The Use of Rifaximin in Patients With Cirrhosis.

Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited.

Severe Upper Gastrointestinal Hemorrhage Caused by Reflux Esophagitis.

BACKGROUND: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB). AIMS: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH). METHODS: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed. RESULTS: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH. CONCLUSIONS: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically.

Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis is a leading cause of end-stage liver disease. Hepatic steatosis and lipotoxicity cause chronic necroinflammation and direct hepatocellular injury resulting in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emricasan is a pan-caspase inhibitor that inhibits excessive apoptosis and inflammation; it has also been shown to decrease portal pressure and improve synthetic function in mice with carbon tetrachloride-induced cirrhosis. METHODS: This double-blind, placebo-controlled study randomized 217 individuals with decompensated NASH cirrhosis 1:1:1 to emricasan (5 mg or 25 mg) or placebo. Patients were stratified by decompensation status and baseline model for end-stage liver disease-sodium (MELD-Na) score. The primary endpoint comprised all-cause mortality, a new decompensation event (new or recurrent variceal hemorrhage, new ascites requiring diuretics, new unprecipitated hepatic encephalopathy ≥grade 2, hepatorenal syndrome, spontaneous bacterial peritonitis), or an increase in MELD-Na score ≥4 points. RESULTS: There was no difference in event rates between either of the emricasan treatment groups and placebo, with hazard ratios of 1.02 (95% CI 0.59-1.77; p = 0.94) and 1.28 (95% CI 0.75-2.21; p = 0.37) for 5 mg and 25 mg of emricasan, respectively. MELD-Na score progression was the most common outcome. There was no significant effect of emricasan treatment on MELD-Na score, international normalized ratio, total serum bilirubin, albumin level or Child-Pugh score. Emricasan was generally safe and well-tolerated. CONCLUSIONS: Emricasan was safe but ineffective for the treatment of decompensated NASH cirrhosis. However, this study may guide the design and conduct of future clinical trials in decompensated NASH cirrhosis. LAY SUMMARY: Patients with decompensated cirrhosis related to non-alcoholic steatohepatitis are at high risk of additional decompensation events and death. Post hoc analyses in previous pilot studies suggested that emricasan might improve portal hypertension and liver function. In this larger randomized study, emricasan did not decrease the number of decompensation events or improve liver function in patients with a history of decompensated cirrhosis related to non-alcoholic steatohepatitis. CLINICALTRIALS. GOV IDENTIFIER: NCT03205345.

A Prognostic Strategy Based on Stage of Cirrhosis and HVPG to Improve Risk Stratification After Variceal Bleeding.

BACKGROUND AND AIMS: A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG. METHODS: A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1-3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation-free survival for 4 years. Another cohort (n = 231) served as the validation set. RESULTS: During follow-up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the "gray zone" (i.e., high-risk patients who had not died on follow-up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results. CONCLUSIONS: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient's baseline HVPG is over 16 mm Hg improves detection of high-risk patients while markedly reducing the number of HVPG measurements required.

Modified (Bai-Jiang style) vagus nerve-preserving versus conventional laparoscopic splenectomy and azygoportal disconnection: a randomized clinical trial.

BACKGROUND: Digestive system complications are among the most important causes of postoperative poor quality of life after open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD). We firstly developed a modified vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (MVLSD). In this study, we aimed to evaluate whether MVLSD is feasible and safe and to determine whether MVLSD can effectively eliminate postoperative digestive system complications, in comparison with CLSD. METHOD: In this randomized controlled single-center study, 60 patients with cirrhosis were randomly assigned to undergo either CLSD (n = 30) or MVLSD (n = 30) between April and December 2018. The primary outcome was delayed gastric emptying (DGE). Endoscopic physicians were blinded to group assignments. RESULTS: One patient who received MVLSD withdrew from the study. There were no significant differences in intraoperative blood loss, incidence of blood transfusion, time to off-bed activity, time to first flatus, and postoperative hospital stay between the two groups. Compared with CLSD, operation time and incidences of DGE, diarrhea, epigastric fullness, and overall postoperative complications were all significantly reduced in the MVLSD group (all P < 0.05). Compared with CLSD, MVLSD was associated with significantly increased weight and albumin levels at 1, 6, and 12 months postoperatively versus preoperative values (all P < 0.05). The curative effect of resolving gastroesophageal variceal bleeding was similar between the groups. CONCLUSION: MVLSD is not only a technically feasible and safe procedure, it is also succinct and convenient. Furthermore, MVLSD effectively reduces postoperative digestive system complications, contributing to improved quality of life.

