Systematic Reviews
Copyright ©The Author(s) 2016.
World J Hepatol. Feb 8, 2016; 8(4): 231-262
Published online Feb 8, 2016. doi: 10.4254/wjh.v8.i4.231
Table 1 Rates of portal hypertensive gastropathy in patients with portal hypertension
Ref.Analyzed patientsTotal numberNo. (%) with PHGNo. (%) with mild PHGNo. (%) with severe PHG
McCormack et al[3]Portal hypertension12765 (51%)37 (29%)28 (22%)
Sarin et al[5]Portal hypertension13610 (7%)
DeWeert et al[6]Non-alcoholic liver disease8123 (28%)Not reportedNot reported
McCormick et al[7]Portal hypertension93 endoscopies in 74 patients85 endoscopies (91%)6 (6%), moderate 61 (66%)18 (19%)
Sarin et al[8]Portal hypertension1074 (3.7%) (only cirrhotic)Not reportedNot reported
Parikh et al[9]Portal hypertension11871 (60%)41 (58%)30 (42%)
Sarin et al[10]Portal hypertension with prior variceal bleeding96786 (9%)56 (5.8%)30 (3.1%)
Itha et al[11]EHPVO in children163(12%)Not reportedNot reported
Rana et al[12]Portal hypertension4127 (66%)19 (46%)8 (20%)
El-Rifai et al[13]Portal hypertension2414 (58%)10 (42%) - moderate4 (16%)
Sogaard et al[14]Portal vein thrombosis6728 (42%)Not reportedNot reported
Figueiredo et al[15]Portal hypertension; cirrhosis3627 (75%)5 (46%)
Erden et al[16]Portal hypertension5715 (26.3%)Not reportedNot reported
Duché et al[17]Children, portal hypertension with biliary atresia12527 (21%)Not reportedNot reported
Aydoğan et al[18]Portal hypertension5130 (58%)Not reportedNot reported
dos Santos et al[19]Portal hypertension4322 (51%)Not reportedNot reported
Pantham et al[20]Esophageal varices undergoing TEE2412 (50%)Not reportedNot reported
Abdollahi et al[21]Autoimmune hepatitis6027 (45%)Not reportedNot reported
de Alcantara et al[22]Chronic liver disease vs EHPVO35 vs 187 (20%) vs 8 (44.4%)Not reportedNot reported
Aoyama et al[23]Portal hypertension11935 (29%)Not reportedNot reported
Table 2 Rates of portal hypertensive gastropathy in patients with cirrhosis
Ref.PatientsTotal numberPHGMildSevere
Sacchetti et al[24]Cirrhosis14238 (27%)28 (20%)10 (7%)
D'Amico et al[25]Cirrhosis212130 (61%)110 (52%)20 (9%)
Calès et al[26]Cirrhosis10098 (98%)57 (57%)41 (41%)
Rabinovitz et al[27]Cirrhosis510(43%)Not reportedNot reported
Iwao et al[28]Cirrhosis4732 (68%)15 (32%)17 (36%)
Taranto et al[29]Cirrhosis394317 (80.5%)Not reportedNot reported
Gupta et al[30]Cirrhosis230(61%)(52%)(9%)
Iwao et al[31]Cirrhosis476254 (53%)208 (43%)46 (9%)
Carpinelli et al[32]Cirrhosis566362 (64%)192 (34%)170 (30%)
Zaman et al[33]Cirrhosis12074 (62%)47 (39%)27 (23%)
Primignani et al[34]Cirrhosis373299 (80%)127 (34%)172 (46%)
Chaves et al[35]Cirrhosis vs schistosomiasis4318 (81%) vs 7 (33%)Not reportedNot reported
Merkel et al[36]Cirrhosis6249 (79%)29 (46%)20 (32%)
Merli et al[37]Cirrhosis, with mild portal hypertension22248 (21%)43 (19%)5 (2%)
Ito et al[38]Cirrhosis4713 (27%)10 (21%)3 (6%)
De Palma et al[39]Cirrhosis3723 (62%)Not reportedNot reported
Menchén et al[40]Cirrhosis549353 (64%)275 (50%)77 (14%)
Yüksel et al[41]Cirrhosis114 total76 (66%)38 (33%)38 (33%)
Fontana et al[42]Cirrhosis or bridging fibrosis from hepatitis C1016374 (37%)345 (34%)29 (3%)
Bresci et al[43]Cirrhosis8536 (42%)Not reportedNot reported
Akatsu et al[44]End stage liver disease2919 (65.5%)18 (62.1%)1 (3.4%)
Zardi et al[45]Cirrhosis26684 (31%)Not reportedNot reported
Barakat et al[46]Cirrhosis with portal hypertensive duodenopathy105105 (100%)17 (16.2%)88 (83.8%)
Bellis et al[47]Cirrhosis5944 (76%)16 (27%)28 (47%)
Gravante et al[48]Liver transplant candidates with cirrhosis8041 (51.2%)Not reportedNot reported
Canlas et al[49]Cirrhosis1913 (68.4%)Not reportedNot reported
Kim et al[50]Cirrhosis8348 (57.8%)Not reportedNot reported
