleen volume gradually increased. Correlation analysis showed that postoperative liver stiffness ( Kpa value) was negatively related to portal vein diameter ( P =0.013, r =-0.338) and positively related to hepatic venous velocity ( P =0.038, r =0.246)., Conclusions: The donor presented a transient liver injury after operation, but tended to be recovery after one week. Despite post-operative hemodynamic undergo a series of changes, but it does not affect the post-operative long-term donor safety., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Background: The adoption of laparoscopic techniques for living donor major hepatectomy has been controversial issue. The aim of this study is to present the preliminary experience of laparoscopic right hepatectomy in China., Methods: All the donors receiving right hepatectomy for adult-to-adult living donor liver transplantation (LDLT) were divided into three groups: pure laparoscopic right hepatectomy (PLRH) group, hand-assisted right hepatectomy (HARH) group and open right hepatectomy (ORH) group. We compared the perioperative data and surgical outcomes of donors and recipients among three groups., Results: From November 2001 to May 2017, 295 donors have received right hepatectomy for LDLT in our center. Among them, 7 donors received PLRH, 26 donors received HARH and 262 donors received ORH. The operation time of PLRH group (509.3 ± 98.9 min) was longer than that of the HARH group (451.6 ± 89.7 min) and the ORH group (418.4 ± 81.1 min, p = 0.003). The blood loss was the least in the PLRH group (378.6 ± 177.1 mL), compared with that in the HARH group (617.3 ± 240.4 mL) and that in the ORH group (798.6 ± 483.7 mL, p = 0.0013). The postoperative hospital stay was shorter in the PLRH group (7, 7-10 days) than that in the HATH group (8.5, 7.5-12 days) and ORH group (11, 9-14 days; p = 0.001). Only one donor had pleural effusion (Grade I) and another one experienced pulmonary infection (Grade II). One recipient (14.3%) in the PLRH group occurred hepatic venous stenosis., Conclusions: Laparoscopic approaches for right hepatectomy contribute to less blood loss, better cosmetic satisfaction, less severe complications, and faster rehabilitation. PLRH is a safe and feasible procedure, which must be performed in highly specialized centers with expertise of both LDLT and laparoscopic hepatectomy, and requires a hybrid-to-pure stepwise development.

There is little information regarding the predictive ability of albumin-bilirubin grades (ALBI) plus platelet-to-lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) following liver resection. In this study, we aimed to evaluate the prognostic power of the ALBI-PLR score in patients with hepatitis B virus-related (HBV-related) HCC within Barcelona Clinic Liver Cancer (BCLC) stage A after liver resection.Around 475 patients were included in this study. Patients with preoperative ALBI grades 1, 2, or 3 were allocated a score of 0, 1, or 2, respectively. Patients with preoperative PLR >150 or ≤150 were allocated a score of 0 or 1, respectively. The ALBI-PLR score was the summary of the ALBI and PLR scores.During the follow-up period, 256 patients experienced recurrence, and 150 patients died. Multivariate analysis revealed tumor size, multiple tumors, positive HBV-DNA load, cirrhosis, and ALBI-PLR score as being independently associated with postoperative recurrence, whereas tumor size, high preoperative α-fetoprotein level, and ALBI-PLR score were independent risk factors for postoperative mortality. HCC patients with high ALBI-PLR score had poor recurrence-free and overall survival.The preoperative ALBI-PLR score is a surrogate marker for predicting HBV-related HCC patient's prognosis after liver resection. A high ALBI-PLR score is associated with a high incidence of postoperative recurrence and mortality.

