Table 3. Adaptation of recommendations according to level of treatment care.
| Original statements | Suggested modifications | |
| Surveillance of esophageal varices | ||
| 1 | In compensated patients with no varices at screening endoscopy and with ongoing liver injury (e. g. active drinking in alcoholics, lack of SVR in HCV), surveillance endoscopy should be repeated at 2-year intervals. | Level I/II/III: No adjustment |
| 2 | In compensated patients with small varices and with ongoing liver injury (e. g. active drinking in alcoholics, lack of SVR in HCV), surveillance endoscopy should be repeated at 1-year intervals. | Level I/II/III: No adjustment |
| 3 | In compensated patients with no varices at screening endoscopy in whom the aetiological factor has been removed (e. g. achievement of SVR in HCV; long-lasting abstinence in alcoholics) and who have no co-factors (e. g. obesity), surveillance endoscopy should be repeated at three year intervals. | Level I/II/III: No adjustment |
| 4 | In compensated patients with small varices at screening endoscopy in whom the etiological factor has been removed (e. g. achievement of SVR in HCV; long-lasting abstinence in alcoholics) and who have no co-factors (e. g. obesity), surveillance endoscopy should be repeated at 2-year intervals). | Level I/II/III: No adjustment |
| Patients with no varices or small varices | ||
| 5 | Patients with small varices with red whale marks or Child-Pugh C class have an increased risk of bleeding and should be treated with non-selective beta blockers (NSBB). | Level I/II/III: No adjustment |
| 6 | Patients with small varices without signs of increased risk may be treated with NSBB to prevent bleeding. Further studies are required to confirm their benefit. | Level I/II/III: No adjustment |
| Patients with medium-large varices | ||
| 7 | Either NSBB or endoscopic band ligation is recommended for the prevention of the first variceal bleeding of medium or large varices. | Level I: NSBB and endoscopic surveillance every 6 months Level II: No adjustment Level III: No adjustment |
| 8 | The choice of treatment should be based on local resources and expertise, patient preference and characteristics, contraindications and adverse events. | Level I/II/III: No adjustment |
| Patients with gastric varices | ||
| 9 | Although a single study suggested that cyanoacrylate injection is more effective than beta blockers in preventing first bleeding in patients with large gastroesophageal varices type 2 or isolated gastric varices type 1, further studies are needed to evaluate the risk/benefit ratio of using cyanoacrylate in this setting before a recommendation can be made). | Level I: NSBB Level II: NSBB and sclerotherapy e. g. submucosal ethanol injection Level III: No adjustment |
| Management of the acute bleeding episode | ||
| Blood volume restitution | ||
| 10 | The goal of resuscitation is to preserve tissue perfusion. Volume restitution should be initiated to restore and maintain hemodynamic stability. | Level I/II/III: No adjustment |
| 11 | Packed red blood cells transfusion should be done conservatively at a target haemoglobin level between 7 and 8 g/ dl, although transfusion policy in individual patients should also consider other factors such as cardiovascular disorders, age, hemodynamic status and ongoing bleeding). | Level I: Blood pressure monitoring and fluid resuscitation with crystalloid fluids Level II: Restrictive blood transfusion strategy based on clinical judgement Level III: No adjustment |
| 12 | Recommendations regarding management of coagulopathy and thrombocytopenia cannot be made on the basis of currently available data. | Level I/II/III: No adjustment |
| 13 | PT/INR is not a reliable indicator of the coagulation status in patients with cirrhosis. | Level I/II/III: No adjustment |
| Antibiotic prophylaxis | ||
| 14 | Antibiotic prophylaxis is an integral part of therapy for patients with cirrhosis presenting with upper gastrointestinal bleeding and should be instituted from admission. | Level I: No adjustment Level II: No adjustment Level III: No adjustment |
| 15 | The risk of bacterial infection and mortality are very low in patients with Child-Pugh A cirrhosis, but more prospective studies are needed to assess whether antibiotic prophylaxis can be avoided in this subgroup of patients. | Level I/II/III: No adjustment |
| 16 | Individual patient risk characteristics and local antimicrobial susceptibility patterns must be considered when determining appropriate first line acute variceal hemorrhage antimicrobial prophylaxis at each center. | Level I/II/III: No adjustment |
| 17 | Intravenous ceftriaxone 1 g/24 h should be considered in patients with advanced cirrhosis, in hospital settings with high prevalence of quinolone-resistant bacterial infections and in patients on previous quinolone prophylaxis. | Level I: Intravenous antibiotics after local preferences and availability Level II: No adjustment Level III: No adjustment |
| Prevention of hepatic encephalopathy | ||