A Novel Score to Predict Esophageal Varices in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Several criteria have been described to noninvasively predict the presence of high-risk esophageal varices in patients with compensated advanced chronic liver disease (cACLD). However, a recent study showed that treatment with ß blockers could increase decompensation-free survival in patients with clinically significant portal hypertension, thereby making it important to predict the presence of any esophageal varices. We aimed to develop a simple scoring system to predict any esophageal varices. METHODS: We retrospectively reviewed patients who had vibration-controlled transient elastography (VCTE) at Cook County Hospital, Chicago, USA. Patients with cACLD and liver stiffness measurement (LSM) ≥ 10 kPa with esophagogastroduodenoscopy performed within one year of VCTE were analyzed. We generated a novel score to predict esophageal varices, using the beta coefficient of predictive variables. The score was validated in an external cohort at the University of Iowa Hospital, USA. RESULTS: There were 372 patients in the development cohort and 200 patients in the validation cohort. LSM, platelet count, and albumin were identified as predictors of esophageal varices and were included for generating the Cook County score as "platelet count * - 0.0155872 + VCTE score * 0.0387052 + albumin * - 0.8549209." The area under receiver operating curve for our score was 0.86 for any varices and 0.85 for high risk varices and avoided more endoscopies than the expanded Baveno VI criteria while maintaining a very low miss rate (negative predictive value > 99%). CONCLUSION: We propose a new, highly accurate, and easy-to-use scoring system to predict the presence of not only high-risk but any esophageal varices in patients with cACLD.

Short-term hemodynamic effects of ß-blockers influence survival of patients with decompensated cirrhosis.

BACKGROUND & AIMS: Whether the effect of ß-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of ß-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. METHODS: Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting ß-blockers and again after 1 to 3 months of treatment (short-term). RESULTS: Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under ß-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with ß-blockers than survivors (21 ± 14% vs. 15 ± 16%; p <0.05) and CO under ß-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004). CONCLUSIONS: In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to ß-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of ß-blockers on CO might adversely influence survival in decompensated cirrhosis. LAY SUMMARY: ß-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of ß-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of ß-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of ß-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.

Hemodynamic Effects of Adding Simvastatin to Carvedilol for Primary Prophylaxis of Variceal Bleeding: A Randomized Controlled Trial.

INTRODUCTION: Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response. METHODS: Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events. RESULTS: The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death. DISCUSSION: Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.

Impact of Intrahepatic Venovenous Shunt on Hepatic Venous Pressure Gradient Measurement.

PURPOSE: To quantitatively analyze the impact of intrahepatic venovenous shunt (IHVS) on hepatic venous pressure gradient (HVPG) measurement. MATERIALS AND METHODS: From 2015 to 2019, 222 HVPG measurements performed during transjugular intrahepatic portosystemic shunt creation were eligible for this study. Digital subtraction angiography (DSA) software color-coded each pixel of a two-dimensional DSA series by time-intensity curve to classify IHVS. Different degrees of IHVS were found in 36.5% of patients (81/222). Mild IHVS was found in 10.8% of patients (24/222), moderate IHVS was found in 10.8% of patients (24/222), and severe IVHS was found in 14.9% of patients (33/222). RESULTS: Mean wedged hepatic vein pressure (WHVP) and HVPG were significantly lower in patients with IHVS compared with patients without IHVS (WHVP: 17.78 mm Hg ± 7.00 vs 24.89 mm Hg ± 8.69, P = .001; HVPG: 11.93 mm Hg ± 5.76 vs 18.6 mm Hg ± 6.85, P < .001). Mild IHVS had little effect on WHVP and HVPG. Mean WHVP and HVPG were 11 mm Hg lower in patients with moderate IHVS (WHVP: 20.38 mm Hg ± 8.38 vs 31.5 mm Hg ± 9.39, P = .026; HVPG: 13.88 mm Hg ± 6.33 vs 25.00 mm Hg ± 9.81, P < .001) and 15 mm Hg lower in patients with severe IHVS (WHVP: 13.45 mm Hg ± 5.28 vs 28.64 mm Hg ± 6.38, P = .017; HVPG: 8.27 mm Hg ± 3.85 vs 23.45 mm Hg ± 6.95, P < .001) than mean portal vein pressure and portal vein gradient. CONCLUSIONS: For patients with moderate or severe IHVS, HVPG might greatly underestimate the actual value of portal vein pressure, and the portal vein should be catheterized to measure portal pressure.

