Efficacy of endoscopic therapy combined with partial splenic embolization versus Hassab's operation for patients with liver cirrhosis with esophageal variceal bleeding and hypersplenism: a multicenter cohort study based on propensity score matching.

BACKGROUND: The prognosis comparison between endoscopic therapy + partial splenic embolization (PSE) and Hassab's operation is unclear in the treatment of esophageal variceal bleeding in patients with liver cirrhosis. This study aimed to compare the outcome of endoscopic therapy + PSE (EP) with a combination of splenectomy + pericardial devascularization procedure, known as Hassab's operation (SH) for esophageal variceal bleeding in patients with liver cirrhosis with hypersplenism. METHODS: We enrolled 328 patients, including 125 and 203 patients who underwent EP and SH, respectively. Each group consisted of 110 patients after propensity score matching (PSM). Subsequently, we recorded and analyzed bleeding episodes and mortality in 6 months and 1, 2, and 5 years after therapies. RESULTS: The median follow-up time in the EP and SH groups was 53 and 64 months, respectively. Bleeding incidence 6 months after therapies in the EP group was lower than that in the SH group (1.8% vs. 10.0%, P = 0.010). Additionally, complications in the perioperative period were not significantly different (0% vs. 3.6%, P = 0.008). However, the bleeding rate between the two groups was not significantly different at 1, 2, and 5 years after therapies (7.3% vs. 12.7%, P = 0.157; 10.9% vs. 16.4%, P = 0.205; 30.6% vs. 31.8%, P = 0.801), as well as mortality rate (4.5% vs 7.3%, P = 0.571). CONCLUSION: Compared with SH therapy, the bleeding rate 6 months after EP therapy was lower, but the long-term bleeding rate was similar.

Prognosis of LSPD versus TIPS for the treatment of esophagogastric variceal bleeding in cirrhosis.

BACKGROUND: This study aimed to compare postoperative complications in patients with esophagogastric variceal bleeding (EVB) who underwent laparoscopic splenectomy combined with pericardial devascularization (LSPD) versus transjugular intrahepatic portosystemic shunt (TIPS) procedures. METHODS: A retrospective collection of medical records was conducted from January 2014 to May 2020 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The study included patients from the departments of trauma surgery, interventional radiology, and general surgery who were diagnosed with EVB caused by portal hypertension and treated with LSPD or TIPS. Follow-up data were obtained to assess the occurrence of postoperative complications in both groups. RESULTS: A total of 201 patients were included in the study, with 104 cases in the LSPD group and 97 cases in the TIPS group. There was no significant difference in the 1-year and 3-year post-surgery survival rates between the TIPS and LSPD groups (P = 0.669, 0.066). The 3-year survival rate of Child-Pugh B patients in the LSPD group was higher than TIPS group (P = 0.041). The LSPD group also had a significantly higher rate of freedom from rebleeding at 3-year post-surgery compared to the TIPS group (P = 0.038). Stratified analysis showed no statistically significant difference in the rebleeding rate between the two groups. Furthermore, the LSPD group had a higher rate of freedom from overt hepatic encephalopathy at 1-year and 3-year post-surgery compared to the TIPS group (P = 0.007, < 0.001). The LSPD group also had a lower rate of severe complications at 3-year post-surgery compared to the TIPS group (P = 0.020). CONCLUSION: Compared to TIPS, LSPD does not increase the risk of mortality and rebleeding, while demonstrating fewer complications. In patients classified as Child-Pugh A and B, the use of LSPD for treating EVB is both safe and effective.

Management of ectopic variceal bleeding with transjugular intrahepatic portosystemic shunt: a systematic review of case reports.

Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for ectopic variceal management. A comprehensive search through PubMed, Scopus, Web of Science, and Embase was conducted until January 16, 2023, using relevant keywords. Case reports and case series with fewer than 10 patients on TIPS for ectopic variceal management were included. The quality assessment followed the Joanna Briggs Institute checklist for case reports. This systematic review evaluated 43 studies involving 50 patients with ectopic varices undergoing TIPS. Patients had a mean age of 54.3 years, half were female, and two were pregnant. Alcoholic liver disease (48%) and hepatitis C infection (26%) were common causes of portal hypertension. Ascites and splenomegaly were reported in 32% and 28% of the patients, respectively. Rectal, oral, and stomal variceal bleeding accounted for 62%, 16%, and 22% of the patients, respectively. Ectopic varices were mainly located in the duodenum (28%) and rectum (26%) regions. Complications affected 42% of the patients, re-bleeding in eleven and hepatic encephalopathy in seven. The follow-up lasted 12 months on average, and finally, 5 received a liver transplant. Mortality post-TIPS was 18%. Despite complications and a notable mortality rate, favorable outcomes were observed in almost half of the patients with ectopic variceal bleeding managed with TIPS. Further research is warranted to refine strategies and improve patient outcomes.

Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports.

Background and Objectives: Variceal bleeding (VB) is the most concerning condition that is difficult to treat after atezolizumab/bevacizumab in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: We would like to introduce the cases of two patients who underwent bevacizumab reduction or discontinuation when VB occurred after atezolizumab/bevacizumab. Results: VB occurred in two patients who showed good tumor response after atezolizumab/bevacizumab treatment, and all VBs were successfully treated with endoscopic variceal ligations. In the first patient, VB did not occur as the tumor response decreased after a 50% reduction in bevacizumab. In the second patient, VB occurred again after a 50% bevacizumab reduction, so bevacizumab was discontinued and treatment with atezolizumab alone has been successfully maintained. Conclusions: Accordingly, we would like to suggest that considering bevacizumab dose reduction instead of changing to tyrosine kinase inhibitor may be a good clinical choice in atezolizumab/bevacizumab patients who develop VB.

Clinical implementation of partial splenic artery embolization for the prevention of recurrent bleeding from esophageal varices in portal hypertension.

OBJECTIVE: Aim: To evaluate the effectiveness of PSAE for secondary prevention of VB episodes in patients with chronic liver disease (CLD) and CSPH. PATIENTS AND METHODS: Materials and Methods: One hundred twenty patients (from 2008 to 2020) were submitted of PSAE as secondary prevention treatment. The results of the treatment of 27 patients between 2008 and 2012 (first period) were compared with those of 93 patients treated with PSAE since 2013 (second period), as procedure and management protocol were modificated. VB recurrence rate and mortality (related and non-related to bleeding episodes) were defined as study end-points in both groups at 12-months follow-up. RESULTS: Results: At 12-months follow-up, 11 (40,7 %) and 54 (58,1 %) patients in groups 1 and 2, respectively, were free from VBs (p=0,129). Overall mortality rate was significantly higher in group 1, as compared to group 2: 10 (37,0 %) versus 6 (6,4 %) patients, respectively (p<0,001), - due to higher frequency of fatal VB events (7 (26,0 %) vs. 3 (3,2 %) patients, respectively; p=0,001). CONCLUSION: Conclusions: PSAE is an effective treatment for secondary prevention of VB in patients with CLD and CSPS. The management protocol modification resulted in the decrease in overall mortality rate and mortality related to recurrent VB episodes.

Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis.

BACKGROUND & AIMS: Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective ß-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding. METHODS: Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression. RESULTS: Eighty-seven patients (carvedilol/propranolol, n = 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective ß-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P = .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P = .034). Cumulative incidences for rebleeding (Gray test, P = .027) and liver-related death (P = .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P = .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P = .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models. CONCLUSIONS: Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.

Secondary Prevention of Esophageal Variceal Bleeding Is Often Imperfect: A National, Population-Based Cohort Study of 3592 Patients.