Higaki et al[51]Cirrhosis218 (38%)Not reportedNot reported
Frenette et al[52]Cirrhosis5045 (90%)28 (56%)17 (34%) moderate
Tarantino et al[53]Cirrhosis15388 (57.5%)Not reportedNot reported
Curvêlo et al[54]Cirrhosis4643 (93.4%)21 (45%)22 (47%)
Anegawa et al[55]Cirrhosis7049 (70%)32 (46%)17 (24%)
Kumar et al[56]Cirrhosis254140 (55%)Not reportedNot reported
Kim et al[57]Cirrhosis331298 (90%)Mild 84 (25.4%)214 (64.7%)
De Lisi et al[58]Cirrhosis611448 (73.3%)37.3%36%
Abbasi et al[59]Cirrhosis10287 (85%)Not reportedNot reported
Ahmed et al[60]Cirrhosis from hepatitis B or hepatitis C360300 (83%)229 (64%)71 (20%)
Garcia-Saenz-de-Sicilia et al[61]Cirrhosis10572 (68.6%)Not reportedNot reported
Abbasi et al[62]Cirrhosis217172 (79.3%)56 (25.8%)116 (53.5%)
Aoyama et al[63]Cirrhosis6013 (22%)Not reportedNot reported
Laleman et al[64]Cirrhosis with refractory chronic hepatic encephalopathy3613 (36%)9 (25%)4 (11%)
Giannini et al[65]Cirrhosis and undergoing surgery for hepatocellular carcinoma15223 (15.1%)Not reportedNot reported
Abdollahi et al[21]Autoimmune hepatitis6027 (45%)Not reportedNot reported
Aoyama et al[23]Portal hypertension11935 (29%)Not reportedNot reported
Aoyama et al[66]Cirrhosis13442 (31%)Not reportedNot reported
Zardi et al[67]Cirrhosis without gastroesophageal varices14575 (51%)45 (31%)30 (20%)
Wu et al[68]Cirrhosis700449 (64%)Mild 208 (29.7), moderate 160 (22.9%)Severe 81 (11.6%)
Table 3 Effects of variceal ligation on frequency of portal hypertensive gastropathy
Ref.No. of patients and etiologyStudy typePHG rate before variceal ligationPHG aggravation after variceal ligationP value of pre vs post EVL
Hou et al[73]90 patients with cirrhosis and recent variceal bleeding, 46 patients underwent EVLRandomized, controlled trialNo PHG-4, mild PHG-33, severe-PHG-9At eradication: 17/37; 17/37 (45.9%) in EVL; at 3 mo: 17/30 (56.7%); at 6 mo 18/29 (62.1%)P > 0.05
Elnaser et al[80]125 patients with upper GI bleeding undergoing variceal ligation, followed for mean of 31 moRetrospective study22/125 (17.6%)50/125 (50%)P < 0.05
Yüksel et al[41]114 patients with cirrhosis and portal hypertension undergoing EVL in 85 patientsRetrospective study27/85 (31.8%) none; 28/85 (32.9%) mild; 30/85 (35.3%) severe14/85 (16.5%) none; 30/85 (35.3%) mild; 41/85 (48.2%) severeP < 0.05
Lo et al[81]77 patients with bleeding from EV underwent variceal ligation and were randomized to receive propranolol (37/77) or control (40/77); patients with severe PHG prior to treatment excluded from the studyProspective, randomized, controlled trialControl group: 7/40 (17%); propranolol group: 8/37 (22%)At variceal ligation: Control group: 67% (does not state number); Propranolol group: 31% (number not stated); 6 mo after treatment: Control group: 85% (number not stated) propranolol group: 48% (number not stated)Pre vs post ligation, both groups; P < 0.05; frequency of PHG significantly higher in control group post ligation when compared to propranolol group; P = 0.002
de la Peña et al[82]93 patients with history of variceal hemorrhage and cirrhosis, randomized to receive either EVS (46/88) or EVL (42/88); 5 patients excluded due to diagnosis of hepatoma, non-cirrhotic portal hypertension or portal vein thrombosisRandomized, prospective studyNot reportedPHG significantly worsened in 23 patients, including 17 patients undergoing EVLP < 0.01
Table 4 Effects of variceal sclerotherapy on frequency of portal hypertensive gastropathy
Ref.No. of patients and etiologyStudy typePHG before procedurePHG aggravation after procedureP value