Smaller-Diameter Covered Transjugular Intrahepatic Portosystemic Shunt Stents Are Associated With Increased Survival.

BACKGROUND & AIMS: We studied the effects of diameter of covered, self-expandable, nitinol stents on survival times of patients with a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We collected data from 185 patients (median age, 55 y; 30% female) who received a covered nitinol stent, from February 2006 through September 2010, using the online multicenter German TIPS registry. TIPS were given to 107 patients for refractory ascites and to 78 patients for variceal bleeding. Patients at risk of hepatic encephalopathy (owing to advanced age, prior episodes) or liver failure (bilirubin level, >3 mg/dL), and bleeding patients receiving variceal embolization at TIPS, received 8-mm stents (n = 53). The remaining patients received 10-mm stents (n = 132). Eighty-one of the 10-mm stents were underdilated using 8-mm dilation balloons. Clinical and biochemical data were collected after TIPS placement at 1 month, 3 months, 6 months, 9 months, 1 year, and thereafter every 3 to 6 months. Groups were compared using propensity score analysis. RESULTS: Patients who received 8-mm stents survived significantly longer (34 ± 26 mo) than patients who received 10-mm stents (18 ± 19 mo), regardless of whether they were fully dilated or underdilated. When we compared 10-mm stents with or without underdilation, we found that a significantly higher proportion of patients who received underdilated stents survived for 1 month after TIPS placement (95% vs 84%; P = .03), but not for 3 months (P = .10). In multivariate analysis, 1-year mortality correlated with full dilation of the stent to 10 mm (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5) and with serum creatinine concentration at baseline (HR, 1.5; 95% CI, 1.0-1.7). Five-year mortality was associated with use of the 10-mm stents (HR, 1.8; 95% CI, 1.4-2.7) and baseline concentration of creatinine (HR, 1.3; 95% CI, 1.1-1.6). CONCLUSIONS: A smaller stent (nominal diameter of 8 mm, but not underdilation of a 10-mm stent) is associated with a prolonged survival compared with 10-mm stents, independent of liver-specific prognostic criteria.

Blood platelet function abnormalities in cirrhotic patients with esophageal varices in relation to the variceal bleeding history.

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis. Methods: The results of impedance aggregometry, von Willebrand factor antigen level and thromboelastometry (TEM) with and without the addition of a platelet inhibitor (FIBTEM®, EXTEM® test, respectively) were compared in two patient groups: Group 1 (n = 32) - patients with moderate or large esophageal or gastric varices, who had never had symptoms of acute gastrointestinal bleeding and Group 2 (n = 26) - patients with history of variceal bleeding. Results: Standard clotting test indicated more hypocoagulable profile in Group 2 compared to Group 1. However, no differences in any TEM component were observed between groups in EXTEM® test. The contribution of platelets to clot strength was significantly higher in Group 2 than in Group 1 [PLT% = 74.2 (67.5-80.4) versus 68.8 (63.7-76.5) %; p = .039]. The aggregation index was also higher in Group 2 compared to Group 1, although not statistically significant [% of healthy = 96.9 (73.2-140.1) versus 67.6 (52.5-118.8) %, p = .195]. No differences in vWF antigen levels were observed between groups. Conclusions: The results of thromboelastometry and aggregometry indicate increased contribution of platelets in clot formation in patients with a history of variceal bleeding compared to cirrhotic patients who never bled. Comparable effectiveness of hemostasis in both groups is most likely associated with the compensatory role of platelets. Increased platelet activity in this group of patients is probably due to a mechanism independent of the von Willebrand factor antigen level.

