Endoscopic Cyanoacrylate Injection Versus Balloon-Occluded Retrograde Transvenous Obliteration for Prevention of Gastric Variceal Bleeding: A Randomized Controlled Trial.

BACKGROUND AND AIMS: The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis. APPROACH AND RESULTS: Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). Primary outcomes were gastric variceal rebleeding or all-cause rebleeding. Patient characteristics were well balanced between two groups. Mean follow-up time was 27.1 ± 12.0 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. Probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (P = 0.024). Probability of remaining free of all-cause rebleeding at 1 and 2 years for cyanoacrylate injection versus BRTO was 77% versus 96.3% and 65.2% versus 92.6% (P = 0.004). Survival rates, frequency of complications, and worsening of esophageal varices were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs. CONCLUSIONS: BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.

Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI < 30 kg/m2] nonalcoholic steatohepatitis) and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] > 10 mmHg and/or liver stiffness by transient elastography > 25 kPa) should receive, if no contraindications, nonselective beta blocker (NSBB) therapy (preferably carvedilol) to prevent the development of variceal bleeding.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in those patients unable to receive NSBB therapy with a screening upper gastrointestinal (GI) endoscopy that demonstrates high risk esophageal varices, endoscopic band ligation (EBL) is the endoscopic prophylactic treatment of choice. EBL should be repeated every 2-4 weeks until variceal eradication is achieved. Thereafter, surveillance EGD should be performed every 3-6 months in the first year following eradication.Strong recommendation, moderate quality evidence. 3: ESGE recommends, in hemodynamically stable patients with acute upper GI hemorrhage (UGIH) and no history of cardiovascular disease, a restrictive red blood cell (RBC) transfusion strategy, with a hemoglobin threshold of ≤ 70 g/L prompting RBC transfusion. A post-transfusion target hemoglobin of 70-90 g/L is desired.Strong recommendation, moderate quality evidence. 4 : ESGE recommends that patients with ACLD presenting with suspected acute variceal bleeding be risk stratified according to the Child-Pugh score and MELD score, and by documentation of active/inactive bleeding at the time of upper GI endoscopy.Strong recommendation, high quality of evidence. 5 : ESGE recommends the vasoactive agents terlipressin, octreotide, or somatostatin be initiated at the time of presentation in patients with suspected acute variceal bleeding and be continued for a duration of up to 5 days.Strong recommendation, high quality evidence. 6 : ESGE recommends antibiotic prophylaxis using ceftriaxone 1 g/day for up to 7 days for all patients with ACLD presenting with acute variceal hemorrhage, or in accordance with local antibiotic resistance and patient allergies.Strong recommendation, high quality evidence. 7 : ESGE recommends, in the absence of contraindications, intravenous erythromycin 250 mg be given 30-120 minutes prior to upper GI endoscopy in patients with suspected acute variceal hemorrhage.Strong recommendation, high quality evidence. 8 : ESGE recommends that, in patients with suspected variceal hemorrhage, endoscopic evaluation should take place within 12 hours from the time of patient presentation provided the patient has been hemodynamically resuscitated.Strong recommendation, moderate quality evidence. 9 : ESGE recommends EBL for the treatment of acute esophageal variceal hemorrhage (EVH).Strong recommendation, high quality evidence. 10 : ESGE recommends that, in patients at high risk for recurrent esophageal variceal bleeding following successful endoscopic hemostasis (Child-Pugh C  ≤ 13 or Child-Pugh B > 7 with active EVH at the time of endoscopy despite vasoactive agents, or HVPG > 20 mmHg), pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) within 72 hours (preferably within 24 hours) must be considered.Strong recommendation, high quality evidence. 11 : ESGE recommends that, for persistent esophageal variceal bleeding despite vasoactive pharmacological and endoscopic hemostasis therapy, urgent rescue TIPS should be considered (where available).Strong recommendation, moderate quality evidence. 12 : ESGE recommends endoscopic cyanoacrylate injection for acute gastric (cardiofundal) variceal (GOV2, IGV1) hemorrhage.Strong recommendation, high quality evidence. 13: ESGE recommends endoscopic cyanoacrylate injection or EBL in patients with GOV1-specific bleeding.Strong recommendations, moderate quality evidence. 14: ESGE suggests urgent rescue TIPS or balloon-occluded retrograde transvenous obliteration (BRTO) for gastric variceal bleeding when there is a failure of endoscopic hemostasis or early recurrent bleeding.Weak recommendation, low quality evidence. 15: ESGE recommends that patients who have undergone EBL for acute EVH should be scheduled for follow-up EBLs at 1- to 4-weekly intervals to eradicate esophageal varices (secondary prophylaxis).Strong recommendation, moderate quality evidence. 16: ESGE recommends the use of NSBBs (propranolol or carvedilol) in combination with endoscopic therapy for secondary prophylaxis in EVH in patients with ACLD.Strong recommendation, high quality evidence.

