Artiin Jurnal UGB

8/6/2019 Artiin Jurnal UGB

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Major causes of upper gastrointestinal bleeding in adults

Authors :Rome Jutabha, MD, Dennis M Jensen, MD

Section Editor : Mark Feldman, MD Deputy Editor, Anne C Travis, MD, MSc, FACG

Last literature review version 18.2: May 2010 | This topic last updated: August 17,

2009 (More)

INTRODUCTION

Upper gastrointestinal (UGI) bleeding is a common medical condition that results in

high patient morbidity and medical care costs. In a study from one large health

maintenance organization, the annual incidence of hospitalization for acute UGI bleeding

was 102 per 100,000; the incidence was twice as common in males as in females, and

increased with age [1].

UGI bleeding commonly presents with hematemesis (vomiting of blood or coffee-

ground like material) and/or melena (black, tarry stools) (table 1). A nasogastric tube

lavage which yields blood or coffee-ground like material confirms this clinical diagnosis.

However, lavage may not be positive if bleeding has ceased or arises beyond a closed

pylorus. The presence of bilious fluid suggests that the pylorus is open and, if lavage is

negative, that there is no active upper GI bleeding distal to the pylorus. In comparison,

hematochezia (bright red or maroon colored blood or fresh clots per rectum) is usually a

sign of a lower GI source (defined as distal to the ligament of Treitz). Although helpful,

the distinctions based upon stool color are not absolute since melena can be seen with

proximal lower GI bleeding, and hematochezia can be seen with massive upper GI bleeding

[2-4]. (See "Approach to the adult patient with lower gastrointestinal bleeding".)

This topic review will summarize issues related to bleeding from peptic ulcers and

esophageal varices. Other causes of bleeding are presented on their corresponding topic

reviews. An overall approach to the patient with an upper GI bleed, the treatment of


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bleeding peptic ulcers, and the less common causes of UGI bleeding are discussed

separately. (See "Approach to upper gastrointestinal bleeding in adults" and "Treatment of

bleeding peptic ulcers" and "Uncommon causes of upper gastrointestinal bleeding".)

CATEGORIES

UGI bleeding can be classified into several broad categories based upon anatomic

and pathophysiologic factors (table 1). Several endoscopic studies have described the most

common causes [5-7]. Results have varied, possibly reflecting trends over time or

differences in study design, populations, and definitions:

A prospective series of 1000 cases of severe UGI bleeding at the UCLA and West Los

Angeles Veterans Administration Medical Centers published in 1996 found the following

distribution of causes [5]:

Peptic ulcer disease 55 percent

Esophagogastric varices 14 percent

Arteriovenous malformations 6 percent

Mallory-Weiss tears 5 percent

Tumors and erosions 4 percent each

Dieulafoy's lesion 1 percent

Other 11 percent

More recent data suggest that the proportion of cases caused by peptic ulcer diseasehas declined [6,8]. Peptic ulcers were responsible for only 21 percent of episodes of upper

gastrointestinal bleeding among 7822 patients included in a national, United States

database between 1999 and 2001 [6]. The most common cause was nonspecific mucosal

abnormalities (42 percent), while esophageal inflammation accounted for about 15 percent,


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and varices about 12 percent. Other causes (arteriovenous malformations, Mallory-Weiss

tears, and tumors) each accounted for less than 5 percent of cases. Among ulcer cases,

gastric ulcers were more common than duodenal ulcers representing about 55 percent of

all ulcers.

A large database study focused on 243,428 upper endoscopies performed between 2000

and 2004 in a practice setting (rather than in tertiary care) [7]. The most common

endoscopic findings in patients with upper gastrointestinal bleeding were an ulcer (33

percent) followed by an erosion (19 percent). Gastric ulcers were more common than

duodenal ulcers (55 versus 37 percent). Patients with variceal bleeding were excluded

from the analysis.