BACKGROUND AND AIMS: Secondary prevention of esophageal variceal bleeding is important to improve prognosis, but uptake of guidelines is unknown in a real-world setting. Here, we determined the proportion of patients receiving appropriate nonselective beta-blocker treatment and repeat upper endoscopy after a first episode of esophageal variceal bleeding within a reasonable time frame. METHODS: Population-based registers were used to identify all patients with a first episode of esophageal variceal bleeding in Sweden from 2006 to 2020. Crosslinkage between registers was performed to receive information on the cumulative incidence of patients with a dispensation of nonselective beta-blockers and repeat upper endoscopy within 120 days from baseline. Overall mortality was investigated using Cox regression. RESULTS: In total, 3592 patients were identified, with a median age of 63 (interquartile range, 54-71) years. The cumulative incidence of a dispensation of nonselective beta-blockers and a repeat endoscopy within 120 days was 33%. A total of 77% received either of these treatments. Overall mortality was high, with 65% of patients dying after esophageal variceal bleeding during the full follow-up period (median 1.7 years). We observed an improved overall mortality during the later years of the study period (adjusted hazard ratio for the 2016-2020 period compared with the 2006-2010 period, 0.80; 95% confidence interval, 0.71-0.89). Patients with receipt of nonselective beta-blockers and repeat upper endoscopy had better overall survival compared with those without (adjusted hazard ratio, 0.80; 95% confidence interval, 0.72-0.90). CONCLUSIONS: Secondary prevention of esophageal variceal bleeding has not been widely undertaken, with many patients not receiving guideline-supported interventions within a reasonable time frame. This highlights a need to raise awareness on appropriate prevention strategies to clinicians and patients.

Carvedilol as the new non-selective beta-blocker of choice in patients with cirrhosis and portal hypertension.

Portal hypertension (PH) is the most common complication ofcirrhosis and represents the main driver of hepatic decompensation. The overarching goal of PH treatments in patients with compensated cirrhosis is to reduce the risk of hepatic decompensation (i.e development of ascites, variceal bleeding and/or hepatic encephalopathy). In decompensated patients, PH-directed therapies aim at avoiding further decompensation (i.e. recurrent/refractory ascites, variceal rebleeding, recurrent encephalopathy, spontaneous bacterial peritonitis or hepatorenal syndrome) and at improving survival. Carvedilol is a non-selective beta-blocker (NSBB) acting on hyperdynamic circulation/splanchnic vasodilation and on intrahepatic resistance. It has shown superior efficacy than traditional NSBBs in lowering PH in patients with cirrhosis and may be, therefore, the NSBB of choice for the treatment of clinically significant portal hypertension. In primary prophylaxis of variceal bleeding, carvedilol has been demonstrated to be more effective than endoscopic variceal ligation (EVL). In patients with compensated cirrhosis carvedilol achieves higher rate of hemodynamic response than propranolol, resulting in a decreased risk of hepatic decompensation. In secondary prophylaxis, the combination of EVL with carvedilol may prevent rebleeding and non-bleeding further decompensation better than that with propranolol. In patients with ascites and gastroesophageal varices, carvedilol is safe and may improve survival, as long as no impairment of the systemic hemodynamic or renal dysfunction occurs, with maintained arterial blood pressure as suitable safety surrogate. The target dose of carvedilol to treat PH should be 12.5 mg/day. This review summarizes the evidence behind Baveno-VII recommendations on the use of carvedilol in patients with cirrhosis.

Risk stratification based on acute-on-chronic liver failure in cirrhotic patients hospitalized for acute variceal bleeding.

BACKGROUND AND AIMS: Acute variceal bleeding (AVB) is a life-threatening complication of cirrhosis. Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of cirrhosis, multiple organ failures and high short-term mortality. This study aimed to evaluate the role of ACLF in the risk stratification of cirrhotic patients with AVB. METHODS: Prospective data of 335 cirrhotic patients hospitalized for AVB were retrospectively extracted from Medical Information Mart for Intensive Care (MIMIC)-IV database. ACLF was defined by European Association for the Study of Liver-Chronic Liver Failure Consortium and diagnosed/graded with chronic liver failure-organ failure (CLIF-OF) score. Cox-proportional hazards regression analysis was performed to identify the risk factors for 6-week morality in AVB patients. Discrimination and calibration of prognostic scores were evaluated by plotting the receiver operating characteristics (ROC) curve and calibration curve, respectively. Overall performance was assessed by calculating the Brier score and R2 value. RESULTS: A total of 181 (54.0%) patients were diagnosed with ACLF (grade 1: 18.2%, grade 2: 33.7%, grade 3: 48.1%) at admission. The 6-week mortality in patients with ACLF was significantly higher than that in patients without ACLF (43.6% vs. 8.4%, P < 0.001) and increased in line with the severity of ACLF (22.5%, 34.2% and 63.8% for ACLF grade 1, 2 and 3, P < 0.001). In multivariate analysis, presence of ACLF remained as an independent risk factor for 6-week mortality after adjusting for confounding factors (HR = 2.12, P = 0.03). The discrimination, calibration and overall performance of CLIF-C ACLF and CLIF-C AD were superior to the traditional prognostic scores (CTP, MELD and MELD-Na) in the prediction of 6-week mortality of patients with and without ACLF, respectively. CONCLUSION: The prognosis of cirrhotic patients with AVB is poor when accompanied by ACLF. ACLF at admission is an independent predictor for the 6-week mortality in cirrhotic patients with AVB. CLIF-C ACLF and CLIF-C AD are the best prognostic scores in AVB patients with and without ACLF, respectively, and can be used for the risk stratification of these two distinct entities.

