Portal Fibrotic Cord is Associated with Transjugular Intrahepatic Portosystemic Shunt Failure and Death in Cirrhotic Patients.

Background and Aims: Occlusive portal vein thrombosis (PVT) often causes portal hypertension-related complications in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for this difficult problem. However, the factors influencing TIPS success and overall survival in patients with occlusive PVT are unknown. This study investigated the factors influencing TIPS success and overall survival in cirrhotic patients with occlusive PVT. Methods: Cirrhotic patients with occlusive PVT were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital between January 2015 and May 2021. Baseline characteristics, TIPS success rate, complications, and survival were collected, and the factors associated with the TIPS success rate and transplant-free survival were analyzed. Results: A total of 155 cirrhotic patients with occlusive PVT were enrolled. TIPS succeeded in 126 (81.29%) cases. The 1-year survival rate was 74%. Compared with those without, patients with portal fibrotic cord had a lower TIPS success rate (39.02% vs. 96.49%, p<0.001), shorter median overall survival (300 vs. 1,730 days, p<0.001) and more operation-related complications (12.20% vs. 1.75%, p<0.01). Logistic regression analysis found that portal fibrotic cord (odds ratio 0.024) was a risk factor for TIPS failure. Univariate and multivariate analysis showed that portal fibrotic cord was an independent predictor of death (hazard ratio 2.111; 95% CI: 1.094-4.071, p=0.026). Conclusions: Portal fibrotic cord increased the TIPS failure rate and is a risk factor for poor prognosis in cirrhotic patients.

Transjugular intrahepatic collateral-systemic shunt is effective for cavernous transformation of the portal vein with variceal bleeding.

BACKGROUND: The transjugular intrahepatic portal collateral-systemic shunt (transcollateral TIPS) is used to treat portal hypertension-related complications in patients with cavernous transformation of the portal vein (CTPV) and whose main portal vein cannot be recanalized. It is still not clear whether transcollateral TIPS can be as effective as portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS). This study aimed to evaluate the efficacy and safety of transcollateral TIPS in the treatment of refractory variceal bleeding with CTPV. METHODS: Patients with refractory variceal bleeding caused by CTPV were selected from the database of consecutive patients treated with TIPS in Xijing Hospital from January 2015 to March 2022. They were divided into the transcollateral TIPS group and the PVR-TIPS group. The rebleeding rate, overall survival, shunt dysfunction, overt hepatic encephalopathy (OHE) and operation-related complications were analyzed. RESULTS: A total of 192 patients were enrolled, including 21 patients with transcollateral TIPS and 171 patients with PVR-TIPS. Compared with the patients with PVR-TIPS, the patients with transcollateral TIPS had more noncirrhosis (52.4 vs. 19.9%, p = 0.002), underwent fewer splenectomies (14.3 vs. 40.9%, p = 0.018), and had more extensive thromboses (38.1 vs. 15.2%, p = 0.026). There were no differences in rebleeding, survival, shunt dysfunction, or operation-related complication rates between the transcollateral TIPS and PVR-TIPS groups. However, the OHE rate was significantly lower in the transcollateral TIPS group (9.5 vs. 35.1%, p = 0.018). CONCLUSION: Transcollateral TIPS is an effective treatment for CTPV with refractory variceal bleeding.

Direct calibration of neutron detectors for laser-driven nuclear reaction experiments with a gated neutron source.

Nowadays, the sustained technological progress in high-intensity lasers is opening up the possibility of super-intense laser pulses to trigger or substantially influence nuclear reactions. However, it is a big challenge to quantitatively measure the reaction products because of the interference of electromagnetic pulses induced by high-intensity lasers. Fast scintillation detectors are widely chosen for fast neutron detection. The calibration of neutron detectors is crucial to measuring the yield of neutron products. Since one large signal superimposed by a number of neutron signals appears during a short period, it is difficult to directly and precisely calibrate the detectors' response for a single neutron. In the present work, we developed a direct calibration method with a gated fission neutron source 252Cf to solve this problem. This work demonstrates that the gated fission neutron source approach, with a unique "Pulse Shape Discrimination & Time of Flight window" function, has the highest background-γ-rejection and improves the confidence level of the final results for both liquid and plastic scintillator. Compared with the result of Compton edge method and neutron beam method, the gated fission neutron source method achieves much cleaner neutron signals and avoids interference caused by the modeling accuracy of the neutron detectors. This approach can be widely used in laser-driven nuclear physics experiments with higher accuracy for neutron detection.

