4-u1.0-B978-1-4160-6189-2..00090-1..DOCPDF

CHAPTER

90 Portal Hypertension and Gastrointestinal BleedingVijay H. Shah and Patrick S. Kamath

CHAPTER OUTLINE

Normal Portal Circulation 1489Hemodynamic Principles of Portal Hypertension 1491Increased Intrahepatic Resistance 1492Hyperdynamic Circulation 1493Collateral Circulation and Varices 1494

Measurement of Portal Pressure 1495Hepatic Vein Pressure Gradient 1495Splenic Pulp Pressure 1496Portal Vein Pressure 1496Endoscopic Variceal Pressure 1496

Detection of Varices 1496Upper Gastrointestinal Endoscopy 1496Ultrasonography 1497Computed Tomography 1497Magnetic Resonance Imaging 1498Endoscopic Ultrasonography 1498

Causes of Portal Hypertension 1498Common Causes 1498Less Common Causes 1500

Clinical Assessment of Patients with Portal Hypertension-Related Bleeding 1501

Treatment of Portal Hypertension-Related Bleeding 1501Pharmacologic Therapy 1501Endoscopic Therapy 1503Transjugular Intrahepatic Portosystemic Shunt 1504Surgical Therapy 1506

Management of Specific Lesions 1508Esophageal Varices 1508Gastric Varices 1510Ectopic Varices 1513Portal Hypertensive Gastropathy and Gastric Vascular Ectasia 1514

Variceal hemorrhage, hepatic encephalopathy, and asci-testhe major complications of cirrhosis of the liverresult from portal hypertension, defined as an increase in hepatic sinusoidal pressure to 6 mm Hg or greater. Portosystemic collaterals decompress the hypertensive hepatic sinusoids and give rise to varices at the gastroesophageal junction and elsewhere. These portosystemic collaterals also may allow ammonia derived from the intestine to reach the brain, thereby resulting in hepatic encephalopathy through a pathologic process of several intermediary steps involving the peripheral benzodiazepine-type receptors, neuro-steroids, and -aminobutyric acid (GABA) receptors (see Chapter 92). Additionally, portal hypertension is associated with renal retention of sodium and water and the formation of ascites (see Chapter 91). Indeed, portal hypertension and its complications remain important clinical problems despite advances in treatment and improved understanding of both the molecular basis and pathophysiology of portal hypertension.

NORMAL PORTAL CIRCULATION

The portal venous system carries capillary blood from the esophagus, stomach, small and large intestine, pancreas, gallbladder, and spleen to the liver. The portal vein is formed by the confluence of the splenic vein and the supe-rior mesenteric vein behind the neck of the pancreas.1 The inferior mesenteric vein usually drains into the splenic

vein. The left gastric vein, also called the left coronary vein, usually drains into the portal vein at the confluence of the splenic vein and superior mesenteric vein (Fig. 90-1). The portal vein is approximately 7.5 cm in length and runs dorsal to the hepatic artery and bile duct into the hilum of the liver. The uppermost 5 cm of the portal vein does not receive any tributaries.2 In the hilum of the liver, the portal vein divides into the left and right portal vein branches, which supply the left and right sides of the liver, respec-tively. The umbilical vein drains into the left portal vein. The cystic vein from the gallbladder drains into the right portal vein, whereas the portal venules drain into hepatic sinusoids that, in turn, are drained by the hepatic veins into the inferior vena cava. The left and middle hepatic veins usually join and drain into the inferior vena cava separately but adjacent to the confluence of the right hepatic vein with the inferior vena cava. The caudate lobe drains separately into the inferior vena cava (see Chapter 71).The circulatory system of the normal liver is a high-

compliance, low-resistance system that is able to accom-modate a large blood volume, as occurs after a meal, without substantially increasing portal pressure. The liver receives a dual blood supply from the portal vein and the hepatic artery that constitutes nearly 30% of total cardiac output. Portal venous blood derived from the mesenteric venous circulation constitutes approximately 75% of total hepatic blood flow, whereas the remainder of blood to the liver is derived from the hepatic artery, which provides highly oxy-genated blood directly from the celiac trunk of the aorta. Portal veinderived and hepatic arteryderived blood flow

1489

1490 Section IX Liver

converge in high-compliance, specialized vascular channels termed hepatic sinusoids. A dynamic and compensatory interplay occurs between hepatic blood flow derived from the portal vein and that from the hepatic artery. Specifically, when portal venous blood flow to the liver is diminished, as occurs in portal vein thrombosis, arterial inflow increases in an attempt to maintain total hepatic blood flow at a con-stant level. Similarly, after hepatic artery occlusion, portal venous inflow increases in a compensatory manner. This autoregulatory mechanism, aimed at maintaining total hepatic blood flow at a constant level, is termed the hepatic arterial buffer response.The sinusoids are highly permeable and thus facilitate the

transport of macromolecules to the parenchymal hepato-cytes that reside on the extraluminal side of the endothelial cells. The hepatic sinusoids are highly permeable because they lack a proper basement membrane and because the

endothelial cells that line the sinusoids contain fenestrae. Other unique aspects of the hepatic sinusoids are the space of Disse, a virtual space located extraluminal to the endo-thelial cell and adjacent to the hepatocyte, and its cellular constituents, the hepatic stellate cell (HSC) and the Kupffer cell (Fig. 90-2; see also Chapters 71 and 72). These two cell types probably play an important role, in concert with the endothelial cell, in regulating sinusoidal hemodynamics and homeostasis and may contribute to the sinusoidal derangements that occur in portal hypertension. Under basal conditions, HSCs maintain a quiescent phenotype and accumulate vitamin A. On activation, however, as occurs in cirrhosis and portal hypertension, these cells are postulated to develop contractile abilities that permit them to function as sinusoidal pericytes. Kupffer cells contribute to vascular homeostasis by generating cytokines with potent cellular and vasoregulatory actions, including tumor necrosis factor. Endothelial cells and smooth muscle cells in nonsinusoidal hepatic vessels such as the portal venule and the terminal hepatic venule are important in hepatic vasoregulation, par-ticularly in the normal liver, where HSCs are quiescent, unactivated, and presumably less contractile.Many studies have established the important role of nitric

oxide (NO), derived from endothelial NO synthase (eNOS), in hepatic vasodilatation. Shear stress, caused by the fric-tional force of blood within the sinusoids, is one of the most potent physiologic stimuli of eNOS-derived NO production in hepatic sinusoids. By contrast, endothelin-1 (ET-1), also released by endothelial cells, promotes hepatic vasocon-striction by binding to ET-A receptors located on HSCs. ET-1 also appears to be generated within HSCs themselves and promotes HSC contraction through an autocrine loop. Of interest, ET-1 may alternatively bind to ET-B receptors on endothelial cells. This signaling pathway paradoxically promotes vasodilatation by activating eNOS. Other vascular mediators implicated in hepatic vasoregulation include carbon monoxide generated by the heme oxygenase system, the sympathetic adrenergic agonist norepinephrine, the renin-dependent vasoconstrictor angiotensin, prostaglan-dins, thromboxane, leukotrienes, and hydrogen sulfide. Of these mediators, angiotensin is of particular interest because it is a potent constrictor of HSCs and is released in increased amounts in cirrhosis owing to systemic sympathetic hyperactivity. A number of angiotensin receptor blockers

Figure 90-1. Anatomy of the portal circulation. Blood vessels that consti-tute the portal circulation and hepatic outflow tracts are depicted.

Liver

Inferiorvena cava

Left, right, andmiddle hepatic veins

Portal vein

Splenic vein Spleen

Leftcolon

Inferiormesenteric

vein

Right colon/small intestine

Superiormesenteric

veinHepatic

sinusoids

Figure 90-2. Anatomy of the hepatic microvasculature. A, Normal sinusoidal microanatomy is depicted. The sinusoidal lumen is lined by fenestrated sinusoidal endothelial cells that allow the transport of macromolecules to the abluminal space of Disse. Quiescent hepatic stellate cells reside within this space, adjacent to hepatocytes and endothelial cells. B, In cirrhosis, a number of changes occur in the hepatic microcirculation, including loss of fenestrae in endothelial cells (defenestration), constriction of sinusoids, and activation of hepatic stellate cells with ensuing deposition of collagen and increased contractility.

Hepatocytes

Hepatic stellate cellSpace of DisseSinusoidal endothelial cell

Sinusoidal lumenFenestrae

Cirrhosis

Deposition of collagenin space of Disse

Activation of hepaticstellate cells

Constriction ofsinusoids

Defenestrationof sinusoidsA B

Normal

1491Chapter 90 Portal Hypertension and Gastrointestinal Bleeding

are undergoing evaluation for the treatment of portal hypertension.

HEMODYNAMIC PRINCIPLES OF PORTAL HYPERTENSION

In cirrhosis, as well as in most noncirrhotic causes of portal hypertension, portal hypertension results from changes in portal resistance in combination with changes in portal inflow. The influence of flow and resistance on pressure can be represented by the formula for Ohms law:

P F R=

in which the pressure gradient in the portal circulation (P) is a function of portal flow (F) and resistance to flow (R).

