Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B.

BACKGROUND: Controversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs) respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response. METHODS: Fifteen chronic hepatitis B patients, with inflammatory flare episode, were recruited prospectively. Based on serum HBV-DNA, HBsAg load, and ALT values, inflammatory flare episode were divided into initial, climax, decline and regression phase. Blood sample and liver biopsy tissues from each individual were taken in these 4 phases respectively. Circulating and intra-hepatic PD1 and PD-L1 expression levels were monitored throughout the inflammatory flare episode by flow cytometry and immunostaining and these expression levels were related to the HBV-specific T-cell changes, expression of pro-inflammatory cytokines, HBV-DNA replication and HBV antigen load. RESULTS: ]The levels of PD-1 and PD-L1 expressions were significantly up-regulated in the inflammation ascending phase, initial and climax period and in parallel with HBV-specific colon expansion. It showed increasing the level of serum ALT and decreasing the HBV-DNA loads. As the level of inflammation reduced, the circulating and intra-hepatic PD1 and circulating PD-L1 decreased progressively in concordance with serum ALT, HBV-DNA and HBsAg loads decreased except intra-hepatic PD-1 expression. Intra-hepatic PD-L1 expression did not decrease significantly during the regression phase of inflammation compared to that in prior period. The intra-hepatic PD-L1 expression remained relatively on higher level when serum HBV-DNA load and ALT decreased to approximately normal range. CONCLUSION: The relatively high level of intra-hepatic PD-L1 expression during the inflammatory regression period may contribute to constitute an immunosuppressive microenvironment, which facilitate persistent HBV infection via the inhibition of HBV-specific T cell clonal expansion.

Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).

Frontiers in liver transplantation for liver cancer: sarcopenia / 中华器官移植杂志

Liver cancer patients scheduled for liver transplantation (LT) are frequently accompanied by liver cirrhosis.Within a state of long-term malnutrition and inflammatory stress, they are prone to sarcopenia with a poor efficacy of LT.Influenced by such multiple factors as surgery, infections and metabolic disorders, there is an elevated risk of exacerbation or a new onset of sarcopenia after LT.Therefore meticulous managements of sarcopenia are required throughout all aspects and periods of LT.A refined recipient stratification system of sarcopenia can accurately predict the efficacy of LT and its evaluating system has been becoming more precise, diverse and intelligent.Currently basic researches of sarcopenia have remained in infancy and its interactions with the related organs have become a novel research field.Sarcopenia has become an emerging challenge of LT for liver cancer.Further mechanistic explorations of sarcopenia are warranted and clinical precision managements should be further optimized.

Prognostic analysis of steatosis donor liver transplantation: a multicenter clinical trial / 中华器官移植杂志

Objective:To explore the early and medium-long term outcomes of steatosis donor liver transplantation(LT)for an optimal clinical application.Methods:From January 2015 to December 2020, this retrospective cohort study was conducted jointly at Shulan (Hangzhou) Hospital, First Affiliated Hospital of Zhejiang University and First Hospital of Jilin University. The relevant clinicopathological and follow-up data were collected from 1535 LT recipients. For comparison, propensity score was utilized for case-control matching of steatosis and non-steatosis donor livers. According to presence or absence of liver steatosis, the recipients were divided into two groups of steatosis donor liver (n=243) and non-steatosis donor liver (n=1292). And 1∶1 propensity score matching was made for two groups. Then early and medium-long term outcomes of two groups were examined. Counts were described as absolute numbers. Kaplan-Meier method was employed for calculating survival time and plotting survival curve and Log-rank test for survival analysis. COX regression model was utilized for univariate and multivariate analyses. Based on basic metabolic disease pre-LT, steatosis donor liver recipients were divided into three subgroups: BMI ≥25 kg/m 2 with hypertension or diabetes (n=21), BMI<25 kg/m 2 and no hypertension or diabetes (n=130) and other recipients (n=92). A comparative study was performed for determining the prognosis of subgroups according to the different characteristics of recipient and donor liver. Results:No significant inter-group difference existed in 2-year survival post-LT ( P=0.174). However, significant inter-group difference in survival existed after 2 years post-LT ( P=0.004). And 3/5-year survival rate of steatosis donor liver was 66.4% and 44.2% respectively. Both were significantly lower than those of non-steatosis donor liver. Multivariate Cox regression analysis indicated that steatosis donor liver and male recipients were independent risk factors for prognosis >2 years survival post-LT( P=0.008, P=0.004). Subgroup analysis of steatosis liver donors showed that the prognosis of patients with BMI ≥25 kg/m 2 with hypertension or diabetes was significantly worse than other subgroups (BMI <25 kg/m 2 with no hypertension or diabetes and other recipients) <2 years survival post-LT ( P=0.029, P=0.043). Conclusions:Steatosis donor liver does not affect early survival of recipients, yet reduces medium-long term survival rate of recipients notably. In steatosis donor liver recipients, early survival rate declines markedly in recipients with preoperative BMI ≥25 kg/m 2 with hypertension or diabetes as compared with BMI <25 kg/m 2 with no hypertension or diabetes group.