Hepatic hydrothorax does not increase the risk of death after transjugular intrahepatic portosystemic shunt in cirrhosis patients.

OBJECTIVES: Hepatic hydrothorax (HH) is a predictor of poor survival in cirrhosis patients. However, whether HH increases the mortality risk of cirrhosis patients treated with transjugular intrahepatic portosystemic shunt (TIPS) is unknown. Our objective was to evaluate the influence of HH on the survival of cirrhosis patients after TIPS. METHODS: Cirrhosis patients with portal hypertension complications were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital from January 2015 to June 2021. Cirrhosis patients with HH were treated as the experimental group. A control group of cirrhosis patients without HH was created using propensity score matching. Survival after TIPS and the related risk factors were analysed. RESULTS: There were 1292 cirrhosis patients with portal hypertension complications treated with TIPS, among whom 255 patients had HH. Compared with patients without HH, patients with HH had worse liver function (MELD, 12 vs. 10, p < 0.001), but no difference in survival after TIPS was observed. After propensity score matching, 243 patients with HH and 243 patients without HH were enrolled. There was no difference in cumulative survival between patients with and without HH. Cox regression analysis showed that HH was not associated with survival after TIPS, and main portal vein thrombosis (> 50%) was a prognostic factor of long-term survival after TIPS in cirrhosis patients (hazard ratio, 1.386; 95% CI, 1.030-1.865, p = 0.031). CONCLUSION: Hepatic hydrothorax does not increase the risk of death after TIPS in cirrhosis patients. KEY POINTS: • Hepatic hydrothorax is a decompensated event of cirrhosis and increases the risk of death. • Hepatic hydrothorax is associated with worse liver function. • Hepatic hydrothorax does not increase the mortality of cirrhosis treated with TIPS.

Electric Insulating Irrigations Mitigates Esophageal Injury Caused by Button Battery Ingestion.

Objective: Accidental ingestion of button batteries (BB), usually occurred in children and infants, will rapidly erode the esophagus and result in severe complications, even death. It has been recommended that treatment of this emergent accident as soon as possible with drinking of pH-neutralizing viscous solutions such as honey and sucralfate before surgical removal can mitigate the esophageal injury. Recently, we reported that the electric insulating solutions such as edible oils could mitigate tissue damage in BB-exposed esophageal segments. In this study, we compared the protective effect of kitchen oil with honey or sucralfate, the recommended pH-neutralizing beverages, and with their mixture on esophageal injury caused by BB ingestion in pig esophageal segments and in living piglets. Methods: Effect of olive oil irrigations was compared to that of honey or sucralfate irrigations in the BB-damaged esophageal segments freshly collected from the local abattoir and in live Bama miniature piglets with the proximal esophagus exposed to BB for 60 min. Also, the effect of olive oil and honey mixture (MOH) irrigations was assessed in live animals. The BB voltage was recorded before insertion and after its removal. Gross and histological analysis of the esophageal injury was performed after BB exposure in segmented fresh esophagus and 7 days after BB exposure in live animals, respectively. Results: Olive oil irrigations demonstrated better protective effect against BB-induced esophageal damage, compared to honey or sucralfate for BB-induced esophageal damage in vitro. But in vivo study showed that olive oil alone exacerbated esophageal injury because all esophagi irrigated with olive oil perforated. Surprisingly, irrigations with the MOH showed considerable protective effect for BB-induced esophageal damage in live animals, significantly better than irrigations with honey alone. The MOH decreased BB discharge, reduced area of surface injury, attenuated injured depth of esophageal wall thickness, and downed the mucosal injury index in comparison to using honey alone. Conclusion: Irrigations with olive oil alone couldn't prevent the BB discharge and is harmful for BB ingestion before surgical removal. However, mixed with honey, olive oil very effectively prevents the BB discharging and produces better esophageal protection than honey.

Risk Stratification Based on Chronic Liver Failure Consortium Acute Decompensation Score in Patients With Child-Pugh B Cirrhosis and Acute Variceal Bleeding.