| 18 | Recent studies suggest that either lactulose or rifaximin may prevent hepatic encephalopathy in patients with cirrhosis and upper gastrointestinal bleeding. However, further studies are needed to evaluate the risk/benefit ratio and to identify high risk patients before a formal recommendation can be made. | Level I: Lactulose and antibiotics according to local preferences and availability Level II: Lactulose and nonabsorbable antibiotics Level III: No adjustment |
| 19 | Although, there are no specific studies in acute variceal bleeding, it is recommended to adopt the recent EASL/AASLD HE guidelines which state that episodic HE should be treated with lactulose (25 ml q 12 h until 2–3 soft bowel movements are produced, followed by dose titration to maintain 2–3 soft bowel movements per day). | Level I: Lactulose and best supportive care Level II: No adjustment Level III: No adjustment |
| 20 | Child-Pugh class C, the updated MELD score, and failure to achieve primary haemostasis are the variables most consistently found to predict six week mortality. | Level I/II/III: No adjustment |
| Pharmacological treatment | ||
| 21 | In suspected variceal bleeding, vasoactive drugs should be started as soon as possible, before endoscopy. | Level I: Octreotide Level II: Octreotide Level III: No adjustment |
| 22 | Vasoactive drugs (terlipressin, somatostatin, octreotide) should be used in combination with endoscopic therapy and continued for up to five days. | Level I: Octreotide Level II: Octreotide and endoscopic therapy is recommended Level III: No adjustment |
| 23 | Hyponatremia has been described in patients under terlipressin, especially in patients with preserved liver function. Therefore, sodium levels must be monitored. | Level I/II/III: No adjustment |
| Endoscopy | ||
| 24 | Following hemodynamic resuscitation, patients with upper gastrointestinal bleeding and features suggesting cirrhosis should undergo esophagogastroduodenoscopy within 12 h of presentation. | Level I. Technical expertise may not be available on a 24 /7 basis Level II. Endoscopy within 24 hours; trained emergency team with necessary technical expertise available Level III. No adjustment |
| 25 | In the absence of contraindications (QT prolongation), pre-endoscopy infusion of erythromycin (250 mg IV 30–120 min before endoscopy) should be considered. | Level I: Endoscopy even when pre-endoscopic erythromycin infusion is not available. Level II: No adjustment Level III: No adjustment |
| 26 | The availability both of an on-call gastrointestinal endoscopist proficient in endoscopic haemostasis and on-call support staff with technical expertise in the usage of endoscopic devices enables performance of endoscopy on a 24 /7 basis and is recommended. | Level I. Technical expertise may not be available on a round-the clock basis Level II. Endoscopy within 24 hours; trained emergency team with necessary technical expertise available Level III. No adjustment |
| 27 | Patients with acute variceal hemorrhage should be considered for ICU or other well monitored units. | Level I: Best supportive care Level II: Best supportive care with best available monitoring of vital parameters Level III: No adjustment |
| 28 | In patients with altered consciousness, endoscopy should be performed with protection of the airway. | Level I: Patients with ongoing active hematemesis should be placed in a stable side position immediately; continuous active suction of blood and gastric contents Level II: Stable side position; continuous sedation; continuous active suction of blood and gastric contents; emergency endoscopy Level III: No adjustment |
| 29 | Ligation is the recommended form of endoscopic therapy for acute oesophageal variceal bleeding. | Level I: Best supportive and octreotide Level II: No adjustment Level III: No adjustment |
| 30 | Endoscopic therapy with tissue adhesive (e. g. N-butyl-cyanoacrylate) is recommended for acute bleeding from isolated gastric varices (IGV) and those gastroesophageal varices type 2 (GOV2) that extend beyond the cardia. | Level I: Best supportive care and NSBB Level II: Endoscopic band ligation can be considered as a salvage treatment in case of acute bleeding from small gastric varices when tissue adhesive is not available Level III: No adjustment |
| 31 | To prevent rebleeding from gastric varices, consideration should be given to additional glue injection (after 2 to 4 weeks), beta-blocker treatment or both combined or TIPS. More data in this area are needed. | Level I: Best supportive care and NSBB Level II: NSBB and endoscopic band ligation when tissue adhesive or TIPS are not available Level III: No adjustment |
| 32 | EVL or tissue adhesive can be used in bleeding from gastroesophageal varices type 1 (GOV1). | Level I: Best supportive care and NSBB Level II: No adjustment Level III: No adjustment |
| Early TIPS placement | ||
