The major causes of portal hypertension are listed in Table 24–4. In all but a few instances, the basic lesion is increased resistance to portal flow. Those associated with increased resistance can be subclassified according to the site of the block as prehepatic, hepatic, and posthepatic; hepatic causes of portal hypertension are further subclassified as presinusoidal, sinusoidal, and postsinusoidal. Cirrhosis accounts for about 85% of cases of portal hypertension in the United States, most commonly from heavy alcohol use. Postnecrotic cirrhosis is next in frequency, followed by biliary cirrhosis. The other intrahepatic causes of portal hypertension are relatively rare in Western countries, although in some parts of the world, hepatic schistosomiasis constitutes the largest single group. Idiopathic portal hypertension occurs with greater frequency in southern Asia.
Table 24–4.Causes of portal hypertension. ||Download (.pdf) Table 24–4. Causes of portal hypertension.
I. Increased resistance to flow
A. Prehepatic (portal vein obstruction)
Congenital atresia or stenosis
Thrombosis of portal vein
Thrombosis of splenic vein
Extrinsic compression (eg, tumors)
Portal cirrhosis (nutritional, alcoholic, Laënnec)
Others (Wilson disease, hemochromatosis)
Acute alcoholic liver disease
Chronic active hepatitis
Congenital hepatic fibrosis
Idiopathic portal hypertension (hepatoportal sclerosis)
Budd–Chiari syndrome (hepatic vein thrombosis)
Valvular heart disease
Right heart failure
Increased portal blood flow
Arterial-Portal Venous Fistula
Increased splenic flow
Splenomegaly (eg, tropical splenomegaly, myeloid metaplasia)
After cirrhosis, extrahepatic portal venous thrombosis or occlusion is the most common cause of portal hypertension in the United States. Patients with this condition are generally younger than cirrhotics, and many are children. Posthepatic obstruction due to Budd–Chiari syndrome (BCS) or constrictive pericarditis is rare.
Portal hypertension is defined as a hepatic venous pressure gradient (HVPG) (the difference between portal-vein pressure and hepatic-vein pressure) greater than 5 mm Hg, but usually become clinically significant when this gradient reaches 10 mm Hg. Portal venous pressure normally ranges from 7 to 10 mm Hg. In portal hypertension, portal pressure exceeds 10 mm Hg, averaging around 20 mm Hg and occasionally rising as high as 50-60 mm Hg. With those portal pressures, since the venous pressure in the right atrium averages 5 mm Hg, the HVPG can easily become greater than 5 mm Hg.
Since pressure in the portal venous system is determined by the relationship Pressure = Flow × Resistance, portal hypertension could result either from increased volume of portal blood flow or increased resistance to flow. Portal hypertension can be classified by pathophysiologic processes as summarized in Table 24–4.
In practice, however, the liver has tremendous reserve capacity to accommodate increased blood flow, and portal hypertension solely due to this mechanism is extremely uncommon. Increased flow may contribute to portal hypertension in patients with arterial-portal venous fistulae (traumatic, congenital). When an arteriovenous fistula occurs, portal hypertension and its clinical manifestations usually do not appear for several months, because sinusoidal capacity is so great that the immediate rise in portal pressure is only moderate. With time, however, sinusoidal sclerosis develops, resistance increases, and portal pressure gradually reaches high levels, leading to the formation of varices.
Nearly all clinically relevant cases of portal hypertension result from increased resistance, in itself due to both structural distortion of the liver vascular architecture by fibrosis and dynamic increases in hepatic vascular tone. In addition to increased vascular resistance in the liver, splanchnic vascular bed resistance decreases, a consequence of local production of vasodilators (eg, nitric oxide) and mesenteric angiogenesis, paradoxically worsening the portal hypertension by increasing the splanchnic blood flow to the liver.
The average portal flow in cirrhotic patients with complications of portal hypertension is nonetheless about 30% of normal, ranging from 0 to 700 mL/min. Hepatic arterial flow is usually reduced by a similar proportion. The range of portal flow rates in different patients may vary greatly; in some, blood in the portal vein moves sluggishly or the direction of flow may even be reversed (hepatofugal) so that the portal vein functions as an outflow tract from the liver. These states of low flow predispose to spontaneous thrombosis of the portal vein, a complication of cirrhosis seen in 16% per year in patients with advanced liver disease. Portal thrombosis usually is associated with acute clinical deterioration and renders the portal vein unsuitable for a shunt to decompress the portal venous system.
Fluctuations in the level of portal hypertension may occur in conjunction with changes in blood volume. This is almost never a problem in patients with a normal liver. However, administration of colloid solutions to a patient with underlying liver disease and a normal or expanded blood volume could theoretically aggravate the clinical manifestations of portal hypertension.
A. Disease-Specific Pathophysiology
In alcoholic liver disease, the abnormal resistance is predominantly hepatic and postsinusoidal, as indicated by the results of wedged hepatic vein pressure studies.* The causes of increased resistance in this disease are thought to be: (1) distortion of the hepatic veins by regenerative nodules and (2) fibrosis of perivascular tissue around the hepatic veins and the sinusoids.
Even in the absence of cirrhosis, acute alcoholic hepatitis can raise portal pressure by producing centrilobular swelling and fibrosis. Sinusoidal resistance to flow is also increased by engorgement of adjacent hepatocytes with fat and resultant distortion and narrowing of vascular channels. Documented cases of normalization or reduction in portal pressure have occurred with resolution of the pathologic changes.
Schistosomiasis can produce a unique form of hepatic presinusoidal obstruction to blood flow from deposition of parasite ova in small portal venules. The subsequent chronic inflammatory reaction leads to fibrosis and cirrhosis. Many patients with schistosomiasis are also at risk for chronic hepatitis, which can exacerbate the liver damage.
BCS (hepatic vein thrombosis) results from obstruction of flow through the hepatic veins. The resulting sinusoidal hypertension produces prominent ascites and hepatomegaly. Conditions (veno-occlusive disease, inferior vena cava obstruction by tumor or congenital webs, right-sided heart failure) that reduce flow through the hepatic veins result in a similar clinical picture.
Banti syndrome was defined as liver disease secondary to primary splenic disease and was incorrectly considered as the cause of portal hypertension now known to result from cirrhosis and other hepatic disorders rather than a consequence of such conditions. Portal hypertension from splenomegaly and increased splenic vein flow has been described in patients with hematologic diseases or tropical splenomegaly and apparently normal liver function. This is extremely uncommon, however, and given the great reserve of the liver to handle increases in portal flow, many such patients probably have some component of liver disease. In cirrhosis, the increased splenic blood flow accompanying “congestive” splenomegaly may occasionally be great enough to warrant splenic artery ligation or splenectomy to decrease portal pressure and improve symptoms, but this situation is rare.
B. Development of Portosystemic Collaterals and Varices
The obstacle to flow through the liver promotes expansion of collateral channels between the portal and systemic venous systems. As the pathologic process develops, portal pressure increases until a level of about 40 cm H2O (30 mm Hg) is reached. At this point, increasing hepatic resistance, even to the point of occlusion of the portal vein, diverts a greater fraction of portal flow through collaterals without significant increments in portal pressure.
The type of portosystemic collaterals that develops depends partly on the cause of the portal hypertension. In extrahepatic portal vein thrombosis (without liver disease), collaterals in the diaphragm and in the hepatocolic, hepatoduodenal, and gastrohepatic ligaments transport blood into the liver around the occluded vein (hepatopetal). In cirrhosis, collateral vessels circumvent the liver and deliver portal blood directly into the systemic circulation (hepatofugal); these collaterals give rise to esophageal and gastric varices. Other common spontaneous collaterals are through a recanalized umbilical vein to the abdominal wall, from the superior hemorrhoidal vein into the middle and inferior hemorrhoidal veins, and through numerous small veins (of Retzius) connecting the retroperitoneal viscera with the posterior abdominal wall.
Isolated thrombosis of the splenic vein causes localized splenic venous hypertension and gives rise to large collaterals from spleen to gastric fundus (sinistral, or left-sided, portal hypertension). From there, the blood returns to the main portal system through the coronary vein. In this condition, gastric varices are often present without esophageal varices.
Of the many large collaterals that form as a result of portal hypertension, spontaneous bleeding is relatively uncommon except from those at the gastroesophageal junction; spontaneous bleeding from gastric varices can sometimes occur and carries a higher rate of death than gastroesophageal varices. Compared with adjacent areas of the esophagus and stomach, the gastroesophageal junction is especially rich in submucosal veins, which expand disproportionately in patients with portal hypertension. The cause of variceal bleeding is most probably rupture due to sudden increases in hydrostatic pressure. Esophagitis is usually mild or absent.
