Portal Hypertensive Gastropathy and Colopathy

Abstract

Portal hypertension, which results from cirrhosis leads to a number of complications, including portal hypertensive gastropathy (PHG) and colopathy (PHC). While common, the pathogenesis of PHG and PHC is not completely understood. Both PHG and PHC have the potential to cause chronic or acute gastrointestinal bleeding. The diagnosis of these entities is made endoscopically, and therefore there is great variability in their assessment. In fact, this is one of the most challenging issues in the field. PHG is typically described as a mosaic-like pattern resembling ‘snake-skin’ mucosa. There are various grading systems that attribute severity to the endoscopic lesion, ranging from different grades to various descriptions of the disease. The most severe form of the disease includes lesions that are discrete red spots, often with bleeding. PHC has been less well described, and is typically characterized by erythema of the colonic mucosa, vascular lesions including cherry red spots, telangiectasias or angiodysplasia-like lesions. Since the endoscopic description of PHG and PHC are so variable a wide prevalence of the lesions have been reported in the literature. Treatment of PHG and PHC is difficult, and range from pharmacological therapies targeted at reduction of portal pressure and mucosal blood flow to endoscopic treatment. In general, results have been inconsistent and therapy is generally difficult. TIPS and shunt surgery have been used as rescue treatments, but again, results have been variable. Secondary prophylaxis of PHG bleeding has typically been with non-selective beta-blockers . Currently, there is not enough evidence to support the use of beta-blockers for primary prevention of for either PHG or PHC bleeding. Further investigation in this field is needed to elucidate the pathogenesis, natural history, and treatment of PHG and PHC.

Introduction and Definition

Portal hypertensive gastropathy (PHG) and colopathy (PHC) are commonly found in patients with sinusoidal portal hypertension. However, PHG and PHC may also occur in patients with pre and post-sinusoidal diseases such as portal vein thrombosis, schistosomiasis, veno-occlusive disease, cardiac failure – all of which may also cause increased portal pressure.

The cause of PHG and PHC is poorly understood; however, it is presumed that portal hypertension in these patients likely causes hemodynamic and mucosal changes in the entire gastrointestinal tract. The mucosal changes associated with PHG and PHC include inflammatory changes and a primary histo-pathological lesion characterized by vascular ectasia (Table 1). PHG and PHC are defined endoscopically, and indeed, these entities are closely tied to their endoscopic appearance - as a mosaic-like pattern called snake skin mucosa with or without red spots¹. It should also be noted that the term portal hypertensive enteropathy is used to describe changes in the small bowel that are similar to those in the stomach^{2, 3} . PHC is perhaps less well characterized than PHG, and can be reflected by erythema of the colonic mucosa, vascular lesions including cherry red spots, telangiectasias or angiodysplasia-like lesions.

Table 1.

Key features of portal hypertensive gastropathy and portal hypertensive colopathy

Features	Portal Hypertensive Gastropathy	Portal Hypertensive Colopathy
Pathology	Dilated capillaries and venules	Edema and capillary dilatation,
	No inflammation	lymphocytes and plasma cells
Endoscopic Characteristics	Classic mosaic pattern	Vascular ectasias
	and red spots	nonspecific mucosal changes
Differential Diagnosis	GAVE	Idiopathic vascular ectasia,
	Inflammatory gastritis	nonspecific inflammation
	nonspecific inflammation
Treatment	Iron replacement therapy	(*) Iron replacement therapy
	Transfusions	Transfusions
	Portal pressure reducing pharmacologic agents	Portal pressure reducing pharmacologic agents
		APC, sclerotherapy, ligation
Salvage Treatment	TIPS/Shunt surgery	TIPS/Shunt surgery
	APC	Surgery
	Liver transplantation	Liver transplantation

^(*)There is insufficient data for standard recommendations in PHC bleeding

Current practice is largely based on case and case series reports.

Adapted from Urrunaga, N. H. Rockey, D. C.. Portal hypertensive gastropathy and colopathy. Clin Liver Dis. 2014.

