Concurrent large spontaneous portosystemic shunt embolization for the prevention of overt hepatic encephalopathy after TIPS: A randomized controlled trial.

BACKGROUND AND AIMS: Large spontaneous portosystemic shunt (SPSS) is associated with increased risk of HE in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to evaluate whether prophylactic embolization of large SPSS at the time of TIPS creation could reduce the incidence of post-TIPS HE in patients with cirrhosis and variceal bleeding. APPROACH AND RESULTS: From June 2014 to August 2017, 56 patients with cirrhosis and large SPSS planning to undergo TIPS for the prevention of variceal bleeding were randomly assigned (1:1) to receive TIPS alone (TIPS group, n = 29) or TIPS plus simultaneous SPSS embolization (TIPS+E group, n = 27). The primary endpoint was overt HE. TIPS placement and SPSS embolization was successful in all patients. During a median follow-up of 24 months, the primary endpoint was met in 15 patients (51.7%) in the TIPS group and six patients (22.2%) in the TIPS+E group (p = 0.045). The 2-year cumulative incidence of overt HE was significantly lower in the TIPS+E group compared with the TIPS group (21.2% vs. 48.3%; HR, 0.38; 95% CI, 0.15-0.97; p = 0.043). The 2-year incidence of recurrent bleeding (TIPS+E vs. TIPS, 15.4% vs. 25.1%; p = 0.522), shunt dysfunction (12.3% vs. 18.6%, p = 0.593), death (15.0% vs. 6.9%, p = 0.352), and other adverse events was not significantly different between the two groups. CONCLUSIONS: In patients with cirrhosis treated with TIPS for variceal bleeding, concurrent large SPSS embolization reduced the risk for overt HE without increasing other complications. Concurrent large SPSS embolization should therefore be considered for prophylaxis of post-TIPS HE.

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.

Novel predictors of stent under-expansion regarding calcified coronary lesions assessed by optical coherence tomography.

A previous calcium scoring system using circumferential angle, thickness, and length of coronary calcium by OCT could assist in predicting stent under-expansion. However, this scoring system only reflects the calcification distribution within a single cross-section and fails to consider the lumen's original size. The current study aims to investigate whether novel parameters to quantify calcium lesions, including calcium burden, area, and volume assessed by optical coherence tomography (OCT), could predict stent under-expansion related to calcium lesions. Consecutive patients admitted between March 10th to October 19th 2021 with calcified coronary lesions undergoing percutaneous coronary intervention (PCI) with OCT guidance were screened for inclusion. The calcium burden, area, and volume of the target lesions were measured using OCT at pre-PCI. After successful stent implantation, stent expansion at the corresponding lesions was also measured by OCT. A total of 125 patients who underwent OCT-guided PCI were included in this study. While the calcium grades by angiography failed to show a significant correlation with stent expansion, maximum and average calcium burden, maximum calcium area, and calcium volume exhibited a moderate correlation with stent expansion. According to the receiver operating characteristic curves, the optimal cutoffs of calcium volume and area for predicting stent under-expansion were 4.37 mm3 and 2.48 mm2 , respectively. Calcium burden, area, and volume by OCT are more favorable predictors of stent under-expansion given its better performance than calcium grades by angiography. Using cutoffs of calcium area and volume could identify high-risk patients of under-expansion and might guide future clinical practice.

Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization.

OBJECTIVES: Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS: A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS: Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS: ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS: • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.

Anticoagulation and Transjugular Intrahepatic Portosystemic Shunt for the Management of Portal Vein Thrombosis in Cirrhosis: A Prospective Observational Study.

INTRODUCTION: Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis. METHODS: Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus. RESULTS: During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n = 25) or complete (n = 287) recanalization, with 9 (3.1%) having rethrombosis, 64 patients (16.2%) developed major bleeding (anticoagulation-related bleeding in 7 [1.8%]), 88 patients (22.2%) developed overt hepatic encephalopathy, and 100 patients (25.3%) died. In multivariate competing risk regression models, TIPS and anticoagulation were associated with a higher probability of recanalization. Long-term anticoagulation using enoxaparin or rivaroxaban rather than warfarin was associated with a decreased risk of rethrombosis and an improved survival, without increasing the risk of bleeding. However, the presence of complete superior mesenteric vein thrombosis was associated with a lower recanalization rate, increased risk of major bleeding, and poor prognosis. DISCUSSION: In patients with cirrhosis with PVT, the individualized treatment algorithm achieves a high-probability recanalization, with low rates of portal hypertensive complications and adverse events.

Cyclosporine A Nanosuspensions for Ophthalmic Delivery: A Comparative Study between Cationic Nanoparticles and Drug-Core Mucus Penetrating Nanoparticles.