Hou et al[73]90 cirrhotic patients with recent variceal bleeding; EVS 44, EVL 46Randomized, controlled trialPre EVS group: 6 none/24 mild/14 severe; pre EVL group: 4 none/33 mild/9 severe; total: 10 none/57 mild/23 severeAt eradication: 14/29 (48.3%) in EVS; 17/37 (45.9%) in EVL; at 3 mo: 15/26 (57.7%) in EVS; 17/30 (56.7%) in EVL; at 6 mo 15/25 (60%) in EVS; 18/29 (62.1%) in EVLNon-significant difference in PHG aggravation between EVS and EVL; P > 0.05
Itha et al[11]163 children with extrahepatic portal vein obstruction presenting with variceal bleeding underwent endoscopic injection sclerotherapyNot reported12% overall PHG (actual number not stated), 1 patient with severe PHG41% overall PHG (actual number not stated), 12 patients with severe PHGP < 0.001 for overall PHG; P < 0.001 for severe PHG
Poddar et al[83]186 children with extrahepatic portal vein obstruction presenting with variceal bleeding undergoing endoscopic sclerotherapy, and mean follow up of 38 ± 30 moRetrospective studyPHG: 46/186 (24.7%), severe PHG: 6/186 (3.2%)PHG: 96/186 (51.6%), severe PHG: 29/186 (15.6%)P < 0.001 for overall PHG; P < 0.05 for severe PHG
Yüksel et al[41]114 patients with cirrhosis and portal hypertension undergoing EVS (29/114) or EVL (85/114)Retrospective studyPre EVS group: 11/29 (37.9%) none; 10/29 (24.5%) mild; 8/29 (27.6%) severe; pre EVL group: 27/85 (31.8%) none; 28/85 (32.9%) mild; 30/85 (35.3%) severePost EVS group: 4/29 (13.8%) none; 8/29 (27.6%) mild; 17/29 (58.6%) severe; post EVL group: 14/85 (16.5%) none; 30/85 (35.3%) mild; 41/85 (48.2%) severePre EVS vs post EVS; P < 0.05; pre EVL vs post EVL; P < 0.05; pre EVS vs pre EVL; P > 0.05; post EVS vs post EVL; P > 0.05
Sarin et al[10]967 patients with variceal bleeding underwent endoscopic sclerotherapy; out of whom 88 patients fulfilled the inclusion criteria (including presence of endoscopic lesions consistent with PHG or GAVE, before or within 4 wk after obliteration) were prospectively followed (out of whom 2 had only GAVE)Prospective study22 patients had PHG prior to EVS; 2/22 transient (9%); 17/22 persistent (77%); 3/22 progressive (14%)Additional development in 64 patients post procedure, 28/64 transient (44%), 31/64 persistent (48%), 5/64 progressive (8%)Only statistically significant difference was the transient PHG that disappeared in 28 (44%) of patients in the group that developed PHG post procedure; P < 0.05
Gupta et al[30]230 patients with liver cirrhosis; of which 44 underwent variceal eradication with sclerotherapyProspective study24/44 (54%)33/44 (75%)P < 0.05
Sarin et al[8]107 patients with portal hypertension presenting with variceal bleeding that underwent sclerotherapy with mean follow-up of 23.2 ± 3.4 moProspective study4/107 (3.7%)21 additional patients, 25/107 (23%)Does not state if this was statistically significant
de la Peña et al[82]93 patients with history of variceal hemorrhage and cirrhosis, randomized to receive either EVS (46/88) or EVL (42/88); 5 patients were excluded due to diagnosis of hematoma, non-cirrhotic portal hypertension or portal vein thrombosisProspective studyNot reportedPHG worsened in 23 patients total; statistically significantly more in EVL group than EVS group (17 vs 6 patients respectively)P < 0.01
D'Amico et al[25]212 cirrhotic patients of which 75 had an episode of variceal bleeding and were treated with sclerotherapy; 137 without bleeding were not treated with sclerotherapyProspective studyNo EVS group at admission: 104/137 (75%) none; 28/137 (20%) mild; 5/137 (4%) severe; EVS group at admission: 50/75 (66%) none; 17/75 (22%) mild; 8/75 (11%) severeNo EVS group at end of study 69/137 (50%) none; 61/137 (45%) mild; 7/137 (5%) severe; EVS group at end of study: 13/75 (17%) none; 49/75 (65%) mild; 13/75 (17%) severeThe conclusion was that sclerotherapy is a significant indicator of the risk of PHG in a multivariate analysis (P = 0.00032)