PHG and PHC most often lead to chronic gastrointestinal bleeding. However, they may also present with acute gastrointestinal bleeding, and in one study, PHG accounted for some 10% of all causes of upper gastrointestinal bleeding⁴. Both disorders are very often confused with other diseases that can present similarly, in particular with other types of inflammatory mucosal disorders causing similar appearing lesions (i.e. irritant or inflammatory gastritis or colitis). A high index of suspicion is required in order to make a timely and accurate diagnosis and to institute specific treatment.

Pathogenesis of PHG and PHC

Although the pathogenesis of PHG is poorly understood, a unifying theme is that the presence of some degree of portal hypertension appears to be essential. It should be noted that though proposed, a direct correlation between the degree of portal hypertension and the severity of PHG has not been well documented^{5, 6}. Perhaps the best evidence that portal hypertension is required as part of the pathogenesis are studies that demonstrate improvement of PHG after shunt surgery or TIPS^{7, 8}.

It has been suggested that the pathogenesis of PHG and PHC requires some form of local injury to the mucosa. This is supported by histologic findings typical in PHG such as dilatation of capillaries and venules in the mucosa and submucosa without significant inflammation⁹ (Table 1). There also appear to be abnormalities in the mucosal microcirculation in PHG^10–12. Two specific factors that have gained considerable attention include 1) hypoxia and 2) inflammation, which may or may not be interrelated. Hypoxia appears to be related to the dysregulation of the mucosal microcirculation (particularly in PHG)¹⁰. This abnormality in turn may lead to epithelial cell injury and set up a milieu in which there is overproduction of oxygen free radicals, nitric oxide, TNF-α, endothelin-1, prostaglandins, and/or other factors that cause cell injury^{10, 13–17}. TNF-α, an inflammatory cytokine, appears to be prominent. Further, because of these changes and injury to the epithelium, it has been proposed that the abnormal mucosa in PHG and PHC is unable to repair normally and thus may be predisposed to bleeding¹⁸. However, the precise mechanism of bleeding remains unclear.

The pathogenesis of PHC is likely similar to that of PHG in that portal hypertension appears to be essential¹⁹. Evaluation of colonic mucosa has demonstrated that vessels are dilated (including both small and large vessels with an increased mean cross-sectional vascular area, and thickness of the capillary wall (i.e. in cirrhotic patients compared to those without cirrhosis or PHC and/or rectal varices)²⁰. Dilated and congested capillaries as well as capillaries with irregular thickening of the wall are typical²¹. Colonic mucosal edema and capillary dilation and evidence of inflammation (manifest by lymphocytes and plasma cells in the lamina propia) is typical, and may resemble chronic colitis.

It has also been proposed for both PHG and PHC that dysregulation of nitric oxide synthase may be involved²², leading to local changes in mucosal blow flow. It has been proposed that excess nitric oxide generated by increased expression of inducible nitric oxide synthase leads to vascular and hemodynamic changes seen in portal hypertensive mucosal lesions.

PHG

Epidemiology

The prevalence of PHG in patients with cirrhosis varies greatly - from 20 to 98%^{6, 23–27}. The cause of this variation is likely multifactorial, and is a result of (1) variation in endoscopic descriptions, (2) reports in different populations of patients, and (3) the lack of uniform diagnostic criteria and classification. Although it has been proposed that PHG is more prevalent in patients with advanced liver disease^{5, 25, 26, 28}, available data suggest that it remains “mild” in most patients²⁶. Although it has also been speculated that that the prevalence of PHG may increase during esophageal variceal obliteration²⁴, weak data support this possibility.

Clinical Findings

PHG typically presents in patients with symptoms related to chronic GI bleeding and chronic blood loss, often manifest as iron deficiency anemia. Data characterizing the frequency of chronic bleeding from PHG are old, prevalence has been reported in from 3 to 60% of patients^{23, 29, 30}. The definition of chronic bleeding varies, but is most often taken to be a decrease of hemoglobin of 2g/dL within a 6 month time period without evidence of overt bleeding and NSAID use³¹.

Acute gastrointestinal hemorrhage occurs less commonly than chronic bleeding. The prevalence of acute gastrointestinal bleeding from PHG in patients with cirrhosis has been reported between 2% and 12%^{4, 25, 32}. In a recent study of patients with cirrhosis and acute upper GI bleeding, approximately 10% of patients had PHG⁴, consistent with the idea that PHG can lead to acute bleeding, but it is not as common as other forms of bleeding. The diagnosis of acute hemorrhage from PHG is made when active hemorrhage from PHG lesions is visualized, or in the setting of endoscopic PHG without another likely source of bleeding. It should be emphasized that caution is urged prior to assigning bleeding to PHG in patients with trivial lesions (see also below).

