In July 2024， the European Association for the Study of the Liver released the latest edition of EASL Clinical Practice Guidelines on liver transplantation. The purpose of the EASL guidelines presented here is not to cover all aspects of liver transplantation， but to focus on important advances since the release of the 2016 edition of EASL guidelines. This article gives an excerpt of the recommendations in the guidelines.

The result of liver transplantation (LT) for the treatment of hepatocellular carcinoma (HCC) is constrained by the high rates of tumor recurrence and metastasis. To remove this bottleneck, precise patient selection is crucial for individuals with HCC, and the goal of down-staging therapy is to transform patients exceeding transplantation criteria into suitable candidates. The difficulty in treating tumor recurrence and metastasis post-transplantation calls for more breakthroughs. Immunotherapy, as an emerging treatment modality, requires further exploration to enhance its safety and efficacy. The immunosuppression strategy is also a key factor in reducing tumor recurrence, requiring precise assessment and balanced control.

Objective:To investigate the influence of COX-2 expression in hepatocellular carcinoma (HCC) on the infiltration and immune response of conventional type 1 dendritic cells (cDC1).Methods:Clinicopathological data from 111 HCC patients undergoing radical hepatectomy at Peking University People's Hospital from Jan 2016 to Jun 2017 were retrospectively analyzed. Immunofluorescence staining was employed to evaluate the cDC1 infiltration and COX-2 expression in tumor tissues. Patients were divided into two groups based on cDC1 infiltration: cDC1 enrichment and cDC1 depletion, and the correlation between COX-2 expression and cDC1 infiltration was analyzed. Single-cell sequencing of HCC tumor tissues was used to further investigate the correlation between PTGS2, the encoding gene of COX-2, and cDC1 infiltration. Hematopoietic stem cells (HSC) were utilized for in vitro generation of cDC1. HSC-derived cDC1s were sorted by FACS and cocultured with HCC cell line SNU423. Celecoxib, a selective COX-2 inhibitor, was used to suppress the COX-2 expression in HCC cell line SNU423. The functions of cDC1 were explored by FITC-dextran uptake assay, flow cytometry, and Luminex multiplex cytokine assay. Results:COX-2 expression was significantly higher in the cDC1 depletion group ( n=73) compared to the cDC1 enrichment group ( n=38) ( P=0.004 2). Patients with higher PTGS2 expression had significantly lower proportion of cDC1. Increased cDC1 infiltration in the HCC tumor microenvironment correlated with improved patient overall survival rates ( P=0.037) and disease-free survival rates ( P=0.048). Results from FITC-dextran uptake assay, flow cytometry, and Luminex assay indicated that cDC1 co-cultured with HCC showed significantly reduced antigen uptake function, co-stimulatory molecule expression, and cytokine secretion, but partially abrogated with celecoxib treatment. Conclusions:The intratumoral infiltration of cDC1 is positively correlated with favorable prognosis in HCC patients. Elevated COX-2 expression in HCC impedes the intratumoral accumulation of cDC1 and compromises their immune response capabilities. COX-2 inhibitors hold promise for enhancing cDC1 function in HCC.

Objective:To investigate the predictive value of procalcitonin to platelet ratio (PPR) and C-reactive protein to albumin ratio (CAR) in severe acute pancreatitis (SAP) and the value of SAP and concomitant acute liver injury (ALI).Methods:Total of 195 patients with AP from June 2021 to December 2022 from 374 patients were screened for inclusion in the study and were divided into non-severe acute pancreatitis (NSAP) and SAP groups. The ALI group was divided into non-acute liver injury (NALI) and ALI groups according to ALI criteria, and then into hepatocellular ALI subgroup, cholangiocellular ALI subgroup and mixed ALI subgroup. Laboratory tests for procalcitonin (PCT), C-reactive protein (CRP), albumin and platelet (PLT) were completed within 48 h. Risk factors for SAP, ALI and each subgroup of ALI were analysed by binary logistic regression. Subject work characteristic (ROC) curves were plotted and the optimal thresholds for PPR and CAR were calculated. The predictive value of PPR, CAR and their combination for SAP, ALI and each type of ALI was determined.Results:The AUCs for predicting SAP by plotting ROC curves and calculating the bedside index score of acute pancreatitis severity (BISAP score), PPR, CAR, PPR combined with CAR, PPR combined with BISAP score, CAR combined with BISAP score and combined PPR, CAR and BISAP score were 0.82, 0.85, 0.79 and 0.86. The areas under the ROC curves for PPR, CAR and combined prediction of ALI were 0.81, 0.85 and 0.88, respectively; the areas under the ROC curves for PPR, CAR and combined prediction of hepatocellular ALI were 0.93, 0.77 and 0.92, respectively; and the areas under the ROC curves for PPR, CAR and combined prediction of cholangiocellular ALI were 0.76, 0.76 and 0.77, respectively. The area under the ROC curves for PPR, CAR and combined prediction of mixed ALI were 0.83, 0.76 and 0.82Conclusions:Elevated PPR and CAR are risk factors for SAP and for the development of ALI in AP. PPR has better predictive value than CAR for hepatocellular and mixed ALI, and CAR has better predictive value than PPR for cholangiocellular ALI.

