Approximately 40% to 95% of people with liver cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed within about one to three years after diagnosis. Several different treatments are available, including, among others, endoscopic sclerotherapy, variceal band ligation, somatostatin analogues, vasopressin analogues, and balloon tamponade. However, there is uncertainty surrounding the individual and relative benefits and harms of these treatments.

To compare the benefits and harms of different initial treatments for variceal bleeding from oesophageal varices in adults with decompensated liver cirrhosis, through a network meta-analysis; and to generate rankings of the different treatments for acute bleeding oesophageal varices, according to their benefits and harms.

We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until 17 December 2019, to identify randomised clinical trials (RCTs) in people with cirrhosis and acute bleeding from oesophageal varices.

We included only RCTs (irrespective of language, blinding, or status) in adults with cirrhosis and acutely bleeding oesophageal varices. We excluded RCTs in which participants had bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those in whom initial haemostasis was achieved before inclusion into the trial, and those who had previously undergone liver transplantation.

We performed a network meta-analysis with OpenBUGS software, using Bayesian methods, and calculated the differences in treatments using odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. We performed also the direct comparisons from RCTs using the same codes and the same technical details.

We included a total of 52 RCTs (4580 participants) in the review. Forty-eight trials (4042 participants) were included in one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those with and without a previous history of bleeding. We included outcomes assessed up to six weeks. All trials were at high risk of bias. A total of 19 interventions were compared in the trials (sclerotherapy, somatostatin analogues, vasopressin analogues, sclerotherapy plus somatostatin analogues, variceal band ligation, balloon tamponade, somatostatin analogues plus variceal band ligation, nitrates plus vasopressin analogues, no active intervention, sclerotherapy plus variceal band ligation, balloon tamponade plus sclerotherapy, balloon tamponade plus somatostatin analogues, balloon tamponade plus vasopressin analogues, variceal band ligation plus vasopressin analogues, balloon tamponade plus nitrates plus vasopressin analogues, balloon tamponade plus variceal band ligation, portocaval shunt, sclerotherapy plus transjugular intrahepatic portosystemic shunt (TIPS), and sclerotherapy plus vasopressin analogues). We have reported the effect estimates for the primary and secondary outcomes when there was evidence of differences between the interventions against the reference treatment of sclerotherapy, but reported the other results of the primary and secondary outcomes versus the reference treatment of sclerotherapy without the effect estimates when there was no evidence of differences in order to provide a concise summary of the results. Overall, 15.8% of the trial participants who received the reference treatment of sclerotherapy (chosen because this was the commonest treatment compared in the trials) died during the follow-up periods, which ranged from three days to six weeks. Based on moderate-certainty evidence, somatostatin analogues alone had higher mortality than sclerotherapy (OR 1.57, 95% CrI 1.04 to 2.41; network estimate; direct comparison: 4 trials; 353 participants) and vasopressin analogues alone had higher mortality than sclerotherapy (OR 1.70, 95% CrI 1.13 to 2.62; network estimate; direct comparison: 2 trials; 438 participants). None of the trials reported health-related quality of life. Based on low-certainty evidence, a higher proportion of people receiving balloon tamponade plus sclerotherapy had more serious adverse events than those receiving only sclerotherapy (OR 4.23, 95% CrI 1.22 to 17.80; direct estimate; 1 RCT; 60 participants). Based on moderate-certainty evidence, people receiving vasopressin analogues alone and those receiving variceal band ligation had fewer adverse events than those receiving only sclerotherapy (rate ratio 0.59, 95% CrI 0.35 to 0.96; network estimate; direct comparison: 1 RCT; 219 participants; and rate ratio 0.40, 95% CrI 0.21 to 0.74; network estimate; direct comparison: 1 RCT; 77 participants; respectively). Based on low-certainty evidence, the proportion of people who developed symptomatic rebleed was smaller in people who received sclerotherapy plus somatostatin analogues than those receiving only sclerotherapy (OR 0.21, 95% CrI 0.03 to 0.94; direct estimate; 1 RCT; 105 participants). The evidence suggests considerable uncertainty about the effect of the interventions in the remaining comparisons where sclerotherapy was the control intervention.

Based on moderate-certainty evidence, somatostatin analogues alone and vasopressin analogues alone (with supportive therapy) probably result in increased mortality, compared to endoscopic sclerotherapy. Based on moderate-certainty evidence, vasopressin analogues alone and band ligation alone probably result in fewer adverse events compared to endoscopic sclerotherapy. Based on low-certainty evidence, balloon tamponade plus sclerotherapy may result in large increases in serious adverse events compared to sclerotherapy. Based on low-certainty evidence, sclerotherapy plus somatostatin analogues may result in large decreases in symptomatic rebleed compared to sclerotherapy. In the remaining comparisons, the evidence indicates considerable uncertainty about the effects of the interventions, compared to sclerotherapy.

The outcomes of treatment of ruptured varices in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) are unclear. We therefore evaluated the long- (rebleeding and death) and short-term (immediate death within 24 h of variceal bleeding diagnosis) outcomes of patients with PVTT who underwent emergency variceal band ligation.

Data on 62 patients with PVTT and endoscopically proven esophageal or gastric variceal bleeding from 2007 to 2012 were studied. In most cases, the varices were treated using endoscopic variceal band ligation (EVL). We assessed the patients' rebleeding-free and overall survival using the Kaplan-Meier method, and a Cox proportional hazard model was used to analyze effect of independent factors on rebleeding-free and overall survival times.

Most patients had decompensated cirrhosis and were classified as Child-Pugh class B (56%) or C (36%). A total of 35 patients (56%) had PVTT in the main portal trunk. Among all patients, 58 (94%) and 4 (6%) had esophageal and gastric variceal bleeding, respectively. Bleeding was managed using EVL in all, but one patient (98%) who was treated with a Sengstaken-Blakemore tube. A total of 24 patients (39.3%) experienced rebleeding, and these patients had a median overall survival time of 36 days. A PVTT in the main portal trunk was predictive of rebleeding (hazard ratio 3.706, p = .0223), and α-fetoprotein-L3 levels <37.4% (hazard ratio 0.464, p = 0.015) and Child-Pugh class A/B (hazard ratio 0.398, p = 0.007) were associated with overall survival. We observed 95 bleeding events in 62 patients. EVL achieved hemostasis in 92 of the 95 bleeding events, whereas seven immediate deaths occurred due to variceal bleeding (7/92, 7.6%). All three bleeding events treated with modalities other than EVL resulted in immediate deaths.