Table 5 Well-established, important risk factors for portal hypertensive gastropathy
Portal hypertension
Non-cirrhotic portal hypertension[8,14]
Cirrhotic portal hypertension[8,9,34]
Longer duration of cirrhosis[34,71]
Greater severity of cirrhosis[55,67]
Greater size of esophageal varices[34,62]
Eradication of esophageal varices
Endoscopic therapies
Endoscopic variceal ligation[11,41]
Endoscopic sclerotherapy[11,83]
Percutaneous transhepatic variceal embolization[85]
Table 6 Therapies affecting the severity or the risk of bleeding from portal hypertensive gastropathy
Therapies reducing severity of PHGRef.
Transcatheter splenic arterial embolization[99]
Surgical shunt
Portocaval shunt[100]
Central splenorenal shunt[101]
Laparoscopic splenectomy (in patients with hypersplenism)[55]
Liver transplantation[44]
Therapies reducing risk of bleeding from PHG
Surgical shunt (portocaval or splenorenal)[100,101]
Nonselective b β-adrenergic receptor antagonists (e.g., propranolol)[103 (in rats),104]
Somatostatin family of drugs
Vasopressin family of drugs
Therapies that increase incidence or risk of bleeding from PHG
Endoscopic therapies for varices
Variceal ligation[11,41]
Variceal sclerotherapy[11,83]
Interventional angiography
Percutaneous transhepatic variceal embolization[85]
Table 7 Factors not affecting risk of portal hypertensive gastropathy
Factors not affecting risk of portal hypertensive gastropathyRef.
Etiology of cirrhosis[8,28,30]
Etiology of non-cirrhotic portal hypertension[8,14,35,83,108]
NSAID use[42]
Use of COX-2 inhibitors[42]
Smoking tobacco[42]
Gastric infection with Helicobacter pylori[109,110]
Table 8 Different classification systems for portal hypertensive gastropathy
McCormack et al[3]Fine pink speckling (scarlatina type rash)Discrete red spots (analogous to cherry
Superficial reddening, especially on rugal surface (striped appearance)red spots in esophagus)
Fine white reticular pattern separating areas of raised edematous mucosa (snake skin)Diffuse hemorrhagic gastritis
McCormick et al[7]Mosaic or snake skin appearancePresence of erythemaPresence of erosions or hemorrhagic gastritis
Tanoue et al[180]Mild reddening, congestive mucosa, no mosaic - like patternSevere redness and a fine reticular pattern separating the areas of raised edematous mucosa (mosaic-like pattern) or a fine specklingGrade III (severe)
Point bleeding + grade II (moderate)
Spina et al[70] (NIEC)Mosaic-pattern: Presence of small,Red point lesions (1 mm in diameter, flat)
polygonal areas surrounded by aCherry-red spots (2 mm, slight protrusion)
whitish-yellow depressed borderBlack-brown spots (irregularly shaped, persistently present after washing)
Sarin et al[8]Discrete cherry red spots, with or without mosaic patternPresence of confluent red spots, diffusely distributed in a large portion of the stomach
Sarin et al[181] (Baveno II Consensus Workshop)[181]Mild ≤ 3 points1Severe ≥ 4 points1
Gastric antral ectasia
Absent (0)
Present (2)
Yoo et al[182]Fine pink speckling (scarlatina type rash)Discrete red spots
2-category classificationSuperficial reddeningDiffuse hemorrhagic lesion
Mosaic pattern
Yoo et al[182]Mild reddeningFlat red spot in center of a pink areolaDiffusely red areola
3-category classificationCongestive mucosaSevere redness and a fine reticular patternPinpoint bleeding
Diffuse pink areolaDiscrete or confluent red mark lesion
Table 9 Differences between portal hypertensive gastropathy and gastric antral vascular ectasia
ParameterPortal hypertensive gastropathyGastric antral vascular ectasiaRef.