Differential Diagnosis

The diagnosis of PHG is typically made at the time of endoscopy, in the appropriate clinical setting. Endoscopic features of PHG include a typical “snakeskin mosaic” pattern, flat or bulging red marks or red spots resembling vascular ectasias found in the stomach (Figure 1). The most common location for PHG is the fundus and body of the stomach (i.e., proximal)^{33, 34}.

Figure 1. Endoscopic images of PHG.

For comparison, normal gastric mucosa is seen in image A, while mild PHG is visualized in B, and C. Severe PHG is seen in image D, including evidence of bleeding. From Urrunaga, N. H. Rockey, D. C.. Portal hypertensive gastropathy and colopathy. Clin Liver Dis. 2014.

The differential diagnosis of PHG includes several entities, which the endoscopist must be cognizant of. Perhaps the major distinction is with gastric antral vascular ectasia (GAVE) or watermelon stomach. GAVE also presents with flat red spots, but typically without the mosaic pattern³⁵ and GAVE often (but not always) appears endoscopically as streaks of erythema, appearing to emanate from the pylorus – appearing like a watermelon rind – thus the name watermelon stomach. Importantly, GAVE is usually located in the distal stomach (antrum). Thus, the location of the lesions (PHG – proximal stomach, GAVE - distal stomach) may help distinguish the disorders. However, there is overlap in the location of the lesions, and red spots can coalesce throughout the entire stomach (proximal and distal) leading to diffuse gastric vascular ectasia. When the endoscopic diagnosis is in question, biopsy and histologic assessment of the mucosa should be considered (biopsy in the absence of severe coagulopathy is generally considered to be safe). The histological findings of GAVE are usually distinct from PHG and include vascular ectasia, spindle cell proliferation and fibrin thrombi and fibrohyalinosis³⁶.

Although the distinction between GAVE and PHG may be difficult in some situations, it is important because the treatment is typically different. It should also be noted that acute bleeding in cirrhotic patients from GAVE is much less common than bleeding from PHG⁴. GAVE is also identified in patients with a diverse array of other diseases including chronic renal failure, bone marrow transplantation, autoimmune and connective tissue diseases including scleroderma, atrophic gastritis, pernicious anemia, sclerodactyly^{35, 37}. The major treatment issue (see also below) is that, despite scattered reports, GAVE does not appear to be caused by portal hypertension and thus does not respond to treatments aimed at portal hypertension^{7, 38}. The primary mode of treatment for GAVE lesions is with endoscopic ablative methods (most often thermal) and not beta-blockers or TIPS.

It should also be mentioned that that the diagnosis of PHG may be made with capsule endoscopy (CE); in one study, it was shown to have a sensitivity of 74% and specificity of 83% when compared to EGD³⁹ Another study of 119 patients showed that the sensitivity of CE for detection of PHG was 69% and the specificity was 99%⁴⁰. However, the diagnostic yield in the gastric body was significantly greater than in the fundus (100% vs. 48%, respectively). These data suggest that the role of CE is likely more important in the assessment of small bowel enteropathy than PHG⁴¹.

Non-endoscopic modalities with which to make a diagnosis of PHG include magnetic resonance and computed tomography^{42, 43}. With CT scan, PHG can be identified via enhancement of the inner layer of the gastric walls - which may reflect gastric congestion. In a study of 32 patients, 10 had PHG and 22 did not⁴². Magnetic resonance has been used in patients with portal hypertension to examine collateral veins, including the left gastric, paraesophageal and azygos veins⁴³. However, in 57 patients the mean diameters of these veins were not different in patients with and without PHG, suggesting that this technique is not ready for clinical use.