Increases in portal resistance or portal flow can contribute to increased pressure. Portal hypertension almost always results from increases in both portal resistance and portal flow (Fig. 90-3). One exception is that of an arteriovenous fistula, which in the initial stages causes portal hyperten-sion largely through an increase in portal flow in the absence of an increase in resistance. The mechanism of the increase in portal resistance depends on the site and cause of portal hypertension; in the Western world, the most common cause is liver cirrhosis (see later). Because of the increase in hepatic resistance and the decrease in hepatic compli-ance, small changes in flow that do not increase pressure in the normal liver can have a prominent stimulatory effect on portal pressure in the cirrhotic liver. The increase in portal venous inflow is part of a generalized systemic derangement termed the hyperdynamic circulatory state. Collateral vessels that dilate and new vascular sprouts that form connect the high-pressure portal venous system with

Figure 90-3. Vascular disturbances in portal hypertension and sites of action of portal pressure-reducing therapies. Portal hypertension typically results from increased resistance, usually from within the liver, in combination with increased portal venous flow. The increase in hepatic resistance results from mechanical factors in combination with dynamic vasoconstriction mediated by decreased nitric oxide (NO) production and increased endothelin-1 (ET-1) production. The increase in portal venous flow occurs as a result of vasodilatation in the splanchnic circulation that is mediated by increased NO produc-tion. A collateral circulation, including esophageal varices, develops between the hypertensive portal vasculature and systemic venous system; however, these collaterals are inadequate to decompress the hypertensive portal circulation fully. Collateral development is mediated by dilatation of existing col-lateral vessels, as well as development of new blood vessels and sprouts (angiogenesis). Therapies aimed at the different sites of hemodynamic distur-bances are shown. CC, contractile cell (e.g., hepatic stellate cell, vascular smooth muscle cell); EC, endothelial cell.

Dilatation Angiogenesis

EC

NO NO

Splanchnic circulation

EC

NO

Dilatation

Constriction CC

Beta adrenergicblockers

SclerotherapyVariceal ligation

Collateral circulation

Hepatic circulation

EC

NO ET-1

Surgical and transjugularintrahepatic shunts

NitratesAngiotensin receptor blockersPrazosin

Somatostatin analogsVasopressin analogsBeta adrenergic blockersNitrates

CC

Beta adrenergic blockersAngiogenesis

inhibitors


lower-pressure systemic veins. Unfortunately, this process of angiogenesis and collateralization is insufficient for normalizing portal pressure and actually causes complica-tions of portal hypertension, such as esophageal varices.3 Approaches to block this angiogenic process are a compel-ling target for drug development.The changes in portal flow and resistance also can be

viewed as originating from mechanical and vascular factors. Mechanical factors include the fibrosis and nodularity of the cirrhotic liver with distortion of the vascular architecture and the remodeling that is recognized to occur in the systemic and splanchnic vasculature in response to the chronic increases in flow and shear stress that char-acterize the hyperdynamic circulatory state. Vascular factors include intrahepatic vasoconstriction, which contributes to increased intrahepatic resistance, and the splanchnic and systemic vasodilatation that accompanies the hyperdy-namic circulatory state. The vascular factors that contribute to portal hypertension are particularly important because they are reversible and dynamic and therefore compelling targets for experimental therapies (Fig. 90-4). Conversely, effective therapies for the fixed, mechanical component of portal hypertension caused by scar, regenerative nodules, and vascular remodeling are currently lacking. Indeed, most available therapies for portal hypertension focus on correc-tion of hemodynamic alterations in the portal circulation. Approaches include use of nonselective b-adrenergic block-ing agents, octreotide, and vasopressin to reduce the hyper-dynamic circulation, portal venous inflow, and splanchnic vasodilatation.4,5 Alternative agents reduce the increased intrahepatic resistance and include angiotensin receptor blockers and mononitrates.

INCREASED INTRAHEPATIC RESISTANCEIn cirrhosis, increased portal resistance occurs in great part as a result of mechanical factors that reduce vessel diameter. In addition to regenerative nodules and fibrotic bands, these mechanical factors include capillarization of the sinusoids and swelling of cells, including hepatocytes and Kupffer cells. As discussed earlier, however, reduced hepatic vessel diameter resulting in increased portal resis-tance, even when caused by cirrhosis, is not a purely mechanical phenomenon.6 Hemodynamic changes in the hepatic circulation also contribute to increased intrahepatic resistance.7,8 These changes are characterized by hepatic vasoconstriction and impaired responses to vasodilatory stimuli. The increase in intrahepatic resistance is deter-mined largely by changes in vessel radius, with small reduc-tions in vessel radius causing prominent increases in resistance. Blood viscosity and vessel length also can influ-

ence resistance, albeit to a much smaller extent. The factors that regulate resistance can be viewed in the context of the law of Poiseuille:

R L r= 8 4 pi

in which R is resistance, L is the product of blood viscosity and vessel length, and r is vessel radius.Although vasoactive changes were estimated initially to

account for 10% to 30% of the increase in portal resistance in cirrhosis, subsequent studies have suggested that these figures actually may underestimate the contribution of hepatic vasoconstriction to the increased resistance observed in the cirrhotic liver. In noncirrhotic causes of portal hyper-tension, the increase in resistance may occur at sites upstream (prehepatic) or downstream (posthepatic) of the liver, as in portal vein thrombosis and hepatic vein throm-bosis, respectively (Fig. 90-5). Furthermore, the site of increased intrahepatic resistance can be further delineated as the sinusoids (sinusoidal), upstream from the sinusoids within the portal venules (presinusoidal), or downstream from the sinusoids in the hepatic venules (postsinusoidal), as in alcoholic cirrhosis, schistosomiasis, and sinusoidal obstruction syndrome, respectively. Pressure is increased only in the portal circulation behind the site of increased resistance, and in isolated portal vein thrombosis, hepatic function frequently remains largely preserved despite prom-inent portal hypertension.Most evidence suggests that a decrease in the production

of the vasodilator NO and an increase in the production of the vasoconstrictor ET-1 jointly contribute to the increase in hepatic vascular resistance. In experimental models of cirrhosis, the bioavailability of hepatic NO is diminished because of a reduction in the production of NO by endothe-lial cells.7,9,10 A similar paradigm is observed in the human cirrhotic liver.11 Most studies indicate that the reduction in NO production occurs not through a reduction in hepatic eNOS protein levels9,10 but through defects in the steps necessary to activate existing eNOS protein. For example, increases in the production of the eNOS-inhibiting protein caveolin-1 have been observed in experimental models of cirrhosis10 and in human cirrhosis. Another pathway that contributes to deficient generation of NO by eNOS is a reduction in the level of AKT (protein kinase B) phosphory-lation of eNOS and upregulation of the eNOS inhibiting protein, GRK (G protein-coupled receptor kinase), in the cirrhotic liver.12 Irrespective of the mechanism of deficiency, the lack of availability of NO is thought to allow HSCs, which are activated and highly contractile in liver cirrhosis, to constrict the sinusoids that they envelop, thereby increas-ing portal pressure. The role of the HSCs in this process remains controversial, however, because evidence is mixed regarding whether the site of the increase in intrahepatic resistance in cirrhosis is the sinusoids, where stellate cells reside, or the pre- or postsinusoidal venules (or both), which are devoid of stellate cells and in which endothelial cells signal smooth muscle cells. Furthermore, increasing evi-dence points toward diverse origins of these myofibroblastic cells within the cirrhotic sinusoids, with portal myofibro-blasts as well as HSC postulated to play important roles.13 In this regard, therapies that target myofibroblast migration may be a compelling therapeutic target by limiting the density of these contractile cells within the hepatic sinu-soids.14 Finally, the contribution of HSCs to hepatic angio-genesis may also be an important target for treating fibrosis and portal hypertension.15

In clinical practice, NO can be delivered by NO donor agents such as mononitrates. NO donor agents exert their

Figure 90-4. Representative vasodilator and vasoconstrictor molecules implicated in the vascular abnormalities in portal hypertension.

VasodilatorsAdenosineCarbon monoxideEndothelium-derived hyperpolarizing factorHydrogen sulfideNitric oxideProstacyclinSerotonin

VasoconstrictorsAngiotensinEndothelin-1LeukotrienesNorepinephrineSerotoninThromboxane


beneficial effects in part by relaxing the actively contractile stellate cells.16,17 The systemic actions of these agents, however, tend to cause side effects and exacerbate the hyperdynamic circulatory state. In studies utilizing a liver-specific NO donor compound, the increased intrahepatic vascular resistance could be corrected by the generation of additional NO and consequent relaxation of HSCs.18 In cir-rhosis, however, deficient endothelial cell NO generation may be accompanied by impaired stellate cell relaxation in response to NO,19 perhaps because of diminished response of the NO second messenger cyclic guanosine monophos-phate (cGMP) in activated cells.16 In this situation, a promi-nent beneficial effect of NO donors is less predictable.Excessive ET-1 also contributes to increased intrahepatic

vasoconstriction in portal hypertension through vasocon-strictive effects in the liver, presumably by enhancing HSC contractility.20,21 In experimental models, ET-1 protein and receptor expression are increased, most notably in HSCs and endothelial cells.20,22,23 In humans with portal hyperten-sion, plasma and liver ET-1 levels also are increased.24 The reason for activation of the ET-1 system in portal hyper-tension is not known, but this effect may be secondary to transforming growth factor-b (TGF-b), a key fibrogenic growth factor.23 Clinical trials of ET antagonists in patients with portal hypertension are in progress; however, the vari-able effects of ET modulation in experimental models of portal hypertension, as well as the possible hepatotoxicity of these compounds, have limited enthusiasm for studies in humans.25 Other therapies for portal hypertension may provide benefit through the ET pathway. For example, somatostatin, which reduces portal pressure by constricting the splanchnic circulation, also may act by inhibiting ET-1dependent HSC contraction.26

Other vasoactive mediators, including cysteinyl leukotri-enes, thromboxane, angiotensin, and hydrogen sulfide, also have been implicated in the development of increased intra-hepatic resistance in cirrhosis.27,28 Some of these mediators, particularly angiotensin, which causes contraction of HSCs, have been studied in humans. Attempts to reduce portal pressure using pharmacologic agents that inhibit angioten-sin activation of HSC contraction have met with mixed results thus far.29