DC Portal vein thrombosis: a predictable milestone in cirrhosis? J Hepatol 2009;51:632.
S Hepatic venous pressure gradient measurement in clinical hepatology. Dig Liver Dis 2011;43:762.
et al.. Portal hypertension and its complications. Gastroenterology 2008;134:1715.
D Noninvasive assessment of portal hypertension in patients with cirrhosis. Hepatology 2011;53:683.
Varices develop in 5%-15% of cirrhotic patients per year. Most patients with cirrhosis develop varices, but only about one-third experience variceal hemorrhage. Each bleeding episode is associated with a mortality rate of up to 25%, and 70% of untreated patients die within a year of the first episode. This high death rate reflects not only the massive hemorrhage but also the frequent presence of severely compromised liver function and other systemic disease that may or may not be related to alcohol abuse. Malnutrition, pulmonary aspiration, infections, and coronary artery disease are frequent coexisting conditions. Additional complicating factors in this patient population include lack of cooperation with treatment and acute alcohol withdrawal, which in its worst manifestation (delirium tremens) adds greatly to the already high mortality rate.
If cirrhosis or varices have been documented on previous examinations, hematemesis would strongly suggest bleeding varices as the cause. Patient with significant hemorrhage present with alteration of mental status, hypotension, and tachycardia, often in hypovolemic shock. It must be emphasized that bleeding from varices cannot be accurately diagnosed on clinical grounds alone even though the history or the appearance of the patient may strongly suggest the presence of cirrhosis or portal hypertension. Most patients with bleeding varices have alcoholic cirrhosis, and the diagnosis may seem obvious in a patient with hepatomegaly, jaundice, and vascular spiders who admits to recent binge drinking. Splenomegaly, the most constant physical finding, is present in 80% of patients with portal hypertension regardless of the cause. Ascites is frequently present. Massive ascites and hepatosplenomegaly in a nonalcoholic would suggest the much less common BCS.
Most patients with alcoholic liver disease and acute upper gastrointestinal bleeding have compromised liver function. The bilirubin is usually elevated, and the serum albumin is often below 3 g/dL. The leukocyte count may be elevated. Anemia may be a reflection of chronic alcoholic liver disease or hypersplenism as well as acute hemorrhage. The development of a hepatoma by a cirrhotic may first manifest by hemorrhage from varices; CT scan and marked elevation of the serum α-fetoprotein make the diagnosis. Thrombocytopenia and coagulopathy are common.
Treatment of Acute Bleeding
The general goal of treatment is to control the bleeding as quickly and reliably as possible using methods with the fewest possible side effects. The methods in use for acute variceal bleeding are listed in Table 24–5 and presented into a current treatment algorithm in Figure 24–6. Over the past decades, improvement in medical, endoscopic, and endovascular technique studied in the setting of randomized control trials has lessened the need for surgical interventions.
Table 24–5.First line management of acute bleeding from esophageal varices. ||Download (.pdf) Table 24–5. First line management of acute bleeding from esophageal varices.
Ceftriaxone (if doubt of quinolone resistance)
3. Interventional, nonsurgical
Endoscopic variceal ligation
Transjugular intrahepatic portosystemic shunt (TIPS)
Balloon tamponade (Sengstaken–Blakemore)
Emergency portasystemic shunts
Esophageal transection and reanastomosis
Suture ligation of varices
Algorithm for the management of acute variceal bleeding.
The initial management of the patient with massive gastrointestinal hemorrhage is discussed in Chapter 23. Critical initial steps include airway protection, particularly in patients with altered mental status or those with hemodynamic instability, and resuscitation with fluid and blood products. In the cirrhotic patients, correction of coagulopathy and thrombocytopenia should also be initiated early. Patients admitted with variceal hemorrhage are often bacteremic as a result of a concomitant infectious process (spontaneous bacterial peritonitis, urinary tract infection, or pneumonia). Clinical trials have shown better outcomes when empiric antibiotic therapy is initiated during an episode of variceal bleed, and usually a third-generation cephalosporin such as ceftriaxone is favored.
Vasoconstrictive drugs which reduce portal pressure (somatostatin and vasopressin analogs) and endoscopic variceal ablation (ligation and sclerotherapy) are the mainstay of initial management. The combined pharmacologic and endoscopic therapy has been shown in single trials and meta-analysis to be more effective in controlling acute bleeding than endoscopic treatment alone. With this initial strategy, control of bleeding can be achieved in 80%-85% of episodes. Endoscopic intervention requires a skilled endoscopist; banding has been shown effective and is considered the treatment of choice, although very profuse bleeding makes ligation a challenge, and sclerotherapy with cyanoacrylate may be useful in this setting if special expertise is available. Balloon tamponade is no longer used routinely but is rather reserved for failure of the pharmacologic/endoscopic therapy for the hemodynamically unstable patients, and when the next line of treatment cannot readily be implemented.
The failure rate of the standard medical therapy for all comers is of 10%-20%, highest in patients with Child-Pugh class C disease, and early rebleeding rate has been reported in up to 30% of patients. Placement of a transjugular intrahepatic portosystemic shunt (TIPS) is currently considered the salvage therapy of choice in this situation. TIPS may not be an option in some cases, for example in face of portal thrombosis, in which situation surgical shunt or devascularization procedures are indicated.
Death rates rise rapidly in patients requiring more than 10 units of blood, and in general, patients still bleeding after 6 units—or those whose bleeding is still unchecked 24 hours after admission—should be considered for portal decompression procedures. Even when the bleeding is brought under control by the initial intervention, the mortality rate remains high (about 35%) as a result of liver failure and other complications.
1. Acute endoscopic sclerotherapy or ligation
Emergency esophagogastroscopy is the most useful procedure for the diagnosis and the treatment of bleeding varices and should be performed as soon as the patient’s general condition is stabilized by blood transfusion, correction of coagulopathy, administration of vasoconstrictors, and antibiotics are given. Endotracheal intubation is usually necessary for airway control. Varices appear as three or four large, tortuous submucosal bluish vessels running longitudinally in the distal esophagus. The bleeding site may be identified, but in some cases the lumen fills with blood so rapidly that the lesion is obscured. Using fiber-optic endoscopy, 13 mL of sclerosant solution is injected into the lumen of each varix, causing it to become thrombosed. Variations in the type of endoscope or sclerosant solution or whether or not the varices are physically compressed appear to have little influence on the outcome. Endoscopy is usually repeated within 48 hours and then once or twice again at weekly intervals, at which time any residual varices are injected.
Sclerotherapy controls acute bleeding in 80%-85% of patients, and rebleeding during the same hospitalization is about half (25% vs. 50%) the rebleeding rate of patients treated with a combination of vasopressin and balloon tamponade. Even though controlled trials show improvement in the control of bleeding with sclerotherapy, the evidence for increased patient survival is conflicting.
A similar effect is achieved by endoscopic ligation of the varices. The varix is lifted with a suction tip, and a small rubber band is slipped around the base. The varix necroses to leave a superficial ulcer. Several controlled trials have reported rubber band ligation to be more effective in controlling long-term bleeding episodes compared to sclerotherapy, although comparisons in the acute setting are limited. Band ligation is associated with fewer complications and fewer procedures are needed for complete eradication and has thus emerged as the initial endoscopic treatment of choice.
2. Somatostatin and analogs
Octreotide (brand name Sandostatin), is an octapeptide that mimics the hormone somatostatin pharmacologically. Purified somatostatin is not available in the United States. Somatostatin infusion reduces portal pressure without any impact on systemic hemodynamics; this effect may be less pronounced for octreotide. Somatostatin has been shown, in a prospective randomized trial, to effectively control acute bleeding, although other studies have had equivocal results. A meta-analysis of all studies using somatostatin or its analogs did show a significant risk reduction in control of hemorrhage. The efficacy of octreotide remains uncertain, but it appears to reduce the rebleeding rate when used in conjunction with endoscopic therapy. It should be emphasized that no study of somatostatin or octreotide has shown improved survival after an acute bleeding episode. Octreotide is given as an initial bolus of 50 μg followed by a continuous infusion of 50 μg/h for 2-5 days.