Spleen and Liver Stiffness to Detect Esophageal Varices in Children with Biliary Atresia.

OBJECTIVES: The aim of the study was to determine the accuracy of noninvasive parameters, such as liver (LS) and spleen stiffness (SS) to detect esophageal varices (EV) in children with biliary atresia (BA). METHODS: Children with BA between 2000 and 2015 were recruited. All underwent esophagogastroduodenoscopy and transient elastography. Demographic data, laboratory investigations, alanine transferase-to-platelet ratio index (APRI), and Varices Prediction Rule (VPR) score were collected. RESULTS: A total of 51 children (mean age 10.63 years, standard deviation (SD) = 6.08 years; 53% boys) were enrolled. There were differences in onset and outcome of portoenterostomy, spleen palpablility, platelet count, albumin, LS, SS, and VPR between the varice and varice-free groups (P < 0.05). In the varice group, the median LS was 18.12 (interquartile ratio, IQR 13.15-19.12) and the median SS was 46.85 (IQR 25.95-54.55) kPa. In the varice-free group, the median LS was 7.85 (IQR 5.88-16.75) and the median SS was 16.54 (IQR 11.75-21.75) kPa. Both LS and SS were higher in the varice than the varice-free group (P < 0001). The area under the receiver operating characteristic curve of LS, SS, spleen palpability, platelet count, APRI, and VPR were 0.734, 0.870, 0.817, 0.810, 0.751, and 0.794, respectively. Using a cut-off value of 12.5 kPa for LS, the sensitivity and specificity were 80 and 70%, respectively. Using a cut-off value of 28.9 kPa for SS, the sensitivity and specificity were 75 and 87%, respectively. Combination of LS and SS to diagnose varices increased the specificity to 93%. CONCLUSIONS: SS as a single marker had the best diagnostic value to predict esophageal varices in children with BA. The combination of SS and LS furthermore, increased the diagnostic yield.

Varices on computed tomography are surrogate of clinically significant portal hypertension and can predict survival in compensated cirrhosis patients.

BACKGROUND AND AIM: To investigate prognostic value of varices on computed tomography (CT) and redefine surrogate criteria for clinically significant portal hypertension (CSPH). METHODS: We retrospectively enrolled 241 patients with compensated cirrhosis who underwent hepatic venous pressure gradient (HVPG) measurement from 2008 to 2013. Using CT and upper endoscopy findings obtained within 3 months from HVPG measurement, patients were classified into three groups: presence of standard surrogate for CSPH, defined as presence of varices on upper endoscopy and/or splenomegaly associated with thrombocytopenia (Group 1, n = 139); varices on CT without standard surrogate for CSPH (Group 2, n = 41); and free from both (Group 3, n = 61). HVPG value and overall survival (OS) rates were compared among three patient groups. Revised surrogate for CSPH was defined as presence of standard surrogate and/or presence of varices on CT (i.e. both Group 1 and Group 2). RESULTS: Mean HVPG value in Group 2 was significantly higher than that in Group 3 (10.3 mmHg vs 6.5 mmHg, P < 0.001), but significantly lower than that in Group 1 (10.3 mmHg vs 13.1 mmHg, P < 0.001). Seven-year OS rates in Group 2 was similar to those in Group 1 (57.0% vs 62.7%, P = 0.591), but significantly poorer than those in Group 3 (57.0% vs 84.0%, P = 0.015). The presence of revised surrogate for CSPH was a significant predictive factor for OS (P = 0.025, Hazard ratio = 2.71 [1.14-6.45]) on multivariate analysis whereas standard surrogate for CSPH was not (P = 0.849). CONCLUSION: The presence of varices on CT was a significant sign for CSPH, predicting poor OS outcome in patients with compensated cirrhosis.

Thromboelastography Parameters Are Associated with Cirrhosis Severity.