Association Between Severe Portal Hypertension and Risk of Liver Decompensation in Patients With Hepatitis C, Regardless of Response to Antiviral Therapy.

BACKGROUND & AIMS: Hepatic venous pressure gradient (HVPG) is associated with a risk of liver events in patients with chronic hepatitis C. Antiviral therapies that lead to a sustained virologic response (SVR) reduce portal pressure and prevent liver disease progression. However, it is not clear to what extent the progression of hepatitis C is modified once patients develop cirrhosis with severe portal hypertension (CSPH) (HVPG ≥ 10 mm Hg). We assessed the effects of HVPG and SVR on the risk of liver decompensation, hepatocellular carcinoma, and/or death in patients with hepatitis C-related cirrhosis. METHODS: We collected data from 100 patients with hepatitis C and compensated cirrhosis who underwent HVPG measurement 3 months or less before (baseline) and 24 weeks after therapy with pegylated interferon alfa-2a and ribavirin at 4 hospitals in Spain, from 2001 through 2009. SVR was defined as undetectable serum HCV RNA level 24 weeks after treatment ended. Clinical data were collected until death, liver transplantation, or December 2012 (median, 5 y; interquartile range, 1.4-7 y). RESULTS: Seventy-four patients had CSPH at baseline and 35% of patients achieved an SVR. During the follow-up period, 19 patients developed liver decompensation (ascites, variceal bleeding, or encephalopathy). The actuarial probability values for liver decompensation at 1, 5, and 7 years were 3%, 19% and 22%, respectively. The baseline level of HVPG, but not SVR, was associated independently with the risk of liver decompensation. CONCLUSIONS: Patients with CSPH, regardless of an SVR to therapy for hepatitis C, remain at risk for liver decompensation within the first 5 years after treatment; they should be monitored closely.

Management of gastric varices.

According to their location, gastric varices (GV) are classified as gastroesophageal varices and isolated gastric varices. This review will mainly focus on those GV located in the fundus of the stomach (isolated gastric varices 1 and gastroesophageal varices 2). The 1-year risk of GV bleeding has been reported to be around 10%-16%. Size of GV, presence of red signs, and the degree of liver dysfunction are independent predictors of bleeding. Limited data suggest that tissue adhesives, mainly cyanoacrylate (CA), may be effective and better than propranolol in preventing bleeding from GV. General management of acute GV bleeding must be similar to that of esophageal variceal bleeding, including prophylactic antibiotics, a careful replacement of volemia, and early administration of vasoactive drugs. Small sample-sized randomized controlled trials have shown that tissue adhesives are the therapy of choice for acute GV bleeding. In treatment failures, transjugular intrahepatic portosystemic shunt (TIPS) is considered the treatment of choice. After initial hemostasis, repeated sessions with CA injections along with nonselective beta-blockers are recommended as secondary prophylaxis; whether CA is superior to TIPS in this scenario is not completely clear. Balloon-occluded retrograde transvenous obliteration (BRTO) has been introduced as a new method to treat GV. BRTO is also effective and has the potential benefit of increasing portal hepatic blood flow and therefore may be an alternative for patients who may not tolerate TIPS. However, BRTO obliterates spontaneous portosystemic shunts, potentially aggravating portal hypertension and its related complications. The role of BRTO in the management of acute GV bleeding is promising but merits further evaluation.

Early use of TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients). RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events. CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)

Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study.

BACKGROUND & AIMS: Recurrence of hepatitis C virus (HCV) infection is a relevant problem of liver transplantation programs. We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients. METHODS: Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n = 54) were randomized to no treatment (group A, n = 27) or peginterferon alfa-2b/ribavirin for 48 weeks (group B, n = 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n = 27). All patients (n = 81) underwent a liver biopsy at baseline and after follow-up; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients. RESULTS: Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed > or =1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P = .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P = .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] =3.7, 95% confidence interval [CI] 1.3 to 10, P = .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P = .01; respectively). CONCLUSIONS: Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.

Patency of stents covered with polytetrafluoroethylene in patients treated by transjugular intrahepatic portosystemic shunts: long-term results of a randomized multicentre study.