Vasopressin and its analog terlipressin (triglycyl lysine vasopressin) lower portal blood flow and portal pressure by directly constricting splanchnic arterioles, thereby reducing inflow. Vasopressin or terlipressin alone controls acute bleeding in about 80%-85% of patients, and this rate is increased when combined with endoscopic therapy or balloon tamponade. Cardiac output, oxygen delivery to the tissues, hepatic blood flow, and renal blood flow are also decreased—effects that occasionally produce complications such as myocardial infarction, cardiac arrhythmias, and intestinal necrosis. These unwanted side effects may sometimes be prevented without interfering with the decrease in portal pressure by simultaneous administration of nitroglycerin or isoproterenol. Terlipressin has fewer untoward cardiovascular side effects than vasopressin.
Although the results are somewhat contradictory, controlled trials generally indicate that vasopressin plus nitroglycerin is superior to vasopressin alone and that vasopressin alone is superior to placebo in controlling active variceal bleeding. Survival is not increased, however. In fact, while several vasoactive agents effectively stop acute hemorrhage, only terlipressin has been shown to improve survival after an acute event. Vasopressin is given as a peripheral intravenous infusion (at about 0.4 units/min), which is safer than bolus injections. Nitroglycerin can be given intravenously or sublingually. Terlipressin undergoes gradual conversion to vasopressin in the body and is safe to give by intravenous bolus injection (2 mg intravenously every 6 hours); this drug is, however, not available in the United States.
Tubes designed for tamponade have two balloons that can be inflated in the lumen of the gut to compress bleeding varices. There are three or four lumens in the tube, depending on the type: two are for filling balloons within the stomach and the esophagus, and the third permits aspiration of gastric contents. A fourth lumen in the Minnesota tube is used to aspirate the esophagus orad to the esophageal balloon. The main effect results from traction applied to the tube, which forces the gastric balloon, generally inflated first and with 200 mL of air, to compress the collateral veins at the cardia of the stomach. Inflating the esophageal balloon probably contributes little, since barium x-rays suggest that it does not actually compress the varices (Figure 24–7).
Sengstaken–Blakemore tube with both gastric and esophageal balloons inflated.
The most common serious complication is aspiration of pharyngeal secretions and pneumonitis. Another serious hazard is the occasional instance of esophageal rupture caused by inflation of the esophageal balloon. The esophageal balloon is therefore infrequently used.
About 75% of actively bleeding patients can be controlled by balloon tamponade, usually applied for 6-12 hours. When bleeding has stopped, the balloons are left inflated for another 24 hours. They are then decompressed, leaving the tube in place. If bleeding does not recur, the tube should be withdrawn. The efficacy of other therapies combined with potential complications associated with balloon catheters have led to a marked reduction in the use of the latter approach, which is now reserved as a salvage treatment or temporary bridge in patients who fail medical and endoscopic therapy.
5. Transjugular Intrahepatic Portosystemic Shunt
TIPS is a minimally invasive means of creating a portosystemic shunt by creating a direct communication between the portal and hepatic venous systems within the liver parenchyma. A catheter is introduced through the jugular vein and, under radiologic control, positioned in the hepatic vein. From this point, the portal vein is accessed through the liver, the tract is dilated, and the channel is kept open by inserting an expandable metal stent, which is left in place. This technique is of great value in controlling portal hypertension and variceal bleeding and is used most commonly as a salvage therapy to stop acute bleeding for the 10%-20% of patients in whom medical and endoscopic therapy fails. TIPS is also indicated to prevent rebleeding in patients with advanced liver disease at high risk for recurrent variceal bleeding. In this latter category of patients, early use of TIPS has been shown in randomized controlled trial to improve survival. The shunt remains open in most patients for up to a year, at which point intimal overgrowth lead to thrombosis and occlusion in many cases. The use of polytetrafluoroethylene (PTFE)-covered stents now appears to have improved the patency rate.
TIPS should not be regarded as definitive therapy, however, even though the shunt usually remains patent for many months. Patients with advanced liver disease are the principal candidates for TIPS, proved most useful as a bridge to transplantation. Patients with less severe cirrhosis should generally be considered for beta-blocker therapy and in some cases for surgical devascularization procedure when transplantation is not a suitable option.
The operative procedures to control active bleeding are emergency portosystemic shunt and variceal ligation or esophageal transection.
a. emergency portacaval shunt
Although TIPS, when technically feasible, has largely supplanted more invasive surgical shunts as a salvage procedure for variceal bleed, emergency portacaval shunt success has a success rate of 95% in stopping bleeding in this context. The death rate of the operation is not insignificant, generally related to the status of the patient’s liver function (eg, Child–Pugh classification; Table 24–1) as well as the rate and amount of bleeding and its effects on cardiac, renal, and pulmonary function. Some patients with advanced liver disease, especially those with severe encephalopathy and ascites, have an extraordinarily poor survival regardless of the treatment. In such patients, surgery is usually not warranted, even in the face of continued bleeding. On the other hand, patients with good liver function usually recover after an emergency shunt. A controlled trial showed that the death rate in acutely bleeding Child–Pugh C patients was insignificantly lower after endoscopic sclerotherapy (44%) than after emergency portacaval shunt (50%).
For active bleeding, a nonselective end-to-side portacaval shunt is most commonly performed (Figure 24–8C). A side-to-side portacaval shunt might be preferable in an acutely bleeding patient with severe ascites (Figure 24–8B), and this approach (or a variant such as an H-mesocaval shunt) would be required for someone with BCS.
Types of portacaval anastomoses: A: Normal. B: Side-to-side. C: End-to-side. D: Mesocaval. E: Central splenorenal. F: Distal splenorenal (Warren). The H-mesocaval shunt is not illustrated.
The central splenorenal shunt, in which the portal vein is decompressed via the splenic vein into the left renal vein, is more complicated than portacaval shunts and has no specific advantages. Selective shunts, such as the distal splenorenal (Warren) shunt, in which the gastrosplenic collaterals are decompressed via the splenic vein into the left renal vein, leaving the portal vein intact, are usually too time-consuming for use in emergency operations.
Although the risk of variceal rebleeding is low, approximately 40% of patients develop encephalopathy after portacaval surgical shunting. Hepatic insufficiency is accelerated and liver failure is the cause of death in about two-thirds of those who die after an emergency portacaval shunt. Portacaval shunts can also render liver transplantation more difficult. Renal failure, which is often accompanied by ascites, is another potentially lethal problem. Metabolic alkalosis and delirium tremens are not uncommon postoperatively in alcoholics.
b. esophageal transection
Varices may be obliterated by firing the end-to-end stapler in the distal esophagus after tucking a full-thickness ring of tissue into the cartridge with a circumferential tie. This procedure has gained popularity in the past decade, and in many surgical units it is considered a last resort therapy when nonsurgical methods fail.
If transection is performed, it must be done as soon as it is recognized that a second attempt at sclerotherapy or band ligation has failed. The results (eg, survival) are better in patients with nonalcoholic cirrhosis. Stapled transection has replaced the older technique of direct suture ligation of the varices. Transection must be viewed as an emergency measure to stop persistent bleeding—not as definitive treatment—since the underlying portal hypertension is not corrected and varices recur months later in many patients.
et al.. Predictors of early re-bleeding and mortality after acute variceal hemorrhage in patients with cirrhosis. Gut 2008;57:814.
S Treatment of acute variceal bleeding. Dig Liver Dis 2008;40:328.
et al.. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: a randomized, controlled trial. Hepatology 2008;47:1604.
et al.. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010;362:2370–2379.
et al.. Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis. Ann Intern Med 2008;149:109.
et al.. Comparative study of 2 variants of a modified esophageal transection in the Sugiura-Futagawa operation. Arch Surg[Archives of Surgery Full Text]
Gastroesophageal varices are present in almost half of patients with cirrhosis at the time of diagnosis. Development and growth of esophageal varices each occur at a rate of 7% per year. Patients with varices that have never bled have a 30% chance of bleeding at some point; of those who bleed, 50% die. For patients who do not bleed during the first year after diagnosis of varices, the risk of bleeding subsequently decreases by half and continues to drop thereafter. Patients who have bled once from esophageal varices have a 60%-70% chance of bleeding again, and about two-thirds of repeat bleeding episodes are fatal.
A. Portal Flow and Pressure Measurements
Measurements of pressure and flow in the splanchnic vasculature have been used for diagnosis and as a guide to therapy and prognosis in portal hypertension. Portal pressure can be measured directly at surgery or preoperatively by any of the following techniques:
Wedged hepatic venous pressure (WHVP) accurately reflects free portal pressure when portal hypertension is caused by a postsinusoidal (or sinusoidal) resistance, as in cirrhosis. The portal pressure can be determined with the catheter in the wedged position, corrected by subtracting the free hepatic venous pressure; the HVPG (the pressure gradient from the portal to the hepatic venous systems) can also be determined. This is the most commonly used technique.