Timing of endoscopy in patients with cirrhosis and acute variceal bleeding: a single-center retrospective study.

BACKGROUND: The optimal timing of endoscopy in liver cirrhosis with acute variceal bleeding (AVB) remains controversial in current guidelines and studies. METHODS: Consecutive patients with liver cirrhosis and AVB were screened. The timing of endoscopy was calculated from the last presentation of AVB or the admission to endoscopy. Early endoscopy was defined as the interval < 12 h, < 24 h, or < 48 h. A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding and in-hospital mortality were evaluated. RESULTS: Overall, 534 patients were included. When the timing of endoscopy was calculated from the last presentation of AVB, PSM analysis demonstrated that the rate of 5-day failure to control bleeding was significantly higher in early endoscopy group defined as < 48 h (9.7% versus 2.4%, P = 0.009), but not < 12 h (8.7% versus 6.5%, P = 1.000) or < 24 h (13.4% versus 6.2%, P = 0.091), and that the in-hospital mortality was not significantly different between early and delayed endoscopy groups (< 12 h: 6.5% versus 4.3%, P = 1.000; <24 h: 4.1% versus 3.1%, P = 1.000; <48 h: 3.0% versus 2.4%, P = 1.000). When the timing of endoscopy was calculated from the admission, PSM analyses did not demonstrate any significant difference in the rate of 5-day failure to control bleeding (< 12 h: 4.8% versus 12.7%, P = 0.205; <24 h: 5.2% versus 7.7%, P = 0.355; <48 h: 4.5% versus 6.0%, P = 0.501) or in-hospital mortality (< 12 h: 4.8% versus 4.8%, P = 1.000; <24 h: 3.9% versus 2.6%, P = 0.750; <48 h: 2.0% versus 2.5%, P = 1.000) between early and delayed endoscopy groups. CONCLUSION: Our study could not support any significant association of timing of endoscopy with cirrhotic patients with AVB.

A Retrospective Analysis of the Efficacy of Endoscopic Variceal Ligation versus Endoscopic Tissue Adhesive Injection in the Treatment of Esophagogastric Variceal Bleeding.

BACKGROUND: The aim of the study was to investigate the effectiveness and safety of endoscopic variceal ligation (EVL) and endoscopic tissue adhesive injection (TAI) in the treatment of esophagogastric variceal bleeding (EVB). METHODS: A total of 245 patients with EVB who attended the First Affiliated Hospital of Bengbu Medical College from December 2017 to June 2021 were retrospectively collected. The participants were divided into the esophageal EVL (E-EVL) + gastric EVL (G-EVL) group (n = 103) and E-EVL + gastric TAI (G-TAI) group (n = 142), according to the procedure, comparing and assessing the clinical characteristics, laboratory results, operation time, rebleeding rate, efficacy, and complications. RESULTS: The E-EVL + G-EVL group had significantly less varicose vein diameter and operative time than the E-EVL + G-TAI group (p < 0.05). No statistical difference in the length of hospital stay between the two groups was noted (p > 0.05). The total rebleeding rate in the E-EVL + G-EVL group was 9.7%, whereas that of the E-EVL + G-TAI group was 11.9%; no statistical difference between the two groups was noted (p > 0.05). The overall effective rate of the E-EVL + G-EVL group was 90.21%, whereas that of the E-EVL + G-TAI group was 92.81%; no statistical difference between the two groups was observed (p > 0.05). The postoperative ulcer in the E-EVL + G-EVL group was smaller and more superficial than that in the E-EVL + G-TAI group, and the wound surface was smoother. CONCLUSION: Both EVL and TAI have good therapeutic effects on EVB. Furthermore, owing to its effectiveness in preventing rebleeding, no reduction in efficacy and no increase in complications, shortened operative time, smaller and superficial ulcer, and smoother wounds, gastric EVL is worthy of further clinical promotion.