BACKGROUND AND AIMS: Optimal candidates for early transjugular intrahepatic portosystemic shunt (TIPS) in patients with Child-Pugh B cirrhosis and acute variceal bleeding (AVB) remain unclear. This study aimed to test the hypothesis that risk stratification using the Chronic Liver Failure Consortium Acute Decompensation score (CLIF-C ADs) may be useful to identify a subgroup at high risk of mortality or further bleeding that may benefit from early TIPS in patients with Child-Pugh B cirrhosis and AVB. APPROACH AND RESULTS: We analyzed the pooled individual data from two previous studies of 608 patients with Child-Pugh B cirrhosis and AVB who received standard treatment between 2010 and 2017 in China. The concordance index values of CLIF-C ADs for 6-week and 1-year mortality (0.715 and 0.708) were significantly better than those of active bleeding at endoscopy (0.633 [P < 0.001] and 0.556 [P < 0.001]) and other prognostic models. With X-tile software identifying an optimal cutoff value, patients were categorized as low risk (CLIF-C ADs <48), intermediate risk (CLIF-C ADs 48-56), and high risk (CLIF-C ADs >56), with a 5.6%, 16.8%, and 25.4% risk of 6-week death, respectively. Nevertheless, the performance of CLIF-C ADs for predicting a composite endpoint of 6-week death or further bleeding was not satisfactory (area under the receiver operating characteristics curve [AUC], 0.588). A nomogram incorporating components of CLIF-C ADs and albumin, platelet, active bleeding, and ascites significantly improved the prediction accuracy (AUC, 0.725). CONCLUSIONS: In patients with Child-Pugh B cirrhosis and AVB, risk stratification using CLIF-C ADs identifies a subgroup with high risk of death that may derive survival benefit from early TIPS. With improved prediction accuracy for 6-week death or further bleeding, the data-driven nomogram may help to stratify patients in randomized trials. Future external validation of these findings in patients with different etiologies is required.

Prevalence of prothrombotic factors in patients with Budd-Chiari syndrome or non-cirrhotic nonmalignant portal vein thrombosis: A hospital-based observational study.

BACKGROUND AND AIM: Comprehensive investigations on the prothrombotic factors of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and non-cirrhotic nonmalignant portal vein thrombosis (PVT), in Eastern patients are scarce. METHODS: Between March 2012 and July 2017, 812 consecutive patients, including 418 BCS and 394 non-cirrhotic nonmalignant PVT patients, were admitted to Xijing Hospital (a Chinese tertiary academic hospital) and screened for prothrombotic factors. Odds ratios (ORs), 95% confidence intervals (CIs), and P-trends were calculated by using conditional logistic regression. RESULTS: The prevalence of myeloproliferative neoplasms (MPNs) was only 6.3% among BCS patients but 28.3% among PVT patients. Notably, the presence of MPNs was associated with a higher risk of hepatic vein-type BCS (OR 9.9, 95% CI 3.6-26.7, P-trend < 0.001) and extensive thrombosis in PVT (OR 4.1, 95% CI 1.9-8.9, P-trend < 0.001). Calreticulin mutations existed in 2.7% of SVT patients. Furthermore, the prevalence of antiphospholipid antibody syndrome and protein C, protein S, or antithrombin deficiency in BCS patients was 7.3% and 22.5%, respectively, similar to that in patients with PVT (7.4% and 25.7%). In addition, factor V Leiden mutation, prothrombin G20210A mutation, and paroxysmal nocturnal hemoglobinuria were identified in < 1% of both BCS and PVT patients. CONCLUSION: There is a significant positive association between MPNs and hepatic vein-type BCS or non-cirrhotic nonmalignant PVT with extensive thrombosis. Additionally, calreticulin mutations should be tested in JAK2V617F -negative SVT patients in China. However, screening for factor V Leiden mutation, prothrombin G20210A mutation, and paroxysmal nocturnal hemoglobinuria may be unnecessary.

Long-term results of variceal bleeding management in 302 patients with chronic extrahepatic portal vein obstruction.