Direct measurement of splenic pulp pressure is obtained by a percutaneously placed needle.
Percutaneous transhepatic catheterization of the intrahepatic branches of the portal vein is the method of choice in patients thought to have presinusoidal block or BCS.
Catheterization of the umbilical vein is accomplished through a small incision, and the catheter is threaded into the portal system. With each of these methods, one may also obtain anatomic information by performing angiography through the catheter.
HVPG predicts decompensation and death. Reduction in the HVPG, either spontaneously or after therapy, may help predict the risk of rebleeding in some patients. It has therefore been suggested that HVPG can be used to guide therapy. However, its value currently has been shown primarily in alcoholic liver disease. Also, it is an invasive study that requires special expertise and is not always readily available. Duplex ultrasonography is an accurate noninvasive means of assessing the amount and direction of flow in the portal vein. Preoperatively, duplex ultrasonography is useful to determine patency of the portal vein and direction of flow. Because of spontaneous thrombosis, about 10% of patients with cirrhosis have a portal vein unsuitable for a portacaval shunt. If flow in the portal vein is reversed (hepatofugal), a selective shunt (eg, splenorenal, distal) is not recommended, because it compromises the ability of portal tributaries to serve as an outflow tract for liver blood. Duplex ultrasonography can also be used to follow changes in portal perfusion after shunt operations.
The portal venous anatomy is often studied preoperatively by angiographic techniques. The objectives are to determine the patency, location, and size of the veins tentatively chosen for a shunt, to demonstrate the presence of varices, and to estimate the degree of prograde portal flow. Some of this information can now be obtained less invasively by duplex ultrasonography. When a splenorenal shunt is contemplated, the left renal vein should be opacified, either by injection of the renal artery or renal vein.
The treatment options consist of expectant management, endoscopic sclerotherapy, nonselective beta-blocker (eg, propranolol, nadolol), portosystemic shunts, devascularization of the esophagogastric junction, and miscellaneous rarely used operations. The treatment of patients with varices that have never bled is usually referred to as prophylactic therapy (eg, prophylactic endoscopic variceal ligation (EVL) or prophylactic propranolol). By convention, procedures performed on patients who have bled previously are referred to as therapeutic (eg, therapeutic shunts).
Prophylactic therapy is of value, since the mortality rate of variceal bleeding is high (25%), the risk of bleeding in patients with varices is relatively high (30%), and varices can often be diagnosed before the initial episode of bleeding. In patients who have never had a bleeding episode, the following have been shown to be related to the risk of hemorrhage: Child–Pugh classification, the size of the varices, and the presence of red wale markings (longitudinal dilated venules resembling whip marks) on the varices. This information can be used to identify high-risk patients (up to 65% risk of bleeding within a year) who are most likely to benefit from prophylactic treatment.
In cirrhotic patients without varices, treatment with nonselective beta-blockers is not recommended because they do not prevent the development of varices and are associated with side effects. In patients with low-risk varices (small, no red wale marks, no severe liver dysfunction), nonselective beta-blockers may delay variceal growth and thereby prevent hemorrhage. The alternative is to schedule periodic endoscopic screening for detection of variceal growth, at what time medical treatment can be initiated.
In patients who have never bled but have a high risk (medium to large varices or small varices with red wale markings and/or decompensated cirrhosis), EVL, or nonselective beta-blockers are considered equally adequate, as high-quality randomized controlled trial have concluded to similar survival of patients with either approaches. It has been suggested that beta-blocker therapy should be the first-line treatment, with EVL used in patients who cannot tolerate or have contraindications to beta-blockade. Endoscopic sclerotherapy is no longer routinely used as primary prophylaxis. More recently, low-dose carvediol as shown lower rates of first variceal hemorrhage when compared to EVL (10% vs. 23%), but those results needs to be validated in other trials.
B. Therapy of Patients Who Have Bled Previously
As noted earlier, patients who recover from an episode of variceal bleeding have an approximately 60%-70% chance of bleeding again. Much effort has been expended to ascertain the best treatment for these patients. The methods of greatest interest include nonselective beta-blocker therapy, endoscopic band ligation, and portosystemic shunts.
1. Nonselective beta-blocker therapy
As with patients with esophageal varices who have never bled, nonselective beta-adrenergic blocking agents (propranolol, nadolol) effectively reduce the risk of recurrent bleeding episodes. These agents work by decreasing cardiac output and splanchnic blood flow and consequently portal blood pressure. Chronic propranolol therapy, 20-160 mg twice daily (a dose that reduces resting pulse rate by 25%), decreases by about 40% the frequency of rebleeding from esophageal or gastric varices, deaths from rebleeding, and overall mortality. The benefits are greater in Child–Pugh A and B than in Child–Pugh C cirrhotics. Beta-blocker therapy has been compared to endoscopic sclerotherapy, with no difference in rebleeding or mortality seen but with higher complications in the sclerotherapy group. On the other hand, randomized controlled trials have shown that the combined use of EVL and nonselective beta blockers could further lower the risk of rebleeding. The addition of nitrate drugs to beta-blocker therapy appears to result in a greater reduction of portal pressure compared to beta-blockade alone. This approach is often favored in patients who are not candidates for EVL. Abstinence from alcohol should always be emphasized and may help prevent further bleeding but may not necessarily decrease the mortality related specifically to variceal hemorrhage, as was previously thought.
2. Endoscopic band ligation
Endoscopic band ligation, as described earlier, is an effective means of preventing recurrent bleeding episodes and has been shown to be superior to sclerotherapy in this regard. Both band ligation and beta-blocker therapy appear to be similarly effective in preventing rebleeding. However, the combination of both therapies has been shown to significantly reduce not only the risk of rebleeding but also the recurrence of varices. Thus, combination therapy appears to be the most effective treatment after an initial bleeding episode.
3. Endoscopic sclerotherapy
The technique of endoscopic sclerotherapy was described earlier in this chapter. Sclerotherapy was previously used routinely to reduce the risk of rebleeding but has been replaced by band ligation.
4. Transjugular intrahepatic portosystemic shunt
The TIPS technique is described in the preceding section. TIPS is effective in preventing rebleeding episodes, more so than either endoscopic or pharmacologic therapy alone. However, this advantage is offset by its higher morbidity and mortality rate from the development of hepatic encephalopathy and liver failure. For this reason, as well as the lack of a clear survival or cost-benefit advantage, TIPS is used mainly to salvage patients who fail endoscopic and/or pharmacologic treatment.
TIPS has generally superseded shunt surgery in most patients who fail first-line therapy. A recent large multicenter randomized trial showed that TIPS and surgical shunts had similar rates of rebleeding, encephalopathy, and mortality in Child–Pugh A and B cirrhotic patients. There was a higher incidence of shunt dysfunction in the TIPS patients, perhaps because of the type of stent used, the first generation not being covered with PTFE. The use of TIPS covered with PTFE has significantly lower occlusion rate. The choice between TIPS and surgical shunts therefore currently depends on expertise, anatomical considerations, and patient’s preference.
The objective of surgical procedures used to treat portal hypertension is either to obliterate the varices or to reduce blood flow and pressure within the varices (Table 24–6). A third option, liver transplantation, can treat both the underlying liver dysfunction and the portal hypertension.
Table 24–6.Surgical procedures for esophageal varices. ||Download (.pdf) Table 24–6. Surgical procedures for esophageal varices.
Direct variceal obliteration
Variceal suture ligation
Esophageal transection and reanastomosis
Reduction of variceal blood flow and pressure
Distal splenorenal (Warren)
Left gastric vena caval (Inokuchi)
Reduction of portal blood flow
Splenic artery ligation
Reduction of proximal gastric blood flow
Gastric transection and reanastomosis (Tanner)
Stimulation of additional portasystemic venous collaterals
Measures to preserve hepatic blood flow after portacaval shunt
Arterialization of portal vein stump
Any relatively young patient with cirrhosis who has survived an episode of variceal hemorrhage should be considered a candidate for liver transplantation, since any other form of therapy carries a much higher (about 80%) mortality rate within the subsequent 1-2 years as a result of repeat bleeding or complications of hepatic failure. Obviously, continued alcohol use is a contraindication to transplantation in most patients. The good transplantation candidates, however, should not be subjected to portosystemic shunts or other procedures if it appears that they will come to transplantation in the near future. In general, Child-Pugh A patients are candidates for portal decompression; Child-Pugh C patients are candidates for a transplant. A TIPS (see previous section) is an excellent way to control bleeding while the patient is being prepared for a transplant.