PEPTIC ULCER DISEASE

Gastroduodenal ulcer disease remains a common cause of UGI bleeding (picture

1) [5]. There are four major risk factors for bleeding peptic ulcers [9,10]:

Helicobacter pylori infection

Nonsteroidal antiinflammatory drugs (NSAIDs)

Stress

Gastric acid

Reduction or elimination of these risk factors reduces ulcer recurrence and rebleeding

rates [11-14].

Helicobacter pylori Helicobacter pylori is a spiral bacterium that infects thesuperficial gastric mucosa and appears to be transmitted by the fecal-oral route. The

bacterium generally does not invade gastroduodenal tissue. Instead, it renders the

underlying mucosa more vulnerable to acid peptic damage by disrupting the mucous layer,

liberating enzymes and toxins, and adhering to the gastric epithelium. In addition, the host


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immune response to H. pylori incites an inflammatory reaction which further perpetuates

tissue injury. (See "Pathophysiology of and immune response to Helicobacter pylori

infection".)

The chronic inflammation induced by H. pylori upsets gastric secretory physiology

to varying degrees and leads to chronic gastritis which, in most individuals, is

asymptomatic and does not progress. In some cases, however, altered gastric secretion

coupled with tissue injury leads to peptic ulcer disease, while in other cases, gastritis

progresses to atrophy, intestinal metaplasia, and eventually to gastric carcinoma or rarely,

due to persistent immune stimulation of gastric lymphoid tissue, gastric lymphoma [15-18].

(See "Association between Helicobacter pylori infection and gastrointestinal malignancy".)

H. pylori eradication should be attempted for all patients who are diagnosed with

the infection and who have peptic ulcer disease to prevent ulcer recurrence and rebleeding

[19,20]. In one report of 19 published studies, for example, the recurrence rates in cured

versus noncured H. pylori infection was 6 versus 67 percent for duodenal ulcer, and 4

versus 59 percent for gastric ulcer [20]. Various multidrug regimens, which usually

combine one or two antibiotics plus an antisecretory agent, have eradication rates in the

range of 80 to 90 percent [21]. (See "Treatment regimens for Helicobacter pylori".)

Nonsteroidal antiinflammatory drugs NSAIDs, including aspirin, are a common

cause of gastrointestinal ulceration [22-25]. NSAID-induced injury results from both local

effects and systemic prostaglandin inhibition. The majority of these ulcers are

asymptomatic and uncomplicated. However, elderly patients with a prior history of

bleeding ulcer disease are at increased risk for recurrent ulcer and complications [26-28].

NSAIDs also have been implicated as an important factor for non-healing ulcers [29]. (See

"NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity".)

Stress Stress related ulcers are a common cause of acute UGI bleeding in

patients who are hospitalized for life-threatening non-bleeding illnesses [30]. Patients


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with these secondary episodes of bleeding have a higher mortality than those admitted to

the hospital with primary UGI bleeding [31]. The risk of stress ulcer-related bleeding is

increased in patients with respiratory failure and those with a coagulopathy [32]. Primary

ulcer prophylaxis with antisecretory agents such as H2 receptor antagonists or protonpump inhibitors decreases the risk of stress related mucosal damage and UGI bleeding in

high-risk patients [33-35]. (See "Stress ulcer prophylaxis in the intensive care unit".)

Gastric acid Gastric acid and pepsin are essential cofactors in the pathogenesis

of peptic ulcers [36]. Impairment of mucosal integrity by factors such as H. pylori,

NSAIDs, or physiologic stress leads to increased cell membrane permeability to back

diffusion of hydrogen ions, resulting in intramural acidosis, cell death, and ulceration [36].

Rarely, hyperacidity is the sole cause of peptic ulceration, as in patients with the

Zollinger-Ellison syndrome. (See "Clinical manifestations and diagnosis of Zollinger-Ellison

syndrome (gastrinoma)".) Control of gastric acidity is considered an essential therapeutic

maneuver in patients with active UGI bleeding. (See "Approach to upper gastrointestinal

bleeding in adults".)