BACKGROUND AND AIM: Treatment modalities of variceal bleeding or rebleeding for extrahepatic portal vein obstruction (EHPVO) are limited, and their long-term results and prognostic factors are unclear. This study aimed at assessing the long-term results of EHPVO treated with current recommendations and investigating the influencing factors. METHODS: Between 2009 and 2016, 302 consecutive patients with EHPVO were included. Watch-and-wait policy was applied for those with no (n = 59) or small varices (n = 55), nonselective beta-adrenergic blocker and nonselective beta-adrenergic blocker plus endotherapy were for primary (n = 115) and secondary prophylaxis (n = 87), transjugular intrahepatic portosystemic shunt (TIPS) or combination therapy was for those with recurrent bleeding (n = 92). RESULTS: The median follow up was 58.8 months. The 1-, 3-, and 5-year cumulative rates were 3.6%, 19.2%, 32.3% for small varices development and 4.5%, 30.9%, 53.4% for large varices development. The 1-, 3-, and 5-year cumulative rates were 11.1%, 20.9%, and 34.9% for first variceal bleeding and 16.0%, 26.9%, and 33.6% for variceal rebleeding. For those with recurrent variceal bleeding, only TIPS (n = 37, technical success rate: 90.2%) was associated with a reduced risk of variceal rebleeding (1-, 3-, and 5-year: 5.6%, 11.7%, and 21.9%). The 1-, 3-, and 5-year survival rates were 96.9%, 95.8%, and 91.9%. Prothrombotic factors and anticoagulation did not influence the risk of variceal bleeding, rebleeding, and survival. CONCLUSIONS: By applying the same variceal management as recommended for patients with liver cirrhosis, patients with non-cirrhotic EHPVO showed a similar development of varices and variceal bleeding. This is also true for the beneficial effect of TIPS to prevent rebleeding.

Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells.

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16- NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16- and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

Angioplasty with versus without routine stent placement for Budd-Chiari syndrome: a randomised controlled trial.

BACKGROUND: Angioplasty recanalisation is recommended as the first-line interventional procedure for Budd-Chiari syndrome, but subsequent restenosis is common. We aimed to test whether use of routine, non-selective stenting in angioplasty could improve patency and treatment efficacy with adequate safety in Budd-Chiari syndrome. METHODS: We did a randomised controlled trial, for which patients aged 18-75 years with Budd-Chiari syndrome with membranous obstruction or short-length stenosis (≤4 cm), and a Child-Pugh score of less than 13 were considered eligible. Patients were excluded if they had obstruction not amenable to angioplasty, were recommended to be treated with transjugular intrahepatic portosystemic shunt or liver transplantation, or had contraindications for angioplasty. Eligible patients were randomly assigned (1:1) to an angioplasty-only group or an angioplasty plus routine stenting group, with use of a web-based allocation system (Pocock and Simon's minimisation method, stratified by obstruction features and Child-Pugh score). Recanalisation procedures were done within 24 h of randomisation. The statistician and investigators responsible for data collection data and endpoint assessment were masked to group allocation. The primary outcome was the proportion of patients free of restenosis, analysed in the intention-to-treat population. The study is registered on ClinicalTrials.gov (NCT02201485) and is completed. FINDINGS: Between July 28, 2014, and Sept 29, 2017, 88 (59%) of 150 screened patients were enrolled and assigned either the angioplasty-only group (n=45) or the angioplasty plus routine stenting group (n=43). During a median follow-up period of 27 months (IQR 19-41), the angioplasty plus routine stenting group had significantly higher proportion of patients free of restenosis (42 [98%] of 43 patients) than did the angioplasty-only group (27 [60%] of 45 patients; p<0·0001). In the survival analysis, 3-year restenosis-free survival was 96·0% (95% CI 88·6-100·0) in the routine stenting group versus 60·4% (46·4-78·7) in the angioplasty-only group (log-rank p<0·0001). The hazard ratio for restenosis was 0·04 (95% CI 0·01-0·31) in favour of routine stenting, with an absolute risk reduction of 35·6% (95% CI 24·2-55·0). Two (5%) patients in the angioplasty plus routine stenting group and one (2%) patient in the angioplasty-only group died during follow-up. One (2%) patient from the angioplasty plus routine stenting group had puncture site haematoma, which was not related to stenting. No stent fracture or migration occurred. Anticoagulation-related adverse events occurred in five (11%) patients from angioplasty alone group and five (12%) patients from angioplasty plus routine stenting group. INTERPRETATION: Routine stenting with angioplasty is superior to angioplasty alone for preventing restenosis in patients with Budd-Chiari syndrome with short-length stenosis and is safe to use as part of first-line invasive treatment. Further validation is needed in similar settings and other regions in which different characteristics of Budd-Chiari syndrome are more prevalent. FUNDING: National Natural Science Foundation of China, National Key Technology R&D Programme, Optimised Overall Project of Shaanxi Province, Boost Programme of Xijing Hospital.

Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial.

