Systematic Reviews
Copyright ©The Author(s) 2016.
World J Gastroenterol. Jan 7, 2016; 22(1): 446-466
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.446
Table 1 Differential diagnosis of acute upper gastrointestinal bleeding in an alcoholic with advanced liver disease
Bleeding lesionEndoscopic appearancePathophysiologyNonsurgical treatmentRef.
Etiologies related to portal hypertension
Esophageal varicesSerpiginous, bluish-grey, vessels protruding from the mucosa into the lumen that typically are largest just above the gastroesophageal junctionVarices provide a conduit for venous blood blocked from traversing through the liver because of cirrhosis to return to the heartEndoscopy: variceal banding, variceal sclerotherapyGarcia-Tsao et al[13], Beppu et al[14]
Angiography: TIPS
Other: balloon tamponade, octreotide
Gastric varicesSerpiginous, bluish-grey, vessels protruding from the mucosa into the lumen that are most commonly located in the gastric cardia, fundus or bodyVarices provide a conduit for venous blood blocked from traversing through the liver because of cirrhosis to return to the heartAngiography: TIPS Other: balloon tamponade, octreotide Endoscopy: cyanoacrylate injection therapyGarcia-Pagán et al[15]
Formation of gastric varices may be promoted by endoscopic obliteration of esophageal varices
Duodenal varicesResemble esophageal varices in endoscopic appearance, but are located within duodenumRare site of varices which may be promoted by prior esophageal variceal banding or sclerotherapy and prior duodenal surgeryEndoscopy: variceal banding or sclerotherapyCopelan et al[16], Matsui et al[17]
TIPS, angiographic occlusion therapy by embolization or balloon occlusion
Portal hypertensive gastropathyMosaic or snake-skin appearance of gastric mucosa, especially of the gastric fundus and proximal gastric body, due to dilated, ectatic, superficial mucosal vesselsNetwork of microcirculation that drains venous blood blocked from passing through the cirrhotic liver to return to the left atriumTIPSPatwardhan et al[18], Thuluvath et al[19]
Etiologies possibly related to portal hypertension
Gastric antral vascular ectasiaIntensely erythematous streaks on longitudinal folds oriented towards the pylorus in the antrumMay be related to stretch of antral vessels from duodenal bulb prolapse. Vascular engorgement from portal hypertension or from hormonal abnormalities (e.g., hyperestrogenemia with cirrhosis) may also contribute to lesion pathogenesisEndoscopic therapy: APC, thermocoagulation, electrocoagulation, or radiofrequency ablation.McGorisk et al[20], Payen et al[21]
Etiologies possibly related to alcoholism or advanced liver disease
Peptic ulcer diseaseFocal ulcer: (depressed) crater covered by mucopurulent materialMajor causes in general population include H. pylori infection or NSAID use. Idiopathic PUD is increasingly noted. Gastric infections or gastric malignancy may mimic PUD. Pathogenesis of PUD in ALD and cirrhosis discussed in textEndoscopic therapy: discussed in textSiringo et al[22], Vergara et al[23], Kamalaporn et al[24], D’Amico et al[25]
Mallory- Weiss tearLongitudinally oriented erythematous tear or crack in the mucosa that straddles the gastroesophageal junctionLaceration due to mucosal trauma from retching or vomiting. Frequently associated with binge drinking or chronic alcoholismEndoscopic therapy: discussed in textPaquet et al[26], Schuman et al[27], Jensen et al[28]
Dieulafoy’s lesionElevated, pigmented spot that projects into the lumen from the mucosal surface without surrounding ulcerationCaliber-persistent artery near mucosal surface can erupt through thin overlying mucosal cells and cause bleedingEndoscopic therapy: injection therapy, band ligation, electrocoagulation, APCCappell[29], Jeon et al[30], Nojkov et al[31]
