Cysteine protease inhibitor SN(Cystatin SN , CST1), a member of the type 2 cystatins superfamily, regulates tumor biological activities by modulating cysteine protease activity. CST1 is abnormally expressed in digestive system neoplasms, such as esophageal cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic cancer. CST1 influences tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through signaling pathways including Wnt, STAT3, and PI3K-AKT. Its expression levels significantly correlated with tumor stage, metastasis, and patient prognosis, suggesting its potiential as a novel biomarker for early diagnosis, therapeutic evaluation, and prognosis in digestive system neoplasms. This article systematically reviews the molecular characteristics of CST1, its mechanisms of action in digestive system neoplasms, clinical significance, and explores its potential as a therapeutic target.

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that develops on the basis of chronic liver disease. Its key characteristics include acute decompensation of chronic liver disease, severe systemic inflammatory response, and intrahepatic or extrahepatic organ failure, with an exceptionally high short-term (28-day) mortality rate. Currently, liver transplantation is the most effective treatment for ACLF. However, challenges such as liver shortages and organ allocation may lead to delays in transplantation, causing some critically ill ACLF patients to miss the optimal surgical window, thereby significantly worsening their prognosis. Conversely, some ACLF patients may achieve substantial recovery with medical management yet still undergo liver transplantation, leading to unnecessary utilization of scarce donor organs. To maximize patient survival benefits and optimize the use of valuable liver grafts, precise identification of the optimal timing for liver transplantation in ACLF is essential. This review explores the ideal timing for liver transplantation in ACLF patients by examining the definition of ACLF, commonly used scoring systems both nationally and internationally, and the latest research on transplantation indications.

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that develops on the basis of chronic liver disease. Its key characteristics include acute decompensation of chronic liver disease, severe systemic inflammatory response, and intrahepatic or extrahepatic organ failure, with an exceptionally high short-term (28-day) mortality rate. Currently, liver transplantation is the most effective treatment for ACLF. However, challenges such as liver shortages and organ allocation may lead to delays in transplantation, causing some critically ill ACLF patients to miss the optimal surgical window, thereby significantly worsening their prognosis. Conversely, some ACLF patients may achieve substantial recovery with medical management yet still undergo liver transplantation, leading to unnecessary utilization of scarce donor organs. To maximize patient survival benefits and optimize the use of valuable liver grafts, precise identification of the optimal timing for liver transplantation in ACLF is essential. This review explores the ideal timing for liver transplantation in ACLF patients by examining the definition of ACLF, commonly used scoring systems both nationally and internationally, and the latest research on transplantation indications.

Organoid technology for primary liver cancer presents a novel in vitro model that faithfully reproduces the tissue architecture and genetic characteristics of liver cancer, serving as a platform for drug efficacy testing and disease mechanism exploration. Despite hurdles such as modest cultivation success rates and the challenge of fully mimicking the tumor microenvironment, the progression of liver cancer organoid technology holds the potential for advancing personalized medicine and tailored therapies, positioning it as a critical instrument in the investigation of liver cancer treatment strategies. This review delineates the techniques for construction methods of liver cancer organoids, their applications, and the existing constraints.

