ObjectiveTo investigate the risk factors for survival after transjugular intrahepatic portosystemic shunt （TIPS） in patients with liver cirrhosis and esophagogastric variceal bleeding （EGVB）， and to establish a predictive model for survival after TIPS. MethodsClinical data were collected from 352 patients with liver cirrhosis and EGVB who underwent TIPS in Department of Gastroenterology， Affiliated Drum Tower Hospital of Nanjing University Medical School， from January 2015 to December 2018， and the patients were randomly divided into training group （n=248） and validation group （n=104） at a ratio of 7∶3. The Cox regression analysis was used to identify the independent risk factors for survival after TIPS， and a nomogram predictive model was established. The index of concordance （C-index） and the receiver operating characteristic （ROC） curve were used to assess the discriminatory ability of the model， and the calibration curve was used to assess the predictive value of the model. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier analysis was used to calculate cumulative survival rate. ResultsFor the patients in the training group， the 1-，3-， and 5-year cumulative survival rates were 91.1%，79.5%， and 77.0%， respectively. The multivariate Cox regression analysis showed that age （hazard ratio ［HR］=1.047， 95% confidence interval ［CI］：1.032‍ ‍—‍ ‍1.092，P<0.001）， MELD score （HR=1.127，95%CI：1.003‍ ‍—‍ ‍1.268，P=0.045）， and serum sodium （Na） （HR=0.928，95%CI：0.878‍ ‍—‍ ‍0.981，P=0.008） were independent influencing factors for survival， and a predictive model and a nomogram were established based on these factors. The predictive model had a C-index of 0.760 in the training group and 0.757 in the validation group. In the training group， the nomogram had an area under the ROC curve of 0.807，0.788， and 0.787， respectively， in predicting 1-，3-， and 5-year cumulative survival rates. The calibration curve showed relatively high consistency between the results predicted by the nomogram and the actual results. ConclusionA nomogram model is established based on age， MELD score， and Na for predicting survival after TIPS in patients with liver cirrhosis and EGVB， and this model has good discriminatory ability and accuracy.

Objective:To investigate the curative effect and possible mechanism of rifaximin treatment on monocrotaline-induced hepatic sinusoidal obstruction syndrome (HSOS) in mice.Methods:Twenty-four male C57BL/6J mice were divided into three groups and treated with solvent control, monocrotaline, and rifaximin, respectively. The histopathological changes of the liver and intestine were observed by hematoxylin-eosin staining. The differences were compared in liver parameters, serum liver enzymes, inflammatory factors, apoptotic factors, gut microbiota, and gut tight junction proteins among three groups of mice. The inter-group comparison was conducted using a t-test and one-way analysis of variance.Results:The rifaximin-treated group had significantly improved liver histopathology. The serological levels of alanine aminotransferase and aspartate aminotransferase were (559.04±89.42) U/L and (676.90±106.25) U/L, respectively, which were significantly lower than those in the PA-HSOS model group [(846.05±148.46) U/L and (953.87±58.10) U/L, P<0.05], and were accompanied by lower levels of apoptotic cells and inflammatory factors. Additionally, the rifaximin-treated mice group gut microbiota had higher diversity compared with the PA-HSOS group ( P<0.05), and the Shannon index was 7.77±0.10 and 7.16±0.07, respectively, indicating apparent differences in microbiota among different groups. The abundance of Firmicutes in the rifaximin group was 39.58%±0.56%, which was significantly higher than that in the model group (24.25%±0.64%, P<0.05), while the abundance of Bacteroidetes was 54.7%±0.41%, which was significantly lower than that in the model group (70.92%±0.49%, P<0.05). Simultaneously, the expressions of gut tight junction proteins ZO-1 and Occludin showed an upward trend and validated transcription levels compared to the model group following rifaximin intervention ( P<0.05). Conclusion:Rifaximin can alleviate monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice, and its mechanism may be via gut microbiota regulation, which in turn plays a role in improving intestinal barrier function.