Associated conditionsConditions associated with portal hypertension: cirrhotic or non-cirrhotic portal hypertensionCirrhosis, autoimmune disorders, and connective tissue diseases (scleroderma, pernicious anemia, hypothyroidism)[72]
Association with portal hypertensionStrong associationOnly 30% of cases[191,192]
SexMildly more common in males (alcoholic cirrhosis more common in males than females)Much more common in females (80%)[193,194]
AgeCan occur at any age in patients with portal hypertension or cirrhosisTypically elderly (average age > 70 years old)
LocationProximal stomach: Fundus, bodyDistal stomach: Antrum[72,192]
DiagnosisEndoscopy (endoscopic biopsy sometimes useful). Radiologic imaging usually not helpfulEndoscopy (endoscopic biopsy sometimes useful)[72,195]
Appearance at endoscopyMosaic/snakeskin mucosa with red or brown spotsTortuous columns of ectatic vessels in "watermelon" or diffuse pattern; erythematous or hemorrhagic[191]
HistologyEctatic capillaries, mildly dilated mucosal and submucosal veins; no vascular inflammation, no vascular thrombiMarked dilation of capillaries and venules in gastric mucosa and submucosa with areas of intimal thickening, fibrin thrombi, fibromuscular hyperplasia and spindle cell proliferation[72,191,196,197]
Clinical presentation/ complicationsGastrointestinal bleeding: Usually chronic, but sometimes acuteAlmost exclusively chronic gastrointestinal bleeding with guaiac positive stools[37,193]
Primary prophylaxisNot indicatedNot indicated (unless associated with large varices)[198]
Medical therapyNon-selective β-adrenergic receptor antagonists (propranolol), octreotide (for acute bleeding)No benefit of β-adrenergic receptor antagonists[103,106,198-201]
Oral contraceptive pills to temporarily control bleeding
Questionable benefit of octreotide
Endoscopic therapyOccasionally helpful (for focal bleeding)Very helpful at reducing risk of bleeding: Argon plasma coagulation; EBL; Radiofrequency ablation; YAG laser therapy[202-207]
Argon plasma coagulation
Local hemostasis with hemospray
TIPSSignificantly reduces severity and risk of bleeding by reducing portal hypertension. Option for very severe bleeding from PHG or for moderate PHG in patients with variceal bleedingNot recommended. Does not affect severity of GAVE or risk of bleeding[75,77]
Liver transplantationResolves. Ultimate therapy mostly reserved for patients with end-stage liver diseaseImproves or resolves with liver transplantation[75,200,208-210]
Other surgeryUsually resolves with shunt surgery that lowers portal pressure. Partial gastrectomy not recommendedLimited surgical resection (partial gastrectomy) recommended for refractory cases. Shunt surgery not recommended[75,200,211-213]
Prognosis from bleedingBleeding rarely severe and very rarely fatalBleeding occasionally severe[34,71,72]
Table 10 Differences in gastrointestinal bleeding from portal hypertensive gastropathy vs esophageal varices
ParameterPortal hypertensive gastropathyEsophageal varices
EtiologyPortal hypertension: Cirrhotic or non-cirrhoticPortal hypertension: Cirrhotic or non-cirrhotic
ConcurrenceFrequently occur simultaneously with esophageal varices because the two diseases share common risk factorsFrequently occurs simultaneously with PHG because the two diseases have common risk factors
LocationStomach: Predominantly fundus and bodyDistal esophagus: Also can have gastric varices or ectopic varices in other gastrointestinal regions, particularly duodenum
Endoscopic appearanceErythematous small polygonal areas of mucosa surrounded by a fine, whitish, reticular or mosaic/snakeskin mucosa with red or brown spotsSerpiginous mucosal greyish luminal projections in distal esophagus
Clinical presentationMild acute or chronic bleedingAcute gastrointestinal bleeding-typically massive
Severity of bleedingTypically mild and not life-threateningTypically severe and life-threatening
