Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate.

BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options. METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables. RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression. CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.

External validation of the modified CTP score based on ammonia to predict survival in patients with cirrhosis after TIPS placement.

This study aimed to perform the first external validation of the modified Child-Turcotte-Pugh score based on plasma ammonia (aCTP) and compare it with other risk scoring systems to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. We retrospectively reviewed 473 patients from three cohorts between January 2016 and June 2022 and compared the aCTP score with the Child-Turcotte-Pugh (CTP) score, albumin-bilirubin (ALBI), model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) in predicting transplant-free survival by the concordance index (C-index), area under the receiver operating characteristic curve, calibration plot, and decision curve analysis (DCA) curve. The median follow-up time was 29 months, during which a total of 62 (20.74%) patients died or underwent liver transplantation. The survival curves for the three aCTP grades differed significantly. Patients with aCTP grade C had a shorter expected lifespan than patients with aCTP grades A and B (P < 0.0001). The aCTP score showed the best discriminative performance using the C-index compared with other scores at each time point during follow-up, it also showed better calibration in the calibration plot and the lowest Brier scores, and it also showed a higher net benefit than the other scores in the DCA curve. The aCTP score outperformed the other risk scores in predicting survival after TIPS placement in patients with cirrhosis and may be useful for risk stratification and survival prediction.

Histological evaluation of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: Correlation with Drum Tower Severity Scoring.

BACKGROUND: Hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids (PA-HSOS) is a complication of drug-induced liver damage. Few studies have examined the relationship between pathological changes and clinical circumstances in PA-HSOS. The Drum Tower Severity Scoring System (DTSS) was developed using prognostic indicators from clinical treatment outcomes. We hypothesized that the severity of pathological damage is consistent with DTSS. AIMS: We aimed to improve our understanding and assessment of vascular liver injury disease histopathology by studying larger sample sizes of human histopathological samples. We also wanted to confirm the link between histopathological findings and DTSS. METHODS: The study included 62 patients with PA-HSOS who underwent transjugular liver biopsy. Their hepatic pathological tissues were evaluated. Analyses of linear regression and Spearman's correlation were employed to examine the relationship between DTSS and pathological characteristics. RESULTS: Clinical performance and the DTSS score were used to determine histopathological severity. The sinusoidal congestion area (SCA), central venous endothelial injury (CVEI), and fibrinoid exudation in congestion foci (FECF) were significant indicators. SCA was linearly related to the DTSS score. CONCLUSION: Our findings show that hepatic pathological characteristics correlate with DTSS scores in PA-HSOS. SCA, CVEI, and FECF may be helpful for determining PA-HSOS severity.

Safety and Effectiveness of a Novel Tips Access Set with Steerable Cannula in a Swine Model.

PURPOSE: This study aimed to assess the safety, effectiveness, and feasibility of the Liverty™ transjugular intrahepatic portosystemic shunt (TIPS) access set, which has an ergonomic handle that allows for in situ cannula tip deflection and a distal steerable cannula angle, versus the COOK® Rosch-Uchida Transjugular Liver Access Set (RUPS-100) in healthy pigs. METHODS: Twelve pigs randomly underwent TIPS with the Liverty™ set or the RUPS-100 set. Three interventionalists performed 4 TIPS procedures, 2 with each set. The primary outcome was procedural success, defined as successful establishment of the intrahepatic portosystemic shunt and stent placement. RESULTS: The shunt was successfully established in 11 pigs. The procedural success was achieved in all 6 pigs in the Liverty™ group and 5 out of 6 pigs for the RUPS-100 group (Fisher exact test, P > 0.999). The mean duration of puncture was shorter in the Liverty™ group versus the RUPS-100 group (12.3 ± 4.5 min vs. 16.2 ± 8.5 min), but without significant statistical difference (two sample t test, P = 0.359). The cannula angle was adjusted 69% of passes in the Liverty™ group, which was significantly higher than that in the RUPS-100 group (12%, P = 0.004). Overall, the TIPS procedural performance was comparable between the groups. Both sets were safe. No intraabdominal hemorrhage, vascular injuries, tissue or organ injuries, porto-biliary fistula, biliary peritonitis, and infection or abscess occurred in either group. CONCLUSION: The Liverty™ set is safe and has similar procedural metrics to the COOK® RUPS-100 set. It allows in situ adjustment of the angle of the stiffening cannula without increasing procedure time and lessens the occurrences of periprocedural complications.