The advent of TIPS has resulted in a marked decline in the number of shunt operations performed. However, surgical shunts are durable, and good risk patients appear to benefit from these procedures.
Portosystemic shunts can be grouped into those that shunt the entire portal system (total shunts) and those that selectively shunt blood from the gastrosplenic region while preserving the pressure-flow relationships in the rest of the portal bed (selective shunts). All of the shunt operations commonly used today reduce the incidence of rebleeding to less than 10%, compared with about 75% in unshunted patients. Unfortunately, the price of this achievement is an operative mortality rate of 5%-20% (depending on the Child–Pugh classification), further impairment of liver function, and an increase in encephalopathy (greater with total shunts). Therefore, since shunts have these potential drawbacks, clinical trials are needed to pinpoint their place within an overall treatment strategy.
In one well-designed trial, patients who had bled previously were randomized to chronic sclerotherapy or a distal splenorenal shunt (Warren shunt, Figure 24–8F). Patients randomized to chronic sclerotherapy who had recurrent episodes of bleeding during treatment (ie, treatment failures, which amounted to 30% of the sclerotherapy group) were then treated surgically (ie, shunted). The results showed that 2-year survival was better among those originally randomized to sclerotherapy (90%) than among those originally assigned to the shunt group (60%). This trial supports a general treatment plan consisting initially of endoscopic therapy and reserving portosystemic shunts for the patients in whom the former fails to control bleeding adequately (Figure 24–6).
The choice of shunt has been the subject of much debate and several randomized trials. The principal question in recent years has been whether encephalopathy and survival are better with a selective shunt (eg, a distal splenorenal shunt, Figure 24–8F) than with a total shunt (eg, a mesocaval or an end-to-side portacaval shunt, Figure 24–8C and 24–8D). The results are conflicting, but in general they support the contention that there is about half as much severe encephalopathy following selective shunts. None of the trials have shown any particular shunt to be associated with longer survival.
3. Severity of hepatic disease and operative risk
The immediate death rate of an elective shunt procedure can be predicted from the patient’s hepatic function as reflected by the Child–Pugh classification (Table 24–1). In addition to operative death rate, the figures also correlate with the death rate in the first postshunt year. Thereafter, survival curves of the different risk classes become reasonably parallel.
The severity of histopathologic changes in liver biopsies correlates with the immediate surgical death rate, the most ominous findings being hepatocellular necrosis, polymorphonuclear leukocyte infiltration, and the presence of Mallory bodies. The extent of histologic change also correlates with the more easily obtained data in the Child–Pugh classification (ie, severe changes occur in class C patients), so results of biopsies have no independent predictive value.
a. types of portosystemic shunts
Figure 24–8 depicts the various shunts in use currently. Although they differ technically, physiologically there are only three different types: end-to-side, side-to-side, and selective.
The end-to-side shunt completely disconnects the liver from the portal system. The portal vein is transected near its bifurcation in the liver hilum and anastomosed to the side of the inferior vena cava. The hepatic stump of the vein is oversewn. Postoperatively, the WHVP (sinusoidal pressure) drops slightly, reflecting the inability of the hepatic artery to compensate fully for the loss of portal inflow. The side-to-side portacaval, mesocaval, mesorenal, and central splenorenal shunts are all physiologically similar, since the shunt preserves continuity between the hepatic limb of the portal vein, the portal system, and the anastomosis. Flow through the hepatic limb of the standard side-to-side shunt is nearly always away from the liver and toward the anastomosis. The extent to which hepatofugal flow is produced by the other types of side-to-side shunts listed previously is not known.
The end-to-side portacaval shunt gives immediate and permanent protection from variceal bleeding and is somewhat easier to perform than a side-to-side portacaval or central splenorenal shunt. Encephalopathy may be slightly more common after side-to-side than end-to-side portacaval shunts. Side-to-side shunts are required in patients with BCS or refractory ascites (when the latter is treated by a portosystemic shunt).
The mesocaval shunt interposes a segment of prosthetic graft or internal jugular vein between the inferior vena cava and the superior mesenteric vein where the latter passes in front of the uncinate process of the pancreas. The mesocaval shunt is particularly useful in the presence of severe scarring in the right upper quadrant or portal vein thrombosis, and in some cases it may be technically easier than a conventional side-to-side portacaval shunt if a side-to-side type of shunt is necessary. In most cases, portal flow to the liver is lost after this shunt. Evidence has been presented, however, that by limiting the diameter of the prosthetic graft to 8 mm (compared with 12- to 20-mm grafts), prograde flow is preserved in the portal vein, which decreases the incidence of postoperative encephalopathy while still preventing variceal hemorrhage.
Selective shunts lower pressure in the gastroesophageal venous plexus while preserving blood flow through the liver via the portal vein.
The distal splenorenal (Warren) shunt involves anastomosing the distal (splenic) end of the transected splenic vein to the side of the left renal vein, plus ligation of the major collaterals between the remaining portal and isolated gastrosplenic venous system. The latter step involves division of the gastric vein, the right gastroepiploic vein, and the vessels in the splenocolic ligament. The operation is more difficult and time consuming than conventional shunts and except for the experienced operator is probably too complex for emergency portal decompression. If mobilization of the splenic vein is hazardous, the renal vein may be transected and its caval end joined to the side of the undisturbed splenic vein. The segment of splenic vein between the anastomosis and the portal vein is then ligated. Surprisingly, this seems to have little permanent effect on renal function as long as the remaining tributaries are preserved on the oversewn renal vein stump.
In contrast to total shunts, the Warren shunt does not improve ascites and should not be performed in patients whose ascites has been difficult to control. Preoperative angiography should be performed to determine if the splenic vein and left renal vein are large enough and close enough together for performance of this shunt. Recent pancreatitis may preclude safe dissection of the splenic vein from the undersurface of the pancreas.
Another type of selective shunt (Inokuchi shunt) consists of joining the left gastric vein to the inferior vena cava by a short segment of autogenous saphenous vein. The procedure has not become popular, perhaps because of its technical complexity.
Selective shunts tend to become less selective over several years as new collaterals develop between the high-pressure and low-pressure regions of the portal system. This is accompanied by a gradual decrease in portal pressure (measured by WHVP) and evolution of the procedure into a version of side-to-side total shunt. The enlargement postoperatively of small venous tributaries entering the distal splenic vein from the pancreas suggests that this is the path by which nonselectivity develops. It is possible that this can be avoided by mobilizing the splenic vein all the way to the hilum (dividing these small vessels) before performing the splenorenal anastomosis.
A reasonable approach to shunt selection is as follows.
The distal splenorenal shunt is the first choice for elective portal decompression. If ascites is present or the anatomy is unfavorable, an end-to-side portacaval shunt is preferred. Side-to-side shunts would be done for patients with severe ascites or BCS. The H-mesocaval and central splenorenal shunts are reserved for special anatomic situations in which the above operations are unsuitable. An end-to-side shunt or H-mesocaval shunt is performed for emergency decompression.
Portacaval and distal splenorenal shunts are often followed by a rise in platelet count in patients with secondary hypersplenism. The response is unpredictable, however, and hypersplenism need not necessarily dictate the type of shunt since it rarely produces clinical manifestations. A central splenorenal shunt, in which splenectomy is performed, should not be considered preferable to other kinds of shunts just because the patient has a low platelet count.
c. results of portosystemic shunts
Over 90% of portosystemic shunts remain patent, and the incidence of recurrent variceal bleeding is less than 10%. The 5-year survival rate after a portacaval shunt for alcoholic liver disease averages 45%. Some degree of encephalopathy develops in 15%-25% of patients. Severe encephalopathy is seen in about 20% of alcoholics following a total shunt; its occurrence is not related to the severity of preshunt encephalopathy.
D. Devascularization Operations
The objective of devascularization is to destroy the venous collaterals that transport blood from the high-pressure portal system into the veins in the submucosa of the esophagus.
The Sugiura-Futugawa procedure initially described in 1973 was done in two stages. The first stage was performed through a thoracotomy and consisted in division of the dilated venous collaterals between esophagus and adjacent structures, transection of the esophagus at the level of the diaphragm, and reanastomosis. The second stage, a laparotomy, was performed immediately after the thoracotomy if the patient was actively bleeding or deferred 4-6 weeks in elective cases. In the second stage of the operation, the upper two-thirds of the stomach was devascularized, and selective vagotomy, pyloroplasty, and splenectomy performed.
More recently, an analogous one-stage operation has been described in many series and performed through laparotomy that consists of splenectomy, devascularization of 8-10 cm of distal esophagus, devascularization of the lesser and greater curvature with ligation of the left gastric and gastroepiploic vessels, transection and end-to-end anastomosis of the lower esophagus 4-5 cm above the gastroesophageal junction (EEA-stapler), pyloroplasty, and insertion of a feeding jejunostomy.
