42 PORTAL HYPERTENSION AND ESOPHAGEAL VARICES
Ramin Jamshidi B.S., B.S., Gregory V. Stiegmann M.D.

1. Describe the blood supply to the liver.

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Total hepatic blood flow is roughly 1500 mL/min, or 25% of cardiac output. The hepatic artery normally supplies about 30% of blood flow, and the portal vein contributes 70%. The hepatic artery and portal vein each supply 50% of the liver’s oxygen, however. With portal hypertension, portal flow decreases and the relative contribution of the hepatic artery necessarily increases.

2. How is portal hypertension defined?

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The portal venous pressure is normally 5-10 mmHg; > 20 mmHg is defined as portal hypertension. Direct measurement is risky, so the hepatic venous pressure gradient (HVPG) is used instead. This is the change in hepatic vein pressure when flow is occluded by wedging a balloon catheter into it (analogous to the estimation of left atrial pressure by wedging a pulmonary artery). A normal HVPG is 2-6 mmHg; > 12 mmHg is considered portal hypertension.

3. What is hepatopetal flow?

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Appropriate portal blood flow into the liver is termed hepatopetal flow. Reversal of flow in the portal vein can occur with greatly increased hepatic vascular resistance and is called hepatofugal flow. In this case, the hepatic artery must provide the dominant blood flow to the liver.

4. What are the most common causes of portal hypertension?

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* In the world: schistosomiasis
* In the United States: chronic hepatitis C virus infection or alcoholic cirrhosis (Laennec’s disease)
* In children: extrahepatic portal venous occlusion (as in portal vein thrombosis) or biliary atresia

5. What are schistosomiasis and Katayama fever?

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Infection by a freshwater blood fluke that causes an initial dermatitis (”swimmer’s itch”) and rash followed after 1-2 months by fever, myalgias, abdominal pain, and bloody diarrhea (Katayama fever). As these parasites mate and lay eggs in the venous system, the resulting inflammation causes chronic obstructing fibrosis of the organs and vessels, which is manifested by portal hypertension. Katayama fever lasts a few weeks and is second only to malaria as a cause of chronic tropical illness. Treat with praziquantel.
KEY POINTS: CHRONIC PANCREATITIS

1. Portal venous pressure > 20 mmHg (normal = 5-10 mmHg).
2. Most common cause in the United States is alcoholic cirrhosis.
3. Anatomic causes characterized as presinusoidal, sinusoidal, or postsinusoidal.
4. Complications include ascites, esophageal varices, encephalopathy, hypersplenism, hemorrhoids.
5. Initial management is medical; surgery is reserved for refractory cases.

6. How can the causes of portal hypertension be classified anatomically?

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Presinusoidal:

* Extrahepatic: portal or splenic vein thrombosis, congenital biliary atresia, extrinsic compression (e.g., tumor)
* Intrahepatic: primary biliary cirrhosis, schistosomiasis, hepatic metastases, polycystic disease, sarcoidosis

Sinusoidal: hepatic cirrhosis (e.g., viral infection, alcohol, hemochromatosis)
Postsinusoidal: Budd-Chiari syndrome, inferior vena cava obstruction, right heart failure

7. List the four major anatomic connections between the portal and systemic venous systems.

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1. Left gastric (coronary) vein to the esophageal vein (potential esophageal varices)
2. Inferior mesenteric vein through the superior hemorrhoidal veins to the hypogastric vein (potential rectal varices)
3. Portal vein to umbilical vein to superficial veins of the abdominal wall (potential caput medusae)
4. Mesenteric veins to perilumbar veins of Retzius into the inferior vena cava (potential retroperitoneal hemorrhage)

Note that the reason these anastomoses can shunt blood (around the liver) is that the splanchnic veins lack one-way valves.

8. Define sinistral portal hypertension.

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Derived from sinister, the Latin word for “left,” this is “left-sided” portal hypertension specifically caused by splenic vein thrombosis or obstruction. This causes shunting from the short gastric branches of the splenic vein to the left gastric vein, resulting in gastric varices. Splenectomy is the definitive treatment.

9. What are the common complications of portal venous hypertension?

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* Ascites and spontaneous bacterial peritonitis
* Hemorrhage from esophageal varices (the major cause of mortality)
* Hypersplenism
* Rectal varices (hemorrhoids)
* Portosystemic encephalopathy
* Portal hypertensive gastropathy and colopathy

10. What impact can portal hypertension have on other organ systems?

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* Hyperdynamic circulation (decreased systemic vascular resistance with increased cardiac output and low blood pressure)
* Hepatorenal syndrome
* Hepatopulmonary syndrome or portopulmonary hypertension

11. Liver function is classified according to what system?

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The modified Child-Turcott-Pugh system defines three classes of liver disease based on mortality; the points should be totalled from Table 42-1.