EVL is a safe and effective treatment of variceal ruptures in patients with HCC and PVTT. After successful hemostasis, alleviation of the underlying liver function impairment and tumor control are equally important for a good prognosis.

Acute variceal bleeding (AVB) is a life-threatening complication of liver cirrhosis or less commonly splenic vein thrombosis. Pharmacological and endoscopic interventions are cornerstones in the management of variceal bleeding but may fail in 10 - 15 % of patients. Rescue therapy with balloon tamponade (BT) or transjugular intrahepatic portosystemic shunt (TIPS) may be required to control refractory acute variceal bleeding effectively but with some limitations. The self-expanding metal stent (SEMS) is a covered, removable tool that can be deployed in the lower esophagus under endoscopic guidance as a rescue therapy to achieve hemostasis for refractory AVB.

To evaluate the technical feasibility, efficacy, and safety of SEMS as a rescue therapy for AVB.

In this review article, we have performed an extensive literature search summarizing case reports and case series describing SEMS as a rescue therapy for AVB. Indications, features, technique, deployment, success rate, limitations, and complications are discussed.

At present, 103 cases have been described in the literature. Studies have reported 97.08 % technical success rates in deployment of SEMS. Most of the stents were intact for 4 - 14 days with no major complications reported. Stent extraction had a success rate of 100 %. Successful hemostasis was achieved in 96 % of cases with only 3.12 % found to have rebleeding after placement of SEMS. Stent migration, which was the most common complication, was observed in 21 % of patients.

SEMS is a safe and effective alternative approach as a rescue therapy for refractory AVB.

The aim of the Mexican Consensus on Portal Hypertension was to develop documented guidelines to facilitate clinical practice when dealing with key events of the patient presenting with portal hypertension and variceal bleeding. The panel of experts was made up of Mexican gastroenterologists, hepatologists, and endoscopists, all distinguished professionals. The document analyzes themes of interest in the following modules: preprimary and primary prophylaxis, acute variceal hemorrhage, and secondary prophylaxis. The management of variceal bleeding has improved considerably in recent years. Current information indicates that the general management of the cirrhotic patient presenting with variceal bleeding should be carried out by a multidisciplinary team, with such an approach playing a major role in the final outcome. The combination of drug and endoscopic therapies is recommended for initial management; vasoactive drugs should be started as soon as variceal bleeding is suspected and maintained for 5 days. After the patient is stabilized, urgent diagnostic endoscopy should be carried out by a qualified endoscopist, who then performs the corresponding endoscopic variceal treatment. Antibiotic prophylaxis should be regarded as an integral part of treatment, started upon hospital admittance and continued for 5 days. If there is treatment failure, rescue therapies should be carried out immediately, taking into account that interventional radiology therapies are very effective in controlling refractory variceal bleeding. These guidelines have been developed for the purpose of achieving greater clinical efficacy and are based on the best evidence of portal hypertension that is presently available.

Varices are a late complication in primary biliary cirrhosis (PBC). However, patients without clinical jaundice do bleed from varices; whether their prognosis differs is unknown.

Evaluate PBC patients, particularly those with bilirubin <or=34 micromol/l at the time of bleeding.

One hundred and two variceal bleeders were present (median, follow-up 20.5 months, range 0-180), who at diagnosis had: pruritus (51%), fatigue (32%) and 23 (22.5%) variceal bleeding. Histologically advanced disease was present in 96 of 100 patients (stage 3: 14 and stage 4: 82); 83 died, 24 within 6 weeks of first bleeding. At the time of bleeding, 26 patients had bilirubin <or=34 micromol/l. In this group, 24 patients were stage 4, in 13 bleeding was the first presentation of PBC and they were older (59.4 vs. 55.4 years, P=0.09), had lower alkaline phosphatase (491.5 vs. 510, P=0.03) but similar albumin values, surviving a median 61 versus 12 months, compared with the 76 patients with bilirubin >34 micromol/l (P=0.001, log rank test). Hazard ratios (95% confidence intervals) for independent predictors of mortality after bleeding were: age 1.02 (1-1.05), log10 bilirubin 4.64 (2.56-8.41), ascites 2.13 (1.29-3.51) and hepatic encephalopathy 2.72 (1.56-4.74).

Variceal bleeding complicates histologically advanced PBC. A distinct subgroup with near normal bilirubin and lower alkaline phosphatase first presents with variceal bleeding in 50% of cases and has a better prognosis than jaundiced PBC variceal bleeders.

To date, no study has analyzed nationwide trends of in-hospital mortality related to oesophageal variceal hemorrhage in the USA. The aim of this study was to analyze trends of in-hospital mortality related to oesophageal variceal bleeding over the past two decades using a large national database. In addition, our aim was to study patient demographics and to identify risk factors for in-hospital mortality based on administrative data routinely collected in this population.

The nationwide inpatient sample database was used from 1988 to 2004. Patients with an International Classification of Diseases, ninth revision, Clinical Modification discharge diagnosis of oesophageal variceal bleeding were included. Patient demographics, hospital, and admission characteristics were collected. t-test and Poisson regression analysis were used to evaluate trends. Logistic regression analysis was performed to determine the relationship between mortality and patient/hospital characteristics.

From 1988 to 2004, crude in-hospital mortality decreased from 18 to 11.5%, whereas the age-adjusted in-hospital mortality rate decreased 45.4% from 1289 per 100,000 to 704 per 100,000 (P<0.01). Mortality was consistently higher for males and for African-Americans over the study period. For the 2001 dataset, multivariate logistic regression analysis showed that male sex, African-American race, age, large hospital size, urban location, teaching hospitals, and hospitals located in the northeast were independent risk factors for increased mortality.