BACKGROUND: The survival benefit of early placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with cirrhosis and acute variceal bleeding is controversial. We aimed to assess whether early TIPS improves survival in patients with advanced cirrhosis and acute variceal bleeding. METHODS: We did an investigator-initiated, open-label, randomised controlled trial at an academic hospital in China. Consecutive patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomly assigned (2:1) to receive either early TIPS (done within 72 h after initial endoscopy [early TIPS group]) or standard treatment (vasoactive drugs continued to day 5, followed by propranolol plus endoscopic band ligation for the prevention of rebleeding, with TIPS as rescue therapy when needed [control group]). Randomisation was done by web-based randomisation system using a Pocock and Simon's minimisation method with Child-Pugh class (B vs C) and presence or absence of active bleeding as adjustment factors. The primary outcome was transplantation-free survival, analysed in the intention-to-treat population, excluding individuals subsequently found to be ineligible for enrolment. This study is registered with ClinicalTrials.gov, number NCT01370161, and is completed. FINDINGS: From June 26, 2011, to Sept 30, 2017, 373 patients were screened and 132 patients were randomly assigned to the early TIPS group (n=86) or to the control group (n=46). After exclusion of three individuals subsequently found to be ineligible for enrolment (two patients in the early TIPS group with non-cirrhotic portal hypertension or hepatocellular carcinoma, and one patient in the control group due to non-cirrhotic portal hypertension), 84 patients in the early TIPS group and 45 patients in the control group were included in the intention-to-treat population. 15 (18%) patients in the early TIPS group and 15 (33%) in the control group died; two (2%) patients in the early TIPS group and one (2%) in the control group underwent liver transplantation. Transplantation-free survival was higher in the early TIPS group than in the control group (hazard ratio 0·50, 95% CI 0·25-0·98; p=0·04). Transplantation-free survival at 6 weeks was 99% (95% CI 97-100) in the early TIPS group compared with 84% (75-96; absolute risk difference 15% [95% CI 5-48]; p=0·02) and at 1 year was 86% (79-94) in the early TIPS group versus 73% (62-88) in the control group (absolute risk difference 13% [95% CI 2-28]; p=0·046). There were no significant differences between the two groups in the incidence of hepatic hydrothorax (two [2%] of 84 patients in the early TIPS group vs one [2%] of 45 in the control group; p=0·96), spontaneous bacterial peritonitis (one [1%] vs three [7%]; p=0·12), hepatic encephalopathy (29 [35%] vs 16 [36%]; p=1·00), hepatorenal syndrome (four [5%] vs six [13%]; p=0·10), and hepatocellular carcinoma (four [5%] vs one [2%]; p=0·68). There was no significant difference in the number of patients who experienced other serious adverse events (ten [12%] vs 11 [24%]; p=0·07) or non-serious adverse events (21 [25%] vs 19 [42%]; p=0·05) between groups. INTERPRETATION: Early TIPS with covered stents improved transplantation-free survival in selected patients with advanced cirrhosis and acute variceal bleeding and should therefore be preferred to the current standard of care. FUNDING: National Natural Science Foundation of China, National Key Technology R&D Program, Optimized Overall Project of Shaanxi Province, Boost Program of Xijing Hospital.

TIPSS for variceal bleeding in patients with idiopathic non-cirrhotic portal hypertension: comparison with patients who have cirrhosis.

BACKGROUND: In patients with idiopathic non-cirrhotic portal hypertension (INCPH), the usual recommended strategy for management of variceal bleeding is the same as that in cirrhosis. However, this policy has been challenged by the different natural history between INCPH and cirrhosis. AIM: To compare outcomes after transjugular intrahepatic portosystemic shunt (TIPSS) between INCPH and cirrhotic patients admitted for variceal bleeding. METHODS: Between March 2001 and September 2015, 76 consecutive patients with biopsy-proven INCPH undergoing TIPSS for variceal bleeding in a tertiary-care centre were included. 76 patients with cirrhotic portal hypertension receiving TIPSS for variceal bleeding, and matched for age, sex, Child-Pugh class, stent type and index year of TIPSS creation served as controls. RESULTS: Patients with INCPH, compared to those with cirrhosis, had significantly lower mortality (11% vs 36% at 5 years, adjusted HR, 0.37; 95% CI 0.15-0.87, P = 0.022), overt hepatic encephalopathy (16% vs 33% at 5 years, adjusted HR, 0.35; 95% CI 0.16-0.75, P = 0.007) and hepatic impairment, despite similar rates of further bleeding (33% vs 32% at 5 years, adjusted HR, 0.72; 95% CI 0.36-1.44, P = 0.358), and shunt dysfunction (35% vs 36% at 5 years, adjusted HR, 0.84; 95% CI 0.41-1.72, P = 0.627). These findings were consistent across different relevant subgroups. CONCLUSIONS: Patients with INCPH treated with TIPSS for variceal bleeding had similar progression of portal hypertension (further bleeding and shunt dysfunction) but fewer complications of liver disease (overt hepatic encephalopathy and hepatic insufficiency) and lower mortality rate compared with cirrhotic patients with comparable liver function.