Treatment A variety of endoscopic methods have been described to control

active bleeding from peptic ulcers. The most commonly used are injection and

cautery/thermal techniques. (See "Treatment of bleeding peptic ulcers".)

ESOPHAGOGASTRIC VARICES

The prospective series of 1000 patients at the UCLA and West Los Angeles

Veterans Administration Medical Centers found that esophagogastric varices were the

second most common cause of UGI bleeding, accounting for 14 percent of episodes

(picture 2A-B) [5]. Esophagogastric varices develop as a consequence of systemic or

segmental portal hypertension. The most common causes of systemic portal hypertension in


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the United States are alcoholic liver disease and chronic active hepatitis. (See "Prediction

of variceal hemorrhage in patients with cirrhosis".)

Isolated gastric varices can result from segmental portal hypertension due to

obstruction of the splenic vein from pancreatic carcinoma or chronic pancreatitis (picture

3). In addition, secondary gastric varices may develop after obliteration of esophageal

varices with endoscopic therapies. The risk factors for bleeding from gastric varices are

similar to the risk factors for bleeding from esophageal varices [37]. (See "Prediction of

variceal hemorrhage in patients with cirrhosis".)

Diagnosis Endoscopy is the diagnostic modality of choice for esophagogastric varices

[5]. If endoscopy is inconclusive and gastric variceal bleeding is suspected, one of the

following tests should be considered to confirm the clinical suspicion:

Endoscopic ultrasound may be useful for differentiating gastric varices from gastric

folds.

Portal vein angiography or an abdominal CT scan may show venous collaterals andrecanalization of the umbilical vein (picture 4).

Barium X-rays may image large esophageal varices or large gastric folds suggestive of

gastric varices (picture 5).

Capsule endoscopy of the esophagus (PillCam ESO) may represent a minimally invasive

alternative to endoscopy for the detection of esophageal varices and portal hypertensive

gastropathy. (See "Wireless video capsule endoscopy".)

Prognosis Variceal bleeding stops spontaneously in over 50 percent of patients, but the

mortality rate approaches 70 to 80 percent in those with continued bleeding. Each episode

of variceal hemorrhage is associated with a 30 percent risk of mortality [38]. The risk of

rebleeding is high (60 to 70 percent) until gastroesophageal varices are obliterated.


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The risk of rebleeding can be substantially reduced by follow-up endoscopic therapy to

obliterate residual varices. However, long-term survival depends upon the severity of liver

disease and may not be improved following successful variceal obliteration. The

administration of a nonselective beta blocker such as propranolol can also decrease therisk of rebleeding. (See "Prevention of recurrent variceal hemorrhage in patients with

cirrhosis".)

The onset of massive UGI bleeding from gastroesophageal varices usually signifies

advanced liver disease (Child class B or C). Liver transplantation is the only treatment that

significantly improves the long-term prognosis in these patients.

Treatment Primary prophylaxis against variceal hemorrhage is desirable in view

of the relatively high rate of bleeding from esophageal varices and the high mortality

associated with this complication. Prophylactic propranolol or nadolol therapy is the only

cost-effective therapy in this setting [39]. Endoscopic variceal ligation also may be

beneficial for high-risk patients [40,41]. In contrast, prophylactic endoscopic

sclerotherapy is not indicated due to the risks and complications of this procedure

[39,42,43]. (See "Primary prophylaxis against variceal hemorrhage in patients with

cirrhosis".)

Various treatments are available for acute hemostasis. Endoscopic band ligation and

sclerotherapy continue to be the most commonly used. (See "General principles of the

management of variceal hemorrhage".)

