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

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. 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). 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.

Lv Y ，Wang Z ，Li K ，Wang Q ，Bai W ，Yuan X ，Yu T ，Niu J ，Yang Z ，Zhu X ，Zhao J ，Xue H ，Jiang Z ，Zhuge Y ，Zhang C ，Sun J ，Ding P ，Ren W ，Li Y ，Zhang K ，Zhang W ，Guo W ，Luo B ，Li X ，Yuan J ，Han N ，Zhu Y ，He C ，Yin Z ，Fan D ，Han G ... -  《-》

CLIF-C AD score predicts survival benefit from pre-emptive TIPS in individuals with Child-Pugh B cirrhosis and acute variceal bleeding.

Among individuals with Child-Pugh B cirrhosis and acute variceal bleeding (AVB), the Baveno VII workshop recommended pre-emptive TIPS in those with a Child-Pugh score of 8-9 and active bleeding at initial endoscopy (Child B8-9 + AB criteria). Nevertheless, whether this criterion is superior to the CLIF-Consortium acute decompensation score (CLIF-C ADs) remains unclear. Data on 1,021 consecutive individuals with Child-Pugh B cirrhosis and AVB from 13 university hospitals in China who were treated with pre-emptive TIPS (n = 297) or drug plus endoscopic treatment (n = 724) between 2010 to 2019 were retrospectively analysed. A competing risk regression model was used to compare the outcomes between the two groups after adjusting for confounders. The concordance-statistic for benefit (c-for-benefit) was used to evaluate a models' ability to predict treatment benefit (risk difference between treatment groups). Pre-emptive TIPS was associated with reduced mortality compared to drug plus endoscopic treatment (adjusted hazard ratio 0.62, 95% CI 0.44 to 0.88). A higher baseline CLIF-C AD score was associated with greater survival benefit (i.e., larger absolute mortality risk reduction). After adjusting for confounders, a survival benefit was observed in individuals with CLIF-C ADs ≥48 or Child-Pugh B8-9 with active bleeding, but not in those with CILF-C ADs <48, no active bleeding or Child-Pugh B7 with active bleeding. The c-for-benefit of CILF-C ADs for predicting survival benefit was higher than that of Child B8-9+AB criteria. In individuals with Child-Pugh B cirrhosis and AVB, CLIF-C ADs predicts survival benefit from pre-emptive TIPS and outperforms the Child B8-9+AB criteria. Prospective validation should be performed to confirm this result, especially for other aetiologies of cirrhosis. In this study, among individuals with Child-Pugh B cirrhosis and acute variceal bleeding, the CLIF-Consortium acute decompensation (CLIF-C AD) score could predict the survival benefit from pre-emptive TIPS, with patients with higher CLIF-C AD scores benefiting more from pre-emptive TIPS. Furthermore, the CLIF-C AD score outperformed the Child B8-9 plus active bleeding criteria in terms of discriminating between those who obtained more benefit vs. less benefit from pre-emptive TIPS. Depending on prospective validation, the CLIF-C AD score could be used as the model of choice to determine who should undergo pre-emptive TIPS.

Lv Y ，Bai W ，Zhu X ，Xue H ，Zhao J ，Zhuge Y ，Sun J ，Zhang C ，Ding P ，Jiang Z ，Zhu X ，Ren W ，Li Y ，Zhang K ，Zhang W ，Li K ，Wang Z ，Luo B ，Li X ，Yang Z ，Wang Q ，Guo W ，Xia D ，Yang C ，Pan Y ，Yin Z ，Fan D ，Han G ... -  《-》

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

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. 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. 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. 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.

Lv Y ，Zuo L ，Zhu X ，Zhao J ，Xue H ，Jiang Z ，Zhuge Y ，Zhang C ，Sun J ，Ding P ，Ren W ，Li Y ，Zhang K ，Zhang W ，He C ，Zhong J ，Peng Q ，Ma F ，Luo J ，Zhang M ，Wang G ，Sun M ，Dong J ，Bai W ，Guo W ，Wang Q ，Yuan X ，Wang Z ，Yu T ，Luo B ，Li X ，Yuan J ，Han N ，Zhu Y ，Niu J ，Li K ，Yin Z ，Nie Y ，Fan D ，Han G ... -  《-》

Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: a Meta-analysis of Individual Patient Data.

Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS. We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients. Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323-0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307-0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253-0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy. In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy.

Nicoară-Farcău O ，Han G ，Rudler M ，Angrisani D ，Monescillo A ，Torres F ，Casanovas G ，Bosch J ，Lv Y ，Thabut D ，Fan D ，Hernández-Gea V ，García-Pagán JC ，Preemptive TIPS Individual Data Metanalysis, International Variceal Bleeding Study and Baveno Cooperation Study groups ... -  《-》

External validation of Chronic Liver Failure-Consortium Acute Decompensation score in the risk stratification of cirrhotic patients hospitalized with acute variceal bleeding.

Acute variceal bleeding (AVB) is a serious life-threatening complication of cirrhosis. This study aimed to validate the predictive value of Chronic Liver Failure-Consortium Acute Decompensation score (CLIF-C ADs) in the risk stratification of cirrhotic patients hospitalized with AVB. A total of 235 cirrhotic patients with AVB and without acute-on-chronic liver failure (ACLF) were retrospectively enrolled. The discrimination, calibration, overall performance and clinical utility of CLIF-C AD were evaluated and compared with traditional prognostic scores. The area under the receiver operating characteristics curve of CLIF-C AD was significantly or numerically higher than that of Child-Turcotte-Pugh (CTP) (0.871 vs. 0.737, P  = 0.03), Model for End-stage Liver Disease (MELD) (0.871 vs. 0.757, P  = 0.1) and MELD-Sodium (MELD-Na) (0.871 vs. 0.822, P  = 0.45). The calibration of CLIF-C AD was excellent and superior to that of CTP, MELD and MELD-Na. The brier score/ R2 value for CLIF-C AD, CTP, MELD and MELD-Na were 0.045/0.278, 0.051/0.090, 0.050/0.123 and 0.046/0.207, respectively, suggesting a superior overall performance of CLIF-C AD to traditional scores. In decision curve analysis, the standardized net benefit of CLIF-C AD was higher to that of traditional scores. Patients with CLIF-C ADs ≤48, 49-59 and ≥60 were, respectively, stratified into low, moderate and high-risk groups (6-week mortality: 2.7% vs. 12.5% vs. 37.5%, P  < 0.001). The prediction performance and clinical utility of CLIF-C AD for 6-week mortality in cirrhotic patients with AVB and without ACLF are excellent and superior to traditional prognostic scores. The new risk stratification with CLIF-C ADs may be useful in guiding rational management of AVB.

Zhu Z ，Jiang H 《-》