Objective: To assess the value of hepatic resection by comparing it with transarterial chemoembolization for hepatocellular carcinoma beyond the Milan criteria with clinically relevant portal hypertension., Methods: A total of 363 patients and 193 propensity score-matched patients who had hepatocellular carcinoma beyond the Milan criteria with clinically relevant portal hypertension and underwent hepatic resection or transarterial chemoembolization were retrospectively analyzed. The short-term and long-term results were compared., Results: Postoperative complications and 30-day mortality were similar between the two groups. The hepatic resection provided a survival benefit over TACE at 1, 2, 3, and 5 years. Similar results were observed in the propensity score analysis. Five variables were identified as independent prognostic factors: treatment, AFP, Child-Pugh classification, tumor number and extension of disease in a multivariate analysis of the whole study population. In addition, only the tumor number was identified as an independent risk factor after propensity matching. The subgroup analysis demonstrated that the survival benefit of the hepatic resection can only be derived in a subset of patients with a single tumor., Conclusions: In a properly selected group of patients with hepatocellular carcinoma beyond the Milan criteria with clinically relevant portal hypertension, hepatic resection appears to be as safe as TACE and provides a significant survival benefit., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Albumin-bilirubin (ALBI) grade has been validated as a simple, evidence-based, and objective prognostic tool for patients with hepatocellular carcinoma (HCC). However, minimal information is available concerning postoperative ALBI grade changes in HCC. This study aimed to investigate the prognostic value of postoperative ALBI grade changes in patients with hepatitis B virus (HBV)-related HCC within the Milan criteria after liver resection., Methods: Patients with HBV-related HCC within the Milan criteria who underwent liver resection between 2010 and 2016 at West China Hospital were reviewed (N = 258). A change in ALBI grade was defined as first postoperative month ALBI grade-preoperative ALBI grade. If the value was >0, postoperative worsening of ALBI grade was considered; otherwise, stable ALBI grade was considered. Cox proportional hazard regression analyses were used to determine the factors that influence recurrence and survival., Results: During the follow-up, 130 patients experienced recurrence and 47 patients died. Multivariate analyses revealed that postoperative worsening of ALBI grade (HR 1.541, 95% CI 1.025-2.318, P = 0.038), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P = 0.004), and multiple tumors (HR 1.676, 95% CI 1.075-2.615, P = 0.023) were associated with postoperative recurrence, whereas MVI (HR 2.737, 95% CI 1.475-5.080, P = 0.001), postoperative worsening of ALBI grade (HR 2.268, 95% CI 1.227-4.189, P = 0.009), high alpha-fetoprotein level (HR 2.055, 95% CI 1.136-3.716, P = 0.017), and transfusion (HR 2.597, 95% CI 1.395-4.834, P = 0.003) negatively influenced long-term survival. Patients with postoperative worsening of ALBI grade exhibited increased incidence of recurrence and worse long-term survival., Conclusion: Postoperative worsening of ALBI grade was associated with increased recurrence and poorer overall survival for patients with HBV-related HCC within the Milan criteria. We should pay attention to liver function changes in HCC patients after liver resection.

Background/aims: To investigate the association between tacrolimus (TAC) blood concentration and the risk of post-transplantation diabetes mellitus (PTDM) development after living donor liver transplantation (LDLT)., Methods: This study reviewed the clinical data of 158 adult LDLT recipients. A cut-off of mean trough concentration of TAC (cTAC) value at the sixth month postoperatively was identified using a receptor operating characteristic curve. Other clinical complications rates were compared between different cTAC groups., Results: Thirty-four (21.5%) recipients developed PTDM during follow-up period. Recipients with PTDM suffered lower 1-, 5- and 10-year overall survival rates (85.2%, 64.9%, and 55.6% vs 92.4%, 81.4%, and 79.1%, p < 0.05) and allograft survival rates (87.9%, 76.9%, and 65.9% vs 94.1%, 88.5%, and 86.0%, p < 0.05) than those without PTDM. The best cut-off value of mean cTAC was 5.9 ng/mL. Recipients with higher cTAC (>5.9 ng/mL) were more likely to develop hyperlipidemia (39.6% vs 21.9%, p < 0.05), cardio-cerebral events (7.5% vs1.0%, p < 0.05), and infections (37.7% vs19.0%, p < 0.05) than recipients exposed to low cTAC (≤5.9 ng/mL). However, the two groups showed no difference in the incidence of acute and chronic rejection., Conclusion: Higher mean cTAC at the sixth month postoperatively is related to increased risk of PTDM in LDLT recipients., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: There is little information concerning futile liver resection for patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C hepatocellular carcinoma (HCC). This study aimed to establish a predictive model of futile liver resection for patients with BCLC stage B/C HCC., Methods: The outcomes of 484 patients with BCLC stage B/C HCC who underwent liver resection at our centre between 2010 and 2016 were reviewed. Patients were randomised and divided 2:1 into training and validation sets. A novel risk-scoring model and prognostic nomogram were developed based on the results of multivariate analysis., Results: Fifty-seven futile operations were observed. Multivariate analyses revealed tumour numbers > 3, Vp4 portal vein tumour thrombosis (PVTT) and alpha-fetoprotein (AFP) > 400 ng/ml independently associated with futile liver resection. A risk-scoring model based on the above-mentioned factors was developed (predictive risk score = 1 × (if AFP > 400 ng/ml) + 2 × (if tumour number > 3) + 3 × (if with Vp4 PVTT)). The area under the receiver-operating characteristic curve of this model was 0.845, with a sensitivity of 60.0% and a specificity of 94.8%. A prognostic nomogram was also developed and achieved a C-index of 0.831. The validation studies optically supported these results., Conclusion: A risk-scoring model and predictive nomogram for futile liver resection were developed in the present study. T`he BCLC stage B/C HCC patients with a high risk obtained no benefit from liver resection.