BACKGROUND: Coagulopathy in cirrhosis represents complex coagulation derangements, and thromboelastography (TEG) measures these complex derangements. AIM: We sought to evaluate associations between TEG parameters and validated measures of cirrhosis severity, which have not been previously investigated. MATERIALS AND METHODS: Adults with cirrhosis undergoing liver transplant (LT) were identified. Patients had TEG drawn immediately prior to LT. TEG parameters included reaction time (R), kinetic time (K), alpha angle (α), and maximum amplitude (MA). The validated measures of cirrhosis severity were MELD-Na and clinical stage of cirrhosis (classified using history of varices, variceal bleeding, or ascites). Multivariable linear and logistic regression analyses were conducted to evaluate the associations between TEG and stage of cirrhosis and MELD-Na. RESULTS: Among 164 patients with cirrhosis, advancing stage of cirrhosis was associated with more hypocoagulable TEG parameters including longer K-time (p = 0.05) and lower MA (p < 0.001). Similarly, with increasing MELD-Na quartiles, K-time was longer (p < 0.001), and both MA and α-angle decreased (p < 0.001, for both). Variceal bleeding within 6 weeks prior to LT was associated with longer R-times (p = 0.02), longer K-times (p = 0.04), smaller α-angle (p = 0.03), and lower MA (p = 0.01). On multivariable analyses, decreasing MA remained statistically significantly associated with advancing stage of cirrhosis and increasing MELD-Na, after adjusting for multiple covariates including platelet count, (p = 0.02 and p < 0.0001, respectively). CONCLUSIONS: Hypocoagulable TEG measurements are associated with advancing stage of cirrhosis and increasing MELD-Na among patients with cirrhosis. These data indicate that TEG, as an informative measure of complex hemostatic function, may be a useful objective marker of liver disease severity in cirrhosis.

Incidence and hemodynamic feature of risky esophageal varices with lower hepatic venous pressure gradient.

Background: To examine the incidence of cirrhosis patients with high-risk esophageal varices (EV) who show hepatic venous pressure gradient (HVPG) < 10 mmHg and to identify their hemodynamic features. Methods: This prospective study consisted of 110 cirrhosis patients with EV, all with the candidate for primary or secondary prophylaxis. Sixty-one patients had red sign, and 49 patients were bleeders. All patients underwent both Doppler ultrasound and HVPG measurement. Results: There were 18 patients (16.4%) with HVPG < 10 mmHg. The presence of venous-venous communication (VVC) was more frequent in patients with HVPG < 10 mmHg (10/18) than in those with HVPG ≥ 10 mmHg (19/92; p = 0.0021). The flow volume in the left gastric vein (LGV) and the incidence of red sign were higher in the former (251.9 ± 150.6 mL/min; 16/18) than in the latter (181 ± 100.5 mL/min, p = 0.02; 45/92; p = 0.0018). The patients with red sign had lower HVPG (13.3 ± 4.5) but advanced LGV hemodynamics (velocity 13.2 ± 3.8 cm/s; flow volume 217.5 ± 126.6 mL/min), whereas those without red sign had higher HVPG (16.2 ± 4.6, p = 0.001) but poorer LGV hemodynamics (10.9 ± 2.3, p = 0.002; 160.1 ± 83.1, p = 0.02). Conclusion: Patients with high-risk EV with HVPG < 10 mmHg showed 16.4% incidence. Although low HVPG may be underestimated by the presence of VVC, the increased LGV hemodynamics compensates for the severity of portal hypertension, which may contribute to the development of red sign.

An unusual cause of postmenopausal vaginal haemorrhage: a case report.

BACKGROUND: Post-menopause vaginal haemorrhage is typically related to gynaecological malignancies. Bleeding from vaginal varices rarely occurs, especially in nonpregnant women. Moreover, nonpregnancy-related causes of vaginal varicosities include portal hypertension, especially that caused by liver cirrhosis, pelvic congestion syndrome and Klippel-Trenaunay syndrome or Parkes-Weber syndrome. Here, we report an unusual cause of nonpregnancy-associated vaginal variceal bleeding. CASE PRESENTATION: A 55-year-old postmenopausal woman presented in our outpatient department with complaints of recurrent bloody vaginal discharge. A group of varicose veins and several haemorrhagic spots were found on her vaginal wall during a vaginal speculum examination. Genital cancers were excluded by colposcopy and transvaginal ultrasonography; furthermore, a pelvic arteriovenous fistula was not found on a pelvic computed tomography (CT) scan. However, congenital varicosities and deep arteriovenous shunts were observed in her left leg on arterial angiography. Moreover, vaginal bleeding was improved after resolution of the underlying deep arteriovenous shunts in her left leg. Therefore, congenital arteriovenous shunts and elevated inferior vena cava pressure might be responsible for her recurrent vaginal varicose bleeding. CONCLUSION: Haemorrhage due to vaginal varices is easily detected with a vaginal speculum examination. However, diagnosis and treatment of the original disease are important after bleeding is controlled.