Pre-transjugular-intrahepatic-portosystemic-shunt measurement of hepatic venous pressure gradient and its clinical application: A comparison study.

BACKGROUND: It is controversial whether transjugular intrahepatic portosystemic shunt (TIPS) placement can improve long-term survival. AIM: To assess whether TIPS placement improves survival in patients with hepatic-venous-pressure-gradient (HVPG) ≥ 16 mmHg, based on HVPG-related risk stratification. METHODS: Consecutive variceal bleeding patients treated with endoscopic therapy + nonselective ß-blockers (NSBBs) or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019. HVPG measurements were performed before therapy. The primary outcome was transplant-free survival; secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). RESULTS: A total of 184 patients were analyzed (mean age, 55.27 years ± 13.86, 107 males; 102 in the EVL+NSBB group, 82 in the covered TIPS group). Based on the HVPG-guided risk stratification, 70 patients had HVPG < 16 mmHg, and 114 patients had HVPG ≥ 16 mmHg. The median follow-up time of the cohort was 49.5 mo. There was no significant difference in transplant-free survival between the two treatment groups overall (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.35-1.05; P = 0.07). In the high-HVPG tier, transplant-free survival was higher in the TIPS group (HR, 0.44; 95%CI: 0.23-0.85; P = 0.004). In the low-HVPG tier, transplant-free survival after the two treatments was similar (HR, 0.86; 95%CI: 0.33-0.23; P = 0.74). Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier (P < 0.001). The difference in OHE between the two groups was not statistically significant (P = 0.09; P = 0.48). CONCLUSION: TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

Liver stiffness-spleen diameter to platelet ratio score (LSPS model) predicts variceal rebleeding for cirrhotic patients.

PURPOSE: The liver stiffness- spleen diameter to platelet ratio score (LSPS model) can identify a high risk of decompensated events in cirrhotic patients. We aimed to evaluate the value of the LSPS model as a risk stratification strategy in the secondary prevention for cirrhotic patients with esophageal and gastric variceal bleeding (EGVB). METHODS: Consecutive EGVB patients who underwent liver stiffness measurement by acoustic radiation force impulse, platelet count and ultrasonography were enrolled between January 2013 and December 2019. We calculated the LSPS of all patients and followed up for over 2 years. The primary outcome was rebleeding. Transplant-free survival and overt hepatic encephalopathy (OHE) were the secondary outcomes. RESULTS: A total of 131 patients were analyzed. The median value of the LSPS model is 0.1879. We developed risk stratification based on the LSPS model and divided the patients into two groups: the high-LSPS (LSPS > 0.1879) group and the low-LSPS (LSPS ≤ 0.1879) group. Sixty-two (47.33%) patients suffered rebleeding, in which there were 21 (31.92%) patients with low LSPS and 41 (63.08%) patients with high LSPS (hazard ratio 2.883; 95% confidence interval, 1.723-4.822, P < 0.001). For the whole cohort, the rates of transplant-free survival and OHE were consistently similar between the two groups at 2 years. CONCLUSION: The LSPS is a reliable, noninvasive method for the detection of a high risk of rebleeding for the secondary prevention of EGVB.

Covered TIPS Procedure-Related Major Complications: Incidence, Management and Outcome From a Single Center.