An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension. The use of covered stents could improve shunt patency; however, long-term effect and safety remain unknown. Eighty patients randomized to be treated by TIPS either with a covered stent (Group 1) or an uncovered prosthesis (Group 2) were followed-up for 2 years. Doppler US was performed every 3 months. Angiography and portosystemic pressure gradient measurement were performed every 6 months or whenever dysfunction was suspected. Actuarial rates of primary patency in Groups 1 and 2 were 76% and 36% respectively (P=0.001). Clinical relapse occurred in four patients (10%) in Group 1 and 12 (29%) in Group 2 (P<0.05). Actuarial rates of being free of encephalopathy were 67% in Group 1 and 51% in Group 2 (P<0.05). Probability of survival was 58% and 45% at 2 years, respectively, in Groups 1 and 2 (NS). The mean Child-Pugh score improved only in Group 1 (from 8.1+/-1.6 to 7+/-2.2 at 2 years -P<0.05). We also compared the Doppler-US parameters between patent and dysfunctioning shunts. In patent shunts, the mean velocity within the portal vein was significantly higher but the performance of Doppler-US was not accurate enough to predict shunt dysfunction. In conclusion, the improvement in TIPS patency by using covered prostheses is maintained over time with a decreased risk of encephalopathy, while the risk of death was not increased.

PTFE-covered stents improve TIPS patency in Budd-Chiari syndrome.

Transjugular intrahepatic portosystemic shunt (TIPS) have been shown to be an efficient portal-systemic derivative treatment for Budd-Chiari syndrome (BCS) patients uncontrolled by medical therapy. However, the main drawback of TIPS for this condition is a very high rate of shunt dysfunction. Recently, polytetrafluoroethylene (PTFE)-covered stents have been shown to reduce the incidence of TIPS dysfunction in patients with cirrhosis. The aim of the study was to assess the incidence of TIPS dysfunction in 2 cohorts of BCS patients treated with bare or PTFE-covered stents. The study included 25 TIPS procedures (16 bare stents and 9 covered stents) with a median follow-up period of 20.4 months (range, 3.9-124.8). Fourteen of 16 patients (87%) receiving bare stents had TIPS dysfunction compared to 3 of the 9 patients (33%) receiving PTFE-covered stents (P = .005). The actuarial rates of primary patency in the bare-stent group were 19% at 1 year compared with 67% in the PTFE-covered stent group (P = .02; log-rank test). The number of additional interventional procedures to maintain TIPS patency was significantly greater in the bare-stent than in the PTFE-covered stent group (1.9 +/- 1.2 vs. 0.6 +/- 0.9; P = .007). The number of patients with clinical relapses was greater in the bare-stent group compared to the PTFE-covered stent group (13 vs. 5 episodes in 9 and 3 patients, respectively). In conclusion, PTFE-covered stents have a considerable advantage over bare stents for the TIPS treatment of BCS patients, with a lower dysfunction rate, a lower number of reinterventions, and fewer prosthesis requirements. PTFE-covered stents are preferable in patients with Budd-Chiari Syndrome.

Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study.

BACKGROUND & AIMS: A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugular intrahepatic portosystemic shunt procedure. Preliminary experimental and clinical studies suggest that the use of stents covered with polytetrafluoroethylene could tremendously decrease this risk. METHODS: Eighty patients with cirrhosis and uncontrolled bleeding (n = 23), recurrent bleeding (n = 25), or refractory ascites (n = 32) were randomized to be treated by transjugular intrahepatic portosystemic shunts with either a polytetrafluoroethylene-covered stent (group 1; 39 patients) or a usual uncovered prosthesis (group 2; 41 patients). Follow-up Doppler ultrasound was scheduled at day 7, at 1 month, and then every 3 months for 2 years. Angiography and portosystemic pressure gradient measurements were performed 6, 12, and 24 months after the transjugular intrahepatic portosystemic shunt procedure and whenever dysfunction was suspected. Dysfunction was defined as a >50% reduction of the lumen of the shunt at angiography or a portosystemic pressure gradient >12 mm Hg. RESULTS: After a median follow-up of 300 days, 5 patients (13%) in group 1 and 18 (44%) in group 2 experienced shunt dysfunction (P < 0.001). Clinical relapse occurred in 3 patients (8%) in group 1 and 12 (29%) in group 2 (P < 0.05). Actuarial rates of encephalopathy were 21% in group 1 and 41% in group 2 at 1 year (not significant). Estimated probabilities of survival were 71% and 60% at 1 year and 65% and 41% at 2 years in groups 1 and 2, respectively (not significant). CONCLUSIONS: The use of polytetrafluoroethylene-covered prostheses improves transjugular intrahepatic portosystemic shunt patency and decreases the number of clinical relapses and reinterventions without increasing the risk of encephalopathy.