INFORMATION FOR PATIENTS Educational materials on this topic are

available for patients. (See "Patient information: Upper endoscopy" and "Patient

information: Peptic ulcer disease" and "Patient information: Gastroesophageal reflux

disease in adults".) We encourage you to print or e-mail these topic reviews, or to refer

patients to our public web site, www.uptodate.com/patients, which includes these and

other topics.


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REFERENCES

1. Longstreth, GF. Epidemiology of hospitalization for acute upper gastrointestinalhemorrhage: A population-based study. Am J Gastroenterol 1995; 90:206.

2. Jensen, DM, Machicado, GA. Diagnosis and treatment of severe hematochezia. The

role of urgent colonoscopy after purge. Gastroenterology 1988; 95:1569.

3. Zuckerman, GR, Trellis, DR, Sherman, TM, Clouse, RE. An objective measure of stool

color for differentiating upper from lower gastrointestinal bleeding. Dig Dis Sci 1995;

40:1614.

4. Wilcox, CM, Alexander, LN, Cotsonis, G. A prospective characterization of upper

gastrointestinal hemorrhage presenting with hematochezia. Am J Gastroenterol 1997;

92:231.

5. Jutabha, R, Jensen, DM. Management of severe upper gastrointestinal bleeding in the

patient with liver disease. Med Clin North Am 1996; 80:1035.

6. Boonpongmanee, S, Fleischer, DE, Pezzullo, JC, et al. The frequency of peptic ulcer as

a cause of upper-GI bleeding is exaggerated. Gastrointest Endosc 2004; 59:788.

7. Enestvedt, BK, Gralnek, IM, Mattek, N, et al. An evaluation of endoscopic indications

and findings related to nonvariceal upper-GI hemorrhage in a large multicenter consortium.

Gastrointest Endosc 2008; 67:422.

8. Loperfido, S, Baldo, V, Piovesana, E, et al. Changing trends in acute upper-GI bleeding:a population-based study. Gastrointest Endosc 2009; 70:212.

9. Hunt, RH, Malfertheiner, P, Yeomans, ND, et al. Critical issues in the pathophysiology

and management of peptic ulcer disease. Eur J Gastroenterol Hepatol 1995; 7:685.


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10. Hallas, J, Lauritsen, J, Villadsen, HD, et al. Nonsteroidal anti-inflammatory drugs and

upper gastrointestinal bleeding, identifying high-risk groups by excess risk estimates.

Scand J Gastroenterol 1995; 30:438.

11. Graham, DY, Hepps, KS, Ramirez, FC, et al. Treatment of H. pylori reduced the rate

of rebleeding in peptic ulcer disease. Scand J Gastroenterol 1993; 28:939.

12. Tytgat, GN. Peptic ulcer and Helicobacter pylori: Eradication and relapse. Scand J

Gastroenterol Suppl 1995; 210:70.

13. Rokkas, T, Karameris, A, Mavrogeorgis, A, et al. Eradication of Helicobacter pylori

reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc 1995;

41:1.

14. Bayerdorffer, E, Neubauer, A, Rudolph, B, et al. Regression of primary gastric

lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori

infection. MALT Lymphoma Study Group. Lancet 1995; 345:1591.

15. Nakamura, S, Yao, T, Aoyagi, K, et al. Helicobacter pylori and primary gastric

lymphoma. A histopathologic and immunohistochemical analysis of 237 patients. Cancer1997; 79:3.

16. Parsonnet, J, Hansen, S, Rodriguez, L, et al. Helicobacter pylori infection and gastric

lymphoma. N Engl J Med 1994; 330:1267.

17. Pajares, JM. H. pylori infection: Its role in chronic gastritis, carcinoma and peptic

ulcer. Hepatogastroenterology 1995; 42:827.

18. Shibata, T, Imoto, I, Ohuchi, Y, et al. Helicobacter pylori infection in patients with

gastric carcinoma in biopsy and surgical resection. Cancer 1996; 77:1044.