Background and Objective: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating complications of portal hypertension. Due to the complexity of anatomy and difficulty of the puncture technique, the procedure itself might brought potential complications, such as puncture failure, bleeding, infection, and, rarely, death. The aim of this study is to explore the incidence, management, and outcome of TIPS procedure-related major complications using covered stents. Methods: Patients who underwent TIPS implantation from January 2015 to December 2020 were recruited retrospectively. Major complications after TIPS were screened and analyzed. Results: Nine hundred and forty-eight patients underwent the TIPS procedure with 95.1% (n = 902) technical success in our department. TIPS procedure-related major complications occurred in 30 (3.2%) patients, including hemobilia (n = 13; 1.37%), hemoperitoneum (n = 7; 0.74%), accelerated liver failure (n = 6; 0.63%), and rapidly progressive organ failure (n = 4; 0.42%). Among them, 8 patients died because of hemobilia (n = 1), accelerated liver failure (n = 4), and rapidly progressive organ failure (n = 3). Conclusion: The incidence of major complications related to TIPS procedure is relatively low, and some of them could recover through effective medical intervention. In our cohort, the overall incidence is about 3%, which causes 0.84% death. The most fatal complication is organ failure and hemobilia.

Number of endoscopic sessions to eradicate varices identifies high risk of rebleeding in cirrhotic patients.

BACKGROUND AND AIMS: Risk stratification to identify patients with high risk of variceal rebleeding is particularly important in patients with decompensated cirrhosis. In clinical practice, eliminating gastroesphageal varices thoroughly after sequential endoscopic treatment reduces the rebleeding rate, however, no simple method has been build to predict high risk of variceal rebleeding. We conducted this study to explore the value of the number of endoscopic sessions required to eradicate gastroesphageal varices in identifying high risk of rebleeding. PATIENTS AND METHODS: Consecutive cirrhotic patients received sequential endoscopic therapy between January 2015 and March 2020 were enrolled. Endoscopic treatment was performed every 1-4 weeks until the eradication of varices. The primary endpoint was variceal rebleeding. RESULTS: A total of 146 patients were included of which 60 patients received standard therapy and 86 patients underwent sequential endoscopic treatment alone. The cut-off value of the number of sequential endoscopic sessions is 3.5 times. Variceal rebleeding was significant higher in patients with endoscopic sessions > 3 times versus ≤ 3 times (61.5% vs. 17.5%, p < 0.001). Variceal rebleeding of patients with endoscopic sessions ≤ 3 times was significant lower than patients with > 3 times in group of standard therapy (19.6% vs. 88.9%, p < 0.001) and endoscopic therapy (15.9% vs. 47.1%, p = 0.028) respectively. CONCLUSION: The number of sequential endoscopic sessions required to eradicate the varices is related to the risk of variceal rebleeding in patients with cirrhosis. If three times of endoscopic treatment can not eradicate the varices, a more aggressive treatment such as TIPS should be seriously considered.

Development of a Drum Tower Severity Scoring (DTSS) system for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

BACKGROUND AND AIMS: There has been no reliable severity system based on the prognosis to guide therapeutic strategies for patients with pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). We aimed to create a novel Drum Tower Severity Scoring (DTSS) system for these patients to guide therapy. METHODS: 172 Patients with PA-HSOS who received supportive care and anticoagulation therapy in Nanjing Drum Tower Hospital from January 2008 to December 2020 were enrolled and analyzed retrospectively. These patients were randomized into a training or validation set in a 3:1 ratio. Next, we established and validated the newly developed DTSS system. RESULTS: Analysis identified a predictive formula: logit (P) = 0.004 × aspartate aminotransferase (AST, U/L) + 0.019 × total bilirubin (TB, µmol/L) - 0.571 × fibrinogen (FIB, g/L) - 0.093 × peak portal vein velocity (PVV, cm/s) + 1.122. Next, we quantified the above variables to establish the DTSS system. For the training set, the area under the ROC curve (AUC) (n = 127) was 0.787 [95% confidence interval (CI) 0.706-0.868; p < 0.001]. With a lower cut-off value of 6.5, the sensitivity and negative predictive value for predicting no response to supportive care and anticoagulation therapy were 94.7% and 88.0%, respectively. When applying a high cut-off value of 10.5, the specificity was 92.9% and the positive predictive value was 78.3%. For the validation set, the system performed stable with an AUC of 0.808. CONCLUSIONS: The DTSS system can predict the outcome of supportive care and anticoagulation in PA-HSOS patients with satisfactory accuracy by evaluating severity, and may have potential significance for guiding therapy.