The in-hospital mortality of patients with oesophageal variceal bleeding has decreased over the past two decades and is likely due to the advances made in the acute management of variceal bleeding as well as improved resuscitative methods. Male sex, African-American race, age, large hospital size, urban location, teaching hospitals, and hospitals located in the northeast are independent risk factors for increased in-hospital mortality.

Variceal ligation has proved more effective and safer than sclerotherapy and is currently the endoscopic treatment of choice for oesophageal varices. In acute bleeding, vasoactive drugs should be started before endoscopy and maintained for 2-5 days. The efficacy of drugs is improved when associated with emergency endoscopic therapy. Antibiotic prophylaxis should also be used. To prevent rebleeding, both endoscopic ligation and the combination of beta-blockers and nitrates may be used. Adding beta-blockers improves the efficacy of ligation. Haemodynamic responders to beta-blockers+/-nitrates (those with a decrease in portal pressure gradient HVPG to <12 mmHg or by >20% of baseline) have a marked reduction in the risk of haemorrhage and will not need further treatment. Beta-blockers significantly reduce the risk of a first haemorrhage in patients with large varices, and they improve survival. As compared to beta-blockers, endoscopic ligation reduces the risk of first bleeding without affecting mortality, and should be used in patients with contraindications or intolerance to beta-blockers.

Management of continued bleeding from esophageal varices despite adequate injection sclerotherapy remains one of the medical and surgical dilemmas. Transabdominal gastroesophageal devascularization and esophageal transection (TGDET) is considered an effective and safe procedure for such patients.

This study aimed at presenting continued evaluation of TGDET. Various problems influencing the early outcome are discussed, and long-term outcome is analyzed.

This was a prospective clinical descriptive study.

Prospective data was collected on 142 consecutive patients managed by one group of surgeons over a 5 year-period and 15 years follow-up after failed injection sclerotherapy for variceal bleeding. Evaluation was made in terms of effectiveness in controlling the acute bleeding, postoperative morbidity and mortality, recurrent bleeding, encephalopathy, and long-term survival.

There were 133 men and 9 women. Mean age was 41.8 years. Etiology of portal hypertension was bilharziasis in 54.9% and posthepatitic in 14.8%. Child-Pugh grading on admission was A: 47.2%, B: 28.8%, and C: 14%. Hemorrhage was controlled in all cases. Clinical leak was observed in 5.6%, portal vein thrombosis in 6.3%, and staple line erosion in 2.1% of cases. No patient developed encephalopathy. In-hospital mortality was 12.7%. Complete eradication of varices was observed in 70.6% patients. Recurrent variceal bleeding was noticed in 6.9% of cases. Actuarial 15-year survival for Child-Pugh A patients was 44%, B was 22.5%, and none for C.

TGDET remains a safe and effective procedure after failure of sclerotherapy when other alternatives are either not indicated or not available.

Transjugular intrahepatic portosystemic stent shunt (TIPSS) is now widely used in the treatment of uncontrolled and recurrent variceal haemorrhage. This study reports the outcome and long-term follow-up of 125 patients who were referred to a single centre for TIPSS.

One hundred and twenty-five patients were referred to undergo TIPSS. All but 10 had variceal haemorrhage. The 10 patients referred with refractory ascites were excluded from the analysis. Our follow-up protocol was to assess shunt patency only if bleeding recurred or there was a clinical indication. The mean age was 51.5 years (range 18-87 years) and 64 patients (56%) were male. The commonest aetiology for chronic liver disease was alcohol (80%). At referral, 19 patients (16%) were Child-Pugh class A, 26 patients (23%) were Child-Pugh class B and 70 patients (61%) were Child-Pugh class C. The mean follow-up period was 20.4 months (range 0-95 months).

TIPSS was successfully placed in 108 of 115 patients (94%). The thirty-day mortality was 30%. One-year and 2-year overall cumulative survival was 52% (survival ratio, 0.525; 95% confidence interval, 0.432-0.619) and 43% (survival ratio, 0.436; 95% confidence interval, 0.340-0.532), respectively.

TIPSS is effective in the treatment of uncontrolled or recurrent variceal bleeding. In comparison with previously published studies, our study suggests no value in regular or routine shunt surveillance to reduce rebleeding episodes or mortality, but this needs to be further assessed in prospective randomized studies.

Treatment of portal hypertension is evolving based on randomised controlled trials. In acute variceal bleeding, prophylactic antibiotics are mandatory, reducing mortality as well as preventing infections. Terlipressin or somatostatin combined with endoscopic ligation or sclerotherapy is the best strategy for control of bleeding but there is no added effect of vasoactive drugs on mortality. Non-selective beta-blockers are the first choice therapy for both secondary and primary prevention; if contraindications or intolerance to beta-blockers are present then band ligation should be used. Novel therapies target the increased intrahepatic resistance caused by microcirculatory intrahepatic deficiency of nitric oxide and contraction of activated intrahepatic stellate cells.

To survey current clinical practice concerning the use of Sengstaken-Blakemore (SB) tubes and to determine whether cooling the tubes alters their stiffness.

A telephone questionnaire was conducted of gastroenterology registrars and ITU departments in the North Thames region. The current clinical practice for insertion of SB tubes and the basis for this practice were determined in each case. The stiffness of the tubes was measured at -10 degrees C and 20 degrees C by measuring the extension (in mm) resulting from an applied load (in newtons). The time for tube warming from -30 degrees C when in stationary air and when in contact with skin was also recorded.

Fifty registrars were contacted and 20 ITU departments were surveyed. All ITU departments involved the gastroenterologists in the management of acute variceal bleeds. Eight registrars had never placed an SB tube. The majority of the remainder (95%) used a cooled SB tube. All of the registrars based this practice upon their clinical teaching, and 75% of these registrars thought cooling aided the insertion of the tube. There was no significant difference in the stiffness of the tubes at -10 degrees C and 20 degrees C. Upon warming, an SB tube took 30 s to rise from 0 degrees C to room temperature (20 degrees C) when in skin contact and 120 s when placed in stationary air.