Angiography: local embolization
Surgery: wedge resection
Table 2 Clinical characteristics of patients with cirrhosis presenting with upper gastrointestinal bleeding unrelated to portal hypertension predominantly from peptic ulcers
Ref.No. of parentsALD (%)Mean agePrevalence of PUB (%)Mortality (%)Predictors of mortalityRebleeding rate (%)Length of follow-up
González-González et al[52]160“Most”56.5 ± 14.450.613.8High BUN, Low albumin, Active ulcer bleeding, Need for endoscopic therapy, Cryptogenic cirrhosis1.9NA
Seo et al[61]1074355.8 ± 116014.5Failure to control bleeding, High creatinine, High AST, High Child-Pugh score, PVT9.36 wk
Morsy et al[62]93NA55.3 ± 11.23014Bacterial infection, Shock, Early rebleeding, Low albumin, Low hemoglobin, Endoscopic therapy4.3Short-term (in-hospital)
Siringo et al[22]854062 ± 1241231Low hemoglobin,06 wk
Alcoholism, High bilirubin, PVT, High Child-Pugh score,
High AST/ALT levels, HCC
Rudler et al[63]2924 (83)55.0 ± 9.029 (100)21 (3)NA2 (7)30 d
Table 3 Key clinical findings regarding peptic ulcer disease in patients with alcoholic cirrhosis
Key finding
Increased prevalence of PUD in patients with cirrhosis. Most common etiology of non-variceal hemorrhage in cirrhotics
Advanced cirrhosis (Child-Pugh stage C) more strongly associated with PUD than early cirrhosis (Child-Pugh stage A)
Most patients with PUD associated with cirrhosis are asymptomatic
Patients with cirrhosis are more likely to bleed from PUD than other patients with PUD
Higher frequency of complications from bleeding PUD in patients with cirrhosis
Higher rate of re-bleeding from PUD in cirrhotics
Alcohol impairs ulcer healing and decreases patient compliance with anti-ulcer therapy
Higher mortality from PUB in cirrhotics compared to non-cirrhotics
Cirrhotic patients with PUD do not have a higher rate of H. pylori infection than non-cirrhotics with PUD
Table 4 Key clinical findings in Dieulafoy’s Lesion associated with chronic liver disease
Key findingsRationaleRef.
Typically presents with acute severe bleedingMicropulsatile bleeding produced by rent in an arteriole which is under high pressureNojkov et al[31], Luis et al[94]
Bleeding typically painlessPrimary vascular event (bursting of a persistent-caliber vessel) without associated inflammation or ulcerationCappell[29]
Appears at endoscopy as an elevated pigmented protuberance with minimal surrounding erosion and no ulcerationFormed by a caliber-persistent artery that erupts through superficial overlying cells on mucosal surfaceNojkov et al[31], Lee et al[93]
Lesion most commonly located in stomach, typically within 6 cm below the gastroesophageal junction along the lesser curveThis gastric region is not perfused by a submucosal plexus, but instead is perfused directly from tributaries of the right and left gastric arteriesCappell et al[29], Fockens et al[90], Lee et al[95]
Often (up to 30% of cases) missed at initial esophagogastroduodenoscopy (EGD)Missed at EGD because lesion is small and inconspicuousNojkov et al[31], Chung et al[96]
Incidence of 1.5% among general population of patients with upper GI bleedingFockens et al[90], Chaer et al[97]
High (25%) mortality if untreated at EGD, which is reduced to about 10% with endoscopic therapyHigh risk of rebleeding if not treated endoscopically. Rebleeding is frequently massiveRomãozinho et al[98]
Dieulafoy’s lesion may be associated with cirrhosisAkhras et al[91], Baettig et al[92]
Bleeding from a Dieulafoy’s lesion is associated with alcoholismAlcohol may precipitate DL rupture manifesting as GI bleeding by weakening the dilated (caliber-persistent) arteriolar wall in Dieulafoy’s lesionBaettig et al[92], Lee et al[95]
Table 5 Summary of clinical features of acute gastrointestinal bleeding from Mallory-Weiss syndrome in patients with underlying liver disease
Key findingsRef.