HYPERDYNAMIC CIRCULATIONIn addition to the increases in portal resistance discussed earlier, a major factor in the development and perpetuation of portal hypertension is an increase in portal venous flow, or the hyperdynamic circulation. The term portal venous inflow indicates the total blood that drains into the portal circulation, not the blood flow in the portal vein itself, which may actually be diminished in portal hypertension because of portosystemic collateral shunts. The hyperdy-namic circulation is characterized by peripheral and splanchnic vasodilatation, reduced mean arterial pressure, and increased cardiac output. Vasodilatation, particularly in the splanchnic bed, permits an increase in inflow of systemic blood into the portal circulation.30

Splanchnic vasodilatation is caused in large part by relax-ation of splanchnic arterioles and ensuing splanchnic hyperemia. Studies of experimental portal hypertension have demonstrated that splanchnic vascular endothelial cells are primarily responsible for mediating splanchnic vasodilatation and enhanced portal venous inflow through excess generation of NO.31-39 This excess generation of NO and ensuing vasodilatation, hyperdynamic circulation, and hyperemia in the splanchnic and systemic circulation con-

Figure 90-5. Classification of portal hypertension. The different sites of increased resistance to portal flow (posthepatic, intrahepatic, and prehepatic) and associ-ated diseases are shown. Many diseases cause a mixed pattern. Portal hypertension rarely can occur exclusively as a result of increased portal flow, as occurs with arteriovenous shunts (not shown).

PosthepaticBudd-Chiari syndromeConstrictive pericarditisInferior vena caval obstructionRight-sided heart failureSevere tricuspid regurgitation

IntrahepaticPresinusoidal Idiopathic portal hypertension Primary biliary cirrhosis Sarcoidosis SchistosomiasisSinusoidal Alcoholic cirrhosis Alcoholic hepatitis Cryptogenic cirrhosis Postnecrotic cirrhosisPostsinusoidal Sinusoidal obstruction syndrome

PrehepaticPortal vein thrombosisSplenic vein thrombosis


trasts with the hepatic circulation, in which NO deficiency contributes to increased intrahepatic resistance.The mechanism of excess NO production from the endo-

thelial cells of the systemic and splanchnic arterial circula-tion is an area of active investigation. Some of the increase in NO production probably occurs from shear stress dependent and shear stressindependent increases in the expression of eNOS, which can be corrected in part by beta blockers.37,40-45 Activation of existing eNOS by cytokines or mechanical factors also seems to contribute to excess sys-temic and splanchnic NO generation through pathways that include eNOS phosphorylation and protein interactions.42-46 The physiologic stimuli that mediate this process are not well understood but may include ET-1, which is increased in the serum of patients with portal hypertension, and the cytokine tumor necrosis factor- (TNF-) because inhibitors of TNF improve portal pressure and the splanchnic circula-tory disturbances in both human and experimental portal hypertension. TNF- may be derived from intestinal endo-toxin, and intestinal decontamination appears to correct the hyperdynamic circulation in humans, suggesting a link with intestinal inflammation.47 Vascular endothelial growth factor (VEGF) has also been implicated in this process by excessively activating eNOS.48 In humans with portal hyper-tension, therapeutic inhibition of NOS has met with mixed clinical results.In one study, inhibition of NOS corrected altered systemic

hemodynamics,49 but other studies have not demonstrated significant portal pressurereducing effects of systemic NOS inhibition.50 Other mediators that may contribute to sys-temic and splanchnic vasodilatation include anandamide, an endogenous vasodilatory cannabinoid,51-53 heme oxygen-ase,17,54-56 and cyclooxygenase.57 Compelling evidence also supports a primary defect in smooth muscle cells in portal hypertension, perhaps because of defects in potassium channels.58-62 In fact, many pharmacologic therapies for portal hypertension target the splanchnic arteriolar smooth muscle cells, rather than endothelial cells, to reduce splanchnic vasodilatation. For example, octreotide, a syn-thetic analog of somatostatin, causes marked but transient reductions in portal pressure by contracting splanchnic smooth muscle cells, thereby limiting portal venous inflow, especially after meals. Nonselective beta blockers and vaso-pressin also reduce portal pressure by constricting splanch-nic arterioles and thereby reducing portal venous inflow. Because intrahepatic resistance persists, therapies targeted toward the increase in portal venous inflow usually do not normalize portal pressure entirely but often blunt the prom-inent increases in portal venous inflow that occur in response to a meal. Combination therapy with an agent that reduces increased intrahepatic resistance, such as a nitrate, and an agent that reduces portal venous inflow, such as a beta blocker, are more effective in reducing portal pressure than is either agent alone.

COLLATERAL CIRCULATION AND VARICESThe portal veinsystemic collateral circulation develops and expands in response to elevation of the portal pres-sure.63 Blood flow in the low volumes that normally perfuse these collaterals and flow toward the portal circulation is reversed in portal hypertension because the increased portal pressure exceeds systemic venous pressure. Therefore, flow is reversed in these collateral vessels, and blood flows out of the portal circulation toward the systemic venous circulation.The sites of collateral formation are the rectum, where the

inferior mesenteric vein connects with the pudendal vein and rectal varices develop; the umbilicus, where the vesti-

gial umbilical vein communicates with the left portal vein and gives rise to prominent collaterals around the umbilicus (caput medusae); the retroperitoneum, where collaterals, especially in women, communicate between the ovarian vessels and iliac veins; and the distal esophagus and proxi-mal stomach, where gastroesophageal varices are the major collaterals formed between the portal venous system and systemic venous system.Four distinct zones of venous drainage at the gastroesoph-

ageal junction are particularly relevant to the formation of esophageal varices.64 The gastric zone, which extends for 2 to 3 cm below the gastroesophageal junction, comprises veins that are longitudinal and located in the submucosa and lamina propria. They come together at the upper end of the cardia of the stomach and drain into short gastric and left gastric veins. The palisade zone extends 2 to 3 cm proxi-mal to the gastric zone into the lower esophagus. Veins in this zone run longitudinally and in parallel in four groups corresponding to the esophageal mucosal folds. These veins anastomose with veins in the lamina propria. The perforat-ing veins in the palisade zone do not communicate with extrinsic (periesophageal) veins in the distal esophagus. The palisade zone is the dominant watershed area between the portal and systemic circulations. More proximal to the pali-sade zone in the esophagus is the perforating zone, where there is a network of veins. These veins are less likely to be longitudinal and are termed perforating veins because they connect the veins in the esophageal submucosa and the external veins. The truncal zone, the longest zone, is approximately 10 cm in length, located proximally to the perforating zone in the esophagus, and usually character-ized by four longitudinal veins in the lamina propria.Veins in the palisade zone in the esophagus are most

prone to bleeding because no perforating veins at this level connect the veins in the submucosa with the periesophageal veins. Varices in the truncal zone are unlikely to bleed because the perforating vessels communicate with the peri-esophageal veins, allowing the varices in the truncal zone to decompress. The periesophageal veins drain into the azygous system, and as a result, an increase in azygous blood flow is a hallmark of portal hypertension. The venous drainage of the lower end of the esophagus is through the coronary vein, which also drains the cardia of the stomach, into the portal vein.The fundus of the stomach drains through short gastric

veins into the splenic vein. In the presence of portal hyper-tension, varices may therefore form in the fundus of the stomach. Splenic vein thrombosis usually results in isolated gastric fundal varices. Because of the proximity of the splenic vein to the renal vein, spontaneous splenorenal shunts may develop and are more common in patients with gastric varices than in those with esophageal varices.65,66

The predominant collateral flow pattern in intrahepatic portal hypertension is through the right and left coronary veins, with only a small portion of flow through the short gastric veins. Therefore, most patients with intrahepatic causes of portal hypertension have esophageal varices or gastric varices in continuity with esophageal varices. Unfor-tunately, portal hypertension caused by cirrhosis generally persists and progresses despite the development of even an extensive collateral circulation. Progression of portal hyper-tension results from (1) the prominent obstructive resistance in the liver; (2) resistance within the collaterals themselves; and (3) continued increase in portal vein inflow. The col-lateral circulatory bed develops through a combination of angiogenesis, the development of new blood vessels, and dilatation and increased flow through preexisting collater-als.3,67 Experimental evidence suggests that VEGF, a key NO


stimulatory growth factor, may contribute to both the angio-genic and collateral vessel responses.55,68 Inhibition of VEGF or NO may attenuate the collateral vessel propagation by inhibiting angiogenic responses in experimental models of portal hypertension and collateralization.67-72 Some pharmacologic agents used in the management of portal hypertension, such as beta blockers and octreotide, may act in part by constricting collateral vessels.73-76 Approaches to inhibiting VEGF and angiogenesis are worth studying therapeutically.48

The development of gastroesophageal varices requires a portal pressure gradient of at least 10 mm Hg. Furthermore, a portal pressure gradient of at least 12 mm Hg is thought to be required for varices to bleed; other local factors that increase variceal wall tension also are needed77 because all patients with a portal pressure gradient of greater than 12 mm Hg do not necessarily bleed. Factors that influence variceal wall tension can be viewed in the context of the law of Laplace:

T Pr w=

where T is variceal wall tension, P is the transmural pressure gradient between the variceal lumen and esopha-geal lumen, r is the variceal radius, and w is the variceal wall thickness. When the variceal wall thins and the varix increases in diameter and pressure, the tolerated wall tension is exceeded and the varix will rupture. These physi-ologic observations are manifested clinically by the observa-tion that patients with larger varices (r) in sites of limited soft tissue support (w), with elevated portal pressure (P), tend to be at greatest risk for variceal rupture from variceal wall tension (T) that becomes excessive. One notable site in which soft tissue support is limited is at the gastroesopha-geal junction. The lack of tissue support and high vessel density may contribute to the greater frequency of bleeding from varices at the gastroesophageal junction. The law of Laplace also has implications for the relevance of pharma-cologic therapies aimed at reducing portal pressure. Reduc-tions in portal pressure will reduce the variceal transmural pressure gradient, thereby reducing the risk that variceal wall tension will become excessive and varices will rupture. Clinically, a reduction in the hepatic venous pressure gradi-ent to less than 12 mm Hg almost negates the risk of variceal hemorrhage. The changes in portal pressure and local vari-ceal factors, however, are dynamic and influenced by a number of physiologic (an increase in intra-abdominal pressure, meal-induced increases in portal pressure), diurnal (circadian changes in portal pressure), and patho-physiologic (acute alcohol use) factors, and portal pressure and esophageal variceal pressure may vary at different times.