The current clinical practice of trainees for the insertion of SB tubes is to cool the tubes in the belief that this 'standard' practice aids tube insertion. We found no significant change in SB tube stiffness even after cooling to temperatures that would not be achieved during routine insertion. Furthermore, the rapid rise in tube temperature means that tubes approach room temperature by the time they reach the bedside. In the present era of evidence based medicine the current dogma that SB tubes should be cooled prior to insertion must be discarded.

Increased portal pressure during variceal bleeding may have an influence on the treatment failure rate, as well as on short- and long-term survival. However, the usefulness of hepatic hemodynamic measurement during the acute episode has not been prospectively validated, and no information exists about the outcome of hemodynamically defined high-risk patients treated with early portal decompression. Hepatic venous pressure gradient (HVPG) measurement was made within the first 24 hours after admission of 116 consecutive patients with cirrhosis with acute variceal bleeding treated with a single session of sclerotherapy injection during urgent endoscopy. Sixty-four patients had an HVPG less than 20 mm Hg (low-risk [LR] group), and 52 patients had an HVPG greater than or equal to 20 mm Hg (high-risk [HR] group). HR patients were randomly allocated into those receiving transjugular intrahepatic portosystemic shunt (TIPS; HR-TIPS group, n = 26) within the first 24 hours after admission and those not receiving TIPS (HR-non-TIPS group). The HR-non-TIPS group had more treatment failures (50% vs. 12%, P =.0001), transfusional requirements (3.7 +/- 2.7 vs. 2.2 +/- 2.3, P =.002), need for intensive care (16% vs. 3%, P <.05), and worse actuarial probability of survival than the LR group. Early TIPS placement reduced treatment failure (12%, P =.003), in-hospital and 1-year mortality (11% and 31%, respectively; P <.05). In conclusion, increased portal pressure estimated by early HVPG measurement is a main determinant of treatment failure and survival in variceal bleeding, and early TIPS placement reduces treatment failure and mortality in high risk patients defined by hemodynamic criteria.

Increased portal pressure during variceal bleeding may have an influence on the treatment failure rate, as well as on short- and long-term survival. However, the usefulness of hepatic hemodynamic measurement during the acute episode has not been prospectively validated, and no information exists about the outcome of hemodynamically defined high-risk patients treated with early portal decompression. Hepatic venous pressure gradient (HVPG) measurement was made within the first 24 hours after admission of 116 consecutive patients with cirrhosis with acute variceal bleeding treated with a single session of sclerotherapy injection during urgent endoscopy. Sixty-four patients had an HVPG less than 20 mm Hg (low-risk [LR] group), and 52 patients had an HVPG greater than or equal to 20 mm Hg (high-risk [HR] group). HR patients were randomly allocated into those receiving transjugular intrahepatic portosystemic shunt (TIPS; HR-TIPS group, n = 26) within the first 24 hours after admission and those not receiving TIPS (HR-non-TIPS group). The HR-non-TIPS group had more treatment failures (50% vs. 12%, P =.0001), transfusional requirements (3.7 +/- 2.7 vs. 2.2 +/- 2.3, P =.002), need for intensive care (16% vs. 3%, P <.05), and worse actuarial probability of survival than the LR group. Early TIPS placement reduced treatment failure (12%, P =.003), in-hospital and 1-year mortality (11% and 31%, respectively; P <.05). In conclusion, increased portal pressure estimated by early HVPG measurement is a main determinant of treatment failure and survival in variceal bleeding, and early TIPS placement reduces treatment failure and mortality in high risk patients defined by hemodynamic criteria.

Over the past two decades, new treatment modalities have been introduced for the management of variceal bleeding. The aim of this retrospective study in a single center was to assess whether these treatments have improved the prognosis for cirrhotic patients with variceal bleeding. We reviewed the clinical records of all patients with cirrhosis admitted to our Liver Intensive Care Unit due to variceal bleeding during the years 1980, 1985, 1990, 1995, and 2000. Whereas balloon tamponade was still the first-line treatment in 1980, patients treated in 2000 received a vasoactive agent, an endoscopic treatment, and an antibiotic prophylaxis in, respectively, 90%, 100%, and 94% of cases. The in-hospital mortality rate steadily decreased over the study period: 42.6%, 29.9%, 25%, 16.2%, and 14.5% in 1980, 1985, 1990, 1995, and 2000, respectively (P < .05). Mortality decreased from 9% in 1980 to 0% in 2000 in Child-Turcotte-Pugh class A patients, from 46% to 0% in class B patients, and from 70% to 32% in class C patients. This improved survival was associated with a decrease of rebleeding (from 47% in 1980 to 13% in 2000) and bacterial infection rates (from 38% to 14%). On multivariable analysis, endoscopic therapy and antibiotic prophylaxis were independent predictors of survival. In conclusion, in-hospital mortality of patients with cirrhosis and variceal bleeding decreased threefold over the past two decades, in concurrence with an early and combined use of pharmacological and endoscopic therapies and short-term antibiotic prophylaxis.

The purpose of the present study was to compare the efficacy of emergency endoscopic variceal sclerotherapy (EVS) using 3% aqueous phenol as an initial procedure to control acute oesophageal variceal bleed.

One hundred and ninety-five consecutive patients presenting with acute variceal bleed were included in the study. Protocol based endoscopic sclerotherapy and management of bleeding oesophageal varices was done. Immediate cessation of bleeding, re-bleeding within the first 72 h, success of first injection, final success of EVS, short-term mortality, influence of aetiology of portal hypertension and severity of liver disease on these results were studied.