Background: There is currently limited information regarding the prognostic ability of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) for hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of the dNLR-PNI in patients with intermediate-to-advanced HCC after transarterial chemoembolization (TACE)., Methods: A total of 761 HCC patients were enrolled in the study. The dNLR-PNI was retrospectively calculated in these patients, as follows: patients with both an elevated dNLR and a decreased PNI, as determined using the cutoffs obtained from receiver operating characteristic curve analysis, were allocated a score of 2, while patients showing one or neither of these alterations were allocated a score of 1 or 0, respectively., Results: During the follow-up period, 562 patients died. Multivariate analysis suggested that elevated total bilirubin, Barcelona Clinic Liver Cancer C stage, repeated TACE, and dNLR-PNI were independently associated with unsatisfactory overall survival. The median survival times of patients with a dNLR-PNI of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 22.5-39.5), 16.0 (95% CI 12.2-19.7) and 6.0 (95% CI 4.8-7.2) months, respectively (P < 0.001)., Conclusions: The dNLR-PNI can predict the survival outcomes of intermediate-to-advanced HCC patients undergoing TACE, and should be further evaluated as a prognostic marker for who are to undergo TACE treatment.

The aim of this study was to evaluate different surgical therapies for hepatic alveolar echinococcosis in different clinical stages.We analyze the clinical data of 115 patients who received surgical treatment in West China Hospital from January 2004 to June 2016. Among these patients, 77 cases underwent radical hepatic resection (group A, n = 77); 17 cases underwent palliative resection (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21) with 12 cases of orthotopic liver transplantation and 9 cases of liver autotransplantation.The postoperative complication rate of radical hepatic resection group was 13.0% (10/77), which is statistically significant (P < .05) than the rate of palliative resection group 29.4% (5/17) or liver transplantation group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall median survival rate of radical resection was 72/77, higher than the rate of palliative group (12/17) or transplantation group (17/21), which was also statistically significant (P < .01).In our study, we believe in that all stages of hepatic alveolar echinococcosis should take active surgical interventions, and radical hepatic resection should be considered as the first-choice treatment for early stage of alveolar echinococcosis, while palliative surgery is still helpful to relieve symptoms and improve the life quality for advanced patients. Liver transplantation might also be an alternative option for the late-stage hepatic alveolar echinococcosis.

Here, we report a case of severe immune thrombocytopenia that occurred after orthotopic liver transplant. On day 16 after transplant, the patient was readmitted to our hospital with a platelet count of 0 cells/mL, with the count remaining at a low level of 1000 to 10 000 cells/mL for 46 days. A diagnosis was made, after exclusion of other causes, of thrombocytopenia. Platelet blood transfusion and high-dose prednisone (1mg/kg/d) combined with intravenous immunoglobulin (0.5g/kg/d) were administered with no improvement. After additional treatments, which included altered use of immunosuppressive agents, changing adefovir to lamivudine and continuous steroid therapy, the patient was discharged with a platelet count of 55 000 cells/mL. Both liver and renal functions generally stayed well during hospitalization. The patient was discharged uneventfully and achieved remission during 10-month follow-up after discharge.

Background: Many studies have confirmed that serum total cholesterol (sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver. However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed., Methods: Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group (sTC <1.42 mmol/L, 57 recipients) and high sTC group (sTC =1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short- and long-term outcomes were compared between the two groups., Results: Recipients with sTC <1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction (38.6% vs 10.3%, P<0.001), 90-day mortality (28.1% vs 10.9%, P=0.002) and severe complications (29.8% vs 17.2%, P=0.041) compared to recipients with sTC =1.42 mmol/L. The multivariate analysis demonstrated that sTC <1.42 mmol/L had a 4.08-fold (95% CI: 1.83-9.11, P=0.001) and 2.72-fold (95% CI: 1.23-6.00, P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC <1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC =1.42 mmol/L (67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%, 68% and 66%, P=0.026, respectively). Cox multivariate analysis showed that sTC <1.42 mmol/L was an independent predicting factor for total recipient survival (HR=2.043; 95% CI: 1.173-3.560; P=0.012) and graft survival (HR=1.905; 95% CI: 1.115-3.255; P=0.018)., Conclusions: sTC <1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short- and long-term outcomes., (Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.)