Agreement between Wedged Hepatic Venous Pressure and Portal Pressure in Hepatic Sinusoidal Obstruction Syndrome.

Background: Wedge hepatic vein pressure (WHVP) accurately estimates the portal pressure (PP) in chronic sinusoidal portal hypertension patients. Whether this applies to patients with acute portal hypertension due to hepatic sinusoidal obstruction syndrome (HSOS) is unclear. Our aim was to assess the agreement between WHVP and PP in patients with HSOS by comparing them to decompensated cirrhosis patients. Methods: From December 2013 to December 2021, patients with pyrrolidine alkaloid-induced HSOS (PA-HSOS) receiving hepatic venous pressure gradient (HVPG) measurement and transjugular intrahepatic portosystem shunt (TIPS) were retrospectively collected and matched with those of patients with virus- or alcohol-related cirrhosis as a cirrhosis group. Pearson's correlation (R), intraclass correlation coefficient (ICC), scatter plots, and the Bland−Altman method were performed for agreement evaluation. Results: A total of 64 patients were analyzed (30 PA-HSOS and 34 cirrhosis groups). The correlation between WHVP and PP was moderate in the PA-HSOS group (R: 0.58, p = 0.001; ICC: 0.68, p = 0.002) but good in the cirrhosis group (R: 0.81, p < 0.001; ICC: 0.90, p < 0.001). The percentage of patients with inconsistent WHVP and PP in the two groups was 13 (43.3%) and 15 (26.5%) (p = 0.156), respectively, and an overestimation of PP was more common in the PA-HSOS group (33.3% vs. 2.9%, p = 0.004). HVPG and portal pressure gradient (PPG) consistency was poor in both groups (R: 0.51 vs. 0.26; ICC: 0.65 vs. 0.41; p < 0.05). Conclusions: WHVP in patients with PA-HSOS did not estimate PP as accurately as in patients with virus- or alcohol-related cirrhosis, which was mainly due to PP overestimation.

Inhibition of ribosomal RNA processing 15 Homolog (RRP15), which is overexpressed in hepatocellular carcinoma, suppresses tumour growth via induction of senescence and apoptosis.

Recent studies suggest that RRP15 (Ribosomal RNA Processing 15 Homolog) might be a potential target for cancer therapy. However, the role of RRP15 in hepatocarcinogenesis remains poorly delineated. In this study, we aimed to evaluate the expression and biological function of RRP15 in human hepatocellular carcinoma (HCC). We show that RRP15 was up regulated in HCC cell lines and tumours. Up-regulation of RRP15 in HCC tumours was also correlated with unfavorable prognosis. We further show that the frequent up-regulation of RRP15 in HCCs is at least partly driven by recurrent gene copy gain at chromosome 1q41. Functional studies indicated that RRP15 knockdown suppresses HCC proliferation and growth both in vitro and in vivo. Mechanistically, RRP15 depletion in p53-wild-type HepG2 cells induced senescence via activation of the p53-p21 signalling pathway through enhanced interaction of RPL11 with MDM2, as well as inhibition of SIRT1-mediated p53 deacetylation. Moreover, RRP15 depletion in p53-mutant PLC5 and p53-deleted Hep3B cells induced metabolic shift from the glycolytic pentose-phosphate to mitochondrial oxidative phosphorylation via regulating a series of key genes such as HK2 and TIGAR, and thus, promoted the generation of ROS and apoptosis. Taken together, our findings provide evidence for an important role of the RRP15 gene in hepatocarcinogenesis through regulation of HCC proliferation and growth, raising the possibility that targeting RRP15 may represent a potential therapeutic strategy for HCC treatment.