MEASUREMENT OF PORTAL PRESSURE

Portal pressure may be measured indirectly or directly. The most commonly used method of measuring portal pressure is determination of the hepatic vein pressure gradient (HVPG), which is an indirect method. Measurement of splenic pulp pressure and direct measurement of the portal vein pressure are invasive, cumbersome, and infrequently used approaches. Variceal pressure also can be measured but is not routinely performed in clinical practice. Measure-ment of liver stiffness using ultrasound fibroelastography or magnetic resonance elastography (MRE) may indicate the presence of portal hypertension but cannot yet be used to measure portal pressure.

HEPATIC VEIN PRESSURE GRADIENTThe HVPG is the difference between the wedged hepatic venous pressure (WHVP) and free hepatic vein pressure (FHVP). The HVPG has been used to assess portal hyper-tension since its first description in 1951,78 and has been validated as the best predictor for the development of com-plications of portal hypertension.Measurement of the HVPG requires passage of a catheter

into the hepatic vein under radiologic guidance until the catheter can be passed no further, that is, until the catheter has been wedged in the hepatic vein. The catheter can be passed into the hepatic vein through the femoral vein or using a transjugular venous approach. The purpose of wedging the catheter is to form a column of fluid that is continuous between the hepatic sinusoids and the catheter. Therefore, the measured pressure of fluid within the cath-eter reflects hepatic sinusoidal pressure. One of the draw-backs of using a catheter that is wedged in the hepatic vein is that the WHVP measured in a more fibrotic area of liver may be higher than the pressure measured in a less fibrotic area because of regional variation in the degree of fibrosis. Using a balloon-occluding catheter in the right hepatic vein to create a stagnant column of fluid in continuity with the hepatic sinusoids eliminates this variation in measurement of WHVP because the balloon catheter measures the WHVP averaged over a wide segment of the liver.79 HVPG is not effective for detecting presinusoidal causes of portal hyper-tension. For example, in portal hypertension secondary to portal vein thrombosis, the HVPG is normal. Moreover, the HVPG may underestimate sinusoidal pressure in primary biliary cirrhosis and other presinusoidal causes of portal hypertension.80 Therefore, HVPG is accurate for detecting only sinusoidal and postsinusoidal causes of portal hypertension.The HVPG represents the gradient between the pressure

in the portal vein and the intra-abdominal inferior vena caval pressure. An elevation in intra-abdominal pressure increases both WHVP and FHVP equally, so that the HVPG is unchanged. The advantage of the HVPG is that variations in the zero reference point have no impact on the HVPG.81 The HVPG is measured at least three times to demonstrate that the values are reproducible. Total occlusion of the hepatic vein by the inflated balloon to confirm that the balloon is in a wedged position is demonstrated by injecting contrast into the hepatic vein. A sinusoidal pattern should be seen, with no collateral circulation to other hepatic veins. The contrast washes out promptly with deflation of the balloon. Correct positioning of the balloon also is demon-strated by a sharp increase in the recorded pressure on inflation of the balloon. The pressure then becomes steady until the balloon is deflated, when the pressure drops sharply. In experienced hands, measurement of the HVPG is highly reproducible, accurate, and safe.Measurement of the HVPG has been proposed for the fol-

lowing indications: (1) to monitor portal pressure in patients taking drugs used to prevent variceal bleeding; (2) as a prognostic marker82; (3) as an end-point in trials using phar-macologic agents for the treatment of portal hypertension83; (4) to assess the risk of hepatic resection in patients with cirrhosis; and (5) to delineate the cause of portal hyper-tension (i.e., presinusoidal, sinusoidal, or postsinusoidal (Table 90-1), usually in combination with venography, right-sided heart pressure measurements, and transjugular liver biopsy. Although the indication for HVPG measure-ment with the most potential for widespread use is monitor-ing the efficacy of therapies to reduce portal pressure, HVPG monitoring is not done routinely in clinical practice because no controlled trials have yet demonstrated its usefulness.84


SPLENIC PULP PRESSUREDetermination of splenic pulp pressure is an indirect method of measuring portal pressure and involves puncture of the splenic pulp with a needle catheter. Splenic pulp pressure is elevated in presinusoidal portal hypertension, when the HVPG is normal. Because of the potential risk of complications, especially bleeding, associated with splenic puncture, however, the procedure is rarely used.

PORTAL VEIN PRESSUREDirect measurement of the pressure in the portal vein is a rarely used method that can be carried out through a per-cutaneous transhepatic route, transvenous approach, or, rarely, intraoperatively (although anesthesia can affect portal pressure). The transhepatic route requires portal vein puncture performed under ultrasound guidance. A catheter is then threaded over a guidewire into the main portal vein. With increasing use of the transjugular intrahepatic porto-systemic shunt (TIPS) (see later), radiologists have gained expertise in puncturing the portal vein and measuring portal vein pressure by a transjugular route. Direct portal pressure measurements are carried out when HVPG cannot be measured, as in patients with occluded hepatic veins caused by the Budd-Chiari syndrome, in whom a surgical portosystemic shunt is being contemplated,85 or in patients with intrahepatic, presinusoidal causes of portal hyperten-sion, such as idiopathic portal hypertension, in which the HVPG may be normal.

ENDOSCOPIC VARICEAL PRESSUREVarices rupture and bleed when the expanding force of intravariceal pressure exceeds variceal wall tension. Mea-surement of the difference between intravariceal pressure and pressure within the esophageal lumen (the transmural pressure gradient across the varices) is potentially a more important indicator of bleeding risk than measurement of HVPG,86,87 especially in patients with portal vein thrombosis and other causes of portal hypertension associated with a normal HVPG.Variceal pressure can be measured by inserting a needle

connected to a pressure transducer, through a fluid-filled catheter, into a varix; this approach is currently not justified except when measurement of variceal pressure is followed by variceal injection sclerotherapy. Because variceal sclero-therapy has fallen out of favor (see later), measurement of variceal pressure by variceal puncture is seldom carried out.A miniature pneumatic pressure sensitivity gauge attached

to the tip of an endoscope (Varipres Solid Components, Barcelona, Spain) allows noninvasive measurement of variceal pressure. Patients with previous variceal bleeding have been demonstrated to have higher variceal pressures than those in patients without previous bleeding.88 A vari-ceal pressure greater than 18 mm Hg during a bleeding episode is associated with failure to control bleeding and

predicts early rebleeding.89 Moreover, patients on pharma-cologic therapy who show a decrease in variceal pressure of greater than 20% from baseline have a low probability of bleeding, as compared with patients who do not demon-strate a greater than 20% decrease in variceal pressure, in whom the risk of variceal bleeding is 46%.88 Variceal pres-sure measurements determined with use of Varipres are considered satisfactory when they meet the following crite-ria: (1) a stable intraesophageal pressure; (2) absence of artifacts caused by esophageal peristalsis; and (3) correct placement of the gauge over the varix, as shown by fine fluctuations in the pressure tracing that correspond to the cardiac cycle and respirations. Therefore, measurement of variceal pressure requires both a skilled endoscopist and a cooperative patient, and, even in expert hands, accurate variceal pressure measurements cannot be obtained in 25% of patients.Manometry using an endoscopic balloon to measure vari-

ceal pressure is subject to observer bias because it relies on visual appearance to determine whether the varices have collapsed.90-92 With this technique, a balloon is inserted into the esophagus and inflated until the varices are noted on endoscopy to collapse. The pressure in the balloon required to collapse the varices represents the variceal pressure. In general, techniques of measuring variceal pressure are still considered experimental and not suitable for routine clinical use.