Immediate cessation of bleeding was obtained in 191 out of 195 patients (97.9%). Twenty-seven (13.8%) patients re-bled within 72 h. On re-injection final success of EVS was 87.2% (170/195 patients). There was no significant difference between final success rate in cirrhotic versus non-cirrhotic patients (103/118 (87.3%) vs. 67/77 (87%)). Success of first sclerotherapy session was significantly higher than that of second sclerotherapy session. Surgical rescue was required in 25 (12.8%) patients. Mortality was 3.6%. Failure of EVS and mortality was significantly higher in Child's C group (P = 0.04, Relative risk = 0.5, confidence interval 0.22-1.16).

EVS remains an effective and cost effective modality of treatment to control acute variceal bleeding irrespective of aetiology of portal hypertension provided strict protocol based management is followed. With timely surgical rescue for the failures, the overall mortality can be reduced to less than 5%.

Portal hypertension bleeding is a common and serious complication of cirrhosis. All patients with cirrhosis should undergo endoscopy and be evaluated for possible causes of current or future portal hypertensive bleeding. Possible causes of bleeding include esophageal varices, gastric varices, and PHG. Patients with esophageal varices at high risk of bleeding should be treated with nonselective beta-blockers for primary prevention of variceal hemorrhage. HVPG measurements represent the optimal way to monitor the success of pharmacologic therapy. EVL may be used in those with high-risk varices who do not tolerate beta-blockers. When active bleeding develops, simultaneous and coordinated attention must be given to hemodynamic resuscitation, prevention and treatment of complications, and active control of bleeding. In cases of acute esophageal variceal (Fig. 5) and PHG bleeding, terlipressin, somatostatin, or octreotide should be started. Endoscopic treatment is provided for those with bleeding esophageal varices. If first-line therapy fails, TIPS or surgery may need to be performed. Unlike esophageal variceal or PHG bleeding, there is no established optimal treatment for gastric variceal bleeding. Individual and specific treatment modalities for acute gastric variceal bleeding must be calculated carefully after considering side effects.

Variceal haemorrhage is a common medical emergency with a high mortality (30-50%). Adequate resuscitation is vital, and once stabilised the patient should be moved to a high-dependency area. Antibiotics reduce mortality, and the vasoactive drug terlipressin should be administered if early endoscopy is unavailable. Early endoscopy is essential both to make the diagnosis and to allow therapeutic measures to be performed. The evidence suggests that variceal band ligation is the most effective therapy for oesophageal varices. If gastric varices are found at the index endoscopy the evidence at present is inadequate to be certain which is the best treatment, but both endoscopic therapy with cyanoacrylate or thrombin and transjugular intrahepatic portosystemic stent shunt (TIPSS) have been reported to be of benefit. When initial treatments fail, rescue therapy should be initiated. Most authorities agree that TIPSS is the rescue therapy of choice. Many questions remain concerning the treatment of acute variceal bleeding, particularly the ideal therapy for gastric varices and the role of combination vasoactive and endoscopic therapy. Randomised controlled trials are required to answer these important issues.

Some autopsy studies have dealt with histologic features of esophageal varices after different therapeutic procedures. However, to the best of our knowledge, no reports have been published describing outpatient characteristics that are associated with fatal esophageal variceal hemorrhage in a medicolegal autopsy population.

To (1) assess the incidence of sudden deaths from esophageal variceal hemorrhage in an unselected medicolegal autopsy population and (2) determine demographics of outpatients dying from esophageal variceal hemorrhage with special reference to blood alcohol concentrations at the time of death.

We performed a retrospective study of all autopsy cases of sudden death from esophageal variceal hemorrhage from a total of 6038 medicolegal autopsies performed over a 5-year period (1997-2001). We analyzed individual cases to determine gender, age, location and histology of bleeding esophageal varices, pathogenic mechanism for esophageal varices, concomitant underlying diseases contributing to fatal outcome, body mass index, circumstances at the death scene, and blood alcohol levels at the time of death. We reviewed the results of toxicologic analyses of alcohol concentrations in samples of femoral venous blood and urine obtained at autopsy; concentrations had been determined by gas chromatography with mass spectroscopy and enzymatic assays.

We identified 45 cases of fatal esophageal variceal hemorrhage that occurred out of hospital and presented as sudden death; the corresponding 5-year incidence in this autopsy population was 0.75%. All of the deceased were white; the male-female ratio was 1.6:1, and the mean age was 50.6 years. Ruptured esophageal varices were located in the lower third of the esophagus in 44 cases. Cirrhosis of the liver was present in all cases (alcoholic cirrhosis of the liver in 42 cases), and a hepatocellular carcinoma was present in 3 cases. Alcohol-induced pancreatic tissue alterations were frequently found. The results of toxicologic analysis were positive for alcohol in femoral venous blood and urine in 30 cases. Blood alcohol levels at the time of death were less than 100 mg/dL (21.7 mmol/L) in 15 cases, between 100 and 200 mg/dL (21.7 and 43.4 mmol/L) in 8 cases, and greater than 200 mg/dL (43.4 mmol/L) in the remaining 7 cases.

Apart from abnormalities in coagulation due to poor liver function in long-term alcohol users, acute alcohol intake may represent an important factor influencing mortality in individuals with esophageal variceal hemorrhage. Acute alcohol intake has transient effects on blood clotting time caused by ethanol and its main metabolites. In the present study, bloodstains at the death scene and unusual body positions of the deceased that aroused suspicion of a violent death were leading reasons for conducting a medicolegal autopsy. Apart from aspects of forensic pathology, the demographics of our study population are also noteworthy from the viewpoint of social medicine. The data we present stress the importance of fatal esophageal variceal hemorrhage as a relevant cause of sudden death occurring outside the hospital in socially isolated, alcohol-addicted individuals.

Many advances in the management of portal hypertension and variceal hemorrhage have occurred during the last 10 years. Effective therapy for primary prevention of variceal hemorrhage is now available in the form of nonselective beta-blockers. Active bleeding should be managed with terlipressin, somatostatin or its analogues, and endoscopic therapy; TIPS and surgery are reserved as salvage therapy for patients who fail endoscopic treatment. Survivors of a variceal hemorrhage should be evaluated for liver transplantation. Specific treatment may be provided with EVL while these patients await transplantation. Patients who fail endoscopic treatment may be treated by TIPS or surgery.