In June 2017,National Health Commission of the People's Republic of China released Guidelines for the diagnosis and treatment of primary liver cancer(2017 edition),which provided important recommendations for the diagnosis,staging,and treatment of liver cancer.Since then,high-level evidence in line with the principles of evidence-based medicine has been continuously obtained from the research on primary liver cancer in China and globally.Therefore,National Health Commission released Guidelines for the diagnosis and treatment of primary liver cancer(2024 edition).This article gives an interpretation of the updated key points in the guidelines,in order to better guide clinical practice.

Objective:To investigate the clinicopathological characteristics and prognostic factors of different histological subtypes of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clincopathological data of 171 patients with ICC who underwent initial curative resection in Peking University People′s Hospital from January 2015 to December 2023 were collected. There were 94 males and 77 females, aged 60(range, 53-68)years. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi‐square test or Fisher exact probability. The Kaplan‐Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. The COX stepwise regression model was used for univariate and multivariate analyses. Results:(1) Comparison of clinicopathological characteristics of different histological subtypes of ICC. Results of postoperative histopathological examination showed that of the 171 ICC patients, there were 76 cases of large duct type ICC and 95 cases of small duct type ICC. There was a significant difference in cases with concomitant intrahepatic biliary stone between patients with different histological subtypes of ICC ( P<0.05), and there were significant differences in cases with concomitant viral hepatitis, cases with CA19-9 >39 U/mL versus CA19-9 ≤39 U/mL, cases with CA19-9 >1 000 U/mL versus CA19-9 >39-1 000 U/mL, tumor gross morphology, and tumor peri-neural invasion between patients with different histological subtypes of ICC ( χ2=8.906, 18.208, 5.689, 43.886, 6.178, P<0.05). (2) Prognostic analysis of different histological subtypes of ICC. Of the 171 patients, 130 cases were followed up for 22(range, 16-43)months, including 63 cases of large duct type ICC and 67 cases of small duct type ICC. The 5-year overall survival rates of the 63 cases of large duct type ICC and 67 cases of small duct type ICC were 12.60% and 43.70%, respectively, showing a significant difference between them ( χ2=5.799, P<0.05). (3) Analysis of prognostic factors for patients undergoing radical resection of ICC. Results of multivariate analysis showed that tumor perineural invasion and lymph node metastasis were independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC ( hazard ratio=0.447, 0.383, 95% confidence interval as 0.259-0.771, 0.225-0.651, P<0.05). Conclusions:There are differences in both clinicopatholo-gical characteristics and prognosis between patients with large duct type ICC and small duct type ICC. Tumor perineural invasion and lymph node metastasis are independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC.

Objective:To investigate the clinicopathological characteristics and prognostic factors of different histological subtypes of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clincopathological data of 171 patients with ICC who underwent initial curative resection in Peking University People′s Hospital from January 2015 to December 2023 were collected. There were 94 males and 77 females, aged 60(range, 53-68)years. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi‐square test or Fisher exact probability. The Kaplan‐Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. The COX stepwise regression model was used for univariate and multivariate analyses. Results:(1) Comparison of clinicopathological characteristics of different histological subtypes of ICC. Results of postoperative histopathological examination showed that of the 171 ICC patients, there were 76 cases of large duct type ICC and 95 cases of small duct type ICC. There was a significant difference in cases with concomitant intrahepatic biliary stone between patients with different histological subtypes of ICC ( P<0.05), and there were significant differences in cases with concomitant viral hepatitis, cases with CA19-9 >39 U/mL versus CA19-9 ≤39 U/mL, cases with CA19-9 >1 000 U/mL versus CA19-9 >39-1 000 U/mL, tumor gross morphology, and tumor peri-neural invasion between patients with different histological subtypes of ICC ( χ2=8.906, 18.208, 5.689, 43.886, 6.178, P<0.05). (2) Prognostic analysis of different histological subtypes of ICC. Of the 171 patients, 130 cases were followed up for 22(range, 16-43)months, including 63 cases of large duct type ICC and 67 cases of small duct type ICC. The 5-year overall survival rates of the 63 cases of large duct type ICC and 67 cases of small duct type ICC were 12.60% and 43.70%, respectively, showing a significant difference between them ( χ2=5.799, P<0.05). (3) Analysis of prognostic factors for patients undergoing radical resection of ICC. Results of multivariate analysis showed that tumor perineural invasion and lymph node metastasis were independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC ( hazard ratio=0.447, 0.383, 95% confidence interval as 0.259-0.771, 0.225-0.651, P<0.05). Conclusions:There are differences in both clinicopatholo-gical characteristics and prognosis between patients with large duct type ICC and small duct type ICC. Tumor perineural invasion and lymph node metastasis are independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC.