Baveno VII criteria identify varices needing treatment in patients with hepatocellular carcinoma of different Barcelona Clinic Liver Cancer stages.

BACKGROUND: Baveno VII criteria for predicting varices needing treatment (VNT) have not been tested in hepatocellular carcinoma (HCC) population. We evaluated Baveno VII consensus for VNT in HCC patients of different stages according to Barcelona Clinic Liver Cancer (BCLC) stages undergoing curative hepatectomy. METHODS: This was a prospective cohort study of patients with HCC. Patients underwent transient elastography examination before HCC treatment and received at least one upper endoscopic examination afterwards. Patients were prospectively followed for clinical events including VNT. RESULTS: Six hundred and seventy-three patients (83.1% male, median age 62 years) with HCC of BCLC stage 0 (10%), A (57%), B (17%) and C (15%) were recruited and followed for 47 months. The median (range) LSM was 10.5 (6.9-20.4) kPa; 74% had LSM ≤ 20 kPa and 58% had platelet count ≥150 × 10/L, respectively. VNT occurred in 51 (7.6%) patients. In patients who fulfilled Baveno VII criteria, that is, LSM ≤ 20 kPa and platelet count above 150 × 10/L, only 11 (1.6%) patients had VNT. In all BCLC stages of HCC, the proportion of patients with VNT was below 5%, which support the validity and applicability of Baveno VII criteria in all BCLC stages of HCC. CONCLUSIONS: The Baveno VII criteria are valid and applicable in HCC patients undergoing curative hepatectomy for selecting patients to undergo screening endoscopy for VNT. The validity was consistent across different BCLC stages of HCC.

MELD-Lactate Predicts Poor Outcome in Variceal Bleeding in Cirrhosis.

BACKGROUND: Predictors of poor outcome associated with variceal bleeding remain suboptimal. In patients with cirrhosis, serum lactate combined with Model for End-Stage Liver Disease (MELD-LA) improved prediction across heterogeneous populations. However, prognostic properties have not yet been assessed in the context of variceal bleeding. AIMS: We aimed to evaluate the predictive performance of MELD-LA compared to MELD, lactate, and nadir hemoglobin in cirrhosis patients with variceal bleeding. METHODS: In this multicenter study, we identified 472 patients with variceal bleeding from a German primary cohort (University Hospitals Hamburg/Frankfurt/Cologne), and two independent external validation cohorts [Veterans Affairs (VA), Baylor University]. Discrimination for 30-day mortality was analyzed and scores were compared. MELD-LA was evaluated separately in validation cohorts to ensure consistency of findings. RESULTS: In contrast to nadir hemoglobin, MELD and peak-lactate at time of bleeding were significantly higher in 30-day non-survivors in the primary cohort (p = 0.708; p < 0.001). MELD-LA had excellent discrimination for 30-day mortality (AUROC 0.82, 95% CI 0.76-0.88), better than MELD and peak-lactate (AUROC 0.78, 95% CI 0.71-0.84; AUROC 0.73, 95% CI 0.66-0.81). MELD-LA predicted 30-day mortality independently of age, sex, severity of liver disease and vasopressor support (HR 1.29 per 1-point-increase of MELD-LA; 95% CI 1.19-1.41; p < 0.001). Similarly, MELD-LA demonstrated excellent discrimination for 30-day mortality in the VA (AUROC = 0.86, 95% CI 0.79-0.93) and Baylor cohort (AUROC = 0.85, 95% CI 0.74-0.95). CONCLUSIONS: MELD-LA significantly improves discrimination of short-term mortality associated with variceal bleeding, compared to MELD, peak-lactate and nadir hemoglobin. Thus, MELD-LA might represent a useful and objective marker for risk assessment and therapeutic intervention in patients with variceal bleeding.