PHG is typically classified based how severe the lesion appears at the time of endoscopy. Most experts and societies are now recommending a two-category classification system to describe the severity of the lesion - “mild” and “severe”^{44, 45}. A 3-category system has also been proposed^{1, 46}, though this is problematic because it introduces substantial variation in grading. PHG should be classified as mild when the only change consists of a snakeskin mosaic pattern, and should be classified as severe when there is active bleeding and/or flat or bulging red or black-brown spots. The two-category classification system has significantly better reproducibility^{47, 48}. It is intuitively expected that patients with more advanced appearing PHG lesions have a greater chance of acute or chronic bleeding than those with less severe lesions^{25, 49}.

Treatment

Treatment of PHG is difficult, primarily because there is such a wide variety of presentation of the disorder. In most situations, treatment recommendations are targeted according to specific features of the patient’s presentation, and moreover will vary based on the severity of symptoms (especially bleeding) (Figure 2).

Figure 2. PHG management.

Recommended approaches to therapy are shown. PHC is managed similarly. Adapted from Urrunaga, N. H. Rockey, D. C.. Portal hypertensive gastropathy and colopathy. Clin Liver Dis. 2014.

Primary Prophylaxis

Since it is extremely common to identify PHG during endoscopic screening for esophageal varices in patients with cirrhosis or during endoscopy for other reasons. Further, often times, the patient is entirely asymptomatic without any evidence of chronic (or acute) bleeding. Thus, the question of primary prophylaxis to prevent gastrointestinal bleeding in patients with PHG has been raised^{29, 50}. However, this topic has not been assessed rigorously enough to make evidence-based recommendations. In patients with trivial PHG, there is no evidence to support the use of primary prophylaxis with nonselective beta-blockers. In patients with varices nonselective beta-blockers should be used (even if varices are small, since there is evidence that nonselective beta-blockers may delay the progression of small to large varices⁵¹. In patients with severe PHG and no varices, prophylaxis with nonselective β-blocker should be considered. However, this recommendation is largely empiric.

Chronic bleeding

Patients with PHG may present with iron deficiency anemia (IDA), the latter, consistent with chronic blood loss. First, it is important to emphasize that other causes of IDA be excluded⁵². Although fecal blood levels can be measured⁵³, the diagnosis of PHG in patients with cirrhosis and IDA should be considered a diagnosis of exclusion. Iron replacement therapy should be started in all patients with IDA due to PHG; oral preparations are preferred, but IV iron may be used.

In patients with severe chronic bleeding due to PHG, non-selective beta-blockers may be effective. One study demonstrated a reduction in gastric mucosal perfusion in patients with PHG, suggesting a putative mechanism of action⁵⁴. A double blind placebo controlled cross-over trial that included 22 patients with non-bleeding PHG who received either propanol (160mg/day of long acting propanol) or placebo for 6 weeks⁵⁵ showed that PHG improved in 9 patients after propranolol compared to only 3 after placebo. Another randomized control trial (RCT) of 54 patients with cirrhosis and acute and/or chronic bleeding from severe PHG revealed that bleeding was less in the propranolol group at 12 months compared to control (38% vs. 65%) and at 30 months (7% vs. 52%)²⁹. In 77 patients with esophageal varices who were randomized to band ligation alone (40 patients) or combined with propranolol (37 patients), it was found that PHG developed less frequently in patients who received propranolol than in patients who received only banding⁵⁶. Therefore, in patients with severe PHG, iron supplementation and propranolol (the latter, up to 160mg PO BID or to the maximum tolerated dose with goal HR of 50–55 bpm) should be started.

Acute bleeding

In patients with acute bleeding, it is important first to make a clear diagnosis of PHG, by excluding other causes of bleeding. In patients with upper gastrointestinal bleeding, the differential diagnosis includes bleeding varices (which account for approximately two-thirds of the lesions in these patients)⁴ as well as other causes of bleeding such as ulcerative processes, and even malignancy. Management of acute bleeding includes the typical measures such as volume resuscitation and aggressive and early generalized support. Blood transfusion should be performed with goal to maintain hemoglobin level between 7 and 8g/dL and antibiotics and a proton pump inhibitor are recommended. The routine use of nasogastric lavage is not currently recommended in patients with any form of upper GI bleeding – whether in cirrhosis or note⁵⁷. In the U.S., octreotide should be used empirically in patients with known cirrhosis, though it’s effectiveness in patients with PHG is unclear (see below).