Role of thioredoxin reductase 1 in multidrug resistance caused by reactive oxygen species-related cell apoptosis in hepatocellular carcinoma / 临床肝胆病杂志

Objective Drug resistance is the main cause of chemotherapy failure in hepatocellular carcinoma (HCC), and thioredoxin reductase 1 (TXNRD1), as a major influencing factor for reactive oxygen species (ROS) metabolism, has been proven to be associated with the poor prognosis of patients with HCC. This study aims to explore the role of TXNRD1 in the mechanism of multidrug resistance in HCC. Methods BEL/FU cells in BEL-7402 cell line were selected as the multidrug-resistant cell line. The siRNA was used for the intervention of TXNRD1 expression; quantitative real-time PCR and Western blotting were used to measure the expression of TXNRD1; CCK-8 assay and flow cytometry were used to evaluate the effect of TXNRD1 on hepatocyte ROS accumulation, resistance to 5-fluorouracil (5-Fu) and doxorubicin (DOX), and apoptosis in vitro; a xenograft tumor model was established to investigate the effect of auranofin (AUR) on drug resistance in vivo. The two-independent-samples t test was used for comparison of continuous data between two groups. Results As a multidrug-resistant HCC cell line, BEL/Fu showed high mRNA and protein expression levels of TXNRD1 (both P < 0.05). Compared with 5-Fu or DOX treatment alone, the TXNRD1 inhibitor AUR combined with 5-Fu or DOX had had a significant reduction in the number of colony formation ( P < 0.01) and a significant increase in apoptosis ratio ( P < 0.001). The ROS scavenger N-acetylcysteine (NAC) significantly weakened the effect of TXNRD1 knockdown by siRNA on the drug resistance of BEL/Fu cells, and the application of NAC effectively reduced the apoptosis ratio of cells after siRNA interference ( P < 0.001). Animal experiments also confirmed that compared with the nude mice treated with 5-Fu alone, the nude mice treated with 5-Fu and AUR had a significantly lower tumor mass ( P < 0.001) and a significantly smaller tumor volume ( P < 0.001). Conclusion TXNRD1 plays an important role in the drug resistance of HCC, and inhibition of its level in cells can effectively improve drug resistance. As a TXNRD1 inhibitor, AUR has great application prospects in the multimodality therapy for HCC.

Difficulties in diagnosis and treatment of pyogenic liver abscess / 中华肝胆外科杂志

Klebsiella pneumoniae liver abscess accompanied by metastatic infectious complications was firstly reported in 1986. The pathogen was defined as Hypervirulent K. pneumoniae (hvKp) after a series of studies, which is an evolving pathotype and more virulent than classical K. pneumoniae (cKp). At present, it is difficult to distinguish hvKp and cKp in the clinical microbiology lab, which results in delay in early diagnosis and treatment on hvKp-related infections. Biliary tract diseases after cholangiojejunostomy, biliary interventional therapy and liver transplantation have become common causes of recurrent acute cholangitis. The incidence of bacterial liver abscess is on the rise, especially the infection caused by multidrug-resistant bacteria. This article reviews difficulties in the diagnosis and treatment of bacterial liver abscess.