HistologyNot biopsied at endoscopy
Endoscopic therapyLimited roleVariceal ligation recommended as initial therapy. Sclerotherapy an alternative therapy
Medical therapyOctreotideOctreotide
Vasopressin or vasopressin analogues-infrequently recommended any moreVasopressin or vasopressin analogues-infrequently recommended any more
Blakemore tubeNot recommendedSometimes used for refractory bleeding especially as a temporizing measure before performing more definitive therapy
Angiographic therapyTIPS used as a last resortTIPS recommended if endoscopic therapy fails
Transfusion of packed erythrocytesTransfuse only to hematocrit of about 28. Over-transfusion may increase portal pressure and induce greater bleedingTransfuse only to hematocrit of about 28. Over-transfusion may increase portal pressure and induce greater bleeding
Liver transplantationImproves or resolves with liver transplantationImproves or resolves with liver transplantation
PrognosisRarely fatalFrequently fatal
Table 11 Rates of gastrointestinal bleeding from portal hypertensive gastropathy
Ref.Year publishedPopulationBleeding from PHGTransfusions required
McCormack et al[3]1985127 patients with portal hypertension of various etiologies29 patients out of 65 with PHG, representing 25% of the total number of bleeds from all sources; 9 episodes presenting with bleeding; 71 episodes of subsequent bleeding2-15 units required for 60 bleeds
D'Amico et al[25]1990212 patients with cirrhosis; 75 being treated with sclerotherapy
Sarin et al[8]1992107 patients with portal hypertension presenting with variceal bleeding, undergoing sclerotherapyNo bleeding before sclerotherapy from PHG (4/107 had PHG); 2/13 post-sclerotherapy patients who developed PHGAverage of 4 units per patient with range of 2-8 units
Pérez-Ayuso et al[103]199154 cirrhotic patients with PHG, in a RCT to look for rebleeding; propranolol 26 vs control 28First hemorrhage: Acute/chronic bleeding in propranolol group 12/14; in control 12/16, rebleeding: Acute/chronic; in propranolol 6/6; in control 10/12
Gostout et al[217]1993Patients admitted for GI bleeding (1496)12 patients (0.8%), representing 8% of nonvariceal bleeding in patients with liver disease
Primignani et al[34]2000373 patients with cirrhosis; PHG in 299 patients (80.1%)8 PHG patients with acute bleeding; chronic bleeding in 34 patients
Merli et al[37]2004222 cirrhotic patients with portal hypertension; 48 patients with PHG on enrollmentDuring follow up for 47 ± 28 (SD) mo, acute bleeding 9, chronic bleeding 7 from PHG
Kimura et al[218]2014297 patients with living donor liver transplantation; retrospective analysis2 patients bled from PHG within 3 mo after transplantation
Table 12 Treatment of acute or chronic gastrointestinal bleeding from portal hypertensive gastropathy
Acute bleeding
Patient stabilization
Treat severe coagulopathy with highly elevated INR associated with cirrhosis with fresh frozen plasma
Treat severe thrombocytopenia associated with hypersplenism and bone marrow suppression from alcoholism with platelet transfusions
Transfuse packed erythrocytes to main hemoglobin level at about 8 g/dL
Consider antibiotic prophylaxis in patient with cirrhosis
Endoscopic therapy from bleeding-rarely used
Consider argon plasma coagulation
Hemospray - an experimental therapy
Octreotide - first line therapy
Vasopressin or terlipressin - second line therapy
Proton pump inhibitor therapy - adjunct therapy
Propranolol - can be instituted after bleeding controlled and patient stabilized
Interventional therapy
TIPS - for uncontrolled hemorrhage or for bleeding from PHG associated with variceal bleeding
Liver transplantation - for advanced end stage liver disease
Chronic bleeding
Treatment of anemia
Transfusions of packed erythrocytes as necessary
Iron replacement therapy
Consider propranolol