In Eastern and Western series published between 1980 and 1999, the operative mortality ranged from 0% to 36%, up to 80% in Child C patients, the variceal rebleeding rate from 0% to 37%, encephalopathy from 0% to 22%, and esophageal stenosis ranged from 2% to 37%. For cirrhotic patients with extensive portal thrombosis, for who portosystemic shunt cannot be performed, devascularization operations can offer a good alternative.
E. Miscellaneous Operations
Attempts have also been made to decrease portal pressure by decreasing splanchnic inflow through splenectomy or splenic artery ligation. Diseases characterized by marked splenomegaly may rarely be associated with portal hypertension as a consequence of increased splenic blood flow, which has been known to reach levels as high as 1000 mL/min. Splenic blood flow may occasionally be increased enough in patients with cirrhosis to contribute significantly to the portal hypertension. However, splenectomy or splenic artery ligation in cirrhosis most often gives only a transient decrease in portal pressure, and over half of patients having these operations bleed again. Some workers have suggested that the absolute size of the splenic artery (a crude index of splenic flow) correlates with the clinical effectiveness of splenic artery ligation, a good result being predictable if the diameter of the artery is 1 cm or greater.
JC Prevention of recurrent variceal bleeding. Dig Liv Dis 2008;40:337.
J Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med 2010;362:823.
RJ Portal hypertension and variceal bleeding: unresolved issues. Summary of an AASLD and EASLD single topic conference. Hepatology 2008;47:1764.
et al.. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol 2007;102:2842.
et al.. Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis. Ann Intern Med 2008;149:109.
et al.. Distal splenorenal shunt versus TIPS for refractory variceal bleeding: a prospective randomized controlled trial. Gastroenterology 2006;130:1643.
et al.. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt insertion: a decade of experience. QJM 2008;101:493.
et al.. Randomized controlled trial of carvediol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology 2009;50:825.
et al.. Long-term results with the modified Sugiura procedure for the management of variceal bleeding: standing the test of time in the treatment of bleeding esophageal varices. Word J Surg 2012;36:659.
EXTRAHEPATIC PORTAL VENOUS OCCLUSION
Extrahepatic portal vein obstruction is one of many causes of noncirrhotic portal hypertension, the other common cause being noncirrhotic portal fibrosis. These disorders are distinct but appear to share several similar etiological and pathogenetic features, the most notable of which is the clinical manifestation of portal hypertension in the absence of significant hepatic parenchymal dysfunction.
Idiopathic portal vein thrombosis (in the absence of liver disease) is a relatively common cause of portal hypertension in developing countries but is less prevalent in the West. This diagnosis accounts for most cases of portal hypertension in childhood (80%-90%) and for a smaller proportion of cases in adults. Neonatal septicemia, omphalitis, umbilical vein catheterization for exchange transfusion, and dehydration have all been incriminated as possible causes, but collectively they can be implicated in less than half of cases. The causes of portal vein thrombosis in adults include hepatic tumors, cirrhosis, trauma, pancreatitis, pancreatic pseudocyst, myelofibrosis, thrombotic states (eg, protein C deficiency), and sepsis; in particular, cirrhosis and/or hepatocellular carcinoma need to be considered in adult patients. In adult, systemic anticoagulation result in complete portal vein recanalization in approximately 38.3% of cases and partial recanalization in 15%.
Although clinical manifestations may be delayed until adulthood, 80% of patients with idiopathic portal vein thrombosis present between 1 and 6 years of age with variceal bleeding, although hemorrhage from ectopic varices at other locations in the gastrointestinal tract is not uncommon. About 70% of hemorrhages are preceded by a recent upper respiratory tract infection. Some of these children first come to medical attention because of splenomegaly and pancytopenia. Failure to recognize the underlying problem has occasionally led to splenectomy, with the result that portal decompression using the splenic vein is precluded. Ascites is uncommon except transiently after bleeding. Liver function is either normal or only slightly impaired, which probably accounts for the low incidence of overt encephalopathy. There is an increased frequency of neuropsychiatric problems, which may be a subtle form of encephalopathy.
Portal biliopathy refers to abnormalities of the extrahepatic bile ducts, usually the result of bile duct compression from large, dilated venous collaterals within the porta hepatis. These changes result in marked irregularities of the biliary wall that can progress to strictures and even obstructive jaundice and cholangitis in some cases; secondary biliary cirrhosis has been reported. Biliopathy is commonly seen on imaging studies, but most patients remain free of related symptoms.
Because the patient’s general condition and liver function are good, the death rate for sudden massive bleeding is below that for other types of portal hypertension. The diagnosis can be confirmed with cross-sectional imaging or direct mesenteric angiography. WHVP is normal to slightly elevated; liver biopsies are normal or may show mild to moderate periportal fibrosis.
Bleeding episodes in children under age 8 years are usually self-limited and often do not require endoscopic sclerotherapy, administration of vasopressin, or balloon tamponade. Even if such interventions are necessary, however, the bleeding episodes are self-limited and uncommonly fatal, so emergency operations are rarely necessary.
Thrombosed portal veins are unsuitable for shunt procedures. Cavomesenteric shunts are best for young children, whose vessels are small. In older individuals, treatment should be started with sclerotherapy; if that fails to control the bleeding, a distal splenorenal shunt is preferred. Splenectomy alone has no permanent effect and sacrifices the splenic vein, which might be needed later for a shunt operation. Shunts in small children have a high rate of spontaneous thrombosis and should be avoided, if possible, until approximately 8-10 years of age, when the vessels are of larger caliber. Even still, using precise technique, some surgeons have obtained a high rate of anastomotic patency in the very young. Encephalopathy and hepatic dysfunction many years after a total shunt may be improved if converted to a selective shunt.
Splenectomy alone is never indicated in this disease, either for hypersplenism or in an attempt to reduce portal pressure, because the rebleeding rate is 90% and fatal postsplenectomy sepsis is not uncommon. If it is not possible to construct an adequate shunt, expectant management is the best strategy. Repeated severe bleeding episodes should be treated by transendoscopic sclerosis. Esophagogastrectomy with colonic interposition may be effective but should be considered a last resort.
et al.. Management of acute non-cirrhotic and non-malignant portal vein thrombosis: a systematic review. World J Surg
et al.. Non-cirrhotic intrahepatic portal hypertension. Gut 2008;57:1529.
Isolated thrombosis of the splenic vein is a rare cause of variceal bleeding that can be cured by splenectomy. The splenic venous blood, blocked from its normal route, flows through the short gastric vessels to the gastric fundus and then into the left gastric vein, continuing toward the liver. This phenomenon is called left-sided (or sinistral) portal hypertension. As the blood traverses the stomach, large gastric varices are produced that may rupture and bleed. Characteristically, the collateral pattern does not involve the esophagus, so esophageal varices are uncommon.
The principal causes of this syndrome are pancreatitis, pancreatic pseudocyst, neoplasm, and trauma. The mean incidence of splenic vein thrombosis associated with chronic and acute pancreatitis is estimated at 12.4% and 22.6% respectively, with an overall bleeding rate of 12.3%. Splenomegaly is present in two-thirds of patients. Diagnosis can be made by selective splenic arteriography that opacifies the venous phase, but more commonly nowadays on CT scan with portal phase imaging. Splenectomy is curative. Many cases of splenic vein thrombosis are unaccompanied by bleeding varices, and in such cases, no therapy is required. Treatment of acute bleeding from gastric varices is generally endoscopic, and endoscopic variceal obturation with tissue glue appears to be superior to band ligation or sclerotherapy.
et al.. Natural history of pancreatitis-induced splenic vein thrombosis: a systematic review and meta-analysis of its incidence and rate of gastrointestinal bleeding. HPB 2011;13:1477.
et al.. Pattern of venous collateral development after splenic vein occlusion in an extended Whipple procedure: comparison with collateral vein pattern in cases of sinistral portal hypertension. J Gastrointest Surg 2011;15:2070.