19. Soll, AH. Medical treatment of peptic ulcer disease. JAMA 1996; 275:622.


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20. Hopkins, RJ, Girardi, LS, Turney, EA. Relationship between H. pylori eradication and

reduced duodenal and gastric ulcer recurrence: A review. Gastroenterology 1996;

110:1244.

21. Walsh, JH, Peterson, WL. The treatment of Helicobacter pylori infection in the

management of peptic ulcer disease. N Engl J Med 1995; 333:984.

22. Scheiman, JM. NSAID-induced peptic ulcer disease: A critical review of

pathogenesis and management. Dig Dis 1994; 12:210.

23. Bretagne, JF, Raoul, JL. Management of nonsteroidal anti-inflammatory drug-induced

upper gastrointestinal bleeding and perforation. Dig Dis 1995; 13 Suppl 1:89.

24. Bjorkman, DJ, Kimmey, MB. Nonsteroidal anti-inflammatory drugs and

gastrointestinal disease: Pathophysiology, treatment and prevention. Dig Dis 1995; 13:119.

25. Lanas, A, Perez-Aisa, MA, Feu, F, et al. A nationwide study of mortality associated

with hospital admission due to severe gastrointestinal events and those associated with

nonsteroidal antiinflammatory drug use. Am J Gastroenterol 2005; 100:1685.

26. Hansen, JM, Hallas, J, Lauritsen, JM, et al. Non-steroidal anti-inflammatory drugs

and ulcer complications: A risk factor analysis for clinical decision-making. Scand J

Gastroenterol 1996; 31:126.

27. Koch, M, Dezi, A, Ferrario, F, Capurso, I. Prevention of nonsteroidal anti-

inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized

controlled clinical trials. Arch Intern Med 1996; 156:2321.

28. Smalley, WE, Ray, WA, Daugherty, JR, et al. Nonsteroidal anti-inflammatory drugs

and the incidence of hospitalizations for peptic ulcer disease in elderly persons. Am J

Epidemiol 1995; 141:539.


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29. Lanas, AI, Remacha, B, Esteva, F, et al. Risk factors associated with refractory

peptic ulcers. Gastroenterology 1995; 109:1124.

30. Navab, F, Steingrub, J. Stress ulcer: is routine prophylaxis necessary?. Am J


31. Zimmerman, J, Meroz, Y, Siguencia, J, et al. Upper gastrointestinal hemorrhage.

Comparison of the causes and prognosis in primary and secondary bleeders. Scand J


32. Cook, DJ, Fuller, HD, Guyatt, GH, et al. Risk factors for gastrointestinal bleeding in

critically ill patients. N Engl J Med 1994; 330:377.

33. Kuusela, AL, Ruuska, T, Karikoski, R, et al. A randomized, controlled study of

prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal

intensive care unit patients. Crit Care Med 1997; 25:346.

34. Cook, DJ, Reeve, BK, Guyatt, GH, et al. Stress ulcer prophylaxis in critically ill

patients. Resolving discordant meta-analyses. JAMA 1996; 275:308.

35. Balaban, DH, Duckworth, CW, Peura, DA. Nasogastric omeprazole: Effects on gastric

pH in critically ill patients. Am J Gastroenterol 1997; 92:79.

36. Peterson, WL. The role of acid in upper gastrointestinal haemorrhage due to ulcer

and stress-related mucosal damage. Aliment Pharmacol Ther 1995; 9(Suppl 1):43.

37. Kim, T, Shijo, H, Kokawa, H, et al. Risk factors for hemorrhage from gastric fundal

varices. Hepatology 1997; 25:307.

38. Smith, JL, Graham, DY. Variceal hemorrhage. A critical evaluation of survival

analysis. Gastroenterology 1982; 82:968.

39. Teran, JC, Imperiale, TF, Mullen, KD, et al. Primary prophylaxis of variceal bleeding

in cirrhosis: A cost-effectiveness analysis. Gastroenterology 1997; 112:473.