Objective/aim: The aim of this study was to identify a new index to predict early allograft dysfunction following living donor liver transplantation., Methods: The study enrolled 260 adult living donor liver transplantation recipients. Postoperative laboratory variables were assessed for their association with the prevalence of early allograft dysfunction using the inverse probability of treatment weighting and propensity-score matching (n=93 pairs) analysis., Results: Forty-seven recipients (18.1%) developed early allograft dysfunction. In multivariable analysis, the alanine aminotransferase and gamma-glutamyl transpeptidase levels on postoperative day 1 were independent predictors of early allograft dysfunction. The alanine aminotransferase to gamma-glutamyl transpeptidase ratio (AGR) was developed. All cases were divided into two groups (Group 1 [AGR≥8.47, n=103] and Group 2 [AGR<8.47, n=157]). AGR≥8.47 (OR 10.345, 95%CI 4.502-23.772, p<0.001), hepatorenal syndrome (OR 3.016, 95%CI 1.119-8.125, p=0.029), and graft to recipient weight ratio <0.8% (OR 2.155, 95%CI 1.004-4.624, p=0.049) were independent risk factors for early allograft dysfunction. The prevalence of early allograft dysfunction was higher in group 1 (after adjusting for inverse probability of treatment weighting [n=39; 37.9% vs n=8; 5.1%] and propensity-score matching [n=33; 35.5% vs n=2; 2.2%]) than that in group 2 (p<0.001)., Conclusions: The postoperative AGR is a practical index for predicting early allograft dysfunction after living donor liver transplantation., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The neutrophil-to-lymphocyte ratio (NLR) reflects the systematic inflammatory status, and the aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) is a biomarker of liver fibrosis and cirrhosis. These values can be conveniently obtained from routine blood tests; however, their combined clinical utility has not been extensively studied in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This study aimed to investigate the prognostic value of NLR-AAR in patients with unresectable HCC undergoing TACE. Data for 760 patients with newly diagnosed HCC were retrospectively evaluated. The NLR-AAR was calculated as follows: patients in whom both the NLR and AAR were elevated according to the receiver operating characteristic (ROC) curve analysis were assigned a score of 2; patients showing an elevation in one or neither of these indicators were assigned a score of 1 or 0, respectively. Univariate and multivariate analyses were performed to identify the clinicopathological variables associated with overall survival. An ROC curve was also generated and the area under the curve (AUC) was calculated to evaluate the discriminatory ability of each index at 1, 3, and 5 years of follow-up, as well as overall. The NLR-AAR consistently had a greater AUC value at 1 year (0.669), 3 years (0.667), and 5 years (0.671) post-TACE compared with either NLR or AAR alone. The median survival times of patients with a NLR-AAR of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 24.0-38.0), 15.0 (95% CI 11.2-18.8), and 5.0 (95% CI 4.0-5.9) months, respectively (P < .001). Multivariate analysis showed that the NLR-AAR, elevated total bilirubin level, and vascular invasion were independently associated with overall survival. NLR and AAR, when combined to produce an inflammation-based index and fibrosis score, is an independent marker of poor prognosis in patients with HCC receiving TACE.

For many malignancies, inflammation-based scores correlate with survival. The neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are immunonutritional indices associated with postoperative outcomes in patients with hepatocellular carcinoma (HCC). We evaluated whether a combined preoperative NLR and PNI score was prognostically superior to either index alone in 793 patients with unresectable HCC after transarterial chemoembolization. Patient demographic, clinical, and pathological data were also collected and analysed. A receiver-operating characteristic (ROC) analysis was used to classify patients as follows: NLR-PNI 0 group (NLR ≤ 2.2 and PNI > 46), NLR-PNI 1 group (NLR > 2.2 or PNI ≤ 46) and NLR-PNI 2 group (NLR > 2.2 and PNI ≤ 46). Regarding 1-, 3-, and 5-year survival, the NLR-PNI score had superior discriminative abilities (i.e., higher area under the ROC curve), compared with either the NLR or PNI alone, and patients in the NLR-PNI 0, 1, and 2 groups had median survival times of 33 (95% confidence interval: 22.8-43.2), 14 (10.9-17.1), and 6 (9.9-14.1) months, respectively. In multivariate analyses, the Barcelona Clinic Liver Cancer, total bilirubin, vascular invasion, and NLR-PNI score adversely affected overall survival. In conclusion, the NLR-PNI score can improve the accuracy of prognoses for patients with unresectable HCC.