Treatment of acute bleeding for PHG is typically pharmacologic and focused on reduction of portal pressure . In a study of 68 patients comparing octreotide, vasopressin and omeprazole, octreotide controlled bleeding in 100% of patients. Of note, omeprazole and vasopressin alone controlled bleeding in 64 and 59% of patients, respectively⁵⁸. In another study of 26 cirrhotic patients, somatostatin led to cessation of acute bleeding from PHG in, with a rate of relapse of 11.5%⁵⁹. A double blind randomized multicenter study of terlipressin in 68 patients with bleeding esophageal varices and PHG revealed that more patients receiving a higher dose (1mg/4h) stopped bleeding and had less recurrence than patients receiving control; however, methodologic problems limited differentiation of PHG from varices⁶⁰. Vasopressin may reduce gastric mucosal perfusion in patients with PHG⁶¹, but is not generally used in cirrhotic patients any longer because of the concern about vascular related side effects. The use of beta blockers has been evaluated small numbers of patients with acute PHG bleeding. For example, in one small study of 14 patients with acute PHG bleeding who were treated with propranolol, bleeding was controlled within 3 days in 13 of 14 patients (93%)⁵⁵. While these data are intriguing, it is not clear whether non-selective beta-blockers would be expected to have acute effects - thus parenteral vasoactive drugs are preferable acutely.

Endoscopic treatment for acute bleeding secondary to PHG is reserved for situations in which a single or a limited number of lesions are identified, in which case, APC or coagulation therapy may be considered depending on the lesions identified.

Refractory bleeding

Refractory bleeding despite iron and nonselective beta-blocker therapy (i.e., refractory IDA, transfusion dependent, or acute on chronic bleeding⁶² due to PHG is problematic. Additionally, in patients with acute gastrointestinal bleeding secondary to PHG, medical treatment failure should be considered when there is recurrent hematemesis (after 2 or more hours of treatment with vasoactive medications), or a 3g drop in hemoglobin in the absence of transfusion/an inadequate hemoglobin raise after transfusion³¹. In these clinical scenarios, rescue therapies such as transjugular intrahepatic portosystemic shunt (TIPS) may be considered³¹. Surgical shunts may be considered in patients with well-preserved liver function or in those with non-cirrhotic portal hypertension since they have shown to improve gastric mucosal lesions and decreased the number of transfusions^{63, 64}. TIPS is attractive in severe PHG bleeding because it has been shown to improve the endoscopic appearance of lesions within 6 to 12 weeks, and led to reduced transfusion requirements^{7, 8, 65, 66}.

Argon plasma coagulation (APC) is attractive as a potential therapy for PHG because of its ease of application. However, it is difficult, and not practical in those with a large area of stomach involved. Nonetheless, APC was shown, in a group of 11 patients with bleeding from PHG, to lead to a reduction in transfusion requirements in 81% of patients (it should be noted that these were highly selected patients and APC of at least 80% of the involved mucosal surface at 30 to 40 W and 1.5 to 2 L/min of AP flow every 2 to 4 weeks was utilized)⁶⁷. More recently, a hemostatic powder formulation has been found to provide at least temporizing control of bleeding⁶⁸.

Of course, liver transplantation reduces portal pressure and is effective for treatment of refractory PHG. However, transplantation is most appropriate for patients with decompensated liver disease⁶⁹.

Secondary Prevention

Secondary prophylaxis of bleeding in PHG should be undertaken with a nonselective beta-blocker^{29, 31}, although again, data supporting the effectiveness of this approach is limited.

PHC

Epidemiology

PHC mimics PHG in a number of ways, but also has some differences. While both disorders are a result of portal hypertension, PHC appears to be more heterogenous and has been variably associated with vascular ectasias, anorectal or colonic varices, hemorrhoids and even nonspecific inflammatory changes^{20, 21, 70, 71}. Although PHC is likely common in patients with portal hypertension, bleeding from PHC appears to be uncommon.