Early-Recurrent Overt Hepatic Encephalopathy Is Associated with Reduced Survival in Cirrhotic Patients after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To investigate the role of early overt hepatic encephalopathy (OHE) as a clinical marker of prognosis in cirrhosis with a transjugular intrahepatic portosystemic shunt (TIPS) and to assess the relationship between recurrence of OHE and survival after TIPS. METHODS: From January 2012 to December 2013, a retrospective study of consecutive patients with cirrhosis and a TIPS was performed at a single institution. A total of 304 patients (196 males; mean age, 52 years) were enrolled during the study period. The mean Model for End-Stage Liver Disease (MELD) score was 11.6. Time-dependent Cox regression was applied to estimate the predictive ability of early OHE (within 3 months after TIPS) and the effect of its frequency on survival. RESULTS: During a median follow-up of 28.3 months, 115 patients experienced OHE after the TIPS procedure; of these, 54 had at least 2 OHE episodes. Long-term survival worsened in patients with early OHE (hazard ratio [HR] = 2.75; 95% confidence interval [CI]: 1.75-4.32; P < .001). When early OHE was further divided into early-recurrent and single OHE, death was more common in patients with early-recurrent OHE (P < .001) than in patients with early-single OHE (P = .24). After adjustment by MELD score, ascites, serum albumin, indication for TIPS, and age, patients with early-recurrent OHE had a lower probability of survival (HR = 2.91; 95% CI: 1.04-4.89; P < .001). Furthermore, landmark and propensity score analyses confirmed the predictive value of early-recurrent OHE. CONCLUSIONS: Early recurrence of OHE was associated with an increased risk of mortality for patients with cirrhosis who underwent TIPS.

Identifying optimal candidates for early TIPS among patients with cirrhosis and acute variceal bleeding: a multicentre observational study.

OBJECTIVES: Early placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10-13) with cirrhosis and acute variceal bleeding (AVB). However, early TIPS criteria may overestimate the mortality risk in a significant proportion of patients, and the survival benefit conferred by early TIPS in such patients has been questioned. Alternative criteria have been proposed to refine the criteria used to identify candidates for early TIPS. Nevertheless, the true survival benefit provided (or not) by early TIPS compared with standard treatment in the different risk categories has not been investigated in specifically designed comparative studies. DESIGN: We collected data on 1425 consecutive patients with cirrhosis and AVB who were admitted to 12 university hospitals in China between December 2010 and June 2016. Of these, 206 patients received early TIPS, and 1219 patients received standard treatment. The Fine and Gray competing risk regression model was used to compare the outcomes between the two groups that were stratified based on the currently available risk stratification systems after adjusting for liver disease severity and other potential confounders. RESULTS: Overall, early TIPS was associated with an 80% relative risk reduction (RRR) in mortality at 6 weeks (adjusted HR=0.20; 95% CI: 0.10 to 044; p<0.001) and 51% RRR at 1 year (adjusted HR=0.49, 95% CI: 0.32 to 0.73; p<0.001) compared with standard treatment. In stratification analyses, the RRRs in mortality did not significantly differ among the risk categories. However, the absolute risk reductions (ARRs) of mortality were more pronounced in high-risk patients. The ARRs at 6 weeks were -2.1%, -10.2% and -32.4% in Model for End-stage Liver Disease (MELD) ≤11, 12-18 and ≥19 patients and were -1.5%, -9.1% and -23.2% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). The ARRs for mortality at 1 year were -1.7%, -5.4% and -32.7% in MELD ≤11, 12-18 and ≥19 patients, respectively, and -3.6%, -5.2% and -20.3% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). After adjusting for liver disease severity and other potential confounders, a survival benefit was observed in MELD ≥19 or Child-Pugh C patients but not in MELD ≤11 or Child-Pugh A patients. In MELD 12-18 patients, a survival benefit was observed within 6 weeks but not at 1 year. In Child-Pugh B patients, a survival benefit was observed in those with active bleeding but not those without active bleeding. However, the evaluation of active bleeding was associated with a high interobserver variability. Furthermore, early TIPS was associated with a significantly reduced incidence of failure to control bleeding or rebleeding and new or worsening ascites, without increasing the risk of overt hepatic encephalopathy. CONCLUSIONS: Early TIPS was associated with improved survival in patients with MELD ≥19 or Child-Pugh C cirrhosis but not in patients with MELD ≤11 or Child-Pugh A cirrhosis. For MELD 12-18 or Child-Pugh B patients, future studies addressing optimal selection criteria for early TIPS remain highly warranted.