* Class A (5-6 points): 85% 2-year survival
* Class B (7-9 points): 60% 2-year survival
* Class C (≥ 10 points): 35% 2-year survival

12. What is MELD?

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The Mayo end-stage liver disease score is a completely objective measure of disease calculated with international normalized ratio (INR), bilirubin, and creatinine. In 2002, MELD was adopted by the United Network for Organ Sharing (UNOS) for determining liver transplantation priority.

Table 42-1. CHILD-TURCOTT-PUGH SYSTEM OF SCORING LIVER DISEASE

13. How is MELD calculated?

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MELD = 10 x [0.957 x ln (creatinine mg/dL) + 0.378 x In (bilirubin mg/dL) + 1.120 x ln (INR) + 0.643 (0 if cholestatic/alcoholic)]

Result is rounded to the nearest integer.

14. How common are esophageal varices?

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At time of diagnosis of cirrhosis, approximately 30% of patients have esophageal varices, and the incidence of new varix formation in patients with known cirrhosis is roughly 6% per year. There is a 50% point prevalence of varices in cirrhotic patients. However, bleeding occurs in only about one third of patients with varices.

15. Is upper gastrointestinal bleeding in cirrhotic patients with documented varices always variceal?

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Good test-taking skills tell you the answer must be no. Twenty percent of these patients bleed from another source (e.g., alcoholic gastric ulcerations, peptic ulcer disease). This also includes patients with ascites, spider angiomata, and asterixis.

16. Are gastric varices a common bleeding source in patients with portal hypertension?

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No. Only about 5% of variceal bleeds in cirrhotic patients are caused by gastric varices. Portal hypertension with gastric varices and no esophageal varices is usually associated with splenic vein thrombosis. Gastric varices bleed much less frequently-but more severely-than their esophageal counterparts.

17. What factors are predictive of variceal bleeding?

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* Size of varices (the most important factor), which increases vessel wall tension
* Red wale markings on the varices (longitudinal “whip marks”) from decreased wall thickness
* Severity of liver disease
* Active alcohol abuse

All told, variceal hemorrhage occurs in 30% of patients within 2 years of varix documentation.
18. Does the degree of portal hypertension predict bleeding? Show answer
Surprisingly, no. Bleeding risk correlates poorly with the magnitude of portal pressure. However, bleeding rarely occurs with HVPG <12 mmHg; this threshold pressure is considered necessary but not sufficient for bleeding.

19. An initial variceal bleed is associated with what mortality and rebleeding risk?

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Thirty percent of these patients die within 6 weeks, with one third to one half of rebleeds occurring in the first 10 days. If untreated, up to 75% of patients rebleed within the first year.

20. Should selective or nonselective beta blockers be used in the treatment of esophageal varices?

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Nonselective beta blockade best minimizes bleeding by lowering blood pressure and reducing splanchnic flow. Beta1-adrenergic antagonism causes splanchnic vasoconstriction by reflex activation of alpha receptors and decreases myocardial contractility. Beta2 blockade prevents splanchnic and peripheral vasodilation. Nadolol is the drug of choice.

21. What are the major components of acute variceal bleed management?

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* Fluid or blood product resuscitation (be careful not to worsen ascites with excess crystalloid)
* Pharmacologic agents to lower portal pressure and flow to limit bleeding)
* Endoscopy to confirm diagnosis and treat by banding or sclerotherapy
* Antibiotic prophylaxis
* Lactulose catharsis (GI bleeding increases protein load-blood is protein-and may worsen encephalopathy)
* Tamponade, surgery, or transjugular intrahepatic portosystemic shunting (TIPS) if refractory or an early recurrent bleed

22. What pharmacologic treatments are used in acute variceal bleeding?

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Vasopressin (start at 0.2 U/min intravenously [IV] and increase the level while watching the electrocardiogram) decreases splanchnic perfusion and thus portal pressure. Be careful; systemic vasoconstriction can cause myocardial or mesenteric ischemia and infarction.
Terlipressin (2 mg IV every 4 hours) is a synthetic vasopressin analog with fewer side effects and simpler dosing. This has shown clear promise in randomized controlled trials but is not yet available in the United States.
Octreotide (50 μg IV bolus, then 25 μg/h IV) is a synthetic somatostatin analog that decreases portal blood flow by selective splanchnic vasoconstriction, so side effects are limited. Octreotide acts through vasoactive peptides substance P and glucagon.

23. What endoscopic treatments are used in acute variceal bleeding?

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* Sclerotherapy: intravariceal injection of a sclerosing chemical
* Endoscopic band ligation (EBL): direct strangulation of varices with rubber bands, similar to hemorrhoid banding

Either technique typically controls acute bleeding in ≤ 90% of variceal bleeding, but although sclerotherapy can be easier in the face of a large bleed, band ligation is safer (less chance of perforation) and tends to require fewer retreatments. (See Figure 42-1.)