Validation of the Nanjing Criteria for Diagnosing Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstruction Syndrome.

BACKGROUND AND AIMS: Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury to sinusoidal endothelial cells in the liver. The intake of pyrrolizidine alkaloids (PAs) in some Chinese herbal remedies/plants remains the major etiology for HSOS in China. Recently, new diagnostic criteria for PA-induced HSOS (i.e. PA-HSOS) have been developed; however, the efficacy has not been clinically validated. This study aimed to assess the performance of the Nanjing criteria for PA-HSOS. METHODS: Data obtained from consecutive patients in multiple hospitals, which included 86 PA-HSOS patients and 327 patients with other liver diseases, were retrospectively analyzed. Then, the diagnostic performance of the Nanjing criteria and simplified Nanjing criteria were evaluated and validated. The study is registered in www.chictr.org.cn (ID: ChiCTR1900020784). RESULTS: The Nanjing criteria have a sensitivity and specificity of 95.35% and 100%, respectively, while the simplified Nanjing criteria have a sensitivity and specificity of 96.51% and 96.33%, respectively, for the diagnosis of PA-HSOS. Notably, a proportion of patients with Budd-Chiari syndrome (11/49) was misdiagnosed as PA-HSOS on the basis of the simplified Nanjing criteria, and this was mainly due to the overlapping features in the enhanced computed tomography/magnetic resonance imaging examinations. Furthermore, most of these patients (10/11) had occlusion or thrombosis of the hepatic vein, and communicating vessels in the liver were found in 8/11 patients, which were absent in PA-HSOS patients. CONCLUSIONS: The Nanjing criteria and simplified Nanjing criteria exhibit excellent performance in diagnosing PA-HSOS. Thus, both could be valuable diagnostic tools in clinical practice.

Increase in Free Hepatic Venous Pressure Response to Beta-Blockers Predicts Variceal Bleeding in Cirrhotic Patients.

BACKGROUND AND AIMS: Nonselective beta-blockers (NSBBs) are the main drug to prevent portal hypertension. It could alter free hepatic venous pressure (FHVP); however, the significance is unknown. This prospective study was to explore the change of FHVP after use of NSBBs and its predictive value for gastroesophageal varices (GOV) bleeding in cirrhotic patients. Patients and Methods. Cirrhotic patients with medium-large GOV between September 2014 and January 2019 were enrolled. After initial hepatic venous pressure gradient (HVPG) measurement, patients received oral NSBBs. Seven days later, the secondary HVPG was examined to evaluate the FHVP alteration and hemodynamic response. The variceal bleeding between patients with FHVP increased and decreased/unchanged was compared. RESULTS: A total of 74 patients were enrolled, and 62 patients completed the secondary HVPG measurement and was followed up. The cumulative bleeding rate was significantly higher in patients with FHVP increased ≥ 1.75 mmHg than those with FHVP decreased/unchanged (54.5% vs. 22.5%, p = 0.021), while there was no significant difference in bleeding between HVPG responders and nonresponders (32.6% vs. 37.5%, p = 0.520). For HVPG responders, variceal bleeding in patients with FHVP increased ≥ 1.75 mmHg was significantly more than that in patients with FHVP decreased/unchanged (57.9% vs. 28.6%, p = 0.041). Cox regression analysis showed that change of FHVP was an independent predictor of variceal bleeding. CONCLUSION: Increase ≥ 1.75 mmHg in FHVP responding to beta-blockers in cirrhotic patients with GOV indicates high risk of variceal bleeding. Besides HVPG response, change of FHVP should also be valued in hemodynamic evaluation to beta-blockers. This trial is registered with Chinese Clinical Trial Registry ChiCTR-IPR-17012836.

Prevention of variceal rebleeding in cirrhotic patients with spontaneous portosystemic shunts: transjugular intrahepatic portosystemic shunt versus endoscopic treatment.