Prognosis and influencing factors of liver transplantation for hepatocellular carcinoma using steatotic donor liver: a multicenter study / 中华消化外科杂志

Objective:To investigate the prognosis and influencing factors of liver transplantation (LT) for hepatocellular carcinoma (HCC) using steatotic donor liver.Methods:The retrospective cohort study was conducted. The clinicopathological data of 152 pairs of donors and the corresponding recipients undergoing LT for HCC in the two medical centers [89 pairs in Shulan (Hangzhou) Hospital and 63 pairs in the First Affiliated Hospital of Zhejiang University School of Medicine] from January 2015 to December 2019 were collected. Of 152 donors, there were 131 males and 21 females, aged (48±12)years, and there were 130 cases with liver mild steatosis and 22 cases with liver moderate steatosis. Of 152 recipients, there were 138 males and 14 females, aged (52±9)years. Observation indicators: (1) follow-up, overall survival and tumor recurrence free survival of recipients; (2) influencing factors for overall survival and tumor recurrence free survival of recipients; (3) construction and validation of nomogram prediction model for overall survival and tumor recurrence free survival of recipients. Follow-up was conducted using outpatient examination and telephone interview to detect survival and tumor recurrence of recipients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( IQR). Count data were described as absolute numbers. The Kaplan-Meier method was used to calculate the survival time and draw survival curve, and the Log-Rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analysis. The independent risk factors were brought into the R 3.6.2 software to construct nomogram prediction model and draw the receiver operating characteristic (ROC) curve. The accuracy and discrimination of the nomogram prediction model were evaluated using the area under curve (AUC) and the calibration curve. Results:(1) Follow-up, overall survival and tumor recurrence free survival of recipients. All the 152 recipients undergoing LT for HCC using steatotic donor liver were followed up for 45.8(27.6)months, with the overall survival time and tumor recurrence free survival time of 36.5(32.3)months and 30.4(34.6)months. The 1-year, 3-year overall survival rates and tumor recurrence free rates of the 152 recipients were 73.4%, 55.8% and 62.2%, 43.4%, respectively. (2) Influencing factors for overall survival and tumor recurrence free survival of recipients. Results of univariate analysis showed that the donor liver cold ischemia time (CIT), the donor liver warm ischemia time (WIT), graft-to-recipient weight ratio (GRWR), ABO compatibility, recipient body mass index (BMI), recipient tumor diameter, recipient tumor number, recipient tumor differentiation degree, recipient preoperative alpha fetoprotein (AFP) were related factors influencing the overall survival of recipients ( hazard ratio=6.26, 1.90, 2.47, 4.08, 0.55, 5.16, 3.62, 5.28, 2.65, 95% confidence interval as 3.01?13.03, 1.07?3.38, 1.36?4.49, 2.07?8.03, 0.31?0.98, 2.56?10.42, 1.95?6.72, 1.60?17.42, 1.48?5.01, P<0.05) and the donor liver CIT, GRWR, ABO compatibility, recipient tumor diameter, recipient tumor number, recipient tumor differentiation degree, recipient preoperative AFP were related factors influencing the tumor recurrence free survival of recipients ( hazard ratio=4.24, 2.53, 4.05, 3.39, 3.10, 5.19, 2.63, 95% confidence interval as 2.50?7.21, 1.54?4.17, 2.12?7.72, 2.04?5.62, 1.91?5.03, 2.04?13.18, 1.61?4.30, P<0.05). Results of multivariate analysis showed that donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm and recipient preoperative AFP ≥400 μg/L were independent risk factors influencing the overall survival of recipients ( hazard ratio=4.21, 2.58, 4.10, 2.27, 95% confidence interval as 1.98?8.96, 1.24?5.35, 1.35?12.43, 1.13?4.56, P<0.05) and donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm, recipient tumor number ≥3 and recipient preoperative AFP ≥400 μg/L were independent risk factors influencing the tumor recurrence free survival of recipients ( hazard ratio=3.37, 2.63, 2.42, 2.12, 2.22, 95% confidence interval as 1.70?6.67, 1.40?4.96, 1.04?5.66, 1.08?4.18, 1.26?3.90, P<0.05). (3) Construction and validation of nomogram prediction model for overall survival and tumor recurrence free survival of recipients. The donor live CIT, GRWR, recipient tumor diameter, recipient preoperative AFP were used to construct nomogram prediction model for overall survival of recipients and the donor liver CIT, GRWR, recipient tumor diameter, recipient tumor number, recipient preoperative AFP were used to construct nomogram prediction model for tumor recurrence free survival of recipients. The ROC curve showed that the AUC of the nomogram prediction model for overall survival of recipients was 0.84 (95% confidence interval as 0.76?0.92, P<0.05), with the optimal diagnostic value as 7.3 and the specificity and sensitivity as 87.6% and 70.0%. The AUC of the nomogram prediction model for tumor recurrence free survival of recipients was 0.79 (95% confidence interval as 0.71?0.87, P<0.05), with the optimal diagnostic value as 5.8 and the specificity and sensitivity as 97.4% and 52.5%. The calibration curve showed that the nomogram prediction model had good distinction for high risk recipients in overall survival and tumor recurrence free survival. Conclusion:Donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm and recipient preoperative AFP ≥400 μg/L are independent risk factors influencing the overall survival of recipients who underwent LT for HCC using steatotic donor liver and donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm, recipient tumor number ≥ 3 and recipient preoperative AFP ≥400 μg/L are independent risk factors influencing the tumor recurrence free survival of recipients.