The effect of mucin on ocular bioavailability depends on the extent to which it acts as a barrier or retention site. Mucus penetrating particles (MPPs) can evade the mucus entrapment and associated rapid clearance, but cationic nanoparticles have high adhesion to the mucosa. Both formulations can prolong the drug residence time on the surface of the eyes. The purpose of this work is to compare the effects of mucoadhesion of cationic nanoparticles and mucous permeability of MPPs on ocular bioavailability. Cationic nanosuspensions and drug-core MPP nanosuspensions were developed using the anti-solvent precipitation method. The results of X-ray diffraction revealed that CsA was amorphous. In vitro mucoadhesion evaluation demonstrated that cationic nanosuspensions enhanced the interaction with pig mucin about 5.0-6.0 fold compared to drug-core MPP nanosuspensions. A mucus permeation study by the transwell diffusion system showed that the Papp values of drug-core MPP nanosuspensions were 5.0-10.0 times higher than those of cationic nanosuspensions. In vivo ocular bioavailability evaluation of those CsA formulations was conducted in rabbits using a conventional nanosuspension as a comparison. The CsA concentrations in the cornea following the administration of a cationic nanosuspension and a drug-core MPP nanosuspension were 13,641.10 ng/g and 11,436.07 ng/g, respectively, significantly higher than that of the conventional nanosuspension (8310.762 ng/g). The results showed that both the cationic and MPP nanosuspensions were able to deliver CsA to anterior ocular tissues in effective therapeutic concentrations (10-20 µg/g) with topical drop instillation. The cationic nanosuspension could achieve relatively higher bioavailability than the MPP nanosuspension. The cationic nanosuspension would be a promising ocular drug delivery system.

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.

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.

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.

Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study.

BACKGROUND & AIMS: Previous prognostic scores for transarterial chemoembolization (TACE) were mainly derived from real-world settings, which are beyond guideline recommendations. A robust model for outcome prediction and risk stratification of recommended TACE candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: Between January 2010 and May 2016, 1,604 treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh A5-B7 and performance status 0 undergoing TACE were included from 24 tertiary centres. Patients were randomly divided into training (n = 807) and validation (n = 797) cohorts. A prognostic model was developed and subsequently validated. Predictive performance and discrimination were further evaluated and compared with other prognostic models. RESULTS: The final presentation of the model was "linear predictor = largest tumour diameter (cm) + tumour number", which consistently outperformed other currently available models in both training and validation datasets as well as in different subgroups. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were further selected as cut-off values, leading to the "six-and-twelve" score which could divide patients into 3 strata with the sum of tumour size and number ≤6, >6 but ≤12, and >12 presenting significantly different median survival of 49.1 (95% CI 43.7-59.4) months, 32.0 (95% CI 29.9-37.5) months, and 15.8 (95% CI 14.1-17.7) months, respectively. CONCLUSIONS: The six-and-twelve score may prove an easy-to-use tool to stratify recommended TACE candidates (Barcelona Clinic Liver Cancer stage-A/B) and predict individual survival with favourable performance and discrimination. Moreover, the score could stratify these patients in clinical practice as well as help design clinical trials with comparable criteria involving these patients. Further external validation of the score is required. LAY SUMMARY: There is currently no prognostic model specifically developed for recommended or ideal transarterial chemoembolization (TACE) candidates with hepatocellular carcinoma, despite these patients being frequently identified as the best target population in pivotal randomized controlled trials. The six-and-twelve score provides patient survival prediction, especially in ideal candidates of TACE, outperforming other currently available models in both training and validation sets, as well as different subgroups. With cut-off values of 6 and 12, the score can stratify ideal TACE candidates into 3 strata with significantly different outcomes and may shed light on risk stratification of these patients in clinical practice as well as in clinical trials.

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.

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.

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.

Eight millimetre covered TIPS does not compromise shunt function but reduces hepatic encephalopathy in preventing variceal rebleeding.