| 33 | An early TIPS with PTFE-covered stents within 72 h (ideally < 24 h) must be considered in patients bleeding from EV, GOV1 and GOV2 at high risk of treatment failure (e. g. Child-Pugh class C < 14 points or Child-Pugh class B with active bleeding) after initial pharmacological and endoscopic therapy. Criteria for high-risk patients should be refined. | Level I: Best supportive care and NSBB Level II: Maximal endoscopic and pharmacological therapy including NSBB when TIPS is not available Level III: No adjustment |
| Balloon tamponade | ||
| 34 | Balloon tamponade, given the high incidence of its severe adverse events, should only be used in refractory oesophageal bleeding, as a temporary ‘‘bridge’’ (for a maximum of 24 h) with intensive care monitoring and considering intubation, until definitive treatment can be instituted. | Level I: Best supportive care and NSBB Level II: No adjustment Level III: No adjustment |
| Use of self-expandable metal stents | ||
| 35 | Data suggest that self-expanding covered esophageal metal stents may be as efficacious and a safer option than balloon tamponade in refractory oesophageal variceal bleeding. | Level I: Best supportive care and NSBB Level II: No adjustment Level III: No adjustment |
| Management of treatment failures | ||
| 36 | Persistent bleeding despite combined pharmacological and endoscopic therapy is best managed by PTFE-covered TIPS. | Level I: Best supportive care and NSBB Level II: Maximal endoscopic and pharmacological therapy including NSBB when TIPS is not available Level III: No adjustment |
| 37 | Rebleeding during the first 5 days may be managed by a second attempt at endoscopic therapy. If rebleeding is severe, PTFE-covered TIPS is likely the best option. | Level I: Best supportive care and NSBB Level II: Maximal endoscopic and pharmacological therapy including NSBB when TIPS is not available Level III: No adjustment |
| Preventing recurrent variceal haemorrhage and other decompensating events | ||
| Prevention of recurrent variceal haemorrhage | ||
| 38 | First line therapy for all patients is the combination of NSBB (propranolol or nadolol) + EVL. | Level I: NSBB Level II: No adjustment Level III: No adjustment |
| 39 | EVL should not be used as monotherapy unless there is intolerance/contraindications to NSBB. | Level I: No adjustment Level II: No adjustment Level III: No adjustment |
| 40 | NSBB should be used as monotherapy in patients with cirrhosis who are unable or unwilling to be treated with EVL. | Level I: No adjustment Level II: No adjustment Level III: No adjustment |
| 41 | Covered TIPS is the treatment of choice in patients that fail first-line therapy (NSBB + EVL). | Level I: Best supportive care and NSBB Level II: NSBB, EVL, and SEMS Level III: No adjustment |
| 42 | Because carvedilol has not been compared to current standard of care, its use cannot be recommended in the prevention of rebleeding. | Level I/II/III: No adjustment |
| Secondary prophylaxis of portal hypertensive gastropathy (PHG) | ||
| 43 | PHG has to be distinguished from gastric antral vascular ectasia because treatments are different. | Level I/II/III: No adjustment |
| 44 | NSBB are first-line therapy in preventing recurrent bleeding from PHG. | Level I: No adjustment Level II: No adjustment Level III: No adjustment |
| 45 | TIPS might be considered in patients with transfusion-dependent PHG in whom NSBB and/or endoscopic therapies fail. | Level I: NSBB Level II: NSBB when TIPS is not available Level III: No adjustment |
| Treatment of portal hypertension in EHPVO | ||
| 46 | All patients in whom thrombosis has not been recanalized should be screened for gastroesophageal varices within 6 months of the acute episode. In the absence of varices, endoscopy should be repeated at 12 months and 2 years thereafter. | Level I: No adjustment Level II: No adjustment Level III: No adjustment |
| 47 | There is insufficient data on whether beta blockers or endoscopic therapy should be preferred for primary prophylaxis. Thus, guidelines for cirrhosis should be applied. | Level I/II/III: No adjustment |
| 48 | For the control of acute variceal bleeding, endoscopic therapy is effective. | Level I/II/III: No adjustment |
| 49 | Evidence suggests that beta blockers are as effective as endoscopic ligation therapy for secondary prophylaxis. | Level I/II/III: No adjustment |
| 50 | Mesenteric-left portal vein bypass (Meso-Rex operation) should be considered in all children with complications of chronic EHPVO, who should be referred to centres with experience in treating this condition. | Level I: Best supportive care and NSBB Level II: Maximal endoscopic and pharmacological therapy including NSBB Level III: No adjustment |
SVR, sustained virological response; HCV, hepatitis C virus; NSBB, nonselective beta blockers; EASL, European Association for the Study of Liver; AASLD, American Association for the Study of Liver Diseases; HE, hepatic encephalopathy; ICU, intensive care unit; IGV, isolated gastric varices; GOV2, gastroesophageal varices type 2; TIPS, transjugular intrahepatic portosystemic shunt; EVL, endoscopic variceal ligation; GOV1, gastroesophageal varices type 1; PTFE, polytetrafluoroethylene; SEMS, self-expanding metal stent; PHG, portal hypertensive gastropathy; EHPVO, extrahepatic portal vein obstruction