Splenic vascular flow control in the use of laparoscopic spleen-preserving distal pancreatectomy (Kimura) / 中华普通外科杂志

Objective:To investigate the techniques used in blood flow control of Kimura laparoscopic spleen-preserving pancreatectomy (LSPDP).Methods:Forty·five patients with benign or low-grade malignant pancreatic diseases undergoing LSPDP at Huzhou Central Hospital from May 2014 to Oct 2021 were analyzed retrospectively. Patients were divided into splenic vascular flow control group ( n=22) and routine management group ( n=23). Results:There was no significant difference in gender, age, BMI, accompanying symptoms, hypertension, diabetes, lesion size and pathological diagnosis between the two groups (all P>0.05). A higher overall spleen preservation rate (90.9% vs. 52.2%, χ2=8.213, P=0.004), lower incidence of morbidity with Clavien grade ≥ Ⅱ (22.7% vs. 73.9%, χ2=9.911, P=0.002) and shorter postoperative hospital stay [(9.6±4.5) d vs. (14.3±6.6) d, t=2.447, P=0.008] were achieved in the vascular flow control group compared with those in the routine group. Conclusion:Splenic vascular flow control techniques improve the success rate of spleen preservation in laparoscopic distal pancreatectomy, reduce the postoperative complications and shorten the postoperative hospital stay.

Preliminary evaluation of immune checkpoint inhibitors as a salvage treatment of tumor recurrence after liver transplantation for hepatocellular carcinoma / 中华器官移植杂志

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field / 医学前沿

Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host's immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.

Prognosis and influencing factors analysis of liver transplantation elderly recipients: a multicenter study / 中华消化外科杂志