Endovascular Transpulmonary Retrieval of a Migrated Amplatzer Vascular Plug Following Balloon-Occluded Retrograde Transvenous Obliteration.

Gastric varices are a common manifestation of portal hypertension and are associated with a high rate of mortality and rebleeding. Balloon-occluded retrograde transvenous obliteration (BRTO) is a commonly used method to sclerose gastric varices and has a high clinical success. Common complications following BRTO include portal or splenic vein thrombosis, systemic sclerosant extravasation, pulmonary emboli, and inferior vena cava thrombosis. This report describes a patient with vascular plug migration into the left pulmonary artery with subsequent endovascular retrieval.

Application of the Hepatic Transit Time (HTT) in Evaluation of Portal Vein Pressure in Gastroesophageal Varices Patients.

OBJECTIVES: To analyze the clinical significance of using hepatic transit time (HTT) to evaluate portal vein pressure in gastroesophageal varices patients. METHODS: For the observation group, we enrolled 50 gastroesophageal varices patients who had received esophagogastric variceal embolization in our hospital between January 2015 and February 2018. Patients without liver disease populated the control group and were recruited during the same time period. All patients underwent contrast-enhanced sonography. In the observation group, free portal pressure (FPP) was detected during esophagogastric variceal embolization with ultrasound guidance. Differences in hepatic artery-hepatic vein transit time (HA-HVTT), portal vein-hepatic vein transit time (PV-HVTT), and parenchyma-hepatic vein transit time (PA-HVTT) were compared between groups. Correlations between HA-HVTT, PV-HVTT, PA-HVTT, and FPP in the observation group were analyzed using the Pearson coefficient and linear regression analysis. RESULTS: HA-HVTT (t = 5.078; P < .001), PV-HVTT (t = 12.163; P < .001), and PA-HVTT (t = 2.649; P = .009) within the observation group were significantly lower than those of the control group. The areas under the curve of HTT were 0.771 (HA-HVTT), 0.951 (PV-HVTT), and 0.652 (PA-HVTT), and the sensitivity and specificity of PV-HVTT at 7.99 seconds were 86.0% and 88.0%, respectively. The HA-HVTT (r = -0.799; P < .001), PV-HVTT (r = -0.554; P < .001), and PA-HVTT (r = -0.735; P < .001) negatively correlated to FPP in the observation group. Linear regression analysis showed y = -0.410x + 7.254 (HA-HVTT and FPP), y = -0.335x + 4.983 (PV-HVTT and FPP), and y = -0.566x + 4.997 (PA-HVTT and FPP) in the observation group. CONCLUSION: Compared with the control patients, the HTT of patients with portal hypertension-esophagogastric varices was significantly shorter, and showed an inverse relationship with FPP.

[Expert consensus on diagnosis and treatment of esophagogastric variceal bleeding in cirrhotic portal hypertension (2019 edition)].

Portal hypertension is a clinical syndrome which is a consequence of a pathological increase in portal vein pressure due to various causes, among which, cirrhosis being the most common cause. The most basic pathophysiological features of portal hypertension in cirrhosis are increased portal vein pressure due to blocked portal vein blood flow and open collateral circulation. Among the clinical manifestations of portal hypertension in cirrhosis, esophageal and gastric fundus varicose bleeding is the most urgent and the mortality rate is the highest. In order to standardize the diagnosis and treatment plan of esophagogastric variceal bleeding in cirrhotic portal hypertension, the Chinese Society of Spleen and Portal Hypertension Surgery, Chinese Society of Surgery, have renewed and revised this consensus on diagnosis and treatment of esophagogastric variceal bleeding in cirrhotic portal hypertension (2015 edition) hope to provide references for the clinical practices.