Balloon-compression endoscopic injection sclerotherapy versus transjugular intrahepatic portosystemic shunt for esophageal variceal rebleeding.

BACKGROUND: In cirrhotic patients, recurrent bleeding after the first episode of esophageal variceal bleeding (EVB) is common and lethal. The present study was aimed to compare balloon-compression endoscopic injection sclerotherapy (bc-EIS) with transjugular intrahepatic portosystemic shunt (TIPS) for the prophylaxis of variceal rebleeding. METHODS: Between June 2020 and September 2022, 81 cirrhotic patients with EVB (42 in the bc-EIS group and 39 in the TIPS group) were evaluated retrospectively. The occurrence of rebleeding, hepatic encephalopathy (HE) or other complications, as well as liver functions and survival rate were compared between two groups. RESULTS: During the 12 months of follow-up, variceal eradication was achieved in 40 (95.24%) patients of the bc-EIS group after a mean of 1.80 ± 0.94 sessions. TIPS was successfully performed in 39 (100%) patients. No significant difference in the variceal rebleeding rate was observed between bc-EIS and TIPS groups (16.67 vs. 17.95%; p = 0.111). While the bc-EIS group showed significantly decreased incidence of HE (2.38 vs. 17.95%; p < 0.001) and lower level of total bilirubin (p < 0.05) in comparison with the TIPS group. The difference in mortality between the two groups failed to reach statistical significance (0.00 vs. 7.69%; p = 0.107). CONCLUSION: Bc-EIS is not inferior to TIPS in the survival and control of variceal rebleeding, but associated with decreased risk of HE and liver dysfunction.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Surgical management of extrahepatic portal vein obstruction in children: advantages of MesoRex shunt compared with distal splenorenal shunt.

PURPOSE: To review surgical management of extrahepatic portal vein obstruction (EHPVO) at Red Cross War Memorial Children's Hospital and compare MesoRex shunt (MRS) with distal splenorenal shunt (DSRS). METHODS: This is a single-centre retrospective review documenting pre- and post-operative data in 21 children. Twenty-two shunts were performed, 15 MRS and 7 DSRS, over an 18-year period. Patients were followed up for a mean of 11 years (range 2-18). Data analysis included demographics, albumin, prothrombin time (PT), partial thromboplastin time (PTT), International normalised ratio (INR), fibrinogen, total bilirubin, liver enzymes and platelets before the operation and 2 years after shunt surgery. RESULTS: One MRS thrombosed immediately post-surgery and the child was salvaged with DSRS. Variceal bleeding was controlled in both groups. Significant improvements were seen amongst MRS cohort in serum albumin, PT, PTT, and platelets and there was a mild improvement in serum fibrinogen. The DSRS cohort showed only a significant improvement in the platelet count. Neonatal umbilic vein catheterization (UVC) was a major risk for Rex vein obliteration. CONCLUSION: In EHPVO, MRS is superior to DSRS and improves liver synthetic function. DSRS does control variceal bleeding but should only be considered when MRS is not technically feasible or as a salvage procedure when MRS fails.

Low Urinary Free Cortisol as a Risk Factor for Patients with Variceal Bleeding.