Objective:To investigate the prognosis of liver transplantation (LT) elderly recipients and analyze the influencing factors for prognosis.Methods:The retrospective cohort study was conducted. The clinicopathological data of 400 LT recipients who were admitted to three medical centers from January 2015 to June 2020 were collected, including 368 cases in the First Affiliated Hospital of Zhejiang University School of Medicine, 17 cases in the Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine and 15 cases in the Affiliated Hospital of Qingdao University. There were 297 males and 103 females, aged from 22 to 75 years, with a median age of 60 years. Of the 400 LT recipients,200 cases aged ≥60 years were divided into elderly recipients (ER) group and 200 cases aged <60 years were divided into non-elderly recipients (NER) group. Reci-pients underwent orthotopic LT or modified piggyback LT. Observation indicators: (1) survival of recipients and grafts for two groups; (2) influencing factors for death of LT recipients; (3) stratification analysis of ER group. Follow-up using the outpatient examination and telephone interview was conducted to detect survival and prognosis of patients up to May 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-Rank test was used for survival analysis. COX regression model was used for univariate and multivariate analyses. Results:(1) Survival of recipients and grafts for two groups: 400 recipients were followed up for 1 day to 71.7 months, with a median follow-up time of 16.3 months. Survival analysis showed that the 1-, 3-year overall survival rates and 1-, 3-year graft survival rates for ER group were 72.70%, 60.66% and 72.70%, 59.64%, respectively, versus 78.84%, 75.48% and 78.84%, 74.22% for NER group, showing significant differences in the overall survival and graft survival between the two groups ( χ2=5.712, 5.681, P<0.05). (2) Influencing factors for death of LT recipients: results of univariate analysis showed that age, score of model for end stage liver disease, Child-Pugh score, cold ischemia time(CIT) of liver donor, hypertension, blood type of recipients and donors, volume of intraoperative blood loss, volume of intraoperative red blood cell transfusion, volume of intraoperative plasma transfusion, volume of intraoperative crystalloid fluid transfusion, the maximum alanine aminotransferase within postoperative 7 days, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were related factors for death of LT recipients ( odds ratio=1.026, 1.022, 1.084, 1.070, 1.701, 2.728, 1.000, 1.056, 1.089, 1.000, 1.000, 1.000, 1.003, 95% confidence interval as 1.006-1.045, 1.005-1.040, 1.060-1.170, 1.011-1.132, 1.133-2.554, 1.701-4.374, 1.000-1.001, 1.031-1.082, 1.039-1.142, 1.000-1.003, 1.001-1.004, 1.000-1.002, 1.001-1.004, P<0.05). Results of multivariate analysis showed that age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were independent influencing factors for death of LT recipients ( odds ratio=1.022, 2.761, 1.000, 1.007, 95% confidence interval as 1.001-1.044, 1.612-4.727, 1.000-1.001, 1.002-1.012, P<0.05). (3) Stratification analysis of ER group: ① of 200 recipients in ER group, cases with 0 hour≤CIT≤8 hours, 8 hours<CIT≤12 hours, CIT>12 hours were 96, 73, 31 ,respectively. The 1-year overall survival rates for above recipients were 77.46%, 73.33%, 54.07%, and the 3-year overall survival rates were 62.67%, 65.05%, 41.30%. There was a significant difference in the overall survival between the three groups ( χ2=6.708, P<0.05). ② Of 200 recipients in ER group,182 cases were ABO compatible and 18 were ABO incompatible. The 1-year overall survival rates for above recipients were 77.32%, 27.78%, and the 3-year overall survival rates were 64.63%, 22.22%. There was a significant difference in the overall survival between the two groups ( χ2=23.165, P<0.05). Conclusions:The overall survival of ER is inferior to NER. Age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin are indepen-dent influencing factors for death of LT recipients. Controlling CIT within 12 hours and avoiding ABO incompatible-liver transplantation can significantly improve the prognosis of ER.

Predictive effect of liver fibrosis score and other factors on the prognosis of liver transplantation for liver cancer / 中华器官移植杂志