BACKGROUND: Spontaneous portosystemic shunts(SPSSs) in cirrhotic patients indicate higher incidence of gastric varices, which increases the risk for bleeding and death. However, few studies compared endoscopic therapy with transjugular intrahepatic portosystemic shunt (TIPS) in preventing variceal rebleeding in cirrhotic patients with SPSSs. This research aims to evaluate the effectiveness of the two methods in this group of patients. METHODS: We reviewed consecutive cirrhotic patients with SPSSs who underwent either TIPS or endoscopic treatment to prevent variceal rebleeding between January 2015 and December 2018 in our institution. Outcomes including rebleeding, overt hepatic encephalopathy (OHE), complications and survival were compared. Meanwhile, subgroup analyses were conducted to screen relevant factors affecting the results. RESULTS: A total of 97 patients were included in the study. The TIPS arm contained 50 patients and the endoscopy arm contained 47 patients. Rebleeding rate in TIPS group was statistically lower than endoscopic group [16.0 vs 38.3%, hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.16-0.84, P = 0.01], while OHE was more frequent (16.0 vs 2.1%, HR = 7.59, 95% CI: 0.94-61.2, P = 0.025), the survival rate (92 vs 89.4%, HR = 0.88, 95% CI: 0.22-3.60, P = 0.87) and frequency of complications were comparable between two groups. In the subgroups of GOV2/IGV1 and splenorenal shunt/gastrorenal shunt, compared with endoscopic treatments, TIPS reduced the rate of rebleeding without significantly increasing overt hepatic encephalopathy; however, it did not improve survival rate. CONCLUSIONS: For cirrhotic patients with SPSSs, TIPS brought a lower rebleeding rate but a higher incidence of OHE. However, in the subgroups of GOV2/IGV1 and splenorenal shunt/gastrorenal shunt, TIPS was considered more reasonable due to the lower rebleeding rate and comparable OHE incidence.

Risk factors of poor prognosis in patients with pyrrolidine alkaloid-induced hepatic sinusoidal obstruction syndrome after transjugular intrahepatic portosystemic shunt.

AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective method in treating patients with severe hepatic sinusoidal obstruction syndrome induced by pyrrolidine alkaloids (PA-HSOS). However, some patients still have poor postoperative prognosis. So, we aim to evaluate the predictors associated with poor outcomes in PA-HSOS patients receiving TIPS. METHODS: Patients who were diagnosed as PA-HSOS and received TIPS in our hospital between January 2013 and April 2019 were reviewed retrospectively. Baseline information and clinical data were collected. The hazard ratios (HRs) of factors associated with poor prognosis were analyzed by Cox proportional hazard analysis. The Kaplan-Meier method was used to analyze and compare the cumulative incidence of the poor results and survival rate of patients. RESULTS: During a median of 19.25-month follow-up, death occurred in 17 patients. We found that prothrombin time at baseline with an adjusted HR 1.110 (95% confidence interval 1.014-1.216, p = 0.024) and serum total bilirubin of 9 mg/dl 5 days after TIPS with an adjusted HR 1.114 (95% confidence interval 1.042-1.190, p = 0.001) were independent risk factors for death. The 1-year and 5-year survival rate were 86.2% and 82.1%, respectively. The 1-year survival rate in patients with prothrombin time > 17.85 s at baseline and serum total bilirubin > 9 mg/dl at 5 days after TIPS was significantly lower than that of patients below the corresponding threshold, respectively. CONCLUSIONS: Prolonged prothrombin time at baseline and increased serum total bilirubin levels 5 days after TIPS are independent risk factors for predicting death after TIPS treatment in PA-HSOS patients.

Endoscopic therapy + ß-blocker vs. covered transjugular intrahepatic portosystemic shunt for prevention of variceal rebleeding in cirrhotic patients with hepatic venous pressure gradient ≥16 mmHg.