DETECTION OF VARICES

UPPER GASTROINTESTINAL ENDOSCOPYUpper gastrointestinal endoscopy is the most commonly used method to detect varices. The current consensus is that all patients with cirrhosis of the liver should be screened for esophageal varices by endoscopy. In patients in whom no varices are detected on initial endoscopy, endoscopy to look for varices should be repeated in 2 to 3 years. If small varices are detected on the initial endoscopy, endoscopy should be repeated in 1 to 2 years.93,94 None of the various noninvasive methods of determining which patients benefit most from endoscopic screening are accurate enough to recommend for routine use in clinical practice.95 The role of noninvasive markers in predicting the risk of large esoph-ageal varices requires study in large multicenter trials. Pre-liminary data suggest that wireless video capsule endoscopy (see Chapter 19)96 and computed tomography (CT) imaging are alternative screening modalities in patients who are not candidates for upper endoscopy. Moreover, CT screening may be more cost-effective than endoscopy.97

Endoscopic grading of esophageal varices is subjective. Various criteria have been used to try to standardize the reporting of esophageal varices. The best known of these

Table 90-1 The Use of Hepatic Venous Pressure Gradient in the Differential Diagnosis of Portal Hypertension

TYPE OF PORTAL HYPERTENSION WHVP FHVP HVPG

Prehepatic Normal Normal NormalPresinusoidal Normal Normal NormalSinusoidal Increased Normal IncreasedPostsinusoidal Increased Normal IncreasedPosthepatic Heart failure Increased Increased Normal Budd-Chiari syndrome Hepatic vein cannot be cannulated

FHVP, free hepatic vein pressure; HVPG, hepatic venous pressure gradient; WHVP, wedged hepatic venous pressure.


criteria are those compiled by the Japanese Research Society for Portal Hypertension. The descriptors include red color signs, color of the varix, form (size) of the varix, and loca-tion of the varix.98 Red color signs include red wale mark-ings, which are longitudinal whip-like marks on the varix; cherry-red spots, which usually are 2 to 3 mm or less in diameter; hematocystic spots, which are blood-filled blis-ters 4 mm or greater in diameter; and diffuse redness. The color of the varix can be white or blue. The form of the varix at endoscopy is described most commonly. Esopha-geal varices may be small and straight (grade I); tortuous and occupying less than one third of the esophageal lumen (grade II); or large and occupying more than one third of the esophageal lumen (grade III). Varices can be in the lower third, middle third, or upper third of the esophagus. Of all of the aforementioned descriptors, the size of the varices in the lower third of the esophagus is the most important. The size of the varices in the lower third of the esophagus is determined during withdrawal of the endo-scope (Fig. 90-6). As much air as possible should be aspi-rated from the stomach while the esophageal lumen is fully inflated. Small varices, that is, those occupying less than one third of the lumen, are less than 5 mm in diameter, whereas large varices are greater than 5 mm in diameter.98,99 As a point of reference, any varix larger in diameter than an open pinch biopsy forceps is likely to be greater than 5 mm in diameter. Patients with large esophageal varices, Child (or Child-Pugh) class C cirrhosis (see later), and red color signs on varices have the highest risk of variceal bleeding within 1 year.100 The increase in bleeding risk attributable to the presence of red color signs, however, is not independent of the risk associated with large variceal size. Therefore, prophylactic treatment to prevent variceal bleeding is recommended in all patients with large esopha-geal varices irrespective of the presence or absence of red color signs (see later).

ULTRASONOGRAPHYUltrasound examination of the liver with Doppler study of the vessels has been used widely to assess patients with portal hypertension. Features suggestive of portal hyperten-

sion on ultrasonography include splenomegaly, portosys-temic collateral vessels, and reversal of the direction of flow in the portal vein (hepatofugal flow). Some studies have demonstrated that a portal vein diameter greater than 13 mm and the absence of respiratory variations in the splenic and mesenteric veins are sensitive but nonspecific markers of portal hypertension.101,102 These criteria are not used routinely in clinical practice in most centers. Ultrasound examination can detect thrombosis of the portal vein, which appears as nonvisualization or cavernous transformation (a cavernoma) of the portal vein; the latter finding indicates an extensive collateral network in place of the portal vein.103 Splenic vein thrombosis also can be demonstrated. Portal blood flow can be measured by Doppler ultrasonography, which is the easiest research method for detecting post-prandial increases in splanchnic blood flow.104 Although Doppler ultrasonography is clinically useful in the initial evaluation of portal hypertension, the technique is not widely used to provide quantitative assessments of the degree of portal hypertension. Transient elastography may be useful in detecting portal hypertension but is not suffi-ciently sensitive to recommend as a modality to monitor decreases in portal pressure in patients on pharmacotherapy (see Chapter 73).105

COMPUTED TOMOGRAPHYComputed tomography (CT) is useful for demonstrating many features of portal hypertension, including abnormal configuration of the liver, ascites, splenomegaly, and col-lateral vessels (Fig. 90-7). Detection of varices may be an emerging indication for CT. Diagnosis of fundal varices by multidetector row CT (MDCT) is at least as accurate as endoscopic ultrasonography (see later). CT is especially helpful in distinguishing submucosal from perigastric fundal varices106 and is considered a less invasive alterna-tive to conventional angiographic portography in assessing portosystemic collaterals. At present, however, CT is not a recommended screening method for detecting large esophageal varices, but it may be a cost-effective method of screening for varices and preferred to endoscopy by patients.97

Figure 90-6. Endoscopic appearances of esophageal varices. A, Upper gastrointestinal endoscopy demonstrates dilated and straight veins (small esopha-geal varices) in the distal esophagus (arrows). B, Upper gastrointestinal endoscopy demonstrates large esophageal varices, greater than 5 mm in diameter, with a fibrin plug (arrow) representing the site of a recent bleed.

A B


MAGNETIC RESONANCE IMAGINGGadolinium-enhanced magnetic resonance imaging (MRI) is becoming recognized as a potentially useful method of detecting esophageal varices.107 In addition, MRI can be used to measure portal and azygous blood flow, which is increased in patients with portal hypertension.108 MRI pro-vides excellent detail of the vascular structures of the liver and can detect portal venous thrombosis and spleen stiff-ness in patients with portal hypertension, but the role of MRI in the assessment of portal hypertension requires further study. Unlike transient elastography using ultra-sound, MRI can accurately assess the stiffness of even fatty livers.109

ENDOSCOPIC ULTRASONOGRAPHYEndoscopic ultrasound examination (endosonography) using radial or linear array echo-endoscopes or endoscopic ultrasound mini-probes passed through the working channel of a diagnostic endoscope has been applied as an investiga-tional tool in the evaluation of patients with varices. Endoscopic ultrasonography has been used to study several aspects of esophageal varices, including the cross-sectional area of varices to identify patients at increased risk of bleed-ing77; size of and flow in the left gastric vein, azygous vein, and paraesophageal collaterals; changes after endoscopic therapy; and recurrence of esophageal varices following variceal ligation (see later).110 Endosonography can be com-bined with endoscopic measurement of transmural variceal pressure to allow estimation of variceal wall tension, which is a predictor of variceal bleeding (see earlier).111-113

CAUSES OF PORTAL HYPERTENSION

The usual classification of causes of portal hypertension is based on the site of increased resistance to portal blood flownamely, prehepatic, intrahepatic, and posthepaticand is outlined in Figure 90-5. Intrahepatic sites of increased resistance can be presinusoidal, sinusoidal, or postsinusoi-dal. Many causes of portal hypertension are associated with an increase in resistance at more than one site. For example, alcoholic cirrhosis may be associated with increased resis-tance at the presinusoidal, sinusoidal, and postsinusoidal levels. Therefore, classification based on the site of resis-tance may not be possible for all diseases that cause portal hypertension. A more useful classification is clinically based and considers common and less common causes of portal hypertension (Table 90-2).

COMMON CAUSESCirrhosisComplications related to portal hypertension are the usual clinical manifestations of cirrhosis of the liver. Although all causes of cirrhosis are associated with portal hypertension, some features are disease specific. In alcoholic liver disease, elevation of the portal pressure is accurately reflected by the HVPG; moreover, portal hypertension may occur in the absence of cirrhosis but is more marked when cirrhosis is present. Perivenular lesions implicated in the pathogen-esis in noncirrhotic alcoholic liver injury account for the presinusoidal component of portal hypertension in these

Figure 90-7. Abdominal computed tomography (CT) in patients with portal hypertension. A, CT scan shows an irregular contour of the liver typical of cirrhosis (arrowheads). A small right pleural effusion is evident (straight arrow). The liver is hypointense relative to the spleen (curved arrow), typical of fatty infiltration of the liver in alcoholic cirrhosis. B, Coronal section of a CT scan showing contrast-enhanced esophageal varices (cursor). C, CT scan demon-strating two large esophageal varices (arrows) 5 mm and 6 mm in diameter. Varices are almost opposed to each other. D, CT scan demonstrates a tuft of gastroesophageal collaterals (straight arrow). The enlarged spleen also is seen (curved arrow).

A B

C D


patients.114 Autoimmune hepatitis also may be associated with portal hypertension in the absence of cirrhosis115; however, the risk of variceal bleeding is low in patients with autoimmune hepatitis. In patients with hemochromatosis, portal hypertension may be seen even before cirrhosis; the severity of portal hypertension increases with increasing fibrosis. Patients with hemochromatosis may bleed from varices despite an HVPG less than 12 mm Hg, indicating a presinusoidal component of portal hypertension. Phlebot-omy therapy in patients with hemochromatosis may result in a decrease in portal hypertension.116 In patients with primary biliary cirrhosis, portal hypertension also may occur before cirrhosis has developed. The risk of variceal bleeding increases with an increase in the histologic stage of the disease.117 In earlier stages of primary biliary cirrho-sis, portal hypertension is predominantly presinusoidal, but as the disease progresses, a sinusoidal component develops. Therefore, the HVPG may underestimate portal pressure in patients with primary biliary cirrhosis.80 Portal hyperten-sion occurs in patients with primary sclerosing cholangitis and in those with biliary strictures. A long duration of biliary obstruction usually is required, although portal hypertension has been known to develop in a few months in patients with chronic bile duct obstruction caused by chronic alcoholic pancreatitis.118 Portal hypertension in patients with biliary obstruction regresses following relief of the biliary obstruction.