The prevalence of PHC in patients with cirrhosis is highly variable, ranging from 3% to 71%^{20, 71–73}. The variation in prevalence is undoubtedly related to exactly which mucosal lesions are considered to be consistent with PHC, as well as selection bias in published studies. For example, in a relatively recent study in which the prevalence of PHC was reported to be 71%, a variety of lesions were considered to be consistent with PHC – including “red spots”⁷¹. Additionally, only patients with a previous history of esophageal varices were included, likely increasing the likelihood of portal hypertension and its associated abnormalities. The presence of rectal or colonic varices also varies widely, being reported in from 4% to 40% of patients^{72, 74, 75}. Bleeding from PHC is uncommon, reported to be between 0% and 9%^{72, 75–77}. The reason for the wide variation in reported bleeding rates is similar to that for prevalence estimates, and is due any of the following: variation in patient selection, lack of a clear classification system as to what constitutes PHC, as well as interobserver variability among endoscopists as to endoscopy findings consistent with PHC.

Some studies have reported that PHC is associated with certain clinical features – such as reduced platelet counts⁷⁸, more advanced end-stage liver disease^{19, 78}, gastric varices⁷², higher portal pressure^{19, 79}. However, other studies have failed to find that PHC is associated with the severity of liver disease⁷⁵, portal pressure^{76, 80}, or gastroesophageal varices^{71, 75, 77}. Currently, similar to PHG, there simply is not enough robust data from studies of patients with PHC from which to draw clear conclusions.

Clinical Findings

In general, PHC may present in a fashion similar to PHG – that is with evidence of chronic blood loss (i.e. IDA), or with acute bleeding, in the colon, manifest as hematochezia or bright red blood per rectum (BRBPR)⁷⁰.

Differential Diagnosis

As with PHG, the diagnosis of PHC is made by endoscopy. Patients with cirrhosis and hematochezia may bleed from any number of typical lower GI sources⁸¹. Thus, diagnostic evaluation of the colonic mucosa should generally be performed expeditiously in patients with hematochezia/BRBPR. In patients with aggressive hematochezia and/or significant alterations in vital signs, an upper gastrointestinal source should always be considered⁴.

Typical PHC lesions have been described as slightly raised reddish lesions < 10mm in diameter on an otherwise normal appearing mucosa²⁰. However, considerable variation exists.

Rectal varices in patients with portal hypertension bear mention as these can be confused with PHC. Typical portal hypertensive varices are prominent in the submucosa and are proximal to the pectinate line. These veins were different from normal rectal veins because of their greater diameter and tortuosity (measuring at least 3 to 6mm in diameter). Additionally, colonic varices should be differentiated from hemorrhoids, especially before surgical excision, and angiography may be considered⁸².

The endoscopic appearance of PHC can be sometimes difficult to differentiate from angiodysplasia of the colon secondary to degenerative changes. Other non-inflammatory and inflammatory etiologies of bleeding such as ischemia, radiation changes, and hereditary hemorrhagic telangiectasia are also in the differential diagnosis. Biopsy may or may not be helpful in differentiation of PHC from these other lesions²¹.

Classification

Currently, there is no ideal classification system for grading the severity of mucosal abnormalities in patients with PHC. Several classifications have been proposed. Initially, a histological criteria for the vascular lesions typical of PHC included two types of lesions²⁰ including a so-called “early lesion”, which was characterized by a moderately dilated, tortuous, thin-walled and endothelial-lined vein and venule appearance in the submucosa. In contrast, a so called “late-stage lesion” had progressively more dilated submucosal veins and dilated and tortuous venules and capillaries in the mucosa. Another endoscopic grading system of typical vascular ectasias, or diffuse red spots included Type 1, 2 or 3 lesions as follows: Type 1: a flat, fern-like vascular lesion (spider-like lesion). Type 2: flat or slightly elevated red lesion <10mm in diameter or a cherry red lesion, and Type 3, a slightly elevated submucosal tumor-like lesion with a central red color and depression. A further study proposed a 3 grade classification system as follows: Grade 1: characterized by erythema of the colonic mucosa. Grade 2, erythema of the colonic mucosa with a mosaic-like pattern. Grade 3, vascular lesions in the colon including cherry red spots, telangiectasias or angiodysplasia-like lesions⁸³. In aggregate, classification of the severity of lesions in PHC is difficult and thus it is this author’s practice to simply carefully describe the visualized lesions.

Treatment

Little data exist about the treatment of PHC. Thus, treatment is largely guided by local expertise and experience. As with PHG, for patients with chronic bleeding and IDA, treatment should be supportive and include iron therapy, either oral or parenteral.

