Upper endoscopy in liver disease

Watch a video presentation of this article

Watch the interview with the author

Answer questions and earn CME

Abbreviations

APC

argon plasma coagulation

EGD

esophagogastroduodenoscopy

EVL

endoscopic variceal ligation

GAVE

gastric antral vascular ectasia

GI

gastrointestinal

PHG

portal hypertensive gastropathy

TIPS

transjugular intrahepatic portosystemic shunt

Esophagogastroduodenoscopy (EGD) is an endoscopic procedure that affords views of the esophagus, stomach, and proximal duodenum. Although EGD has a broad role in general gastrointestinal (GI) complaints, it has several applications specific to patients with chronic liver disease, usually for conditions causing GI bleeding.1 This is important given that bleeding is a significant source of morbidity and mortality in advanced liver disease. Portal hypertension associated with cirrhosis plays a role in the development of gastroesophageal varices, portal hypertensive gastropathy (PHG), and gastric antral vascular ectasia (GAVE). All of these leave patients susceptible to bleeding. The utility of EGD in the diagnosis and management of these conditions will be further discussed in this article. However, it is important to note that patients with chronic liver disease can also develop GI bleeding due to causes unrelated to their cirrhosis, such as peptic ulcer disease.

Procedural Considerations (Table 1)

For elective EGD, patients should be kept nothing per oral for 6 hours prior to the procedure.2 For urgent procedures, a prokinetic agent such as erythromycin 3mg/kg intravenously given over 30 minutes can help empty gastric contents, allowing for better visualization.3 EGD confers a low risk of bacteremia, and the routine use of prophylactic antibiotics is generally not recommended. However, in patients with cirrhosis and evidence of active upper GI bleeding, the use of prophylactic antibiotics targeting gram‐negative organisms has been shown to decease the rate of bacterial infections (e.g., spontaneous bacterial peritonitis) and improve survival.4 Cefotaxime 2 g intravenously every 8 hours or ceftriaxone 2 g daily are recommended options, keeping local resistance patterns in mind, with fluoroquinolones offering an alternative to those with allergy to cephalosporins. In patients with cirrhosis, altered sedative metabolism and increased bleeding risk associated with coagulopathy and thrombocytopenia are procedural concerns. Commonly employed sedatives such as benzodiazepines may result in increased complications in patients with cirrhosis, including respiratory depression, delayed recovery, and overt hepatic encephalopathy. As such, hypnotic agents such as propofol, administered under the guide of an anesthesiologist, should be considered for sedation in cirrhotics.5 Given the increased procedural risk of EGD in patients with liver disease, esophageal capsule endoscopy has been proposed as an alternative screening method for esophageal varices, although more investigation is needed into this topic.6

Gastroesophageal Varices

Gastroesophageal varices, distended veins that arise from blood shunted away from a structurally damaged liver, occur in up to 50% of cirrhotic patients (Fig. 1). Variceal hemorrhage occurs in up to one‐third of patients with cirrhosis, and each episode has substantial mortality. As such, it is recommended that an EGD be performed at the time of cirrhosis diagnosis to screen for varices and to institute prophylactic therapy, if needed. The best predictors of hemorrhage are the size of the varices, severity of underlying liver disease, and the presence of red wale signs (longitudinal dilated venules on the surface of varices).7 Esophageal varices are classified as small (< 5mm) or large (> 5 mm), and the use of prophylactic treatments is in part based on size. Patients with small varices should have surveillance endoscopy repeated within 1 year. Patients with large varices are offered endoscopic and/or medical therapies. For individuals in whom no varices are found, screening should be performed every 2 to 3 years.4 Gastric varices can occur in the presence of esophageal varices or in isolation (Fig. 2). In addition to size and the degree of underlying liver dysfunction, gastric variceal bleeding is also influenced by location, with those located in the fundus possessing a higher risk of hemorrhage.8

Figure 1.

Esophageal varices.

Figure 2.

Gastric varices.

Primary prophylaxis, or prevention of first variceal hemorrhage, can be accomplished by pharmacotherapy (typically nonselective beta‐blockers) or endoscopic therapy. Endoscopic variceal ligation (EVL) involves the placement of rubber bands directly onto the varices, utilizing a cap that fits on the tip of the endoscope (Fig. 4). The rubber band chokes off the blood supply to the varix, which leads to its eventual obliteration. Three to four sessions may be required to obliterate all varices; they typically occur 2 to 4 weeks apart, with 3 to 6 bands applied per session. Bleeding is the main risk conferred by EVL. Sclerotherapy is an alternative therapy that involves the injection of a sclerosing agent such as ethanolamine directly into the varix.7 Like EVL, sclerotherapy eventually obliterates the varices but is associated with more complications such as bleeding, stricture, perforation, mediastinitis, and sepsis.

Figure 4.

Endoscopic bond ligation of esophageal varix.