SchistosomiasisSchistosomiasis may be the most common cause of portal hypertension worldwide (see Chapter 82). Bleeding from esophageal varices is a major cause of death in patients with hepatosplenic schistosomiasis. Portal hypertension results from presinusoidal obstruction caused by deposition of eggs of Schistosoma mansoni and Schistosoma japonicum in the presinusoidal portal venules. The host reaction results in granulomatous inflammation, which causes presinusoidal and periportal fibrosis.119 The fibrosis that results is some-times called clay pipestem or simply pipestem fibrosis and usually is associated with sustained heavy infection. The periportal collagen deposition leads to progressive obstruction of portal blood flow, portal hypertension, and variceal bleeding, along with splenomegaly and hypersplen-ism. Lobular architecture usually is preserved. Coinfection with hepatitis B or C virus in patients with hepatic schisto-somiasis can result in more rapid progression of fibrosis, hepatic failure, and an increased risk of hepatocellular carcinoma.120

In the initial stages of schistosomiasis, the HVPG is normal owing to the presinusoidal nature of the obstruction.

Some patients with schistosomiasis and portal hypertension also may have portal vein thrombosis. Patients with schis-tosomiasis often undergo portosystemic shunt surgery to treat variceal bleeding, with excellent long-term outcomes.

Extrahepatic Portal Vein ThrombosisExtrahepatic portal vein thrombosis is a prehepatic, presi-nusoidal cause of portal hypertension and a common cause of portal hypertension in children (see Chapter 83). The most common causes of portal vein thrombosis include hematologic disorders such as polycythemia vera or other myeloproliferative disorders. Other causes include a pro-thrombotic state, such as antithrombin, protein C, or protein S deficiency; antiphospholipid syndrome (or antiphos-pholipid antibody syndrome); paro xysmal nocturnal hemoglobinuria; oral contraceptive use; a neoplasm, usually intra-abdominal; an inflammatory disease, such as pan-creatitis, inflammatory bowel disease, or diverticulitis; abdominal trauma; and postoperative states, especially postsplenectomy. Cirrhosis is a cause of portal vein throm-bosis.121 Older studies suggested that portal vein thrombosis occurs in approximately 6% of patients with cirrhosis and in up to 25% of those with cirrhosis and hepatocellular carcinoma.122 With improved imaging, portal vein thrombo-sis is now known to be a more common complication of cirrhosis, and the association with hepatocellular carci-noma may not be as strong as previously thought. Isolated splenic vein thrombosis caused by a pancreatic neoplasm or pancreatitis usually is not associated with a thrombo-philia. Umbilical vein sepsis may be an etiologic factor in children with portal vein thrombosis, but even in these cases, an associated prothrombotic state may predispose the patient to portal vein thrombosis.Acute and subacute portal vein thrombosis usually does

not manifest with variceal bleeding.1 Chronic portal vein thrombosis is suggested by nonvisualization of the portal or splenic vein and an extensive collateral circulation. Patients may present with nonspecific symptoms or with variceal bleeding and hypersplenism. Bleeding usually is from gas-troesophageal varices but may be from duodenal varices and, rarely, other ectopic sites. Gallbladder varices (Fig. 90-8) also have been described in patients with portal vein thrombosis.123

The treatment of portal vein thrombosis is symptomatic, with the aim of controlling variceal bleeding or preventing

Table 90-2 Causes of Portal Hypertension

CommonCirrhosisExtrahepatic portal vein thrombosisIdiopathic portal hypertensionSchistosomiasisLess CommonFibropolycystic liver diseaseHereditary hemorrhagic telangiectasiaMalignancyMyeloproliferative disordersNodular regenerative hyperplasiaPartial nodular transformation of the liverSarcoidosisSplanchnic arteriovenous fistula

Figure 90-8. Computed tomography image of choledochal varices (arrows).


recurrent variceal bleeding. Patients in whom esophageal varices are not large, and a thrombophilia is detected, are best managed with anticoagulation because in these patients, the benefits of anticoagulation outweigh the risks.124 Local or systemic thrombolytic therapy is seldom required and is generally reserved for patients in whom a portal vein throm-bus extends into the superior mesenteric vein, with danger of impending intestinal ischemia. Endoscopic therapy is used to control acute variceal bleeding and to prevent recur-rent bleeding. Use of pharmacologic agents such as beta blockers to prevent variceal bleeding is probably also effec-tive in patients with portal vein thrombosis, but this approach has not been well studied. Patients with portal vein thrombosis have lower mortality and morbidity rates from variceal bleeding than those reported in patients with cirrhosis and variceal bleeding, owing to the lack of coagu-lopathy and synthetic liver dysfunction. Surgical portosys-temic shunt procedures are carried out in patients in whom bleeding cannot be controlled by conservative measures. If a suitable vein is not available for anastomosis, a large collateral vein may be anastomosed to a systemic vein.125 Placement of a TIPS is possible in some patients with chronic portal vein thrombosis.

Idiopathic Portal HypertensionIdiopathic portal hypertension is uncommon in Western countries but is common in parts of Asia such as India and Japan. This disorder is diagnosed when the portal pressure is elevated in the absence of significant histologic changes in the liver or extrahepatic portal vein obstruction.126 A liver biopsy specimen from affected patients may be entirely normal,122 although increased concentrations of ET-1 have been noted in the periportal hepatocytes, portal venules, and hepatic sinusoids of patients with idiopathic portal hypertension.127 Various terms used (rather loosely) to describe idiopathic portal hypertension include hepatopor-tal sclerosis, noncirrhotic portal fibrosis, and Bantis syn-drome.128,129 Use of the term idiopathic portal hypertension probably is best restricted to portal hypertension in patients in whom no hepatic lesion is found on light microscopy. The term hepatoportal sclerosis suggests obliterative portal venopathy with subendothelial thickening of the intrahe-patic portal veins; thrombosis and recanalization of these veins may follow. Fibrosis of the portal tracts is prominent later in the course.The cause of idiopathic portal hypertension is unclear

in a majority of patients, although chronic arsenic intoxica-tion, exposure to vinyl chloride, and hypervitaminosis A have been implicated (see Chapter 87). These etiologic factors are present in only a minority of patients. The dominant clinical features of the condition are variceal bleeding and hypersplenism related to a markedly enlarged spleen. Liver biochemical test levels are usually normal, although the serum alkaline phosphatase level may be mildly elevated. Ascites is uncommon. The HVPG in this disorder usually is normal because the site of increased resistance is presinusoidal.130 Surgical portosystemic shunts are well tolerated in these patients, although hepatic encephalopathy may occur on long-term follow-up evalua-tion.122 Liver transplantation is rarely required in these patients.Idiopathic portal hypertension may be confused with

incomplete septal cirrhosis, which probably is an unrelated condition characterized by incomplete septa and liver nodularity.131 Patients with incomplete septal cirrhosis are clinically similar to patients with cirrhosis and may progress to end-stage liver disease and require liver transplantation.

LESS COMMON CAUSESNodular Regenerative HyperplasiaNodular regenerative hyperplasia is a histopathologic diag-nosis characterized by atrophy of zone 3 hepatocytes and hypertrophy of zone 1 hepatocytes without significant fibro-sis (see Chapters 35 and 94).132 This disorder has been rec-ognized increasingly as a cause of portal hypertension and may even occur after liver transplantation.133 Similar histo-logic changes may be seen in well-established Budd-Chiari syndrome.134 The nodular hyperplasia may not be apparent on histologic examination unless a reticulin stain is carried out to demonstrate the micronodules. These regenerative nodules are believed to result from an imbalance between hyperperfused areas of the liver, with resulting regenerative nodules, and poorly perfused areas, with resulting atrophy. Nodular regenerative hyperplasia is associated with a variety of conditions, predominantly hematologic and rheumatologic in nature. Liver biochemical abnormalities include mild elevation of the serum aminotransferase levels. Portal hypertension manifesting as variceal bleeding is the predominant clinical presentation. Ascites also may develop in these patients, suggesting that an increase in sinusoidal pressure occurs.135 Hepatocellular carcinoma does not occur, but liver transplantation may be required in some patients.

Partial Nodular Transformation of the LiverPartial nodular transformation of the liver is an uncommon lesion that is characterized by large nodules in the perihilar region.136 These nodules may be visible on imaging studies of the liver. The rest of the liver may be normal or may show changes of nodular regenerative hyperplasia. Liver bio-chemical test levels usually are normal. Like nodular regen-erative hyperplasia, partial nodular transformation of the liver is believed to be related to an imbalance in portal perfusion of the liver, but the abnormality is restricted to the hilar branches, whereas in nodular regenerative hyper-plasia the abnormality is more diffuse. Variceal bleeding is the predominant presentation in partial nodular transforma-tion of the liver, although patients with large nodules may experience abdominal pain. Hepatocellular carcinoma may rarely develop in these regenerating nodules. Treatment with a surgical portosystemic shunt is associated with good long-term results.

Fibropolycystic Liver DiseaseFibropolycystic liver disease is a term which encompasses Carolis disease, Carolis complex (Carolis disease with congenital hepatic fibrosis), congenital hepatic fibrosis, and polycystic liver disease. Congenital hepatic fibrosis usually occurs in association with Carolis disease of the liver, poly-cystic disease of the kidney, and medullary sponge kidney (see Chapter 62). The major manifestation of congenital hepatic fibrosis is variceal bleeding.137 A portosystemic shunt may be placed in these patients to treat refractory variceal bleeding, with a low long-term risk of hepatic encephalopathy. Patients with polycystic liver disease, whether associated with polycystic kidney disease or not, rarely present with portal hypertension (see Chapter 94).138 Portal hypertension may decrease after treatment of the cysts.

SarcoidosisPortal hypertension is an uncommon manifestation of hepatic sarcoidosis (see Chapter 35).139 The site of increased intrahepatic resistance in patients with sarcoidosis seems to be postsinusoidal, in view of the elevated HVPG. In early disease, however, the resistance is predominantly at a


presinusoidal level. Treatment with glucocorticoids may decrease portal hypertension in some patients with hepatic sarcoidosis.