Hand-foot-skin reaction of grade ≥ 2 within sixty days as the optimal clinical marker best help predict survival in sorafenib therapy for HCC.

Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43-0.67, P < 0.001) and likelihood of progression by 26% (adjusted HR 0.74, 95%CI 0.58-0.96, P = 0.020) compared with non-responders. Notably, 2HFSR60 remained an effective discriminator among most subgroups and had superior predictive ability to previous definitions, even according to the landmark analysis. Conclusions Our study demonstrated that 2HFSR60, with the best discriminatory ability compared to currently available definitions of sorafenib-related adverse events, could be the optimal clinical marker to identify sorafenib responders with decreased risk of death by half.

Motor Cortex Mapping in Patients With Hepatic Myelopathy After Transjugular Intrahepatic Portosystemic Shunt.

RATIONALE AND OBJECTIVES: As a special movement disorder, hepatic myelopathy (HM) is characterized by spastic paraperesis and may be secondary to transjugular intrahepatic portosystemic shunt (TIPS). The prediction and diagnosis of HM is difficult due to largely unknown neuropathological underpinnings and a lack of specific biomarkers. We aimed to delve into the alterations in motor system of HM patients' brain and their potential clinical implication. MATERIAL AND METHODS: Twenty-three patients with HM and 23 without HM after TIPS and 24 demographically matched healthy controls were enrolled. High-spatial-resolution structural imaging and functional data at rest were acquired. Motor areas were included as seed regions for functional connectivity analysis. Then, we performed brain volume analysis. RESULTS: We found decreased right supplementary motor area (SMA)-seeded functional connectivity with bilateral insula, thalamus and midbrain, left cerebellum and middle temporal gyrus, and right middle cingulate gyrus in HM compared to non-HM patients (p < 0.001). The right insula revealed decreased volume (p < 0.001), and white matter volume reduced in the right corona radiata beneath the right SMA (p < 0.001) in HM relative to non-HM patients. Furthermore, the strength of right SMA-seeded connectivity with insula was positively correlated with folic acid level in HM patients (r = 0.60, p = 0.03), showing an accuracy of 0.87 to distinguish HM from non-HM. CONCLUSION: Our study demonstrates the HM-specific dysconnectivity with an anatomical basis, and its correlation with laboratory findings and diagnostic value. Detecting these abnormalities might help to predict and diagnose post-TIPS HM.

Association between non-variceal spontaneous portosystemic shunt and outcomes after TIPS in cirrhosis.

BACKGROUND: Whether pre-existing nonvariceal spontaneous portosystemic shunts (SPSSs) in cirrhotic patients affect outcomes after transjugular intrahepatic portosystemic shunt (TIPS) and whether they need to be closed remains unclear. AIM: To assess the effects of the presence or embolization of SPSSs on outcomes after TIPS for cirrhosis. METHODS: From January 2004 to December 2014, 903 consecutive cirrhotic patients who underwent TIPS in a tertiary-care center were included, of which 715 patients had no SPSS (N-SPSS group), 144 patients had an SPSS without embolization (SPSS group), and 44 had an SPSS with embolization (SPSS + E group). RESULTS: During a median follow-up period of 27.7 months, 368 (41%) patients experienced overt hepatic encephalopathy (OHE), 256 (28%) experienced clinical relapse, 164 (18%) developed shunt dysfunction, and 379 (42%) died. The SPSS group had a higher risk of OHE compared with the N-SPSS and SPSS + E groups (adjusted HR [95%CI]: N-SPSS vs SPSS vs SPSS + E: 1 vs 1.36 [1.06-1.75] vs 0.77 [0.46-1.29]; p = 0.027). In stratification analysis, a higher risk of OHE was only observed in patients with a large SPSS (SPSS diameter ≥6 mm) but not a small SPSS. Additionally, SPSS embolization was associated with a lower risk of OHE among patients with a large SPSS (adjust HR = 0.51; 95% CI: 0.29-0.91; p = 0.034). The risks of clinical relapse (p = 0.584), shunt dysfunction (p = 0.267), and mortality (p = 0.4743) did not significantly differ among groups. CONCLUSIONS: Among cirrhotic patients undergoing TIPS, a pre-existing large SPSS was associated with a higher risk of OHE, which could be decreased by SPSS embolization. There was no clear association between the presence/embolization of an SPSS and post-TIPS clinical relapse, shunt dysfunction or mortality.