Figure 42-1 Endoscopic band ligation. A, The endoscope is positioned over a varix and suction is applied to draw it into the ligator. A rubber band is then ejected over the base of the lesion. B, The band strangulates the varix, which sloughs off and passes through the body in about 5-7 days.

24. Why should antibiotics be given to cirrhotic patients admitted for GI bleeding?

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These patients have almost twice the risk of developing bacterial infections while hospitalized than do cirrhotic patients admitted for other reasons (nosocomial infection rates approach 50%). Spontaneous bacterial peritonitis, bacteremia, and pneumonia are the most common infections. Short-term antibiotic prophylaxis decreases infection incidence and early rehemorrhage with a resultant increase in survival. Norfloxacin, 400 mg given orally every day for 7 days, is a proven regimen.

25. What is a Sengstaken-Blakemore tube?

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A large nasogastric tube with two inflatable balloons that can be used to tamponade both the esophagus and the gastric cardia. The gastric balloon is inflated in the stomach (insert 150 mL of saline plus 25 mL of Gastrografin so that you can confirm appropriate positioning by radiograph) and pull this inflated balloon gently up against the gastroesophageal junction. Most bleeds occur in the distal 5 cm of esophagus, so if bleeding continues, the esophageal balloon should be inflated as well. In order to prevent balloon-induced esophageal ischemia or rupture, do not inflate this balloon to > 30 mmHg (portal venous pressure) and limit use to 24 hours. Half of patients rebleed after balloon deflation, and 10-25% suffer aspiration pneumonia. (See Figure 42-2.)

Figure 42-2 Sengstaken-Blakemore tube, with two balloons and suction ports.

26. What are the options for preventing recurrent variceal bleeds?

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Without treatment, 75% of patients rebleed within 1 year. Beta-blockers reduce this to 40%; when combined with sclerotherapy, the rate is 35%, and when combined with EBL, the rate is reduced to 25%. The lowest rebleeding rates are thus accomplished with EBL and chronic nadolol. Interestingly, EBL with beta blockade has demonstrated no difference in 2-year survival when compared with beta-blocker and nitrate treatment alone. Shunt surgery and TIPS are slightly better than all these options at 15% rebleeding per year, but these invasive interventions also increase morbidity.

27. How should a patient with recurrent variceal bleeds be treated?

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Primary treatment should be EBL combined with beta blockade. Failing this treatment, the second-line option is to decompress the portal venous system by shunting blood away with a portosystemic anastomosis. The decision of open versus radiologic shunting is based on the urgency and the patient’s fitness for surgery.

28. What is TIPS?

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TIPS is a percutaneous radiologic technique for diverting portal vein blood directly into the inferior vena cava. Under fluoroscopy, a stent is placed through the hepatic parenchyma to link the hepatic and portal veins. Although TIPS relieves ascites and is superior to EBL in lowering variceal bleed risk, it also exacerbates encephalopathy without any decrease in mortality. New or worsened encephalopathy occurs in at least 25% of patients after TIPS. Stent stenosis and dysfunction occurs in 30% by 1 year and 50% by 2 years. (See Figure 42-3.)

Figure 42-3 TIPS placement. A, From a hepatic vein, a needle punctures through the liver to reach a portal vein. B, The tunnel is widened with a balloon catheter. C, A permanent stent is placed. (From McNally PR (ed): GI/Liver Secrets, 2nd ed. Philadelphia, Hanley & Belfus, 2001.)

29. Describe the basic options for surgical shunting.

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Nonselective (central) shunt: portovacal and mesocaval shunts nonselectively decompress the portal venous system, thus risking hepatofugal flow and worsening hepatic failure. Large amounts of portal blood (not detoxified in the liver) in the systemic circulation worsen encephalopathy. Creating a smaller diameter conduit (partial shunt) helps preserve some anterograde portal flow and limits this effect.
Selective splenorenal (Warren) shunt: anastomosis of the distal splenic vein to the left renal vein with ligation of the left gastric. This does not decompress as thoroughly, and, therefore, this technique enjoys a lower risk of encephalopathy.
As a rule, the more central the shunt site, the more extensive the portal decompression, but the tradeoff is the increased risk of encephalopathy (as demonstrated by TIPS).

30. How can you estimate operative mortality for elective portosystemic shunting?

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Perioperative mortality correlates well with Child-Pugh class (this was the original purpose of the classification). Classes A, B, and C demonstrate 5%, 10%, and 40% mortality, respectively, at 30 days.

31. Is there a definitive treatment for recurrent variceal bleeding?

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Liver transplantation provides portal decompression and restores hepatic function. Listing criteria are strict, and the psychological assessment of the “reformed alcoholic” is particularly arduous. Prior TIPS or shunting operations are not contraindications to transplant.