BACKGROUND & AIMS: Currently, there are no recommendations in guidelines concerning the preferred diameter of stents for transjugular intrahepatic portosystemic shunt (TIPS), owing to the lack of adequate evidence. We therefore compared 8mm stents with 10mm stents, to evaluate whether 8mm stents would achieve similar shunt function, with less hepatic encephalopathy (HE) and better liver function. METHODS: Cirrhotic patients were randomly assigned to receive TIPS with an 8mm or 10mm covered stent to prevent variceal rebleeding. The primary endpoint was shunt dysfunction. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival, their composite endpoint, overt HE (overall and spontaneous) and liver function were designated as the secondary endpoints. RESULTS: From July 2012 to January 2014, 64 and 63 patients were allocated to the 8mm and 10mm groups, respectively. During a median follow-up of 27months in both arms, dysfunction rates (16% vs. 16% at two years, p=0.62), two-year rebleeding (16% vs. 17%, p=0.65), OLT-free survival (95% vs. 86%, p=0.37), and the composite endpoint (p=0.62) were not statistically different between the groups. Despite a marginal decrease in overall overt HE, there were significantly fewer spontaneous overt HE incidents in the 8mm group within two years (27% vs. 43%, p=0.03), with a risk reduction of 47%. Notably, patients receiving 8mm stents also developed less hepatic impairment. CONCLUSIONS: TIPS with 8mm covered stents showed similar shunt function to TIPS with 10mm stents, but halved the risk of spontaneous overt HE and reduced hepatic impairment. Therefore, 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients. Lay summary: The optimal diameter for transjugular intrahepatic portosystemic shunt (TIPS) remained uncertain. This study showed that TIPS with 8mm covered stents did not compromise shunt patency, or influence the efficacy of variceal rebleeding prevention compared to TIPS with 10mm stents, but reduced the risk of spontaneous overt hepatic encephalopathy and the incidence of severe encephalopathy. Moreover, liver function reserve was also better in the 8mm stents group, suggesting that 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients.

Association of Nonmalignant Portal Vein Thrombosis and Outcomes after Transjugular Intrahepatic Portosystemic Shunt in Patients with Cirrhosis.

Purpose To assess the effects of preexisting nonmalignant portal vein thrombosis (PVT) on mortality, clinical relapse, shunt dysfunction, and overt hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) placement. Materials and Methods This retrospective study was approved by the institutional ethics committee, and written informed consent was obtained from all patients. From March 2001 to December 2014, 1171 consecutive patients with cirrhosis (762 men, 409 women; mean age, 50.0 years ± 12.8) and PVT (n = 212; 18%) or without PVT (n = 959; 82%) who underwent TIPS placement were included. The association between PVT and outcomes after TIPS placement was measured by using Fine and Gray competing risk regression model after adjusting for important baseline characteristics or by using propensity score. The Wald test was used to assess the homogeneity of the effects of PVT across different strata (stratified PVT according to the stages, degrees, and extents) and major subgroups. Results During a median follow-up period of 28.4 months, 507 (43%) patients died, 373 (32%) experienced clinical relapse, 217 (19%) developed shunt dysfunction, and 475 (41%) experienced overt HE. Compared with patients without PVT, patients with PVT had a similar risk of mortality (adjusted hazard ratio, 0.82; 95% confidence interval [CI]: 0.63, 1.09; P = .17), clinical relapse (adjusted hazard ratio, 1.24; 95% CI: 0.92, 1.69; P = .15), shunt dysfunction (adjusted hazard ratio, 1.03; 95% CI: 0.70, 1.51; P = .43), and overt HE (adjusted hazard ratio, 0.88; 95% CI: 0.70, 1.11; P = .29). Furthermore, the effects of PVT were consistent across the relevant strata and subgroups. Conclusion There was no evidence that preexisting PVT was associated with an improved or worsened outcome after TIPS. © RSNA, 2017 Online supplemental material is available for this article.

Chemoembolization for Hepatocellular Carcinoma in Patients with Extrahepatic Spread: Prognostic Determinants and Appropriate Candidates.

PURPOSE: To investigate treatment outcome, prognostic factors for overall survival, and appropriate candidates for transarterial chemoembolization among patients with hepatocellular carcinoma (HCC) and extrahepatic spread (EHS). MATERIALS AND METHODS: From January 2010 to June 2014, 111 consecutive patients with HCC and EHS treated by transarterial chemoembolization alone were evaluated. Factors associated with overall survival were evaluated using Cox regression analysis, and a scoring equation was established to subgroup patients with EHS. RESULTS: Median follow-up was 3.8 months, and median overall survival was 3.8 months (95% confidence interval [CI], 2.9-4.7 months). Multivariate analysis demonstrated maximum tumor size ≥ 10 cm (hazard ratio [HR] 1.58; 95% CI, 1.02-2.46; P = .041), multifocal intrahepatic tumors (HR 1.55; 95% CI, 1.03-2.33; P = .037), and portal vein tumor thrombosis (PVTT) (HR 1.81; 95% CI, 1.12-2.91; P = .015) as significant predictors of overall survival. Based on these factors, a scoring equation was developed to predict treatment outcome of transarterial chemoembolization, with an area under the receiver operating characteristic curve of 0.76 in predicting 6-month survival. Using a cutoff score of 5.5, patients with HCC and EHS were divided into 2 groups with significantly different overall survival (8.1 months for EHS1 and 2.4 months for EHS2; P < .001). The described method of subgrouping remained discriminatory regardless of baseline characteristics. CONCLUSIONS: Maximum tumor size, intrahepatic tumor distribution, and presence of PVTT were significant determinants of overall survival for patients with HCC and EHS. Transarterial chemoembolization may be appropriate for patients with EHS but lower intrahepatic tumor burden.