Endoscopic therapy and in particular endoscopic variceal banding ligation, in experienced hands, is the treatment of choice for acute variceal bleeding which remains a major cause of death in patients with cirrhosis and portal hypertension. Pharmacological therapy with Glypressin or somatostatin can be useful to gain time when the endoscopic expertise is not available or to help to obtain a clearer endoscopic view. Transjugular intrahepatic porto-systemic stent shunt is currently used for endoscopic failures, producing similar results with the surgical portacaval shunts. Which one of the two should be preferred, since they both work best in relatively compensated patients, should be a balance between the available surgical and radiological expertise, the urgency of the situation and the expected course of the disease.

Cirrhosis can be the end stage of any chronic liver disease. At the time of diagnosis of cirrhosis varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, large size of varices and the presence of endoscopic red colour signs but only one-third of patients who have variceal haemorrhage have the above risk factors. Recent interest has been directed at identifying haemodynamic factors that may reflect the pathophysiological changes which lead to variceal bleeding, e.g. it has been confirmed that no bleeding occurs if HVPG falls below 12 mmHg and also a hypothesis has been put forward in which bacterial infection is considered a trigger for bleeding. Pharmacological treatment with beta-blockers is safe, effective and is the standard long-term treatment for the prevention of recurrence of variceal bleeding. Combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for reduction in HVPG response needs further study, and surrogate markers of pressure response need evaluation. If endoscopic treatment is chosen, variceal ligation is the modality of choice. The combination of simultaneous variceal ligation and sclerotherapy does not offer any benefit. However, the use of additional sclerotherapy for the complete eradication of small varices after variceal ligation needs to be evaluated. The results of current prospective randomized controlled trials comparing variceal ligation with pharmacological treatment are awaited with great interest. Finally, the use of transjugular intrahepatic portosystemic shunt (TIPS) for the secondary prevention of variceal bleeding is not substantiated by current data, as survival is not improved and because of its worse cost-benefit profile compared to other treatments. In contrast, there still is a role for the selective surgical shunts in the modern management of portal hypertension. The ideal patients should be well compensated cirrhotics, who have had troublesome bleeding - either who have failed at least one other modality of therapy (drugs or ligation), have bled from gastric varices despite medical or endoscopic therapy, or live far from suitable medical services. Recently, ligation has been compared to beta-blockers for primary prophylaxis but so far there is no good evidence to recommend banding for primary prophylaxis, if beta-blockers can be given.

The last half century has witnessed great advances in the understanding of the pathogenesis and natural history of portal hypertension in cirrhotics. Several pharmacologic and endoscopic techniques have been developed for the treatment of portal hypertension. The use of these agents in a given patient must be based on an understanding of the stage in the natural history of the disease and the relative efficacy and safety of the available treatment options.

The role of surgery in the prevention and treatment of variceal hemorrhage is reviewed. Types of available surgery, their physiologic basis, and literature supporting their use are discussed in the context of the natural history of variceal hemorrhage. The evolution of transjugular intrahepatic portosystemic shunt (TIPS) as a treatment modality for variceal hemorrhage is reviewed. The effects of TIPS on portal and systemic hemodynamics and clinical usefulness in the management of variceal hemorrhage are discussed. A treatment algorithm for the integrated use of the various treatments is provided.

Transjugular intrahepatic portosystemic shunts (TIPS) may worsen liver function and decrease survival in some patients. The Child-Pugh classification has several drawbacks when used to determine survival in such patients. The survival of 231 patients at 4 medical centers within the United States who underwent elective TIPS was studied to develop statistical models to (1) predict patient survival and (2) identify those patients whose liver-related mortality post-TIPS would be 3 months or less. Among these elective TIPS patients, 173 had the procedure for prevention of variceal rebleeding and 58 for treatment of refractory ascites. Death related to liver disease occurred in 110 patients, 70 within 3 months. Cox proportional-hazards regression identified serum concentrations of bilirubin and creatinine, international normalized ratio for prothrombin time (INR), and the cause of the underlying liver disease as predictors of survival in patients undergoing elective TIPS, either for prevention of variceal rebleeding or for treatment of refractory ascites. These variables can be used to calculate a risk score (R) for patients undergoing elective TIPS. Patients with R > 1.8 had a median survival of 3 months or less. This model was superior to both the Child-Pugh classification, as well as the Child-Pugh score, in predicting survival. Using logistic regression and the same variables, we also developed a nomogram that indicates which patients survive less than 3 months. Finally, the model was validated among an independent set of 71 patients from the Netherlands. This Mayo TIPS model may predict early death following elective TIPS for either prevention of variceal rebleeding or for treatment of refractory ascites.

Since the introduction of transjugular intrahepatic portosystemic shunt (TIPS) 10 years ago, it has been used increasingly in the management of portal hypertension and its complications. TIPS is now considered the procedure of choice for management of refractory variceal bleeding. Its role in the management of refractory ascites, hepatic hydrothorax, hepatorenal syndrome, and hepatopulmonary syndrome still awaits further prospective studies. The two main complications of TIPS are hepatic encephalopathy and shunt malfunction. Generally, TIPS stenosis or occlusion is a major drawback requiring routine surveillance of TIPS with doppler ultrasound. Venography with balloon dilation of the stent or placement of serial or parallel stents may be required in some cases. Promising modalities of preventing TIPS malfunction (e.g., brachy-therapy, covered stents, or anti-platelet derived growth factor) are currently being investigated.

The aim of this study was to assess systemic hemodynamic changes in patients with Manson's schistosomiasis and portal hypertension during azygoportal disconnection and splenectomy.

Sixteen patients with portal hypertension secondary to hepatosplenic schistosomiasis with indication for surgery were studied prospectively. All underwent invasive hemodynamic monitoring with pulmonary artery catheter. The first systemic hemodynamic assessment was performed preoperatively. In the intraoperative period new hemodynamic data were collected as follows: a) after laparotomy; b) 15-30 min after splenic artery ligature; c) 15-30 min after splenectomy; and d) after ligation of the collateral circulation.