The aim of this study was to compare the outcomes of patients with multiple hepatocellular carcinoma (HCCs) after liver resection (LR) versus liver transplantation (LT). Patients who had multiple HCCs without macrovascular invasion and who underwent LT or LR between 2007 and 2013 were reviewed. A propensity score matching model was used to adjust baseline differences between the two groups. A total of 204 patients were selected for the current study, including 137 LR patients and 67 LT patients. During follow-up, 100 patients experienced recurrence, and 78 patients died. The 5-year recurrence-free survival rate was 71.1% for the LT group and 31.1% for the LR group (P<0.001). The 5-year overall survival rate was 73.4% for the LT group and 39.8% for the LR group (P<0.001). Moreover, the LT group had better recurrence-free survival and overall survival rates than the LR group regardless of whether the patients met or exceeded the Milan criteria. The multivariate analysis showed that microvascular invasion and LR were independent risk factors for postoperative recurrence, whereas only LR was associated with an increased incidence of mortality. After applying one-to-one propensity score matching, similar results were observed in the propensity score matching model. Our study suggested that LT provided a better prognosis for patients with multiple HCCs than LR regardless of whether the patients met the Milan criteria., Competing Interests: CONFLICTS OF INTEREST The authors declared no conflict of interest

Background: There is paucity of information concerning whether AFP change is a predictor of prognosis for recurrent hepatocellular carcinoma (RHCC) patients after trans-arterial chemoembolization (TACE)., Methods: A total of 177 RHCC patients who received TACE as first-line therapy were retrospectively analyzed. The patients were classified into three groups according to their pre-TACE and post-TACE AFP levels (group A: AFP decreased, group B: AFP consistent normal, and group C: AFP increased). The recurrence to death survival (RTDS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared by the log-rank test. Multivariate analyses were performed to identify prognostic factors for OS and RTDS., Results: There was no significant difference among the three groups concerning the baseline characteristics. The median overall survival (OS) was 74.5 months in group A (95% confidence interval (CI): 63.5, 85.6), 64.0 months in group B (95% CI: 52.3, 75.7) and 29.0 months in group C (95% CI: 24.1, 33.9; P<0.001). The median recurrence to death survival (RTDS) was 66.5 months (95% CI: 53.4, 79.6) in group A, 50.4 months (95% CI: 39.5, 61.4) in group B and 17.7 months (95% CI: 13.4, 22.1; P<0.001) in group C. Multivariate analysis revealed that tumor size at resection stage, tumor number at recurrent stage, cycles of TACE, mRECIST response and AFP change after TACE were significant independent risk factors for RTDS and OS., Conclusions: AFP change could predict the prognoses of patients with RHCC who received trans-arterial chemoembolization, which may help clinicians make subsequent treatment decision., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Platelet, neutrophil, and lymphocyte ratio (PNLR) has its own unique role in influencing postoperative recurrence for patients with hepatocellular carcinoma (HCC). Surgical stress can change systemic inflammatory response of patients. Thus the aim of this study was to identify the prognostic value of changes of platelet times neutrophil to lymphocyte ratio in hepatitis B related HCC within Barcelona clinical liver cancer (BCLC) stage A.Data of patients with HCC within BCLC stage A were reviewed. Pre-, intra- and postoperative variables were retrospectively and statistically analyzed. The postoperative variable was calculated based on the data obtained on the first postoperative month following liver resection.A total of 556 patients were included in present study. During the follow-up period, 257 patients experienced recurrence and 150 patients died. Multivariate analyses suggested multiple tumors (hazard ratio [HR] = 2.409; 95% confidence interval [CI] = 1.649-3.518; P < .001), microvascular invasion (MVI) (HR = 1.585; 95% CI = 1.219-2.061; P = .001), and increased postoperative PNLR (HR = 1.900; 95% CI = 1.468-2.457; P < .001) independently associated with postoperative recurrence, whereas MVI (HR = 1.834; 95% CI = 1.324-2.542; P < .001), postoperative neutrophil to lymphocyte ratio (NLR) (HR = 1.151; 95% CI = 1.025-1.294; P = .018) and increased postoperative PNLR (HR = 2.433; 95% CI = 1.667-3.550; P < .001) contributed to postoperative mortality. The 5-year recurrence-free survival and overall survival rates of patients with increased postoperative PNLR (N = 285) versus those with decreased postoperative PNLR (N = 271) were 36.8% versus 61.5% and 47.6% versus 76.4% respectively (P < .001).Changes of PNLR was a powerful prognostic indicator of poor outcomes in patients with HCC within BCLC stage A. PNLR should be monitored in our postoperative follow-up.