BCS is a rare disorder resulting from obstruction of hepatic venous outflow, which can arise at several different levels, from the small hepatic venous tributaries within the liver parenchyma to the major hepatic venous trunks to the inferior vena cava up to the level of the right atrium. The prevalence of BCS is estimated as 1:100,000, and the largest published series reported on 237 patients treated at four centers in the United States, the Netherlands, and France between 1984 and 2001. Most cases are caused by spontaneous thrombosis of the hepatic veins, often associated with myeloproliferative disorders (polycythemia vera, essential thrombocytosis) or the use of birth control pills. Other common associated conditions include factor V Leiden and factor II gene mutations. Other predisposing factors include protein C and S deficiencies, antiphospholipid syndrome, antithrombin III deficiency, paroxysmal nocturnal hemoglobinuria, Behçet syndrome, and trauma. Some patients present with idiopathic membranous stenosis of the inferior vena cava located between the hepatic veins and right atrium, which is usually associated with secondary thrombosis of the hepatic veins; this condition appears to be more common in Asia than in Western countries. Many patients with BCS are HBsAg-positive, and others have malignancies (eg, hepatocellular carcinoma). Vena caval webs were once thought to be congenital, but more recent evidence suggests that they are the consequence of thrombus formation. Primary BCS originates from within the lumen of the hepatic veins or venules, and occlusion results from thrombosis, webs, or endophlebitis. By contrast, secondary BCS results from extrinsic compression of the venous outflow tract, usually related to a neoplasm or abscess.
Veno-occlusive disease and congestive hepatopathy are two conditions that can cause hepatic venous outflow obstruction, and although the clinical picture of both may be indistinguishable from that of BCS, they differ in the level of obstruction and in predisposing conditions. Veno-occlusive disease is primarily a problem affecting the sinusoids and terminal venules, while congestive hepatopathy reflects a problem at the level of the heart.
Posthepatic (postsinusoidal) obstruction raises sinusoidal pressure, which is transmitted proximally to cause portal hypertension. Because the parenchyma is relatively free of fibrosis, filtration across the sinusoids and hepatic lymph formation increase greatly, producing marked ascites.
Symptoms usually begin with a mild prodrome consisting of vague right upper quadrant abdominal pain, postprandial bloating, and anorexia. After weeks or months, a more florid picture develops consisting of gross ascites, hepatomegaly, and hepatic failure. At this stage, the AST is usually markedly increased, the serum bilirubin is slightly elevated, and the alkaline phosphatase is inconsistently abnormal.
Except in patients with membranous obstruction of the vena cava, liver scans (CT or MRI) usually demonstrate a marked perfusion abnormality throughout most of the liver except for a small central area representing the caudate lobe, whose venous outflow is spared (it goes directly to the vena cava through multiple small tributaries). CT scans show pooling of intravenous contrast media in the periphery of the liver; patent hepatic veins cannot be seen on ultrasound scans. An enlarged azygos vein may be seen on chest x-rays of patients with caval obstruction. Liver biopsy reveals grossly dilated central veins and sinusoids, pericentral necrosis, and replacement of hepatocytes by red blood cells. Centrilobular fibrosis develops late. The clinical diagnosis should be confirmed by venography, which shows the hepatic veins to be obstructed, usually with a beaklike deformity at their orifice. The inferior vena cava should be opacified to verify its patency, which is a requirement for a successful portacaval shunt. Previously, direct venography was used, but the required information may now be obtained using noninvasive methods, such as CT or MR angiography. The x-rays may show compression of the intrahepatic cava by the congested liver.
Treatment of BCS relies on expert consensus given the low incidence of this disease. Anticoagulation is recommended in the presence of recent or long-standing thrombosis to allow recanalization or to avoid propagation of venous thrombosis. Management of ascites and treatment or prevention of portal hypertension and variceal hemorrhage follows the same algorithms as for cirrhotic patients. Surgical or radiological approaches to relieve sinusoidal pressure have been advocated and are now considered appropriate only for symptomatic patients who do not improve with medical management. In recent years, the development of interventional radiology techniques using thrombolysis and angioplasty has shown possible to insert TIPS in selected patients with recent thrombosis or with short-length stenosis of the IVC or hepatic veins with good outcomes. Portosystemic surgical shunts are considered effective for relieving sinusoidal hypertension with the potential to reverse hepatic necrosis and prevent cirrhosis.
Focal membranous obstruction of the suprahepatic cava may be treated by excision of the lesion with or without the addition of a patch angioplasty. Some cases may be managed nonsurgically by percutaneous transluminal balloon dilation of the stenosis. Occlusion of the inferior vena cava by thrombosis or compression from the liver requires a mesoatrial shunt using a prosthetic vascular graft. Because the incidence of graft thrombosis is relatively high, it may be advisable to perform a second-stage side-to-side portacaval shunt a few months after mesoatrial shunt decompression of the liver in patients with hepatic vein thrombosis whose vena cava was originally blocked by a congested liver. Development of hepatocellular carcinoma is common in patients with membranous obstruction of the vena cava. The postoperative results are excellent in patients without malignant neoplasms.
Liver transplantation is required when medical treatment and portosystemic shunts fail in patients presenting progressive liver failure either from cirrhosis or as part of the acute syndrome. The 1-, 5-, 10-year survival rates with transplantation are of 76%, 71%, and 68%, respectively, and the risk of later hepatocellular carcinoma is eliminated.
et al.. Portal vein thrombosis and Budd-Chiari syndrome. Hematol Oncol Clin North Am 2011;25:1049.
et al.. TIPS for Budd-Chiari syndrome: long-term results and prognostic factors in 124 patients. Gastroenterology 2008;135:808.
JD, San Miguel
JA Budd-Chiari syndrome: illustrated review of current management. Liver Int 2008;28:455.
et al.. Spectrum of imaging in Budd-Chiari syndrome. J Med Imaging Radiat Oncol 2012;569:75.
Ascites is a common manifestation of chronic liver disease, resulting from sinusoidal hypertension as the specific pathophysiologic abnormality. Ascites in hepatic disease results from (1) increased formation of hepatic lymph (from sinusoidal hypertension), (2) increased formation of splanchnic lymph (from splanchnic vasodilatation), (3) hypoalbuminemia, and (4) salt and water retention by the kidneys. Before therapy is started, paracentesis should be performed and the following examinations made on a sample of ascitic fluid: (1) Culture and leukocyte count—spontaneous bacterial peritonitis is common and may be clinically silent. A white count above 250/μL is highly suggestive of infection. (2) LDH levels—a ratio of LDH in ascites to serum that exceeds 0.6 suggests the presence of cancer or infection. (3) Serum amylase—a high level suggests pancreatic disease. (4) Albumin—the ratio of serum to ascites albumin concentrations is above 1.1 in liver disease and below 1.1 in malignant ascites. (5) Cytology—this is pertinent only in patients with a cancer diagnosis or a suspicion of cancer.
Nonhepatic ascites can result from congestive heart failure, chylous leak, peritoneal carcinomatosis, infections such as tuberculosis, coccidiomycosis, and chlamydia, and some autoimmune disease involving the connective tissues, such as systemic lupus erythematosus. Treatments of ascites in these contexts depend on the underlying cause and are not discussed in this chapter.
In general, the intensity of medical therapy required to control ascites can be predicted from the pretreatment 24-hour urine Na+ output as follows: A Na+ output below 5 mEq/24 h requires strong diuretics; 5-25 mEq/24 h, mild diuretics; and above 25 mEq/24 h, no diuretics. Initial treatment is usually with spironolactone, 200 mg/d. The objective is to stimulate a weight loss of 0.5-0.75 kg/d except in patients with peripheral edema who can mobilize fluid faster. If spironolactone alone is insufficient, another drug such as furosemide should be added. A loop diuretic (eg, furosemide, ethacrynic acid) should be given only in combination with a distally acting diuretic (eg, spironolactone, triamterene). Alternatively, massive ascites may be treated by one or more large volume (eg, 5-L) paracenteses; this is often accompanied by an intravenous infusion of albumin, although the benefits of albumin remain controversial. Caution is required in patients with evidence of renal dysfunction, since aggressive fluid removal can result in renal failure. Close monitoring of serum electrolytes should be done. Because the development of ascites in cirrhosis is a result of renal sodium retention, dietary sodium restriction is a mainstay of treatment. A typical American diet contains 4-6 g of sodium per day. Patients are educated to have a diet of maximum 2 g of sodium per day. Fluid restriction is only indicated in patients with severe hyponatremia, but all should avoid excessive fluid intake.
A history of ascites that has been easy to control need not influence the choice of shunt operation intended to treat variceal bleeding. When ascites has been severe, however, a side-to-side shunt (eg, side-to-side portacaval, H-mesocaval, central splenorenal) may be considered, because it reduces sinusoidal as well as splanchnic venous pressure. A side-to-side portacaval shunt is rarely indicated just to treat ascites (eg, in patients in whom several LeVeen shunts have thrombosed), although the incidence of severe postoperative encephalopathy is high under these circumstances. TIPS is another effective intervention for refractory ascites, probably a better option than repeated paracentesis in good-risk patients, although there is an associated risk of hepatic encephalopathy.