Objective:To study the effects of different single cell phenotypes on the prognosis of patients with intrahepatic cholangiocarcinoma by using spatial analysis, providing clues for obtaining potential immunotherapeutic targets.Methods:This study was a retrospective cohort study. A total of 41 intrahepatic cholangiocarcinoma (ICC) patients who underwent surgery in Beijing Youan Hospital Affiliated to Capital Medical University from February 2013 to June 2019 were enrolled. According to the 5-year survival situation, the patients were divided into survival group ( n=10) and death group ( n=31). A metal label-based tissue imaging mass panel containing 36 related markers was designed and constructed for staining different components in tumor samples. Through the analysis of the type and quantity of different metacluster and spatial location information and combined with the clinical outcomes of patients with information, certain metaclusters were found related to the prognosis of patients. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), paired t-test was used for comparison between groups. Measurement data with skewed distribution were expressed as median, and rank sum test was used for comparison between groups. The chi-square test was used to compare the counting data between groups. Results:36 biomarkers of 41 ICC patients were located and quantified to generate 1 476 single-cell resolution histological images. The expression information of various markers was analyzed by t-distributed Stochastic Neighbor Embedding (tSNE), and subgroups annotations (1-29) were added. It revealed that the density of metacluster 7(CD8 + T cells) was lower in survival group. The density of metacluster 16(Bcl-2 + CK7 + cancer cells) within tumors, as well as the density of metacluster 3(Vista + GB + CD11b + neutrophils) within stroma were higher in death group. Conclusion:The density of metacluster 7(Activated CD8 + T cells), metacluster 16(Bcl-2 + CK7 + tumor cells) and a novel neutrophil metacluster 3(Vista + GB + CD11b + neutrophils) correlated with ICC patients prognosis.

Objective To investigate the long-term safety and effectiveness of withdrawal of hepatitis B immuneglobulin (HBIG) and/or nucleos(t)ide analogues (NAs) to prevent hepatitis B virus (HBV) reinfection in liver transplant recipients with hepatitis B-related diseases after successful vaccination. Methods Baseline data of 76 liver transplant recipients undergoing hepatitis B immune reconstitution after receiving hepatitis B vaccines were retrospectively analyzed. The vaccination and response, the follow-up results of respondents with HBIG and/or NAs withdrawal, and the reinfection of HBV after withdrawal of HBIG and/or NAs were analyzed. Results The time interval from liver transplantation to hepatitis B vaccination was 26 (20, 40) months. The time interval from vaccination to response was 15 (8,27) months. Initially, 76 recipients withdrew HBIG, and 36 recipients withdrew HBIG and NAs. During the follow-up, 12 of 76 recipients who withdrew HBIG resumed use of HBIG, and 16 of 36 recipients who withdrew HBIG and NAs resumed use of NAs. The withdrawal time of HBIG and NAs was 135 (98,150) and 133 (34,149) months, respectively. Sixteen respondents did not receive booster, and 36 respondents received boosters on a regular basis. The time interval between the first booster and HBIG withdrawal was 44 (11,87) months. No significant differences were observed in baseline data between the respondents with and without boosters (all P>0.05). During the follow-up, 9 recipients were lost to follow-up, 5 were re-infected with HBV, 3 died, and 1 recipient developed graft loss and underwent secondary liver transplantation. Among 5 recipients re-infected with HBV, 4 cases had virus mutation. Significant differences were found between re-infected and uninfected patients regarding withdrawal of NAs and hepatitis B e antigen (HBeAg) positive before transplantation (both P<0.05). Conclusions Long-term withdrawal of HBIG is feasible and safe for recipients with successful hepatitis B immune reconstitution after liver transplantation for hepatitis B-related diseases. Nevertheless, whether antiviral drugs can be simultaneously withdrawn remains to be validated.

Objective:To investigate the safety and efficacy of combining programmed death-1 (PD-1) with tyrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC) before liver transplantation(LT).Methods:The data of six males with a mean ± s. d. age of (57.5±4.3) years who were treated with PD-1 inhibitors combined with TKIs for advanced HCC before LT at Beijing You'an Hospital, Capital Medical University and the First Medical Center of Chinese PLA General Hospital were retrospectively analysed. The tumor stagings, the use of PD-1 inhibitors and TKIs with their discontinuation in pre-LT/post-LT liver function recovery durations, incidences of complication. The tumor recurrence and disease-free survival rates were determined on follow-up of these patients at outpatients clinics.Results:For the 6 patients included in this study, four patients were classified by the Barcelona Clinic Liver Cancer Staging (BCLC) as C and the China Liver Cancer Staging (CNLC) as Ⅲa, and two patients were classified by the BCLC staging as B and the CNLC asⅡb. The mean cycle of PD-1 inhibitor used was 5.5 (1-20), and the mean duration of PD-1 inhibitor discontinuation was 19.5 (12-45) days pre-LT. All patients who were treated with PD-1 inhibitors combined with TKIs reached the liver transplantation standard, and all successfully underwent orthotopic liver transplantation. The liver function recovered well without any serious complications post-LT. All the patients survived without developing any acute rejection or other complications. The follow-up time ranged from 8.2 to 27.3 months, with a median of 11.9 months. No patients had died, and 2 patients developed tumor recurrence. The median (range) tumor-free survival time was 10.9 (2.9-27.3) months.Conclusion:Patients with advanced HCC could benefit from combined PD-1 inhibitors with TKIs therapy pre-LT. There were no increased incidences of acute rejection and other complications post-LT.