Background and Objectives: Specificity and reliability issues of the current cortisol assessment methods lead to limitations on the accurate assessment of relative adrenal insufficiency. Although free cortisol provides a more accurate evaluation of adrenal cortisol production, the expense and time-consuming nature of these assays make them impractical for routine use. Research has, thus, focused on alternative methods, such as indirectly measuring free cortisol using Coolens' equation or directly assessing salivary cortisol concentration, which is considered a more favorable approach despite associated challenges like sampling issues and infection risks. The aim of this study was to explore correlations between 24 h urinary free cortisol (UFC), free plasma cortisol, serum total cortisol, and salivary cortisol as potential reliable indices of free cortisol in the setting of variceal bleeding. Additionally, we assessed the predictive value of UFC for 6-week mortality and 5-day treatment failure in patients with liver cirrhosis and variceal bleeding. Materials and Methods: A total of 40 outpatients with liver cirrhosis and variceal bleeding were enrolled. Free cortisol levels in serum, saliva, and urine were assessed using the electrochemiluminescence immunoassay method. For the measurement of plasma-free cortisol, a single quadrupole mass spectrometer was employed. The quantification of free cortisol was fulfilled by analyzing the signal response in the negative ESI-MS mode. Results: UFC was significantly correlated to free plasma cortisol. Negative correlations were demonstrated between UFC, the Child-Pugh (CP) score, and C reactive protein (CRP) levels. In the multivariate analysis, CP stage C was associated with 6-week mortality risk and portal vein thrombosis with 5-day treatment failure using Cox regression and binary logistic regression analyses, respectively. Patients who experienced rebleeding, infection, or death (or any combination of these events) presented with lower levels of UFC. Conclusions: This study suggests that low levels of UFC may impose a risk factor for patients with liver cirrhosis and variceal bleeding. The use of UFC as an index of adrenal cortisol production in variceal bleeding warrants further investigation.

[Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

Transient hemodynamic instability caused by TIPS.

Variceal bleeding belongs to the one of the complications of portal hypertension and is a life-threatening condition. A transjugular intrahepatic portosystemic shunt (TIPS) is indicated in case of failure of the pharmacological and endoscopic therapy, even if it is associated with complications. Stent migration to the heart, is a rare event which may cause perforation of the right cardiac chambers or damage to the tricuspid valve. However, it may not be a problem in some cases. There are two approaches to extraction - percutaneous or surgical. Leaving the stent in situ is possible, especially in polymorbid patients. Choosing an optimal approach often requires interdisciplinary cooperation.

Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis.

BACKGROUND & AIMS: Hyperammonaemia is central in the pathogenesis of hepatic encephalopathy. It also has pleiotropic deleterious effects on several organ systems, such as immune function, sarcopenia, energy metabolism and portal hypertension. This study was performed to test the hypothesis that severity of hyperammonaemia is a risk factor for liver-related complications in clinically stable outpatients with cirrhosis. METHODS: We studied 754 clinically stable outpatients with cirrhosis from 3 independent liver units. Baseline ammonia levels were corrected to the upper limit of normal (AMM-ULN) for the reference laboratory. The primary endpoint was hospitalisation with liver-related complications (a composite endpoint of bacterial infection, variceal bleeding, overt hepatic encephalopathy, or new onset or worsening of ascites). Multivariable competing risk frailty analyses using fast unified random forests were performed to predict complications and mortality. External validation was carried out using prospective data from 130 patients with cirrhosis in an independent tertiary liver centre. RESULTS: Overall, 260 (35%) patients were hospitalised with liver-related complications. On multivariable analysis, AMM-ULN was an independent predictor of both liver-related complications (hazard ratio 2.13; 95% CI 1.89-2.40; p <0.001) and mortality (hazard ratio 1.45; 95% CI 1.20-1.76; p <0.001). The AUROC of AMM-ULN was 77.9% for 1-year liver-related complications, which is higher than traditional severity scores. Statistical differences in survival were found between high and low levels of AMM-ULN both for complications and mortality (p <0.001) using 1.4 as the optimal cut-off from the training set. AMM-ULN remained a key variable for the prediction of complications within the random forests model in the derivation cohort and upon external validation. CONCLUSION: Ammonia is an independent predictor of hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis and performs better than traditional prognostic scores in predicting complications. LAY SUMMARY: We conducted a prospective cohort study evaluating the association of blood ammonia levels with the risk of adverse outcomes in 754 patients with stable cirrhosis across 3 independent liver units. We found that ammonia is a key determinant that helps to predict which patients will be hospitalised, develop liver-related complications and die; this was confirmed in an independent cohort of patients.