MalignancyPortal hypertension has been associated with leukemias, lymphomas, and systemic mastocytosis (see Chapters 34 and 35).140 Portal hypertension also may occur in patients with hepatocellular carcinoma independent of the presence of cirrhosis (see Chapter 94). The pathogenesis of portal hypertension in patients with hepatocellular carcinoma is thought to be multifactorial; contributing factors include portal vein thrombosis, pressure by the tumor on the portal vein, and, in some cases, a hepatic arteryportal vein fistula. Esophageal varices may be seen in patients with hepatic metastases, although variceal bleeding is unusual.141

Splanchnic Arteriovenous FistulaSplanchnic arteriovenous fistula should be suspected when the onset of ascites and variceal bleeding is acute, especially in the presence of an abdominal bruit. When a splanchnic artery ruptures into a mesenteric vein, the portal pressure increases acutely, reaching levels of systemic arterial pres-sure.142 The result is acute portal hypertension with devel-opment of ascites and variceal bleeding. A bruit may be heard in the left upper quadrant of the abdomen with a splenic arteriovenous fistula and in the right upper quadrant with a hepatic arteryportal vein fistula. With a long- standing fistula, secondary hepatic changes of perisinusoi-dal fibrosis related to an increase in portal venous inflow may be present. In the early stages, embolization or ligation of the fistula will ameliorate the portal hypertension. In late stages, however, portal fibrosis may be advanced, and the portal hypertension may not correct completely with embo-lization of the fistula.

Hereditary Hemorrhagic TelangiectasiaHereditary hemorrhagic telangiectasia (HHT), or Osler-Weber-Rendu disease, is an unusual cause of portal hypertension (see also Chapters 19 and 36). Diagnostic criteria include mucocutaneous telangiectasias, epistaxis, arteriovenous fistulas of the viscera (usually lung or liver), and a family history of the disorder. Manifestations of HHT depend on the site of fistula formation. A fistula between the hepatic artery and hepatic vein manifests predomi-nantly as biliary disease, mainly biliary strictures and cho-langitis, and high-output cardiac failure. A fistula between the hepatic artery and portal vein results in portal hyperten-sion and biliary strictures, whereas a fistula between the portal vein and hepatic vein, which is rare, results in hepatic encephalopathy.143 Nodular regenerative hyperplasia, which develops in some patients with HHT, may worsen portal hypertension.144 Although symptomatic liver disease in HHT is rare, involvement of the liver is found in a majority of patients.145

CLINICAL ASSESSMENT OF PATIENTS WITH PORTAL HYPERTENSION-RELATED BLEEDING

Patients with esophageal or gastric variceal bleeding present with hematemesis or melena (or both). Chronic blood loss is a more common presentation of portal hypertensive gas-tropathy or gastrointestinal vascular ectasia. The classic presentation of patients with variceal bleeding is with effortless and recurrent hematemesis; the vomitus is described as dark red in color.

Portal hypertension should be suspected in all patients with gastrointestinal bleeding and peripheral stigmata of liver diseasenamely, jaundice, spider angiomata, palmar erythema, Dupuytrens contractures, parotid enlargement, testicular atrophy, loss of secondary sexual characteristics, ascites, and encephalopathy. Splenomegaly is an important clue to the presence of portal hypertension, and the pres-ence of ascites makes the presence of esophageal varices even more likely. Caput medusae, suggestive of an intrahe-patic cause of portal hypertension, is present around the umbilicus; the flow of blood is away from the umbilicus. In Budd-Chiari syndrome, by contrast, veins are dilated in the flanks and back, and blood flows in a cephalic direction.85 A bruit may be heard in the left or the right upper quadrant in a patient with a splanchnic arteriovenous fistula. A venous hum may be heard in the epigastrium of a patient with portal hypertension and represents collateral flow in the falciform ligament.Laboratory studies frequently reveal evidence of hepatic

synthetic dysfunction, including prolongation of the pro-thrombin time, hypoalbuminemia, and hyperbilirubinemia, as well as anemia. Thrombocytopenia and leukopenia, reflecting hypersplenism and, in alcoholics, bone marrow suppression, may be noted. Patients with severe bleeding may present with hypovolemic shock and renal insuffi-ciency. Abdominal imaging studies frequently reveal sple-nomegaly, collateral vessels, abnormal liver echotexture and contour, and ascites.

TREATMENT OF PORTAL HYPERTENSION-RELATED BLEEDING

The treatment of portal hypertension is aimed either at reducing portal blood flow with pharmacologic agentssuch as beta blockers or vasopressin and its analogsor at decreasing intrahepatic resistance, with pharmacologic agentssuch as nitrates or by radiologic or surgical creation of a portosystemic shunt. Treatment also may be directed at the varices with use of endoscopic or radiologic techniques.

PHARMACOLOGIC THERAPYThe pharmacologic agents used in the treatment of portal hypertension are divided into two groups: those that decrease splanchnic blood flow and those that decrease intrahepatic vascular resistance (Table 90-3). The agents that decrease splanchnic blood flow acutely are vasopressin and its analogs and somatostatin and its analogs. b-adrenergic blocking agents (beta blockers) also decrease portal blood flow but are used only to prevent variceal bleeding and rebleeding. Agents that target intrahepatic vas-cular resistance include -adrenergic blocking agents,

Table 90-3 Drugs Used in the Treatment of Portal Hypertension

Drugs That Decrease Portal Blood FlowNonselective b-adrenergic blocking agentsSomatostatin and its analogsVasopressinDrugs That Decrease Intrahepatic Resistance1-Adrenergic blocking agents (e.g., prazosin)Angiotensin receptor blocking agentsNitrates


angiotensin receptor blocking agents, and nitrates, but only nitrates are now considered for clinical use. Diuretics, by decreasing plasma volume, may reduce portal pressure but are not recommended as sole agents for the treatment of portal hypertension. Metoclopramide and other gastric prokinetic agents may decrease intravariceal pressure by contracting the lower esophageal sphincter, but these agents have not been evaluated in clinical trials and are not recommended.

Vasopressin and Its AnalogsVasopressin is an endogenous peptide hormone that causes splanchnic vasoconstriction, reduces portal venous inflow, and reduces portal pressure. This drug is associated with serious systemic side effects, however. By causing constric-tion of systemic vessels, vasopressin may result in necrosis of the bowel. Additionally, vasopressin has direct negative inotropic and chronotropic effects on the myocardium that lead to reduced cardiac output and bradycardia, respectively. An increase in cardiac afterload can result in myocardial infarction, and antidiuresis, resulting from the action of vasopressin on the kidney, can result in hyponatremia.Terlipressin, or triglycyl-lysine-vasopressin, is a semisyn-

thetic analog of vasopressin that is cleaved by endothelial peptidases to release lysine vasopressin. Compared with vasopressin, terlipressin results in lower circulatory levels of the vasopressin analog and a lower rate of systemic side effects. Vasopressin and terlipressin have been used in com-bination with nitrates to decrease the risk of systemic side effects. Terlipressin is preferred over vasopressin because of its superior safety profile. In addition, an increase in survival has been demonstrated in patients with variceal bleeding treated with terlipressin. Terlipressin is not currently available in the United States, although it is undergoing evaluation by the U.S. Food and Drug Administration (FDA).

Somatostatin and Its AnalogsSomatostatin is a 14-amino-acid peptide. Five somatostatin receptorsSRTR 1 to SRTR 5are recognized, but the actual distribution of the receptors in humans is not clear. Following intravenous injection, somatostatin has a half-life in the circulation of one to three minutes; therefore, longer-acting analogs of somatostatin have been synthesized. The best known of these analogs are octreotide, lanreotide, and vapreotide.146 Somatostatin decreases portal pressure and collateral blood flow by inhibiting release of glucagon.147 The optimal dose and duration of use of somatostatin have not been adequately studied. Following a single 250-g bolus injection of somatostatin, portal and azygous blood flow decrease, but the effect lasts only a few minutes.148 Use of higher doses is associated with a more impressive decrease in HVPG. Somatostatin also decreases portal hypertension by decreasing postprandial splanchnic blood flow.149 Following a variceal bleed, blood in the gastrointes-tinal tract acts like a meal, leading to an increase in portal flow and elevation in the portal pressure; this elevation in pressure is ameliorated by the use of somatostatin.Following intravenous administration, octreotide has a

half-life in the circulation of 80 to 120 minutes. Its effect on reducing portal pressure is not prolonged, however. More-over, continuous infusion of octreotide does not decrease portal pressure despite decreasing the postprandial increase in portal pressure.62,150

Available evidence is insufficient to prove the superiority of somatostatin and its analogs to placebo in the control of acute variceal bleeding.134 Some randomized controlled

trials, however, support the view that somatostatin or octreotide may be equivalent in efficacy to sclerotherapy or terlipressin for controlling acute variceal bleeding. Also, early administration of vapreotide may be associated with improved control of bleeding but without a significant reduction in mortality rate.151 In clinical practice, treatment with somatostatin or octreotide is combined with endo-scopic management of variceal bleeding (see later).