Objective:To study the impact and the mechanism of splenectomy combined with pericardial devascularization on cirrhotic livers.Methods:Serum samples and clinical data were collected preoperatively and postoperatively from 54 patients with cirrhosis who underwent splenectomy combined with pericardial devascularization from May 2013 to Oct 2014 at Beijing You’an Hospital, Capital Medical University. Changes in hepatic arterial and portal venous blood flow, liver function and fibroscan results were analyzed. The levels of nitric oxide (NO), endothelin-1 (ET-1), interleukin-6 (IL-6), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 1 (MMP1) were measured.Results:There were 31 males and 23 females, aged(45.48±10.21)years. Free portal vein pressure decreased significantly from (37.0±7.1) cmH 2O (1 cmH 2O=0.098 kPa) to (26.1±5.7) cmH 2O after surgery ( P<0.05). Significant increases in postoperative lumen diameter (4.0±1.0) mm vs (3.1±0.7) mm were observed, accompanied by increase in peak flow velocity and blood flow of the hepatic artery. Significant deductions in lumen diameter (11.9±2.0) mm vs (13.1±1.9) mm, accompanied by reduction of peak flow velocity and blood flow of the portal vein were observed following surgery (all P<0.05). The NO level was significantly elevated immediately after splenectomy and was subsequently remained at high levels. The ET-1 level decreased 2 days after surgery and became fluctuated at low levels. The IL-6 and HGF levels increased significantly 2 days after surgery and decreased gradually after 7 days and 1 month, respectively. The TGF-β1 and the MMP1 levels increased after surgery. The endotoxin level decreased significantly after surgery (all P<0.05). Conclusion:Splenectomy combined with pericardial devascularization induced hepatic blood flow restoration, hepatocyte regeneration and reversal of fibrosis in cirrhotic livers. Splenectomy has a protective effect on cirrhotic liver when combined with pericardial devascularization.