Findings generally associated with Mallory-Weiss syndrome
Characterized by longitudinally oriented mucosal lacerations in the distal esophagus or very proximal stomachKnauer[101]
Accounts for about 5% of acute upper GI bleedingMichel et al[100]
Mortality of bleeding from Mallory-Weiss syndrome is only about 3%-5%. Risk factors for mortality include age > 65 yr and significant comorbiditiesLjubičić et al[105]
Findings associated with Mallory-Weiss syndrome associated with alcoholism
MWS strongly associated with alcoholismKnauer[101]
MWS very frequently (40%-80%) associated with alcoholism or recent binge drinkingWatts et al[106]
Overall prevalence of bleeding from MWS in cirrhosis is up to 10%del Olmo et al[38], Feng et al[82]
Alcoholics with portal hypertension have higher prevalence of bleeding from MWS (up to 16%)Paquet et al[26], Schuman et al[27]
MWS may be the first bleeding episode in > 1/3 (37%) of these patients
Patients with cirrhosis have more severe bleeding from MWS and more likely to rebleed from MWS (compared to non-cirrhotics)Schuman et al[27], Jensen et al[28], Kim et al[107]
Re-bleeding risk particularly high in alcoholics
Contradictory data on effect of portal hypertension on severity of bleeding from MWSSchuman et al[27], Jensen et al[28]
Bleeding from MWS can precipitate liver failure with its attendant mortality in about 3% of patients with alcoholic cirrhosisdel Olmo et al[38]
Table 6 Special considerations in therapy for alcoholics with liver disease presenting with acute upper gastrointestinal bleeding
Recommended clinical practiceRationaleRef.
Consider early intubation for severe upper GI bleeding in a patient with alcoholism or alcoholic cirrhosisThese patients are at higher risk of aspiration because variceal bleeding related to alcoholism or cirrhosis is frequently massive, arises from the esophagus which is much closer to the trachea than other types of gastroduodenal bleeding; and the patient may be obtunded from hepatic encephalopathy from cirrhosisHerrera[109], Rudolph et al[110]
Avoid sedatives and narcotics in patients with advanced liver diseaseMay precipitate hepatic encephalopathy from cirrhosisBamji et al[120], Prabhakar et al[121]
Monitor for hepatic encephalopathyPatients with advanced cirrhosis at risk for hepatic encephalopathyRahimi et al[122]
Monitor for delirium tremensAcute alcoholic withdrawal in hospital can induce delirium tremensFerguson et al[123], Holloway et al[124]
Avoid over-transfusion (maintain hemoglobin level at about 8 gm/dL)Over-transfusion may exacerbate variceal bleeding by increasing portal hypertensionHerrera[109]
Patients often have thrombocytopenia which may contribute to the bleedingThrombocytopenia due to splenic sequestration from splenomegaly from portal hypertension and from direct alcohol toxicity to bone marrowPradella et al[125]
Patients often have a prolonged INR which may contribute to the bleedingINR prolonged due to inadequate synthesis of liver-dependent clotting factors, such as factor V, due to advanced liver diseaseLata et al[126]
Administer thiaminePrevent Wernicke’s syndrome from thiamine deficiency which is common in alcoholicsHack et al[127]
Monitor for electrolyte abnormalities which may be more prominent in alcoholicsKnochel[117]
Consider early (urgent) esophagogastroduodenoscopyImportant to distinguish esophageal variceal bleeding from other etiologies of upper GI bleeding because esophageal variceal bleeding has different therapiesBuccino et al[37], del Olmo et al[38]
Consider empiric octreotide therapy before endoscopyAlcoholics or patients with cirrhosis frequently have GI bleeding from esophageal varices which can be treated by octreotide therapyLudwig et al[128]
Perform paracentesis, as necessary, to exclude spontaneous bacterial peritonitisPatients with cirrhosis and ascites are at high risk to develop spontaneous bacterial peritonitis due to mild immunosuppression with cirrhosisGoulis et al[119]
Administer antibiotics in the presence of acute GI bleeding in a cirrhotic patientEmpiric antibiotic therapy lowers mortality because of decreased sepsisBernard et al[118]