The results indicated preoperatively that the patients presented with an increased cardiac index (4.40 +/- 0.94 L/min/m2) together with a reduction in the systemic vascular resistance index (1692.25 +/- 434.91 dyne.s/cm5.m2). The stroke index (53.74 +/- 10.40 ml/beat/m2) and both left (5.71 +/- 1.50 kg.m/m2) and right heart work indexes (1.12 +/- 0.74 kg.m/m2) were also elevated. The mean pulmonary artery pressure was increased (17.81 +/- 9.00 mm Hg) and the pulmonary vascular resistance index decreased (164.31 +/- 138.69 dyne.s/cm5.m2). From the moment that the splenic artery was ligated until the end of the procedure, the cardiac index (3.45 +/- 0.90 L/min/m2) was reduced and the systemic vascular resistance index (2059.50 +/- 590.05 dyne.s/cm5.m5) increased. The systolic index (44.25 +/- 11.01 ml/beat/m2) and the left ventricle work index (4.33 +/- 1.29 kg.m/m2) also reduced. The mean pulmonary artery pressure (19.18 +/- 9.21 mm Hg) and the right ventricle work index (0.94 +/- 0.62 mm Hg) remained elevated after the surgical procedure.

The data allowed us to conclude that hepatosplenic schistosomiasis induces a hyperdynamic circulatory state that was corrected after splenectomy and azygoportal disconnection, remaining a mild pulmonary hypertension. Therefore, these changes are correlated with the portosystemic collateral circulation, especially as a consequence of splanchnic hyperflow.

Patients with cirrhosis, especially those who have a platelet count of less than 100,000, who are considered compliant, and have no contraindications to beta-blocker therapy, should have a screening endoscopy to ascertain the presence of esophageal varices. Patients with medium to large esophageal varices who are appropriate candidates should be placed on a nonselective beta-blocker (propranolol hyrdochloride, nadolol, timolol maleate) for the prevention of initial variceal hemorrhage. Patients presenting with acute variceal hemorrhage, as determined endoscopically, should be treated with a combination of vasoactive drugs and endoscopic therapy (sclerotherapy or variceal ligation) for the control of acute variceal bleeding and the prevention of early rebleeding. Transjugular intrahepatic portosystemic shunt (TIPS) should be reserved for failures of initial medical therapy. After successful control of initial variceal bleeding is reached, the rebleeding rate approaches 70% in most studies, with the highest risk period being in the first 6 months after control of the index bleed is obtained. Therefore, all patients should be placed on therapy to prevent recurrent variceal bleeding. Options include pharmacologic therapy, endoscopic therapy, and combinations of endoscopic and pharmacologic therapy. TIPS, surgical shunts, and liver transplantation should be reserved for special circumstances and in general, should only be considered for failures of initial medical therapy.

For 25 years the optimal management of bleeding oesophageal varices has included endoscopic injection sclerotherapy (EIS) both to arrest bleeding and to prevent rebleeding. However, the recent innovation of endoscopic variceal ligation (EVL) may be a more effective treatment; this paper reviews its efficacy.

All Medline (National Library of Medicine, Washington DC, USA) articles containing the text words 'oesophageal varices', 'sclerotherapy' or 'band ligation' were reviewed. Prospective randomized studies comparing sclerotherapy with band ligation, or combinations thereof, were included.

After an acute variceal bleed EVL is as effective as EIS for control and eradication of oesophageal varices. Initial control of bleeding is similar, but eradication is achieved in fewer sessions with EVL. EVL is associated with lower rebleeding rates and fewer procedure-related complications; it is also more effective for control of active bleeding at initial endoscopy. Combination therapy (EIS plus EVL) confers no advantage over EVL alone.

EVL is similar to EIS for control of bleeding varices, but the former has less associated morbidity, lower rebleeding rates and achieves more rapid variceal eradication. EVL should be considered the endoscopic treatment of choice in the management of variceal haemorrhage.

Despite the increased cardiac output and oxygen delivery, an impaired oxygen uptake has been noted in patients with cirrhosis. We recently observed that endoscopic variceal ligation decreased the cardiac output due to a reduction in the cardiac preload. It is thus possible that a variceal ligation decreases the oxygen delivery and thereby negatively influences tissue oxygenation in patients receiving such treatment. We thus investigated the effects of variceal ligation on oxygen delivery, oxygen uptake, and the arterial lactate levels.

There were 22 patients with compensated cirrhosis and risky esophageal varices (Child's class A:B=13:9). Twelve patients underwent an endoscopic variceal ligation and 10 patients received gastroscopy as a control. The cardiac function, blood gas status, oxygen delivery, and arterial lactate concentration were also assessed before and after variceal ligation. The oxygen uptake was calculated by the Fick equation.

Following variceal ligation, there was an immediate decrease in the cardiac output and oxygen delivery. The reduction in oxygen delivery was associated with a slight but significant increase in the arterial lactate concentration. The decreased oxygen delivery was also associated with a concomitant decrease in the oxygen uptake. In the control subjects, gastroscopy did not alter the systemic hemodynamics, arterial oxygen status, or arterial lactate levels.

We found a significant decrease in the oxygen delivery in patients undergoing an endoscopic variceal ligation. Such deteriorated tissue oxygenation may be serious especially in patients with a low oxygen transport ability such as in patients with variceal hemorrhage with anemia. However, the clinical significance of these changes remains unclear and further studies are therefore warranted.