In an animal study of rats using a PHC model, each propranolol and octreotide improved typical PHC changes in colonic mucosa (including mucosal edema, hyperemia and hemorrhage), though the effects of octreotide were found to be more prominent than with propanolol⁸⁴. In patients with lower gastrointestinal bleeding secondary to PHC, treatment with long acting octreotide, or beta blockers has been reported to be effective^{1, 83, 85}. The risk of bleeding from PHC in patients with portal hypertension who are taking beta-blockers may also be reduced⁸³. Given the known effects of non-selective beta blockers on portal pressure, it is reasonable to institute beta blocker therapy as tolerated to achieve a resting heart rate of 50 to 55 bpm is reasonable.

In patients with acute bleeding, pharmacologic therapies should be attempted (octreotide/terlipressin), though evidence of their effectiveness is limited. Octreotide has been reported to be effective in isolated patients with severe bleeding from PHC⁸⁶. Non-selective beta blockers should be started as soon as is possible. Depending on the severity of the bleeding and the number of vascular lesions present, local therapies such as APC may be effective. Other local therapies with sclerosis or band ligation, or even coil embolization may be attempted^{70, 87}. Cryotherapy⁸⁸ or even hemostatic powder⁶⁸ may be effective. Again, such treatments largely depend on local experience and expertise.

As for PHG, in patients with refractory bleeding that does not respond to vasoactive medications or beta blockers, TIPS may be used as a rescue therapy for PHC – although data are limited largely to case reports^{70, 89, 90}. Other reports suggest that the use of TIPS may effectively control bleeding due to portal hypertensive anorectal and/or colonic varices⁹¹. It should be noted that prior to performing TIPS in this setting, it is critical to ensure that bleeding is portal hypertensive in etiology.

Prophylaxis

There are no data with which to guide recommendations about secondary prophylaxis of bleeding due to PHC. In patients with an indication for non-selective beta-blockers, these should be used. If local measures (banding, sclerotherapy, APC, etc… are used), ongoing surveillance is indicated.

Summary

PHG and PHC typically cause chronic gastrointestinal bleeding. When they cause acute gastrointestinal bleeding, careful attention to differential diagnosis is essential. The pathogenesis of PHG and PHC is incompletely understood, but appears to be closely tied to portal hypertension and local changes in vascular blood flow in intestinal mucosa. Diagnosis for both of these disorders is endoscopic and it is important to recognize that the differential diagnosis may be difficult. Management of PHG and PHC depends on individual patient factors; for acute bleeding, hemodynamic stabilization with IV fluids, IV antibiotics, and blood transfusion as needed are indicated. Pharmacologic therapy to decrease portal pressure followed by nonselective beta blockers as soon as the patient is hemodynamically stable are appropriate. In patients with chronic bleeding, therapy with beta blockers and iron replacement is recommended. Patients with refractory bleeding from either PHG or PHC represent difficult clinical challenges and are best managed on an individual basis. TIPS or shunt procedures may be appropriate in some situations. Liver transplantation reduces portal hypertension in cirrhotic patients and is highly effective at reducing portal pressure.

Key Points.

• Portal hypertensive gastropathy and portal hypertensive colopathy are common in patients with cirrhosis and portal hypertension.

• The diagnosis of each of portal hypertensive gastropathy and portal hypertensive colopathy is endoscopic, and grading systems to categorize severity are suboptimal. For portal hypertensive gastropathy, the best system appears to be simply “mild” and “severe”.

• Treatment of acute bleeding due to portal hypertensive gastropathy and portal hypertensive colopathy is initially pharmacologic to lower portal pressure; however, a number of salvage therapies are currently available and typically are informed by local expertise.

• When needed, chronic therapy is typically with nonselective beta-blockers. Again, specific endoscopic therapies and more aggressive lowering of portal pressure with TIPS may be effective in some patients.

Abbreviations

PHG

portal hypertensive gastropathy

PHC

portal hypertensive colopathy

EGD

esophagogastroduodenoscopy

CE

capsule endoscopy

GAVE

gastric antral vascular ectasia

IDA

iron deficiency anemia

BRBPR

bright red blood per rectum