Monitor BUN and creatinine levels to detect early hepatorenal syndrome. Avoid nephrotoxic medications such as NSAIDsAt high risk for renal deterioration due to decreased renal perfusion associated with cirrhosis and hypovolemia from GI hemorrhageGinès et al[129]
Exclude acute portal vein thrombosis in patients who suddenly develop severe esophageal varices by abdominal imaging studies (e.g., Doppler ultrasound or CT angiography)Portal vein thrombosis in a patient with preexistent cirrhosis may exacerbate the portal hypertension and cause acute variceal bleedingD’Amico et al[25]
Table 7 Local endoscopic therapies
Injection therapies
Dilute epinephrine
Ablation therapies
Contact methods
Thermocoagulation: heater probe
Electrocoagulation: BICAP (bipolar electrocoagulation probe), Gold Probe
Noncontact methods
APC (argon plasma coagulation)
Mechanical therapy
Endoscopic suturing
Table 8 Classification of endoscopic stigmata of recent hemorrhage for acute upper gastrointestinal bleeding from peptic ulcer disease
Endoscopic SRHEndoscopic appearanceEndoscopic therapyEndoscopic therapy and rationale for therapy
Major SRH
Active bleedingActive bleeding observed at EGDYesReduction from 90% to 15% risk of ongoing bleeding with performance of endoscopic therapy
Nonbleeding visible vesselPigmented elevation (projection) from ulcer base, whether red, blue or gray in colorYesReduction from about 50% to 15% risk of rebleeding with performance of endoscopic therapy
Intermediate SRH
Adherent clotFocal clot that is resistant to removal by mild-to-moderate irrigationRecommended by most endoscopists
Active oozing of bloodActive oozing observed at EGDGenerally recommendedMay reduce risk of rebleeding from 28% to 15% with endoscopic therapy
Minor SRH
Flat pigmented spotPigmented spot, whether red, blue or gray, which lies flat on the ulcer baseNoLow risk of rebleeding of about 13% with medical therapy alone
Homogeneous, clean-based ulcerSimple ulcer with no bleeding, no adherent clot, no visible vessel and no pigmented spotNoExtremely low risk of rebleeding of about 4% that does not warrant the risks of endoscopic therapy
Table 9 Efficacy of endoscopic therapy for gastrointestinal bleeding from Dieulafoy's lesion in cirrhotics
Endoscopic procedure(Number of patients)HemostatictechniqueLesion locationStudy typeFollow-upPatient outcomeRef.
EGD (12)1Epinephrine + PolidocanolStomach/duodenumRetrospective5 moNo rebleeding, 3 of cirrhotic pts died from hepatic decompensation within 5 moBaettig et al[92]
EGD (6)Not reportedStomach/duodenumRetrospectiveNA (6 yr period reviewed)No rebleeding in 5 of 6 pts (83%), 1 pt (17%) underwent surgery for rebleedingAkhras et al[91]
EGD (5)Histoacryl (3)StomachRetrospective18 moNo rebleedingCheng et al[159]
Epinephrine + heater probe (2)
EGD (4)HemoclipStomach/duodenumProspective54 mo9% of whole cohort of 34 pts rebled. No data whether any of the cirrhotics rebledYamaguchi et al[160]
EGD (2)Rubber band ligationStomachRetrospective30 dNo rebleeding, 1 of 2 pts died from hepatic decompensation within 30 dMumtaz et al[157]
EGD (1)Argon plasma coagulationStomachRetrospective29 moNo rebleedingIacopini et al[158]
Table 10 Efficacy of endoscopic therapy for gastrointestinal bleeding from Mallory-Weiss syndrome in cirrhotics
Number of patientsHemostasisTechniquen (%) with active alcohol abuseTime of EGDStudy typeFollow-upOutcomeRef.
55Aetoxysklerol injection40 (73)Within 6 hRetrospective2 yrNo rebleeding or deathPaquet et al[26]
141Epinephrine injection/elec-trocoagulation6 (43)Within 24 hRetrospective5 yrNo rebleeding or death2Schuman et al[27]
7Band ligation 4Not reportedWithin 12 hRetrospective5 dNo rebleeding or deathLecleire et al[165]
Hemoclips and epinephrine 3
3Heater probe/Bicap electrocoagulation3 (100)“Urgently” after presentationRetrospective17 moFailed to control bleeding in 1/3 pts (33%)Jensen et al[28]
1Hemoclip and Endoscopic band ligation1 (100)“Emergent-ly” at presentationRetrospectiveNAFailed to stop bleeding with both techniques; patient underwent surgery and died of liver failure 3 d after surgeryYin et al[104]