If variceal hemorrhage occurs, pharmacologic therapy with terlipressin or somatostatin and its analogs (octreotide), in combination with endoscopic therapy, offers the most effective method to control bleeding. Pharmacotherapy is typically continued for 3 to 5 days, and EVL should be repeated every 1 to 2 weeks until obliteration occurs. Once hemodynamically stable, beta‐blocker therapy should also be started for secondary prophylaxis. In the setting of uncontrolled bleeding, or rebleeding despite combination therapy, transjugular intrahepatic portosystemic shunt (TIPS) placement can be considered.8 For gastric varices, EVL is typically not utilized due to ineffectiveness. Injection of tissue adhesives such as cyanoacrylate glue is the preferred treatment modality to control hemorrhage and prevent rebleeding (Fig. 3). TIPS represents an alternative option if these are ineffective or not available.9, 10 For equivocal lesions, endoscopic ultrasound has been employed to distinguish varices from other submucosal lesions and may help with administrating sclerosants and glue.11

Figure 3.

Cyanoacrylate glue injection into gastric varix.

Portal Hypertensive Gastropathy

PHG occurs in 50% of patients with portal hypertension and may reflect the severity of liver disease. It should be suspected in patients with liver disease who present with either acute or chronic anemia. The diagnosis is established by endoscopy, with characteristic appearances ranging from snake‐skin mosaicism (mild PHG) to bulging red and brown spots (severe PHG) (Fig. 7). Prophylaxis against bleeding in asymptomatic PHG is not recommended; however, in the setting of chronic anemia, nonselective beta‐blockers should be initiated.12 Bleeding from PHG has traditionally been thought not to be amenable to endoscopic therapy, but recent investigations demonstrated a reduction in transfusion requirements and less clinically significant upper GI bleeding in patients treated with argon plasma coagulation (APC).13 Medical therapies with beta‐blockers or TIPS are alternative options.

Figure 7.

Portal hypertensive gastropathy.

Gastric Antral Vascular Ectasia

The pathogenesis of GAVE remains poorly understood. GAVE is present in 2% to 3% of patients with cirrhosis and is also associated with other conditions such as connective tissue disease and chronic renal failure.11 Endoscopically, GAVE can have the appearance of “watermelon stomach,” with erythematous stripes projecting radially from the pylorus or as diffuse red spots representing dilated antral blood vessels (Fig. 5).14 GAVE, similar to PHG, most commonly presents as chronic anemia, but unlike PHG, its management is primarily endoscopic.12 APC fulguration is the most effective tool to rapidly treat the large mucosal areas (Fig. 6). Directly applied coagulation techniques such as heater probe or bipolar probe cauterization can be utilized as well, but they are more difficult and take longer to apply to larger areas of involvement. For refractory cases, radiofrequency ablation and band ligation may be considered.

Figure 5.

Gastric antral vascular ecstasia (watermelon stomach).

Figure 6.

APC therapy of GAVE.

Conclusion

EGD remains the modality of choice for the diagnosis and management of bleeding complications associated with chronic liver disease. Given the altered pharmacodynamics and increased bleeding risk in these patients, care must be taken when sedating and performing endoscopic therapy in cirrhotics. The benefit of endoscopic interventions such as EVL, cyanoacrylate glue therapy, and APC fulguration are well established and should be considered for both the prophylaxis and treatment of portal hypertension‐associated bleeding.

Table 1.

Patient Guide: What to Expect During Upper Endoscopy (EGD)?

Why is this test done?	This test allows the doctor to look in your upper digestive tract for active or potential sources of bleeding. Areas of concern will be treated accordingly with various maneuvers (bands, clips, cautery, etc.) to stop current bleeding or prevent future bleeding. Areas of concern (ulcers, growths, etc) may be sampled with biopsy to rule out certain diseases (malignancy, inflammation, infection with certain bacteria, etc.).
How should I prepare for my procedure?	Your stomach should be completely empty. Do not eat or drink after midnight on the night before your procedure. Tell your doctor about you medications prior to scheduling the procedure. Some of these (blood thinners, anticoagulation, etc.) may need to be held for several days prior to the procedure. Tell your doctor or nurse about any allergies to medications. Tell your doctor if you have a pacemaker, defibrillator, or other cardiac devices. You will be asked to wear a hospital gown and remove dentures, contact lenses, or eyeglasses at the time of the procedure.
What do I do during the procedure?	Vital signs will be taken, and an intravenous placed for medication administration. You will be asked to lie on your left side, and a “bite‐blocker” will be used to protect your teeth. After sedation, the scope will be passed through your mouth, down your esophagus, and into the stomach and beginning of your small intestine. The scope will not be placed in your airway, and you will still be able to breathe during the EGD. Treatment of bleeding sites and biopsies may then occur. The procedure typically lasts 20‐30 minutes.
What happens after the procedure?	You will be monitored while anesthesia and sedation will wear off. You may feel drowsy afterward and will need an escort home. Do not operate machinery for 24 hours. This includes driving. You may notice a sore throat and bloating after the procedure. This is not uncommon and will get better. Call your doctor immediately if you have any complications (see below).
Are there risks involved?	Complications are rare but can occur. These include but are not limited to: Bleeding and requiring blood transfusions Adverse reaction to sedatives Breathing, respiratory, or cardiac complications A tear in the lining (perforation) of the digestive tract Need for emergency surgery
When should I contact my doctor?	Call with any questions or if you experience the following: Fever of 100.4°F or higher Trouble swallowing Difficulty breathing Blood in vomit or stool Increasing throat, chest, or abdominal pain