Background: Increasing studies have suggested that surgical resection (SR) or liver transplantation (LT) could bring survival benefits for patients with hepacelluar carcinoma (HCC) beyond Milan criteria. This study compared the long-term survival of patients beyond the Milan criteria who received SR or LT., Material and Methods: A total of 461 HCC patients were retrospectively collected. Analysis was performed using propensity score matching (PSM), the Kaplan-Meier method and the Cox proportional hazards model., Results: Prognosis was significantly better for the LT group than the SR group before (P < 0.001) and after PSM(p = 0.003). In subgroup analysis, for patients with lower AFP level, the 1-, 3-, and 5-year OS rates for the two groups were significantly different (86.7, 71.9, and 71.9% for group LT vs. 75.8, 48.1, and 10.7% for group SR, P = 0.003). For patients with smaller tumor size, the 1-, 3-, and 5-year OS rates were 78.3, 66.7, and 66.7% for group LT, and 83.8, 42.6, and 18.6% for group SR, p = 0.009). Transplantation was a favorable factor associated with prognosis before and after propensity score matching (HR 2.643)., Conclusion: Our propensity model suggested that LT provided significantly better long-term survival than SR for HCC beyond Milan criteria before and after PSM., (Copyright © 2017. Published by Elsevier Ltd.)