Objective:To explore the value of aspartate aminotransferase(AST)and platelet (PLT)ratio index(APRI)in the prognosis of liver transplantation(LT)for hepatocellular carcinoma and establish a nomogram model for evaluating its clinical application potential.Methods:From January 2015 to December 2019, retrospective review was conducted for clinical data of LT for hepatocellular carcinoma(HCC)at First Affiliated Hospital of Zhejiang University School of Medicine and Shulan(Hangzhou)Hospital(601 cases). They were randomized into two groups of modeling (399 cases)and validation(202 cases)and then divided into low and high APRI groups according to the APRI value at Month 1 post-transplantation. The independent risk factors of recurrence and prognosis post-LT were screened in modeling group using univariate and multivariate Cox regression analyses and were further used for constructing a nomogram prediction model. The receiver operating characteristic curve(ROC)and survival curve were utilized for verifying the accuracy of nomogram prediction model.Results:Univariate and multivariate Cox regression analyses revealed that independent risk factors for the prognosis of HCC-LT included cold ischemic time(CIT) >8 h, beyond Hangzhou criteria, surgical bleeding volume >1 000 ml and APRI >1.5. The AUC of HCC-LT recurrence prediction model was 0.734(95%CI: 0.681~0.787)and 0.749(95%CI: 0.671~0.817)in modeling and validation groups; the AUC of HCC-LT mortality prediction model was 0.735(95%CI: 0.679~0.790)and 0.758(95%CI: 0.682~0.834)in modeling and validation groups.Conclusions:APRI>1.5 is an independent risk factor for postoperative recurrence and mortality after HCC-LT. The nomogram prediction model based upon CIT, Hangzhou criteria, intraoperative bleeding volume and APRI can effectively predict the recurrence and overall survival of LT for HCC.

Upper gastric tract bleeding due to cholecystoduodenal fistula: a case report.

A 50-year-old man was admitted to our hospital because of a single episode of hematemesis followed by melena for about 14 hours. On gastroendoscopy a 1.2 x 1.4 cm2 deep ulcer was visualized in the back wall of the first part of the duodenum with active bleeding. Digital subtracted angiography showed an obvious leakage of contrast agents from the gallbladder artery. So hemobilia and cholecystoduodenal fistula with upper gastric tract bleeding were diagnosed. Cholecystectomy was performed after the duodenal fistula was resected and repaired. Common bile duct was intubated with a T-tube after no bleeding and stones were verified inside. A pathologic examination confirmed the presence of chronic cholecystitis with the formation of suppurate granulomatosis. The postoperative course was uneventful. He has been doing well without any recurrence of bleeding for the last 7 months.

Research progress on factors influencing early liver dysfunction after liver transplantation / 中华肝脏病杂志

Liver transplantation is the most effective treatment for end-stage liver disease, and early graft dysfunction often occurs after surgery. Early liver dysfunction after liver transplantation has become one of the complications after liver transplantation, which seriously affects the graft and patient survival. Therefore, reducing its occurrence can be an important means to improve the prognosis of recipients after liver transplantation. This paper discusses the research progress on the definition, influencing factors, and prognosis and prediction model in order to provide better prevention and effective reference for improving the success rate and prognosis of early liver dysfunction in recipients after liver transplantation.

Efficacy of Preoperative Chemotherapy in Treatment of Children With Wilms' Tumor: A Meta-Analysis.

CONTEXT: To assess the efficacy of preoperative chemotherapy in Wilms' tumor patients and explore its true value for specific subgroups. OBJECTIVES: In the presence of these controversies, a meta-analysis that examines the efficacy of preoperative chemotherapy in Wilms' tumor patients and specific subgroups is needed to clarify these issues. The objective of this meta-analysis is to assess the efficacy of preoperative chemotherapy in Wilms' tumor patients and explore its true value for specific subgroups. DATA SOURCES: Computer-based systematic search with "preoperative chemotherapy", "Neoadjuvant Therapy" and "Wilms' tumor" as search terms till January 2013 was performed. STUDY SELECTION: No language restrictions were applied. Searches were limited to randomized clinical trials (RCTs) or retrospective studies in human participants under 18 years. A manual examination of references in selected articles was also performed. DATA EXTRACTION: Relative Risk (RR) and their 95% Confidence Interval (CI) for Tumor Shrinkage (TS), total Tumor Resection (TR), Event-Free Survival (EFS) and details of subgroup analysis were extracted. Meta-analysis was carried out with the help of the software STATA 11.0. Finally, four original Randomized Clinical Trials (RCTs) and 28 retrospective studies with 2375 patients were included. RESULTS: For preoperative chemotherapy vs. up-front surgery (PC vs. SU) group, the pooled RR was 9.109 for TS (95% CI: 5.109 - 16.241; P < 0.001), 1.291 for TR (95% CI: 1.124 - 1.483; P < 0.001) and 1.101 for EFS (95% CI: 0.980 - 1.238; P = 0.106). For subgroup short course vs. long course (SC vs. LC), the pooled RR was 1.097 for TS (95% CI: 0.784 - 1.563; P = 0.587), 1.197 for TR (95% CI: 0.960 - 1.493; P = 0.110) and 1.006 for EFS (95% CI: 0.910 - 1.250; P = 0.430). CONCLUSIONS: Short course preoperative chemotherapy is as effective as long course and preoperative chemotherapy only benefits Wilms' tumor patients in tumor shrinkage and resection but not event-free survival.