Objective:To investigate the risk factors for short-term mortality and long-term survival after liver transplantation in patients with hepatitis B related acute-on-chronic liver failure.Methods:Forty patients with hepatitis B related acute-on-chronic liver failure performing liver transplantation were prospectively collected from August 2018 to July 2021 in Beijing YouAn Hospital of Capital Medical University. The mean age was (44.5±8.79) years, there were 36 males and 4 females. The basic data, including liver and kidney function, blood routine, coagulation function, lactic acid, infection indexes as well as MELD score, MELD-Na score, CLIF-C ACLFs score, CLIF OFs score, CLIF grade within 48 hours before liver transplantation were counted. The post-LT mortality within 90 days and long-term survival were observed for these patients who were divided into survival group ( n=34) and death group ( n=6) according to the survival in 3 months after liver transplantation. The measurement data conforming to the normal distribution were expressed by mean ± standard deviation ( ± s), and the comparison was performed by t-test between groups; The skewness data were expressed by M ( Q1, Q3), and the rank sum test was used for inter-group comparison. The counting data were tested by Chi square test or Fisher exact probability method. The risk factors of short-term mortality and long-term survival were analyzed through univariate and multivariate analysis as well as survival analysis. The sensitivity, specificity and cut off value were calculated by ROC curve. The patients were divided into ≥ 48.5 scores group ( n=10) and < 48.5 scores group ( n=30) by CLIF-C ACLFs score 48.5 as cut-off value. Kaplan Meier was used for survival analysis and comparison. Results:The total bilirubin (TBIL), creatinine (CR), platelet count, international normalized ratio (INR), lactic acid and neutrophil/lymphocyte ratio (NLR) within 48 hours before liver transplantation were 24.30 (13.45, 33.95) mg/dL, 0.68 (0.53, 1.11) mg/dL and 56 (39, 82)×10 9/L, 3.12(2.33, 4.46), 2.14(1.59, 4.14) mmol/L, 4.06(2.12, 9.13) for all forty patients, respectively. The mean MELD, MELD Na, CLIF OFs, CLIF-C ACLFs and AARC scores within 48 hours before transplantation were (32.1±6.3), (33.2±5.3), (11.2±2.6), (43.8±8.8) and (10.6±2.4) scores, respectively. 65% of patients were complicated with hepatic encephalopathy, 17 patients with controllable systemic infection, 10 patients with renal function injury, 2 patients with variceal bleeding and 6 patients underwent ventilator-assisted ventilation (endotracheal intubation). All 40 patients underwent emergency orthotopic liver transplantation. The incidence of postoperative complications was 47.5%, the most common was post-LT infection (27.5%), followed by renal insufficiency (17.5%). There were significant differences in neutrophil lymphocyte ratio (NLR), lactic acid, MELD score, MELD Na score, CLIF-C ACLFs score, CLIF OFs score, CLIF grades, hepatic encephalopathy, infection and renal injury between survival group and death group ( P<0.05). Univariate logistic regression analysis showed that NLR, MELD Na score, CLIF-C ACLFs score and CLIF OFs score were the risk factors for short-term mortality after liver transplantation ( P<0.05). Multivariate logistic regression analysis showed that CLIF-C ACLFs score was an independent risk factor for 3-month mortality after liver transplantation. ROC curve showed that the area under the curve of CLIF-C ACLFs score was 0.895 (95% CI: 0.779-1.000, P=0.002), and the diagnostic sensitivity and specificity were the highest, 83.3% and 85.3% respectively when cut off value was 48.5. Meanwhile, there was significant difference in long-term survival between the patients with CLIF-C ACLFs score ≥ 48.5 and < 48.5 ( P=0.001). Conclusions:NLR, MELD Na score, CLIF-C ACLFs score and CLIF OFs score within 48 hours before liver transplantation are the risk factors for short-term mortality after liver transplantation, however CLIF-C ACLFs score is an independent risk factor for three-months mortality and long-term survival in patients with hepatitis B related acute-on-chronic liver failure after liver transplantation.

Objective To evaluate the role of live webcast as a new medium in the propaganda and education of liver transplant recipients. Methods According to the contents of live webcast propaganda and education meeting for liver transplant recipients, relevant data of the live webcast meeting were counted and analyzed, including baseline data of participants, participation pattern, viewing frequency and duration, etc. The characteristics between live webcast and traditional propaganda and education meetings were compared. Results By the end of the live webcast meeting, 273 participants were registered, including 2 oversea participants and 271 from China. These domestic participants were from 26 provinces, autonomous regions and municipalities in China. The total number of views was 1 526. Participants attended the meeting by clicking direct link (n=243), WeChat group access (n=22), WeChat chat access (n=7) and Dingding App access (n=1). The viewing duration was (68± 5) min. Compared with the traditional method, the number and places of registers of the live webcast propaganda and education meeting were increased. The questioning methods and filling out follow-up information were more convenient. Participants could attend the meeting free from charge anywhere, and saved more time. The live webcast propaganda and education meeting was not affected by the COVID-19 pandemic, and data statistical method was optimized. Conclusions Live webcast as a new medium, has a wide range of advantages, which provides a novel form of propaganda and education for the recipients after liver transplantation. It is of significance to improve the long-term survival rate and to enhance the quality of life of recipients after liver transplantation.