Objectives: The aim of this study was to investigate the role of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) vs. intrahepatic cholangiocarcinoma (ICC) and primary liver cancer vs. benign liver lesions for surgical decision making., Methods: Data from 328 patients (296 primary liver cancer patients: 232 HCC and 64 ICC patients and 32 benign hepatic lesion patients) who underwent hepatectomy at our center were retrospectively collected from 2010 to 2015. Conventional ultrasound (US) and CEUS were performed for all patients before hepatectomy. Enhancement patterns in CEUS were classified and compared for HCC vs . ICC and for primary liver cancer vs . benign lesions., Results: Primary liver cancer and hepatic benign lesions could be distinguished by CEUS in different phases. The most obvious differences were in the portal and delayed phases, in which benign lesions could still show hyperenhancement (46.9% vs . 0.0% and p < 0.001 in the portal phase; 43.7% vs . 0.0% and p < 0.001 in the delayed phase). For differentiating HCC and ICC, our results revealed that HCC and ICC displayed different enhancement patterns in the arterial phase ( p < 0.001) and the portal phase ( p < 0.001). In the subgroup analyses, both HCC and ICC showed a high rate of homogeneous hyperenhancement during the arterial phase when tumors were ≤5 cm (87.2% vs . 64.0% and p = 0.008) or the Ishak score was ≥5 (75.8% vs. 42.9% and p = 0.023), although there was statistical difference. However, during the portal phase, ICC > 5 cm showed significantly more frequent hypoenhancement (92.3% vs . 54.5% and p < 0.001) and less isoenhancement (7.7% vs . 45.5% and p < 0.001) than HCC; additionally, during the portal phase, there was no statistical difference in the enhancement patterns of ICC with different hepatic backgrounds., Conclusions: Tumor size and hepatic background should be taken into consideration when distinguishing HCC and ICC before surgery. However, CEUS is a helpful tool for differentiating malignant and benign hepatic lesions. For patients who require surgical treatment, CEUS may help with surgical decision making., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: The impact of using liver allografts from donors who are younger than 14 years at the time of donation after cardiac death (DCD) liver transplantation in terms of early allograft dysfunction (EAD) and graft survival is undefined. To determine if adults undergoing DCD liver transplantation who receive a graft from a donor age younger than or equal to 13 years have similar outcomes to recipients of organs from older than 18-year-old donors., Methods: Records from adult patients undergoing DCD liver transplantation between March 2012 and December 2015 who received whole grafts from donors after cardiac death were reviewed. Patients with donors younger than or equal to 13 years (group 1) and older than 18 years (group 2) were compared for EAD rates, hepatic artery thrombosis (HAT), and graft survival., Results: Records of 60 DCD liver transplantation patients were analyzed. The 90-day and 1-year graft survival rate of both groups was 90% versus 96% (P = .427) and 80% versus 84% (P = .668), respectively. The EAD rates of groups 1 and 2 were 30% versus 34% (P = .806). The incidence of HAT was 20% in group 1 compared with 12% in group 2 (P = .610). Also, 0.7% < graft to recipient weight ratio (GRWR) <0.8% was also usable for pediatric donor to adult recipients., Conclusions: Whole liver grafts from donors younger than or equal to 13 years can potentially be used in selected size-matched (GRWR >0.7%) DCD adult recipients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Assessing the outcomes of surgeries for hepatocellular carcinoma (HCC) patients who exceed the Milan criteria is necessary. Some studies have demonstrated that preoperative or postoperative alpha fetoprotein (AFP) can predict HCC patients' prognoses., Methods: A total of 280 HCC patients who were positive for AFP and received curative resection were retrospectively analyzed. The patients were classified into three groups according to their preoperative and postoperative AFP levels (group A: normalized AFP; group B: AFP decreases >50%, but continued abnormality; and group C: AFP decreases <50%). Disease-free survival and overall survival rates were analyzed using the Kaplan-Meier method. The factors associated with AFP changes were evaluated by logistic regression., Results: AFP dynamic changes were independently associated with disease-free survival and overall survival rates. Group A had better 3- and 5-y survivals than groups B or C (58.7% and 39.5% versus 31.3% and 14.9% versus 17.1% and 8.8%, P < 0.001). Preoperative AFP, tumor differentiation, tumor diameter, microvascular invasion, and satellite nodules remained significant risk factors that were associated with AFP changes. Furthermore, in group A, the disappearances of AFP within and beyond 8 wk resulted in similar overall survival rates (P > 0.05). Among those with HCC recurrence, the patients treated with resurgery or radiofrequency ablation achieved the best recurrence to death survivals. Those treated with transcatheter arterial chemoembolization achieved the next best survivals., Conclusions: AFP changes predicted the prognoses of patients with HCC beyond the predictions of the Milan criteria. Preoperative AFP (>400 ng/mL), tumor differentiation, tumor diameter, and satellite nodules were the risk factors related to AFP normalization. The regular follow-up and early detection of recurrent HCCs that are suitable for curative therapies, such as resurgery and radiofrequency ablation, might improve the prognoses. Other therapies, such as transcatheter arterial chemoembolization, might also be effective., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The recurrence of patients with hepatocellular carcinoma (HCC) beyond the Milan criteria after liver resection (LR) is common. This study aimed to clarify whether LR plus postoperative adjuvant transcatheter arterial chemoembolization (TACE) could improve the outcomes of patients with HCC beyond the Milan criteria after LR., Methods: A total of 754 consecutive patients with HCC beyond the Milan criteria who received LR alone (n = 459) or LR + TACE (n = 295) were included. A propensity scoring matched model (PSM) was used to adjust for the baseline differences between the groups., Results: The 1, 3, and 5-y recurrence-free survival (76.7%, 40.4%, and 30.8%, respectively, for the LR-alone group versus 78.3%, 50.5%, and 46.2%, respectively, for the LR + TACE group; P = 0.004) and overall survival (94.1%, 58.3%, and 36.3%, respectively, for the LR-alone group versus 95.3%, 71.3%, and 54.9%, respectively, for the LR + TACE group; P < 0.001) rates of patients who underwent LR alone were much lower than in the LR + TACE group. Multivariate Cox proportional hazards regression analysis showed that LR alone was an independent risk factor for postoperative recurrence and poor long-term survival. After one-to-one PSM, 284 patients who underwent LR alone and 284 patients who underwent LR + TACE were selected for further analyses. Similar results were observed in the PSM model., Conclusions: This study showed that LR + TACE may be beneficial for patients with HCC beyond the Milan criteria. Postoperative adjuvant TACE should be considered to patients with HCC beyond the Milan criteria., (Copyright © 2016 Elsevier Inc. All rights reserved.)