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40. Lay, CS, Tsai, YT, Teg, CY, et al. Endoscopic variceal ligation in prophylaxis of first

variceal bleeding in cirrhotic patients with high-risk esophageal varices. Hepatology 1997;

25:1346.

41. Sarin, SK, Lamba, GS, Kumar, M, et al. Comparison of endoscopic ligation and

propranolol for the primary prevention of variceal bleeding. N Engl J Med 1999; 340:988.

42. Prophylactic sclerotherapy for esophageal varices in men with alcoholic liver disease.

A randomized, single-blind, multicenter clinical trial. The Veterans Affairs Cooperative

Variceal Sclerotherapy Group. N Engl J Med 1991; 324:1779.

43. Jutabha R, Jensen DM, Martin P, Savides T, Han SH, Gornbein J. Randomized study

comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with

high-risk esophageal varices. Gastroenterology 2005; 128:870.


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Prediction of variceal hemorrhage in patients with cirrhosis

Author : Arun J Sanyal, MD

Section Editor : Bruce A Runyon, MD Deputy Editor, Anne C Travis, MD, MSc, FACG

Last literature review version 18.2: May 2010 | This topic last updated: April 5,

2010 (More)

INTRODUCTION

Cirrhosis affects 3.6 out of every 1000 adults in North America, and is responsible

for over one million days of work loss and 32,000 deaths annually. A major cause of

cirrhosis-related morbidity and mortality is the development of variceal hemorrhage, a

direct consequence of portal hypertension. Each episode of active variceal hemorrhage is

associated with a 30 percent mortality [1,2]. In addition, survivors of an episode of active

bleeding have a 70 percent risk of recurrent hemorrhage within one year of the bleeding

episode [3].

Variceal hemorrhage occurs in 25 to 40 percent of patients with cirrhosis [4].

While several modalities are available for primary prophylaxis of variceal bleeding, many

are associated with significant adverse effects. (See "Primary prophylaxis against variceal

hemorrhage in patients with cirrhosis".)

Accurate identification of patients at highest risk of bleeding permits

stratification in an attempt to avoid potentially harmful preventive treatments in the 60

to 75 percent of patients who will never have variceal bleeding. The formation and

progression of varices and the predictive factors and risk classification for bleeding will

be reviewed here.


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FORMATION OF VARICES

Portal pressure is determined by the product of portal flow volume and resistance

to outflow from the portal vein. Portal hypertension (defined as hydrostatic pressure >5

mmHg) results initially from obstruction to portal venous outflow. Obstruction may occur

at a presinusoidal (portal vein thrombosis, portal fibrosis, or infiltrative lesions), sinusoidal

(cirrhosis), or postsinusoidal (veno-occlusive disease, Budd Chiari syndrome) level. Cirrhosis

is the most common cause of portal hypertension; in these patients, elevated portal

pressure results from both increased resistance to outflow through distorted hepatic

sinusoids, and enhanced portal inflow due to splanchnic arteriolar vasodilation.

Varices develop in order to decompress the hypertensive portal vein and return

blood to the systemic circulation. They are seen when the pressure gradient between the

portal and hepatic veins rises above 12 mmHg; patients with lower values neither form

varices nor bleed. The portal-hepatic venous pressure gradient is obtained by hepatic

venous catheterization, with measurement of the difference between the wedged hepatic

venous pressure (which approximates the sinusoidal and portal pressures in cirrhosis) and

the free hepatic venous pressure. This procedure is routinely performed in many European

centers but only rarely in the United States. Although it does not predict the size of

varices, it may be useful for monitoring the success of therapy aimed at lowering portal

pressures, such as beta blockers. A systematic review of 12 studies found that a reduction

of the hepatic vein pressure gradient to 12 was associated with a significant reduction in

the risk of variceal bleeding and mortality [5].

An illustrative study evaluated the relation between the hepatic vein pressure

gradient and the formation of and bleeding from varices [6]. The following observations

were noted:

All 72 patients with varices by endoscopy had a gradient above 12 mmHg.