Objective:To investigate the curative effect and possible mechanism of rifaximin treatment on monocrotaline-induced hepatic sinusoidal obstruction syndrome (HSOS) in mice.Methods:Twenty-four male C57BL/6J mice were divided into three groups and treated with solvent control, monocrotaline, and rifaximin, respectively. The histopathological changes of the liver and intestine were observed by hematoxylin-eosin staining. The differences were compared in liver parameters, serum liver enzymes, inflammatory factors, apoptotic factors, gut microbiota, and gut tight junction proteins among three groups of mice. The inter-group comparison was conducted using a t-test and one-way analysis of variance.Results:The rifaximin-treated group had significantly improved liver histopathology. The serological levels of alanine aminotransferase and aspartate aminotransferase were (559.04±89.42) U/L and (676.90±106.25) U/L, respectively, which were significantly lower than those in the PA-HSOS model group [(846.05±148.46) U/L and (953.87±58.10) U/L, P<0.05], and were accompanied by lower levels of apoptotic cells and inflammatory factors. Additionally, the rifaximin-treated mice group gut microbiota had higher diversity compared with the PA-HSOS group ( P<0.05), and the Shannon index was 7.77±0.10 and 7.16±0.07, respectively, indicating apparent differences in microbiota among different groups. The abundance of Firmicutes in the rifaximin group was 39.58%±0.56%, which was significantly higher than that in the model group (24.25%±0.64%, P<0.05), while the abundance of Bacteroidetes was 54.7%±0.41%, which was significantly lower than that in the model group (70.92%±0.49%, P<0.05). Simultaneously, the expressions of gut tight junction proteins ZO-1 and Occludin showed an upward trend and validated transcription levels compared to the model group following rifaximin intervention ( P<0.05). Conclusion:Rifaximin can alleviate monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice, and its mechanism may be via gut microbiota regulation, which in turn plays a role in improving intestinal barrier function.

Objective:To compare the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic treatment for liver cirrhosis with esophageal gastric variceal bleeding (EGVB) and portal vein thrombosis (PVT).Methods:A total of 183 liver cirrhosis patients with EGVB and PVT in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and the First Affiliated Hospital of Wenzhou Medical University were selected from January 2017 to December 2019, and 66 patients were assigned to the endoscopic group (received endoscopi treatment) and 117 the TIPS group (received TIPS treatment). Propensity score matching was performed according to the 1∶1 ratio, yielding 58 patients in each group for analysis, with a median follow-up time of 36 months in both groups. Postoperative survival, postoperative rebleeding rate, and postoperative hepatic encephalopathy incidence were assessed using Kaplan-Meier survival curves.Results:During the follow-up, the rebleeding rate in the endoscopic group was significantly higher [39.7% (23/58) VS 17.2% (10/58), P=0.005], and the TIPS group had a higher incidence of postoperative hepatic encephalopathy [29.3% (17/58) VS 13.8% (8/58), P=0.048], and no significant difference in survival rate was observed between the two groups [74.1% (43/58) VS 75.9% (44/58), P=0.769]. In the subgroup analysis of mild degree of PVT, there was no significant difference in survival [88.0% (22/25) VS 72.0% (18/25), P=0.164], rebleeding rate [28.0% (7/25) VS 12.0% (3/25), P=0.164], or incidence of hepatic encephalopathy [8.0% (2/25) VS 20.0% (5/25), P=0.202] between the endoscopic group and the TIPS group. In the subgroup analysis of severe degree of PVT, the rebleeding rate in the endoscopic group was significantly higher than that in the TIPS group [48.5% (16/33) VS 21.2% (7/33), P=0.010], while there was no significant difference in the incidence of hepatic encephalopathy [18.2% (6/33) VS 36.4% (12/33), P=0.133], or the survival rate [63.6% (21/33) VS 78.8% (26/33), P=0.154]. Conclusion:For liver cirrhosis patients with mild PVT and EGVB, combining endoscopic therapy with anticoagulation may be superior to TIPS. Conversely, in patients with severe PVT, TIPS may be a more suitable option due to a significantly reduced rebleeding risk without a notable increase in hepatic encephalopathy incidence.