Therapeutic efficacy analysis of ABO incompatible liver transplantation for hepatocellular carcinoma / 中华器官移植杂志

Objective:To explore the efficacy and safety of ABO-incompatible (ABO-I) liver transplantation for hepatocellular carcinoma.Methods:Forty-four ABO-I liver transplantation recipients were matched with ABO-compatible (ABO-C) recipients by propensity score matching in a ratio of 1: 2. The cumulative overall survival (OS) rate, disease-free survival (DFS) rate and complications were compared between two groups.Results:Compared with ABO-C group, the levels of serum creatinine (sCr) were significantly higher in ABO-I group at Days 7 and 14 post-operation (89.1±36.9 vs 74.8±26.2 umol/L, P=0.001; 77.9±27.6 vs 67.6±18.6 umol/L, P=0.002). The incidence of hepatic arterial thrombosis (9.1% vs 1.1%, P=0.024), biliary complications (25.0% vs 8.0%, P=0.007), early allograft dysfunction (52.3% vs 31.8%, P<0.001) and acute kidney injury(68.1% vs 36.4%, P<0.001) also significantly spiked in ABO-I group. The postoperative cumulative OS, DFS and graft survival rate of ABO-C group were significantly higher than those of ABO-I group ( P<0.001). No inter-group difference existed in survival rate or complication incidence in accordance with the Hangzhou criteria. However, OS, DFS and graft survival rates of ABO-I group were significantly lower than those of ABO-C group ( P<0.001) and the incidence of hepatic artery thrombosis (6.7% vs 0.0%, P=0.043), biliary complications (30.0% vs 6.7%, P=0.003), early allograft dysfunction (53.3% vs 28.3%, P=0.020) and acute kidney injury (63.3% vs 28.3%, P<0.001) significantly rose exceeding the Hangzhou criteria. Conclusions:ABO-I liver transplantation does not affect the OS rate, graft survival rate and postoperative complications in accordance with the Hangzhou criteria. For HCC recipients exceeding the Hangzhou criteria, the prognosis of ABO-I liver transplantation is significantly inferior to that of ABO-C liver transplantation. Careful implementations and accurate evaluations should be performed for ABO-I liver transplantation. Patients exceeding the Hangzhou criteria may receive down-staging treatment so as to obtain transplantation opportunities and yield a better prognosis.

Initial investigation of comprehensive minimally invasive surgery / 中华消化外科杂志

Surgical minimally invasive techniques such as image intervention, laparoscopy, endoscopy, and assisted medical robotics have become the mainstream of minimally invasive surgery (MIS). However, the vague concept, diverse misunderstanding, and the lack of standards have led to a lot of malpractice in current MIS. Based on the analysis of the clinical situation and the domestic and foreign literatures, the authors have put forward the theory of comprehensive minimally invasive surgery (CMIS), and established the concepts of minimally invasive prevention, minimally invasive diagnosis and minimally invasive follow-up in the view of hepatobiliary surgery. The authors have proposed "three-All" principles of all personnel, all aspects and all processes, and established a comprehensive four-level criteria of outcomes, complications, time and costs for CMIS, in an attempt to provide feasible and practical concepts and standards for MIS from a clinical practice and theoretical level, with a view to standardizing minimally invasive procedures and solving the problem of MIS.