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The mean gradient in 49 patients with bleeding varices was 20.4 mmHg; none of these

patients had a gradient below 12 mmHg.

The gradient did not predict the size of varices, being similar in those with large and

small varices.

PROGRESSION OF VARICES

The rate of development and progression of esophageal varices in patients with

cirrhosis has not been extensively evaluated. One of the largest prospective studies

included 206 cirrhotic patients (113 without varices and 93 with small esophageal varices

at baseline) who were followed prospectively for an average of 37 months [7]. An

endoscopy was performed annually. The following findings were noted.

New varices developed in 5 percent at year one, and 28 percent at year three.

Small varices progressed in size at a rate of 12 percent in year one, and 31 percent at

year three.

Progression was predicted by the Child-Pugh score, the presence of red wale marks on

the first examination, and an alcoholic cause of cirrhosis.

The two-year risk of bleeding was significantly higher in patients with small varices at

enrollment compared with those without varices (12 versus 2 percent).

PREDICTIVE FACTORS

Numerous clinical and physiologic factors are useful in predicting the risk of

variceal hemorrhage in patients with cirrhosis. These include:

Location of varices

Size of varices

Appearance of varices


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Clinical features of the patient

Variceal pressure

Location of varices

The most common sites for development of varices are the distal esophagus,

stomach, and rectum, although theoretically varices may develop at any level of the

gastrointestinal (GI) tract below the esophagus. Varices develop deep within the

submucosa in the mid-esophagus, but become progressively more superficial (nearer the

mucosa) in the distal esophagus. Thus, esophageal varices at the gastroesophageal junction

have the thinnest coat of supporting tissue and are most likely to rupture and bleed.

Varices in the gastric fundus also bleed frequently. Gastric varices are often

classified according to their location, which correlates with their risk of hemorrhage:

Varices in direct continuity with the esophagus along the lesser and greater curves of

the stomach are called gastroesophageal varices (GOV) types 1 and 2 respectively.

Isolated gastric varices in the fundus (IGV1) occur less frequently than GOVs (10 versus

90 percent) [8].

The relationship between the site of the varices and clinical risk was illustrated in a

prospective study of 568 consecutive patients with varices, 393 of whom were bleeding

[8]. The mean transfusion requirement in patients with bleeding gastric varices was higher

than in those with esophageal varices (4.8 versus 2.9 units per patient). Bleeding from

isolated gastric varices in the fundus (IGV1) occurred much more frequently than either

GOVs or isolated gastric varices at other loci in the stomach (IGV2) (figure 1).

Size of varices The risk of variceal bleeding correlates independently with the diameter

(size) of the varix.The explanation for the relationship between variceal size and bleeding

risk is derived from Laplace's law; small increments in the vessel radius result in a large

increase in wall tension (which is the force tending to cause variceal rupture).


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There are several ways in which esophageal variceal size is quantified; none are exact and

all involve subjective evaluation. A commonly employed system of classification includes the

following (picture 1) [9,10]:

F1: Small straight varices

F2: Enlarged tortuous varices that occupy less than one-third of the lumen

F3: Large coil-shaped varices that occupy more than one-third of the lumen

It is important to insufflate the esophagus while estimating variceal size; failure to do so

leads to overestimation.

Appearance of varices

In addition to size, several morphologic features of varices observed at endoscopy

have been correlated with an increased risk of hemorrhage [7,8,11]. Among these features

include a number relating to a red appearance, or "red signs":

Red wale marks are longitudinal red streaks on varices that resemble red corduroy wales

(picture 2).

Cherry red spots are discrete red cherry-colored spots that are flat and overlie varices.

Hematocystic spots are raised discrete red spots overlying varices that resemble "blood

blisters."

Diffuse erythema denotes a diffuse red color of the varix.