Bacterial infection is frequently diagnosed in cirrhotic patients with variceal hemorrhage. The aim of this study was to assess the incidence of failure to control bleeding in cirrhotic patients during the first 5 days after the episode of variceal bleeding in relation to the diagnosis of bacterial infection and use of antibiotics. One hundred seventy-seven consecutive admissions for gastrointestinal bleeding in 151 patients were evaluated prospectively. From them, 163 admissions for variceal bleeding in 137 patients were included in the main analysis. Bleeding was managed in a standardized protocol using octreotide or terlipressin with sclerotherapy or band ligation for active bleeding at endoscopy. The end points were defined as in Baveno guidelines related to transfusion requirement or fresh hematemesis after 6 hours from time zero. The standardized screening protocol for bacterial infection consisted of chest radiograph and blood, urine, and ascitic fluid cultures. Active bleeding was reported at endoscopy in 86 admissions (53%). Failure to control bleeding occurred in 76 patient admissions (47%). Empirical antibiotic treatment was used in 113 admissions (69%), whereas in 81% of them (91 admissions, 56%) 102 bacterial infections were documented. Multivariate analysis showed that proven bacterial infection (P < .0001) or antibiotic use (P < .003) as well as active bleeding at endoscopy (P < .001) and Child-Pugh score (P < .02) were independent prognostic factors of failure to control bleeding. The results remained unchanged when all patient admissions with gastrointestinal bleeding of any source were included in the multivariate analysis. Bacterial infection is associated with failure to control variceal bleeding and needs to be evaluated in the planning and analysis of clinical trials.

Male alcoholics hospitalized with actively bleeding esophageal varices were treated with sclerotherapy or sham sclerotherapy and the outcomes during the index hospitalization were compared.

The 87 patients were a subset of 253 patients enrolled in a prospective, randomized, single-blind, multicenter, controlled trial conducted in 12 VA medical centers. The patients (44 sclerotherapy, 43 sham therapy) were actively bleeding from esophageal varices at either randomization endoscopy (49) or follow-up endoscopy (38). Events and resource use during the index hospitalization were recorded.

In 40 (91%) of the sclerotherapy and 26 (60%) of the sham therapy patients, bleeding was stopped during the endoscopy session (p < 0.001). During the hospitalization, 10 (25%) sclerotherapy and 21 (49%) sham therapy patients died (p = 0.04, relative risk 2.17, 95% CI [1.02, 4.61]); 9 sclerotherapy and 22 sham therapy patients rebled (p = 0.005). The median transfusion requirement was higher for sham therapy (8 vs 4 units, p = 0.001), the number of median ICU hours was greater (101 vs 55, p < 0.001), and more patients in this group required shunt surgery (6 vs 0, p = 0.01).

Sclerotherapy, compared to no sclerotherapy, stops hemorrhage from actively bleeding esophageal varices and reduces use of resources. Sclerotherapy significantly increased hospital survival.

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure recently introduced for the management of complications of portal hypertension. TIPS can be placed in the liver with relative ease by a skilled radiologist with a low risk of mortality. The major complications following the procedure are infection, especially in patients undergoing emergency TIPS, intra-abdominal haemorrhage from capsular punctures, and long-term problems related to encephalopathy and stenosis of the shunt. Encephalopathy is more of a problem in older patients with wide diameter shunts. Stenosis of the shunt is related to pseudo-intimal hyperplasia, probably related to transection of bile ductules during placement of the shunt. In view of the high rate of encephalopathy and stenosis following the shunt, a careful follow-up of all patients, including ultrasonographic and angiographic examination of the shunt, is mandatory. TIPS is used predominantly for the control of acute variceal haemorrhage, prevention of recurrent variceal bleeding, and refractory ascites when conventional treatment has failed. However, the role of TIPS in the management of complications of portal hypertension still awaits the outcome of clinical trials.

Patients with large esophageal varices who are deemed compliant and have no contraindications to beta-blocker therapy should be started on nonselective beta-adrenergic blockers (Fig. 5). The dose should be titrated to a 25% decrease in resting heart rate, a resting heart rate of 55 to 60 beats per minute, or development of symptoms, in which case the dose should be decreased until the patient's symptoms abate. If available, measurements of the HVPG at baseline and 3 months can be very helpful in ascertaining the response to treatment and in making the appropriate adjustments (e.g., adding a second drug). Sclerotherapy or endoscopic variceal ligation are the preferred therapies for treatment of acute esophageal variceal bleeding. Concomitant use of vasoactive drugs can supplement endoscopic treatment. They offer the advantage of early administration as soon as the diagnosis is suspected while awaiting endoscopy. Unlike endoscopic treatment, they decrease portal pressure and are the only established treatment for nonvariceal sources of bleeding related to portal hypertension. Once the index bleed is controlled, the patient should be started on treatment to reduce the high risk of recurrent variceal hemorrhage (Fig. 6). For patients with well-compensated cirrhosis, pharmacologic therapy may be desirable. For less compliant patients or patients with decompensated cirrhosis, an endoscopic technique, such as variceal ligation, may be preferable. Combinations of pharmacologic agents or pharmacologic agents and endoscopic procedures may offer hope for better control, but their efficacy needs to be demonstrated in RCTs. For patients who rebleed despite maximal pharmacologic or endoscopic therapy, a TIPS procedure, surgically created shunt, or liver transplantation should be considered, with the decision based on the patient's condition and the local availability of these options.

This retrospective analysis studied the effect of sclerotherapy on subsequent oesophageal transection in the management of patients with bleeding oesophageal varices and compared the result with that in those who did not receive sclerotherapy as the primary treatment. Fifty patients were treated by gastro-oesophageal devascularization and oesophageal transection for bleeding oesophageal varices over a 4-year period. Twenty-six patients did not receive sclerotherapy (group 1) and 24 received between one and four sessions of sclerotherapy (group 2) before surgery. Oedema and thickness of the lower end of the oesophagus and some adhesions were noted during surgery in patients who had had previous sclerotherapy; however, stapled oesophageal transection and anastomosis could be performed in all these patients. There was no oesophageal leak in any patient, although there was a higher rate of chest complications (nine versus six patients) in group 2. Six patients (12 per cent) died (three in each group) during the postoperative period; three had Child grade C disease. It is concluded that the decision to operate to control bleeding varices should be made early. One or two sessions of sclerotherapy before surgery does not increase intraoperative difficulty or the postoperative leak rate following oesophageal transection. The outcome of surgery is directly related to the state of liver reserve (Child grade).