BACKGROUND AND OBJECTIVE: Currently, monitoring hepatic venous pressure gradient (HVPG) have been proved to be the best predictor for the risk of variceal bleeding. We performed the study to evaluate the effect of endoscopic therapy + ß-blocker vs. covered transjugular intrahepatic portosystemic shunt (TIPS) for the prevention of variceal rebleeding in cirrhotic patients with HVPG ≥16 mmHg. METHODS: Consecutive cirrhotic patients with HVPG ≥16 mmHg treated with endoscopic therapy + ß-blocker or covered TIPS for variceal bleeding were retrospectively gathered between April 2013 and December 2018. The variceal rebleeding rate, survival, and incidence of overt hepatic encephalopathy (OHE) were compared. RESULTS: A total of 83 patients were analyzed, of which 46 received endoscopic therapy + ß-blocker and 37 covered TIPS. During a median follow-up of 12.0 months, the rebleeding rate (32.6 vs. 10.8%, P = 0.017) and rate of OHE (2.2 vs. 27.0%, P = 0.001) showed significant differences between the two groups, while liver transplantation-free survival (93.5 vs. 94.6%, P = 0.801) was similar. Preoperative and postoperative Child-Turcotte-Pugh scores were similar in either group. In addition, no significant differences of rebleeding rate (25.0 vs. 21.3%, P = 0.484) and survival (97.2 vs. 91.5%, P = 0.282) were observed between patients with 16 mmHg ≤ HVPG < 20 mmHg and HVPG ≥ 20 mmHg. CONCLUSION: Covered TIPS was more effective than endoscopic therapy + ß-blocker in preventing rebleeding in patients with HVPG ≥16 mmHg but did not improve survival. TIPS also induce more OHE.

EUS-guided portal pressure gradient measurement in patients with acute or subacute portal hypertension.

BACKGROUND AND AIMS: EUS-guided portal pressure gradient (EUS-PPG) measurement is a novel method to evaluate portal hypertension severity. In this study, we determined the consistency between EUS-PPG and hepatic venous pressure gradient (HVPG) measurements in patients with acute or subacute portal hypertension. METHODS: Twelve patients were prospectively enrolled. EUS-PPG measurements were performed using a 22-gauge FNA needle and a central venous pressure measurement monitor. The HVPG measurements were performed using the transjugular approach. If an HVPG measurement was not attainable and the patient underwent transjugular intrahepatic portosystemic shunt (TIPS) treatment, a PPG was recorded as a reference standard during the procedure. We assessed the feasibility and safety of EUS-PPG and calculated the correlation between the 2 measurements. RESULTS: EUS-PPG measurements were successful in 11 patients (91.7%). Subsequent HVPG measurements failed in 2 patients with Budd-Chiari syndrome (hepatic vein occlusion subtype), 1 of whom underwent TIPS treatment to obtain transjugular PPG data. A small shunt was found during 1 HVPG measurement that introduced inaccuracy. Nine patients were included in the statistical analysis. Mean EUS-PPG and HVPG/PPG (transjugular) were 18.07 ± 4.32 mm Hg and 18.82 ± 3.43 mm Hg, respectively. Pearson's correlation coefficient between the 2 methods was .923 (P < .001). CONCLUSIONS: EUS-PPG measurement using a 22-gauge FNA needle was a safe and accurate method to evaluate portal hypertension and has the potential to supplement the measurement of HVPG in liver diseases. (Clinical trial registration number: ChiCTR1800017317.).