Clinical features

Several clinical features of the patient are related to the risk of variceal

hemorrhage [12]:


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The degree of liver dysfunction is an important predictor of variceal hemorrhage. The

Child classification is an index of liver dysfunction based upon serum albumin

concentration, bilirubin level, prothrombin time, and the presence of ascites and

encephalopathy (table 1). A higher score in this classification scheme is associated with ahigher likelihood of variceal bleeding.

History of a previous variceal bleed predicts a high likelihood of a subsequent bleeding

episode. As an example, while only one-third of all patients with cirrhosis experience

variceal hemorrhage, over 70 percent experience further episodes of variceal bleeding

after an index bleed. These bleeding episodes may be considered as "early" or "late" with

respect to their temporal relationship to the index bleed; one-third of patients with an

index bleed will rebleed within six weeks, and one-third will rebleed after six weeks [3].

The risk of early rebleeding is greatest in the first 48 hours after admission and declines

subsequently.

Risk factors for early and late rebleeding are listed in the table (table 2) [10,12,13]. The

risk of early rebleeding is greatest immediately after cessation of active hemorrhage (50

percent of such episodes occur within 48 hours) and subsides over time.

Variceal pressure Variceal pressure may be measured accurately and relatively

noninvasively with a pressure-sensitive endoscopic gauge [14]. The variceal pressure may

be an important predictor for variceal hemorrhage. In one study, for example, 87 patients

with cirrhosis and large esophageal varices who had never had variceal bleeding were

followed for 12 months [15]. Variceal hemorrhage developed in 28 patients (32 percent).

Variables predictive of a first bleed included: the level of variceal pressure; risk

classification using the Child class, variceal size, and endoscopic appearance of varices (see

below); and the interval between diagnosis of varices and the start of the study.

Specifically, the incidence of variceal bleeding with different levels of variceal pressure

was as follows:


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13 mmHg - 0/25 (0 percent)\

>13 and 14 mmHg - 1/11 (9 percent)



>16 mmHg - 18/25 (72 percent)

Adding variceal pressure (categorized as > or 15.2 mmHg) to the risk classification

discussed below significantly improved the predictive value of this classification.

RISK CLASSIFICATION

The Child class, variceal size, and presence of red wale markings can be used to

calculate a prognostic index that numerically quantifies the risk of variceal hemorrhage in

an individual patient (table 3) [9]. The calculated risk is greatest in the first one to two

years from the time of identification of these risk factors. As an example, a patient with

Child class C cirrhosis and tense ascites who has large varices with red signs has an

approximately 76 percent likelihood of developing variceal hemorrhage within one year.

Such a patient is clearly a candidate for prophylactic therapy to prevent bleeding. (See

"Primary prophylaxis against variceal hemorrhage in patients with cirrhosis".)

One study evaluated variables that predicted the presence of high risk varices (ie

medium to large varices) in 1000 patients with HCV who had advanced fibrosis but

compensated liver function [16]. Such varices were vanishingly rare in those with a plateletcount over 150,000 (negative predictive value of 99 percent). Whether these data can be

generalized to other forms of liver disease is unclear.


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INFORMATION FOR PATIENTS

Educational materials on this topic are available for patients. (See "Patient

information: Screening for esophageal varices".) We encourage you to print or e-mail this

topic, or to refer patients to our public web site www.uptodate.com/patients, which

includes this and other topics.

SUMMARY

Variceal hemorrhage occurs in 25 to 40 percent of patients with cirrhosis. Accurate

identification of patients at highest risk of bleeding permits targeted use of preventive

measures.

Numerous clinical and physiologic factors are useful in predicting the risk of variceal

hemorrhage in patients with cirrhosis. These include, the location, size and appearance of

varices, their pressure and clinical features of the patient. (See 'Predictive

factors' above.)

These factors can be considered together to help predict the risk of hemorrhage in an

individual patient (table 3). (See 'Risk classification' above.)

REFERENCES

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