Demonstration of laser-produced neutron diagnostic by radiative capture gamma-rays.

We report a new scenario of the time-of-flight technique in which fast neutrons and delayed gamma-ray signals were both recorded in a millisecond time window in harsh environments induced by high-intensity lasers. The delayed gamma signals, arriving far later than the original fast neutron and often being ignored previously, were identified to be the results of radiative captures of thermalized neutrons. The linear correlation between the gamma photon number and the fast neutron yield shows that these delayed gamma events can be employed for neutron diagnosis. This method can reduce the detecting efficiency dropping problem caused by prompt high-flux gamma radiation and provides a new way for neutron diagnosing in high-intensity laser-target interaction experiments.

Covered TIPS versus endoscopic band ligation plus propranolol for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: a randomised controlled trial.

OBJECTIVE: Limited data are available on the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis (PVT). This study aimed to compare transjugular intrahepatic portosystemic shunt (TIPS) with covered stents versus endoscopic band ligation (EBL) plus propranolol for the prevention of variceal rebleeding among patients with cirrhosis and PVT. DESIGN: Consecutive cirrhotic patients (94% Child-Pugh class A or B) with PVT who had variceal bleeding in the past 6 weeks were randomly assigned to TIPS group (n=24) or EBL plus propranolol group (EBL+drug, n=25), respectively. Primary endpoint was variceal rebleeding. Secondary endpoints included survival, overt hepatic encephalopathy (OHE), portal vein recanalisation and rethrombosis, other complications of portal hypertension and adverse events. RESULTS: During a median follow-up of 30 months in both groups, variceal rebleeding was significantly less frequent in the TIPS group (15% vs 45% at 1 year and 25% vs 50% at 2 years, respectively; HR=0.28, 95% CI 0.10 to 0.76, p=0.008), with a significantly higher portal vein recanalisation rate (95% vs 70%; p=0.03) and a relatively lower rethrombosis rate (5% vs 33%; p=0.06) compared with the EBL+drug group. There were no statistically significant differences in survival (67% vs 84%; p=0.152), OHE (25% vs 16%; p=0.440), other complications of portal hypertension and adverse events between groups. CONCLUSION: Covered TIPS placement in patients with PVT and moderately decompensated cirrhosis was more effective than EBL combined with propranolol for the prevention of rebleeding, with a higher probability of PVT resolution without increasing the risk of OHE and adverse effects, but this benefit did not translate into improved survival. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01326949.

Brain white matter fiber tracts involved in post-transjugular intrahepatic portosystemic shunt hepatic myelopathy.

We aimed to detect alterations in diffusion characteristics of brain white matter in hepatic myelopathy (HM) patients. Liver cirrhosis patients with (n=25) and without (n=18) HM after transjugular intrahepatic portosystemic shunt and 26 healthy controls were enrolled in this study. All participants were scanned with diffusion tensor imaging on a 3T Siemens scanner. Tract-based spatial statistics analysis was used to detect abnormalities of intracranial white matter tracts. Correlations between clinical characteristics and diffusion metrics were also calculated. HM patients showed widespread decreased fractional anisotropy values in association fibers, callosal fibers, thalamic fibers, and limbic system fibers (P<0.01, family-wise error-corrected) compared with healthy controls. In addition, HM patients showed lower fractional anisotropy values in the corpus callosum, corona radiata, external capsule, and superior longitudinal fasciculus compared with cirrhosis patients without myelopathy (P<0.01, family-wise error-corrected). Furthermore, limb muscle strength grading was correlated with the diffusion characteristics of the corpus callosum and superior longitudinal fasciculus in HM patients (P<0.05). HM patients suffer from more distinct changes of white matter fiber tracts than cirrhosis patients without myelopathy. In addition, alterations of the corpus callosum and superior longitudinal fasciculus may be associated with the major motor disturbance in HM. Our finding may shed light on the underlying neuropathological mechanism of HM.