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

OBJECTIVE: To investigate the predictive value of pancreatitis activity scoring system (PASS) combined with Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) for infected pancreatic necrosis (IPN) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected, including basic information, vital signs at admission, first laboratory indexes within 48 hours of admission. The PASS scores at admission and 24, 48 and 72 hours after admission were calculated. According to the diagnostic criteria of IPN, the patients were divided into the non-IPN group and the IPN group, and the independent risk factors of SAP complicating IPN were determined by using univariate analysis and multifactorial Logistic regression. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of NLR, CRP, and PASS score, alone and in combination for IPN in patients with SAP. RESULTS: A total of 149 SAP patients were enrolled, including 102 in the non-IPN group and 47 in the IPN group. The differences in PASS score at each time point, NLR, CRP, procalcitonin (PCT), blood urea nitrogen, blood chloride, and days of hospitalization between the two groups were statistically significant. Multifactorial Logistic regression analysis showed that 72 hours admission PASS score [odds ratio (OR) = 1.034, 95% confidence interval (95%CI) was 1.005-1.065, P = 0.022], NLR (OR = 1.284, 95%CI was 1.139-1.447, P = 0.000), and CRP (OR = 1.015, 95%CI was 1.006-1.023, P = 0.001) were independent risk factors for IPN in patients with SAP. ROC curve analysis showed that the area under the ROC curve (AUC) of the PASS score at 72 hours of admission, NLR, and CRP alone in predicting IPN in SAP patients were 0.828, 0.771, and 0.701, respectively. The AUC of NLR combined with CRP, PASS combined with NLR, and PASS combined with CRP were 0.818, 0.895, and 0.874, respectively. The combination of PASS score at 72 hours after admission, NLR, and CRP had a better predictive ability for IPN in patients with SAP (AUC = 0.922, 95%CI was 0.877-0.967), and the sensitivity was 72.3% when the cut-off value was 0.539. CONCLUSIONS The predictive value of the PASS score at 72 hours after admission, NLR and CRP in combination for IPN in SAP patients is better than that of the combination of each two and individual detection and has better test efficacy.
Humans ; Pancreatitis, Acute Necrotizing/diagnosis* ; C-Reactive Protein/metabolism* ; Acute Disease ; Neutrophils/metabolism* ; Retrospective Studies ; ROC Curve ; Lymphocytes ; Prognosis

Objective:To investigate the expression level between AT-Rich Interaction Domain 1A(ARID1A) in intrahepatic cholangiocarcinoma (ICC) and the correlation with tumor microenvironment.Methods:The clinicopathological and survival data of 110 ICC patients undergoing radical hepatectomy in Peking University People's Hospital from Jan 2015 to May 2021 were retrospectively analyzed. Immunohistochemical staining was used to detect the expressions of ARID1A , programmed cell death 1 ligand 1( PD-L1) in tumor tissues , programmed cell death protein 1(PD-1) and cluster of differentiation 8(CD8) in the microenvironment. The relationship between ARID1A expression and PD-L1, PD-1, CD8 protein expression was analyzed.Results:Twenty seven patients did not express ARID1A, absence of ARID1A was associated with high PD-L1, PD-1 and CD8 expression ( P<0.05). Multivariate analysis showed ARID1A expression, preoperative CEA level,preoperative CA19-9 level, lymph node metastasis and tumor number were independent risk factors. Conclusion:Absent expression of ARID1A suggests poor prognosis of ICC patients, high expression of PD-L1,PD-1 and CD8 protein in ICC tumor microenvironment with ARID1A-deficient expression suggests a possible prognosis benefit by using anti-PD-1, anti-PD-L1 and other immunotherapy regimens.