Objective:To explore whether transjugular intrahepatic portosystemic shunt (TIPS) can improve the prognosis of esophagogastric variceal bleeding (EGVB) combined with sarcopenia in cirrhotic patients.Methods:A retrospective cohort study was performed. A total of 464 cases with cirrhotic EGVB who received standard or TIPS treatment between January 2017 and December 2019 were selected. Regular follow-up was performed for the long-term after treatment. The primary outcome was transplantation-free survival. The secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). The obtained data were statistically analyzed. The t-test and Wilcoxon rank-sum test were used to compare continuous variables between groups. The χ2 test, or Fisher's exact probability test, was used to compare categorical variables between groups. Results:The age of the included patients was 55.27±13.86 years, and 286 cases were male. There were 203 cases of combined sarcopenia and 261 cases of non-combined sarcopenia. The median follow-up period was 43 months. The two groups had no statistically significant difference in follow-up time. There was no statistically significant difference in transplant-free survival between the TIPS group and the standard treatment group in the overall cohort ( HR=1.31, 95% CI: 0.97-1.78, P=0.08). The TIPS patient group with cirrhosis combined with sarcopenia had longer transplant-free survival (median survival: 47.76 vs. 52.45, χ2=4.09; HR=1.55, 95 CI: 1.01~2.38, P=0.04). There was no statistically significant difference in transplant-free survival between the two kinds of treatments for patients without sarcopenia ( HR=1.22, 95% CI: 0.78~1.88, P=0.39). Rebleeding time was prolonged in TIPS patients with or without sarcopenia combination (patients without combined sarcopenia: median rebleeding time: 39.48 vs. 53.61, χ2=18.68; R=2.47, 95 CI: 1.67~3.65, P<0.01; patients with sarcopenia: median rebleeding time: 39.91 vs. 50.68, χ2=12.36; HR=2.20, 95 CI: 1.42~3.40, P<0.01). TIPS patients had an increased 1-year OHE incidence rate compared to the standard treatment group (sarcopenia patients: 6.93% vs. 16.67%, χ2=3.87, P=0.049; patients without sarcopenia combination: 2.19% vs. 9.68%, χ2=8.85, P=0.01). There was no statistically significant difference in the long-term OHE incidence rate between the two kinds of treatment groups ( P>0.05). Conclusion:TIPS can significantly prolong transplant-free survival compared to standard treatment as a secondary prevention of EGVB concomitant with sarcopenia in patients with cirrhosis. However, its advantage is not prominent for patients with cirrhosis in EGVB without sarcopenia.

Objective:To evaluate the factors affecting the incidence of intrahepatic venovenous shunt (IVVS) in patients with cirrhosis and its impact on hepatic venous pressure gradient (HVPG).Methods:A retrospective analysis was performed on the data of patients with liver cirrhosis who received HVPG measurement in Nanjing Drum Tower Hospital from April 2013 to March 2022. Univariate and multivariate regression analyses were used to investigate the incidence rate and risk factors of IVVS and its impact on HVPG. The t-test and rank-sum test were used for the measurement data, and the χ2 test was used for the count data. Results:A total of 242 cases with cirrhosis were included in the statistical analysis, including 54 (22.3%) with IVVS and 188 (77.7%) without IVVS. There was a statistically significant difference ( P<0.05) in prothrombin time (PT), HVPG, and splenectomy history between the two groups of patients' baseline data (all P<0.05). The multiple logistic regression analysis results showed that PT was an independent risk factor for the occurrence of IVVS ( P<0.05), and patients combined with IVVS had lower HVPG values [(17.58±5.57) mmHg vs. (11.92±5.38) mmHg, 1 mmHg=0.133 kPa; t=6.623, P<0.001]. Conclusions:Patients with liver cirrhosis have a high incidence rate of IVVS, which is closely associated with a low prothrombin time. Additionally, patients combined with IVVS have low HVPG values, which affect its accuracy.

Non-cirrhotic splanchnic vein thrombosis （NC-SVT） mainly includes portal vein thrombosis， superior mesenteric vein thrombosis， splenic vein thrombosis， and hepatic vein thrombosis （Budd-Chiari syndrome）， and its prevalence rate is increasing with the increase in the incidence rates of related underlying diseases. Due to the harm of NC-SVT， there have been significant improvements in the awareness and ability for diagnosis among clinicians. However， anticoagulation and intervention therapies for thrombosis are often taken seriously in treatment， while the screening for risk factors or underlying diseases leading to SVT is ignored， which may affect the treatment outcome of thrombus in some patients and delay the diagnosis and treatment of the underlying disease. This article mainly introduces the acquired， hereditary， systemic， and local underlying diseases associated with the development of NC-SVT.

Portal vein thrombosis （PVT） refers to thromboembolism that occurs in the extrahepatic main portal vein and/or intrahepatic portal vein branches. PVT is the result of the combined effect of multiple factors， but its pathogenesis remains unclear. Animal models are an important method for exploring the pathophysiological mechanism of PVT. Based on the different species of animals， this article reviews the existing animal models of PVT in terms of modeling methods， principles， advantages and disadvantages， and application.