Initial investigation of comprehensive minimally invasive surgery / 中华消化外科杂志

Surgical minimally invasive techniques such as image intervention,laparoscopy,endoscopy,and assisted medical robotics have become the mainstream of minimally invasive surgery (MIS).However,the vague concept,diverse misunderstanding,and the lack of standards have led to a lot of malpractice in current MIS.Based on the analysis of the clinical situation and the domestic and foreign literatures,the authors have put forward the theory of comprehensive minimally invasive surgery (CMIS),and established the concepts of minimally invasive prevention,minimally invasive diagnosis and minimally invasive follow-up in the view of hepatobiliary surgery.The authors have proposed "three-All" principles of all personnel,all aspects and all processes,and established a comprehensive four-level criteria of outcomes,complications,time and costs for CMIS,in an attempt to provide feasible and practical concepts and standards for MIS from a clinical practice and theoretical level,with a view to standardizing minimally invasive procedures and solving the problem of MIS.

Structural shifts in the intestinal microbiota of rats treated with cyclosporine A after orthotropic liver transplantation / 医学前沿

Understanding the effect of immunosuppressive agents on intestinal microbiota is important to reduce the mortality and morbidity from orthotopic liver transplantation (OLT). We investigated the relationship between the commonly used immunosuppressive agent cyclosporine A (CSA) and the intestinal microbial variation in an OLT model. The rat samples were divided as follows: (1) N group (normal control); (2) I group (isograft LT, Brown Norway [BN] rat to BN); (3) R group (allograft LT, Lewis to BN rat); and (4) CSA group (R group treated with CSA). The intestinal microbiota was assayed by denaturing gradient gel electrophoresis profiles and by using real-time polymerase chain reaction. The liver histopathology and the alanine/aspartate aminotransferase ratio after LT were both ameliorated by CSA. In the CSA group, the numbers of rDNA gene copies of Clostridium cluster I, Clostridium cluster XIV, and Enterobacteriaceae decreased, whereas those of Faecalibacterium prausnitzii increased compared with the R group. Cluster analysis indicated that the samples from the N, I, and CSA groups were clustered, whereas the other clusters contained the samples from the R group. Hence, CSA ameliorates hepatic graft injury and partially restores gut microbiota following LT, and these may benefit hepatic graft rejection.

Clinical analysis of viral hepatitis B recurrence after liver transplantation for HBV-related liver diseases / 中华器官移植杂志

Objective To study the recurrence risks of viral hepatitis B (VHB) after liver transplantation for hepatitis B virus (HBV)-related liver diseases.Methods A total of 599 patients undergoing liver transplantation due to HBV-related liver disease [hepatic cellular cancer (HCC),decompensated liver cirrhosis (DLC),acute liver failure (ALF)] were included in this study.All patients included in this study have been followed up for at least 12 month for liver biochemistry and HBV testing,altogether with the clinic presentation and outcomes.Treatment protocols about prevention of VHB recurrence in perioperative period and after liver transplantation,the time interval and influence factors of VHB recurrence,and the disease prognosis were analyzed.Results Of the 599 patients,36 cases of VHB recurrence were observed.The rate of VHB recurrence was 7.2％ (23/319),5.6％ (13/232) and 0 (0/48) for HCC,DLC and ALF,respectively.The rates of VHB recurrence were 2.3％,5.5％,6％ for 1 year,5 years and 8 years,respectively.The rate of VHB recurrence in the lamivudine group was significantly higher than in enticavir group and combination therapy group [16.5％ (22/133),2.9％ (8/280),and 3.2％ (6/186),respectively,P＜0.05 for all].Conclusion HCC and DLC as liver transplant indications are independent risk factors for VHB recurrence after liver transplant.For liver transplant patients with HBV-related liver disease,entecavir monotherapy and combination therapy (lamivudine and adefovir,or tenofovir) are both more effective on the prophylaxis of VHB recurrence than lamivudine monotherapy.