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Transcript of 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.
-
8/6/2019 Artiin Jurnal UGB
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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
Gastroenterol 1995; 90:708.
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
Gastroenterol 1994; 29:795.
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)
>14 and 15 mmHg - 2/12 (17 percent)
>15 and 16 mmHg - 7/14 (50 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
1. Smith, JL, Graham, DY. Variceal hemorrhage. A critical evaluation of survival analysis.
Gastroenterology 1982; 82:968.
2. DeDombal, FT, Clarke, JR, Clamp, SE, et al. Prognostic factors in upper GI bleeding.
Endoscopy 1986; 18:6s.
3. Graham, DY, Smith, JL. The course of patients after variceal hemorrhage.
Gastroenterology 1981; 80:800.
4. Grace, ND. Prevention of initial variceal hemorrhage. Gastroenterol Clin North Am
1992; 21:149.
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5. D'Amico, G, Garcia-Pagan, JC, Luca, A, Bosch, J. Hepatic vein pressure gradient
reduction and prevention of variceal bleeding in cirrhosis: a systematic review.
Gastroenterology 2006; 131:1611.
6. Garcia-Tsao, G, Groszman, RJ, Fisher, RL, et al. Portal pressure, presence of
gastroesophageal varices and variceal bleeding. Hepatology 1985; 5:419.
7. Merli, M, Nicolini, G, Angeloni, S, et al. Incidence and natural history of small
esophageal varices in cirrhotic patients. J Hepatol 2003; 38:266.
8. Sarin, SK, Lahoti, D, Saxena, SP, et al. Prevalence, classification and natural history of
gastric varices: A long-term follow-up study in 568 portal hypertension patients.
Hepatology 1992; 16:1343.
9. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and
esophageal varices. A prospective multicenter study. The North Italian Endoscopic Club
for the Study and Treatment of Esophageal Varices. N Engl J Med 1988; 319:983.
10. Beppu, K, Inokuchi, K, Koyanagi, N, et al. Prediction of variceal hemorrhage by
esophageal endoscopy. Gastrointest Endosc 1981; 27:213.
11. Kim, T, Shijo, H, Kokawa, H, et al. Risk factors for hemorrhage from gastric fundal
varices. Hepatology 1997; 25:307.
12. de Franchis, R, Primignani, M. Why do varices bleed? Gastroenterol Clin North Am
1992; 21:85.
13. D'Amico, G, Morabito, A, Pagliaro, L. Six week prognostic indicators in upper
gastrointestinal hemorrhage in cirrhotics. Front Gastrointest Res 1986; 9:247.
14. Bosch, J, Bordas, JM, Rigau, J, et al. Noninvasive measurement of the pressure of
esophageal varices using an endoscopic gauge: Comparison with measurements by variceal
puncture in patients undergoing endoscopic sclerotherapy. Hepatology 1986; 6:667.
-
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22/22
15. Nevens, F, Bustami, R, Scheys, I, et al. Variceal pressure is a factor predicting the
risk of a first variceal bleeding: A prospective cohort study in cirrhotic patients.
Hepatology 1998; 27:15.
16. Sanyal, AJ, Fontana, RJ, Di Bisceglie, AM, et al. The prevalence and risk factors
associated with esophageal varices in subjects with hepatitis C and advanced fibrosis.
Gastrointest Endosc 2006; 64:855.