Objective To investigate the risk factors for unplanned readmission within 30 days after discharge in cirrhotic patients with esophagogastric variceal bleeding undergoing transjugular intrahepatic portosystemic shunt(TIPS),and to construct a nomogram predictive model.Methods A total of 241 cirrhotic patients who underwent TIPS due to esophagogastric variceal bleeding in Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2020 to June 2023 were enrolled as subjects,and unplanned readmission within 30 days was analyzed.According to the presence or absence of unplanned readmission,they were divided into readmission group with 36 patients and non-readmission group with 198 patients,and related clinical data were collected from all patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.A logistic regression analysis was used to identify independent risk factors for unplanned readmission.A nomogram prediction model was constructed,and the receiver operating characteristic(ROC)curve was plotted to assess its discriminatory ability for unplanned readmission;the calibration curve was plotted to evaluate the consistency of the nomogram model in predicting unplanned readmission;the ResourceSelection package of R language was used for the Hosmer-Lemeshow goodness-of-fit test to evaluate the degree of fitting of the mode;the decision curve analysis was used to investigate the practicality of the model.Results Age(odds ratio[OR]=2.664,95%confidence interval[CI]:1.139-6.233,P<0.05),CTP score(OR=1.655,95%CI:1.098-2.495,P<0.05),and blood ammonia(OR=1.032,95%CI:1.016-1.048,P<0.05)were independent risk factors for unplanned readmission within 30 days after discharge in the patients undergoing TIPS.The multivariate analysis showed that for the nomogram predictive model constructed in this study,repeated sampling for 1 000 times using the Bootstrap method was performed for internal validation,and the area under the ROC curve was 0.773,which was significantly higher than that of age(0.582),CTP score(0.675),and blood ammonia(0.641).The calibration curve showed good consistency between the probability of unplanned readmission predicted by the nomogram model and the actual probability,and the Hosmer-Lemeshow goodness-of-fit test showed good degree of fitting(c2=5.647 3,P=0.686 7).Conclusion Age,CTP score,and blood ammonia are independent risk factors for unplanned readmission within 30 days after TIPS,and the nomogram prediction model constructed based on these factors can help to predict the risk of unplanned readmission in TIPS patients and provide an accurate decision-making basis for early prevention.

Objective To investigate the effect of interleukin-22(IL-22)on the activation of hepatic stellate cells(HSCs)and its mechanism.Methods The human HSC LX-2 cells were selected for the study,and the LX-2 cells induced by TGF-β1 were used to establish a model of HSC activation.LX-2 cells were treated with IL-22 at gradient concentrations,and Western blot and qRT-PCR were used to measure the expression levels of the activation markers COL1A1 and α-SMA and determine the appropriate working concentration and time of the drug.Western blot,qRT-PCR,and immunofluorescence assay were used to determine the levels of Fn14 and the markers for endoplasmic reticulum stress(ERS)and activation in activated HSCs treated by IL-22.ERS in LX-2 cells was induced by tunicamycin(TM),and Western blot and qRT-PCR were used to measure the levels of markers for ERS and activation in LX-2 cells treated by IL-22.TNF-like weak inducer of apoptosis(TWEAK)and small interfering RNA were used to upregulate and downregulate Fn14,and then the mRNA and protein expression levels of p-IRE1α,IRE1α,XBP1s,COL1A1,and α-SMA were measured.After LX-2 cells induced by TGF-β1 were treated by IL-22,TWEAK was used to upregulate Fn14,and Western blot and immunofluorescence assay were used to measure the levels of Fn14 and the markers for ERS and activation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the Sidak's multiple comparison test was used for further comparison between two groups.Results Compared with the TGF-β1 group,the TGF-β1+IL-22 group had significant reductions in the protein and mRNA expression levels of COL1A1 and α-SMA,with a more significant effect after treatment with 10 ng/mL IL-22 for 24 hours(all P<0.01).Compared with the TGF-β1 group,the TGF-β1+IL-22 group had significant reductions in the expression levels of Fn14,p-IRE1α,and XBP1s(all P<0.05).Compared with the TM group,the TM+IL-22 group had significant reductions in the expression levels of p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Compared with the silenced control group,the Fn14 siRNA group had significant reductions in the expression levels of p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Compared with the normal control group,the TWEAK group had significant increases in the expression levels of Fn14,p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.01).Compared with the TGFβ1+IL-22 group,the TGF-β1+IL-22+TWEAK group had significant increases in the expression levels of Fn14,p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Conclusion IL-22 negatively regulates ERS in HSCs by inhibiting Fn14,thereby inhibiting the activation of HSCs.