-Adrenergic Blocking AgentsNonselective b-adrenergic blocking agents have been used extensively since the landmark study of Lebrec and col-leagues demonstrated the efficacy of these agents in prevent-ing variceal rebleeding.152 Nonselective beta blockers such as propranolol or nadolol are preferred. Blockade of b1-adrenergic receptors in the heart decreases cardiac output. Blockade of b2-adrenergic receptors, which cause vasodila-tation in the mesenteric circulation, allows unopposed action of 1-adrenergic receptors and results in decreased portal flow. The combination of decreased cardiac output and decreased portal flow leads to a decrease in portal pres-sure. Nadolol has advantages over propranolol in that it is excreted predominantly by the kidney, has low lipid solu-bility, and is associated with a lower risk of central nervous system side effects such as depression. The effectiveness of beta blockers is assessed most accurately by monitoring the HVPG; this approach is not widely used in clinical practice. The usual method of monitoring the efficacy of beta block-ers is to observe a decrease in the heart rate, which is a measure of b1-adrenergic receptor blockade. Despite ade-quate b1-adrenergic receptor blockade, however, some patients might benefit from a further increase in the dose of beta blocker, to increase the degree of b2-adrenergic blockade. Raising the dose, however, results in more side effects and the likelihood that treatment will need to be withdrawn.153

NitratesShort-acting (nitroglycerin) or long-acting (isosorbide mono-nitrate) nitrates result in vasodilatation. The vasodilatation results from a decrease in intracellular calcium in vascular smooth muscle cells. Nitrates cause venodilatation, rather than arterial dilatation, and decrease portal pressure pre-dominantly by decreasing portal venous blood flow. The effect on intrahepatic resistance is less impressive than gen-erally has been believed. Nitroglycerin has been used in combination with vasopressin to control acute variceal bleeding. The rate of infusion of nitroglycerin is 50 to 400 g per minute, provided that the systolic blood pressure is greater than 90 mm Hg; however, the combination of vaso-pressin and nitroglycerin is seldom used nowadays. Nitrates are no longer recommended, either alone or in combination with a beta blocker, for primary prophylaxis to prevent first variceal bleeds. For secondary prophylaxis (to prevent vari-ceal rebleeding), isosorbide mononitrate may be added to a beta blocker if the beta blocker alone has not resulted in an appropriate decrease in HVPG. In clinical practice, it is unusual for patients to tolerate nitrates for any length of time because of side effects, especially hypotension and headaches.

Drugs That Decrease Intrahepatic Vascular ResistanceThe ideal agent for treatment of portal hypertension would be a drug that decreases intrahepatic vascular resistance. Unfortunately, such a drug is not currently available. A desirable drug would be one that selectively decreases intra-hepatic vascular resistance without worsening systemic vasodilatation. Agents that may decrease intrahepatic resis-


tance include 1-adrenergic blockers such as prazosin,154 but long-term administration of prazosin causes worsening of the systemic hyperdynamic circulation associated with portal hypertension and consequent sodium retention and ascites.154 The addition of propranolol to prazosin may ameliorate the adverse affects of prazosin on the systemic circulation. Losartan, an angiotensin II receptor type I antagonist, causes a reduction in portal pressure without significant effects on the systemic circulation.155 In rando-mized, controlled trials of losartan or another angiotensin II receptor antagonist, irbesartan, however, portal pressure was not reduced significantly. In fact, renal function has worsened in patients given losartan or irbesartan.156,157 ET-receptor blockers and liver-selective NO donors are promising investigational agents for therapies that target intrahepatic vascular resistance.16 Studies suggest that simvastatin may decrease intrahepatic resistance and main-tain hepatic blood flow while decreasing portal pressure. This effect probably results from simvastatin-mediated NO release.158

ENDOSCOPIC THERAPYEndoscopic therapy is the only treatment modality that is widely accepted for the prevention of variceal bleeding, control of acute variceal bleeding, and prevention of vari-ceal rebleeding. Endoscopic variceal therapy includes vari-ceal sclerotherapy and band ligation.

SclerotherapyEndoscopic sclerotherapy has largely been supplanted by endoscopic band ligation, except when poor visualization precludes effective band ligation of bleeding varices. Avail-able evidence does not support emergency sclerotherapy as first-line treatment of variceal bleeding (Table 90-4).159 The technique involves injection of a sclerosant into (intravari-ceal) or adjacent to (paravariceal) a varix. Some paravariceal injection usually takes place during attempted intravariceal therapy. The sclerosants used include sodium tetradecyl sulfate, sodium morrhuate, ethanolamine oleate, and abso-lute alcohol; the choice of a sclerosant is based on avail-ability, rather than on superior efficacy of one agent over another.Complications of endoscopic sclerotherapy may arise

during or after the procedure. During injection, the patient may experience some degree of retrosternal discomfort, which may persist postoperatively. More serious complica-tions include sclerosant-induced esophageal ulcer-related bleeding, strictures, and perforation. The risk of ulcers caused by sclerotherapy may be reduced by use of oral sucralfate or a proton pump inhibitor after sclerotherapy.

Variceal LigationEndoscopic variceal ligation is the preferred endoscopic modality for control of acute esophageal variceal bleeding and prevention of rebleeding; however, the utility of band ligation in the treatment of gastric varices is limited. Variceal ligation is simpler to perform than injection sclerotherapy. The procedure involves suctioning of the varix into the channel of an endoscope and deploying a band around the varix. The band strangulates the varix, thereby causing thrombosis. Multi-band devices can be used to apply several bands without requiring withdrawal and reinsertion of the endoscope. Varices at the gastroesopha-geal junction are banded initially, and then more proximal varices are banded in a spiral manner at intervals of approx-imately 2 cm; the endoscope is then withdrawn. Varices in the mid- or proximal esophagus do not need to be banded. Endoscopic variceal ligation is associated with fewer com-plications than sclerotherapy and requires fewer sessions to achieve variceal obliteration. Moreover, esophageal variceal ligation during an acute bleed is not associated with a sustained elevation in HVPG, as occurs with sclerotherapy.160

Endoscopic variceal ligation can cause local complica-tions, including esophageal ulcers (Fig. 90-9), strictures, and dysmotility, albeit less frequently than does sclerotherapy. Banding-induced ulcers can be large and potentially serious if gastric fundal varices are banded. Now that overtubes are no longer used to facilitate repeated insertion of the endoscope during a banding session, the mechanical com-plications seen in the past (mucosal tears and esophageal

Table 90-4 Complications of Endoscopic Variceal Therapy*

During ProcedureAspiration pneumoniaRetrosternal chest painFollowing ProcedureBleedingEsophageal dysmotilityEsophageal strictureLocal ulcersMediastinitisPerforationSystemic (Usually with Sclerotherapy)Mesenteric venous thrombosisPulmonary embolismSepsis

*Sclerotherapy and band ligation.

Figure 90-9. Endoscopic views of gastric varices and esophageal variceal ligation-related ulcers. A, The gastroesophageal junction is seen on a retroflexed view following ligation of multiple gastric varices (arrowheads), which resemble polyps. B, Upper endoscopy in the same patient 4 weeks later demonstrates ulcers at the sites of earlier ligation (arrowheads).

A B


perforations) are uncommon. A proton pump inhibitor is usually recommended after variceal ligation even though data to support the use of a proton pump inhibitor are limited.

TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNTA transjugular intrahepatic portosystemic shunt (TIPS)also referred to as a transjugular intrahepatic portosystemic stent shunt (TIPSS)reduces elevated portal pressure by creating a communication between the hepatic vein and an intrahepatic branch of the portal vein. A percutaneous transjugular approach is used to insert the shunt. A TIPS functions as a side-to-side portacaval shunt and has been used to treat complications of portal hypertension, mainly variceal bleeding and refractory ascites, as well as Budd-Chiari syndrome, hepatic hydrothorax, and hepatorenal syndrome (see Chapters 83, 91, and 92). A TIPS can be placed by an interventional radiologist, with a mortality rate of less than 1% to 2%. TIPS placement usually is carried out with the patient under sedation. A platelet count greater than 60,000/mm3 and an acceptable prothrombin time as reflected by an international normalized ratio (INR) less than 1.4 usually are recommended but are not essential in an emergency. Broad-spectrum antibiotic coverage is rec-ommended when TIPS placement is carried out in a patient with primary sclerosing cholangitis and as an emergency procedure.

For this procedure, the hepatic vein is cannulated through a transjugular approach, and using a Rosch needle, the portal vein is cannulated. A guidewire is then passed to connect the hepatic vein and a branch of the portal vein. Following dilation of the tract, a stent is placed and dilated as required to reduce the portacaval pressure gradient (the pressure difference between the portal vein and the inferior vena cava at the confluence of the hepatic vein) to below 12 mm Hg (Fig. 90-10). Whether a lesser reduction of por-tacaval pressure gradient, to only 15 mm Hg or so (instead of 12 mm Hg), could be associated with reduced bleeding or a lower frequency of hepatic encephalopathy requires further study.In the past, the stents most commonly used for a TIPS

were the Wallstent and the Palmaz stent. Nowadays, a coated stent is used (Viatorr, Gore, Flagstaff, Arizona). This stent has an uncoated portion that anchors the stent to the portal vein and a polytetrafluoroethylene-coated portion that lines the tract in the liver parenchyma and the draining hepatic vein. The frequency of shunt stenosis is reduced when coated stents are used instead of uncoated stents.161

A TIPS can be placed successfully by an experienced operator in greater than 95% of cases. Complications following the procedure are classified as procedure related, early (occurring before 30 days), or late (after 30 days) (Table 90-5). The prevention and treatment of pro cedure-related, early, and late post-TIPS complications are outlined in Table 90-6.

Figure 90-10. Creation of a transjugular intrahepatic portosystemic shunt (TIPS). A, Portogram with a catheter in the portal venous system (arrowheads). The portal venous system is clearly outlined (straight arrows). Gastroesophageal collaterals are also demonstrated (curved arrows). B, A stent (arrow) has been placed to bridge the hepatic vein and the portal vein. A balloon (arrowheads) is being used to dilate the parenchymal tract within the liver. C, Fol-lowing expansion of the stent (arrow), injection into the portal vein demonstrates persistence of the gastroesophageal varices (arrowheads). D, Following embolization

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