Spleen Stiffness Predicts Survival after Transjugular Intrahepatic Portosystemic Shunt in Cirrhotic Patients.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications. Little is known about the ability of spleen stiffness (SS) for predicting the survival of cirrhotic patients undergoing TIPS. This study is to evaluate the influence of SS detected by point shear wave elastography (pSWE) in predicting survival after TIPS. METHODS: This retrospective cohort study screened consecutive patients who underwent TIPS and reliable pSWE measurement between October 2014 and September 2017 from our prospectively maintained database. SS values were measured before TIPS. The primary endpoint was the overall survival after TIPS. The Cox regression analysis model was used for univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to calculate the sensitivity, specificity, and positive and negative predictive values. RESULTS: A total of 89 patients were involved in the final analysis. 24 patients (27.0%) died during a median follow-up time of 31 m. Multivariable Cox regression analysis confirmed that higher SS value (P < 0.001), LS value (P = 0.008), diameter of shunt (P = 0.001), and older age (P < 0.001) were independent prognostic factors of survival after TIPS. The risk of death rose 57.440-fold for each SS unit (m/s) increase. SS was also correlated with liver failure after TIPS. ROC analysis showed that the best SS cutoff value was 3.60 m/s for predicting survival, with a sensitivity of 54.2% and specificity of 90.8%. CONCLUSIONS: The SS value determined by pSWE in cirrhotic patients was an independent predictive factor for survival after TIPS.

A nomogram to predict the risk of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in Cirrhotic Patients.

BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a serious complication of decompensated liver cirrhosis, affecting the prognosis of patients underwent transjugular intrahepatic portosystemic shunts (TIPS). We aim to create a nomogram to predict hepatic encephalopathy- free survivals (HEFS) after TIPS in cirrhotic patients and select appropriate candidates for TIPS. METHODS: Cirrhotic patients underwent TIPS from 2015 to 2018 in our department were included. Multivariable Cox regression was conducted to estimate the predictors of overt HE (OHE) after TIPS within one year. A nomogram based on the Cox proportional hazard model using data from a retrospective training cohort (70% of the patients) was developed. Then the prediction model was validated in the remaining 30% patients by Harrell's C-indexes, ROC curves and calibration plots. RESULTS: Of 373 patients, 117 developed postoperative OHE (31.4%). The training and validation groups comprised 83 (31.4%) and 34 (31.2%) patients, respectively. The cumulative survival rates of patients with HE at 1, 2 and 3 years were 90%, 83% and 76%, respectively. The nomogram included the following variables: age, Child-Turcotte-Pugh class (CTP class), diabetes mellitus (DM), serum creatinine and serum sodium (C-index = 0.772). The C-index for HEFS prediction was 0.773 for the validation cohort. The ROC for predicting HEFS was 0.809 and 0.783, respectively. CONCLUSIONS: We created a nomogram of predicting postoperative HEFS in cirrhotic patients received TIPS. This nomogram could be an important tool of HE risk prediction before TIPS to guide the therapeutic strategy in cirrhotic patients.

Clinical efficacy and safety of anticoagulation therapy for Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: a retrospective multicenter cohort study.

AIM: Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome(PA-HSOS) has been reported to have high mortality. We evaluated the efficacy and safety of anticoagulation therapy for the patients with PA-HSOS. METHODS: We collected clinical data on 249 PA-HSOS patients from January 2012 to December 2017 at four tertiary care hospitals. Among them, 151 patients received anticoagulation therapy, and 98 patients received supportive treatment. The outcomes were analyzed using the Fine and Gray competing risk analysis method and Cox regression model. RESULTS: The cumulative complete response rate was higher in the anticoagulation group than in the supportive group (60.9 vs 36.7%; P < 0.0001). The cumulative mortality was 12.6% in the anticoagulation group compared with 43.9% in the supportive group (P < 0.0001). In subgroup analysis, for mild, moderate, severe, and very severe groups, the adjusted hazard ratios [95% confidence interval (CI)] for complete response rates were 7.05 (3.00-16.59), 5.26 (2.31-12.42), 2.59 (0.85-7.87), and 2.05 (0.61-6.92), respectively; and the adjusted hazard ratios (95% CI) for mortalities were 0.02 (0.01-0.09), 0.04 (0.01-0.14), 0.19 (0.01-3.98), and 0.07 (0.02-1.27), respectively (P < 0.0001). There was no significant difference between both groups in the incidence of bleeding events (P = 0.674). CONCLUSIONS: Anticoagulation therapy improves clinical remission and the survival in selected patients with mild or moderate PA-HSOS. Anticoagulation therapy has a similar safety profile to supportive therapy.