B. Peritoneal-Jugular Shunt (LeVeen Shunt, Denver Shunt)
Refractory ascites can be treated with a LeVeen shunt—a subcutaneous Silastic catheter that transports ascitic fluid from the peritoneal cavity to the jugular vein. A small unidirectional valve sensitive to a pressure gradient of 3-5 cm H2O prevents backflow of blood. A modification called the Denver shunt contains a small chamber that can be used as a pump to clear the line by external pressure. In practice, Denver shunts become blocked more often than LeVeen shunts.
In patients with ascites due to cirrhosis, use of a LeVeen shunt should be confined to those who fail to respond to high doses of diuretics (eg, 400 mg of spironolactone and 400 mg of furosemide daily) or who repeatedly develop encephalopathy or azotemia during diuretic therapy.
Peritoneovenous shunts may also be used for ascites associated with cancer. The best results occur in patients whose ascitic fluid contains no malignant cells. A LeVeen shunt is of benefit in BCS but is ineffective for chylous ascites. Because the incidence of complications and early shunt thrombosis is high, a LeVeen shunt is relatively contraindicated if the ascitic fluid is grossly bloody, contains many malignant cells, or has a high protein concentration (> 4.5 g/dL). The incidence of tumor embolization is low (5%).
The ascitic fluid should be cultured a few days before the shunt is inserted. Antibiotic coverage should be given for the procedure. The operation can be done with local anesthesia.
Postoperatively, the patient is outfitted with an abdominal binder and instructed to perform respiratory exercises against mild pressure to increase abdominal pressure and flow through the shunt. Dietary salt should not be restricted. A functioning LeVeen shunt alone is unable to fully eliminate the ascites, but it improves symptoms related to distention and renders the patient much more responsive to diuretics. Therefore, furosemide should be administered postoperatively.
An average of 10 kg of weight is lost during the first 10 days after the operation, and eventually the abdomen assumes a normal configuration. Nutrition and serum albumin levels often improve postoperatively. Urinary sodium excretion increases promptly, and renal function may improve in patients with the hepatorenal syndrome. Serious complications and deaths are most common in patients with advanced hepatorenal syndrome or a serum bilirubin level greater than 4 mg/dL. Although some patients eventually bleed from varices following insertion of a LeVeen shunt, the shunt itself does not increase the risk of bleeding and actually decreases portal pressure. Thus, a previous episode of variceal bleeding is not a contraindication for this procedure. Disseminated intravascular coagulation (manifested by increased fibrin split products, decreased platelet count, etc) occurs in more than half of cases but is clinically relevant in only a few. The frequency and severity of disseminated intravascular coagulation may be minimized by emptying most of the ascitic fluid from the abdomen during operation and partially replacing it with Ringer lactate solution. Lethal septicemia may occur if the ascitic fluid is infected at the time the shunt is inserted. In about 10% of cases, the valve becomes thrombosed and must be replaced.
Hydrothorax, usually on the right side, may develop in patients with cirrhosis and ascites. The fluid reaches the chest through a pinhole opening in the membranous portion of the diaphragm, a pathway that can be demonstrated by aspirating the thoracic fluid, injecting technetium 99mTc colloid into the ascites fluid, and observing rapid accumulation of the label in the chest. Treatment consists of a peritoneovenous shunt and injection of a sclerosing agent into the pleural cavity after it has been tapped dry. If a leak persists, it may be closed surgically by thoracotomy.
et al.. Renal failure and cirrhosis: a systematic review of mortality and prognosis. J Hepatol 2012;56:810.
et al.. Management of critically-ill cirrhotic patients. J Heptaol 2012;56 suppl 1:S13–S24.
FD Ascites. Clin Liver Dis 2012;16;285.
et al.. Denver peritoneovenous shunts for the management of malignant ascites: a review of the literature in the post LeVeen era. Am Surg 2011;77:1070.
Central nervous system abnormalities may be seen in patients with chronic liver disease and are especially likely after portacaval shunts. Portosystemic encephalopathy, ammonia intoxication, hepatic coma, and meat intoxication are older terms used to refer to this condition. The manifestations range from lethargy to coma—from minor personality changes to psychosis—from asterixis to paraplegia. Hypothermia and hyperventilation may precede coma. The changes may be quite subtle and detectable only with the use of neuropsychological or neurophysiological testing.
Hepatic encephalopathy is a reversible metabolic neuropathy that results from the action of chemicals absorbed from the gut on the brain. Increased exposure of the brain to these agents is the result of impaired hepatic metabolism due to cirrhosis or spontaneous or surgically created shunts of portal venous blood around the liver and increased permeability of the blood-brain barrier. The chemical agents responsible for encephalopathy form from the action of colonic bacteria on protein within the gut. Potential aggravating factors include gastrointestinal hemorrhage, constipation, azotemia, hypokalemic alkalosis, infection, excessive dietary protein, and sedatives (Table 24–7). Four main chemical mediators of this syndrome currently attract the most attention. Low-grade cerebral edema appears to be a major component of the pathophysiologic process.
Table 24–7.Factors contributing to encephalopathy. ||Download (.pdf) Table 24–7. Factors contributing to encephalopathy.
Increased systemic toxin levels
Extent of portal-systemic venous shunt
Depressed liver function
Intestinal protein load
Increased sensitivity of the central nervous system
Age of patient
Sedatives, narcotics, tranquilizers
Hypoxia, hypoglycemia, myxedema
A. Amino Acid Neurotransmitters
Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, produces a state similar to hepatic encephalopathy when given experimentally. It is normally synthesized in the brain and by bacteria within the colon; GABA in the gastrointestinal tract is normally degraded by the liver and is found in increased levels in the serum of patients with hepatic encephalopathy. The passage of GABA across the blood-brain barrier is increased in hepatic encephalopathy. Experiments also indicate the presence of increased numbers of GABA receptors in encephalopathy and increased GABA-ergic tone, perhaps due to a benzodiazepine receptor agonist ligand on the receptor complex (GABA/benzodiazepine receptor). This has raised the possibility of treating encephalopathy with benzodiazepine antagonists, and the drug flumazenil has shown promise in preliminary trials.
Ammonia is produced in the colon by bacteria and is absorbed and transported in portal venous blood to the liver, where it is extracted and converted to glutamine. Ammonia concentrations are elevated in the arterial blood and cerebrospinal fluid of patients with encephalopathy, and experimental administration of ammonia produces central nervous system symptoms.
C. False Neurotransmitters
According to this theory, cerebral neurons become depleted of normal neurotransmitters (norepinephrine and dopamine), which are partially replaced by false neurotransmitters (octopamine and phenylethanolamine). The result is inhibition of neural function. Serum levels of branched-chain amino acids (leucine, isoleucine, valine) are decreased, and levels of aromatic amino acids (tryptophan, phenylalanine, tyrosine) are elevated in patients with encephalopathy. Because these two classes of amino acids compete for transport across the blood-brain barrier, the aromatic amino acids have increased access to the central nervous system, where they serve as precursors for false neurotransmitters. Trials of therapy with supplements of branched-chain amino acids have given conflicting results.
D. Synergistic Neurotoxins
This theory postulates that ammonia, mercaptans, and fatty acids, none of which accumulate in the brain in amounts capable of producing encephalopathy, have synergistic effects that produce the full-blown syndrome in patients with liver disease.
Encephalopathy is a major side effect of portacaval shunt and is to some extent predictable. Elderly patients are considerably more susceptible. Patients with alcoholic liver disease fare better than those with postnecrotic or cryptogenic cirrhosis, apparently owing to the invariable progression of liver dysfunction in the latter. Good liver function partially protects against encephalopathy. If the liver has adapted to complete or nearly complete diversion of portal blood before operation, a surgical shunt is less apt to depress liver function further. For example, patients with thrombosis of the portal vein (complete diversion and normal liver function) rarely experience encephalopathy after portosystemic shunt. Encephalopathy is less common after a distal splenorenal (Warren) shunt than after other kinds of shunts.
Increased intestinal protein, whether of dietary origin or from intestinal bleeding, aggravates encephalopathy by providing more substrate for intestinal bacteria. Constipation allows more time for bacterial action on colonic contents. Azotemia results in higher concentration of blood urea, which diffuses into the intestine, is converted to ammonia, and is then reabsorbed. Hypokalemia and metabolic alkalosis aggravate encephalopathy by shifting ammonia from extracellular to intracellular sites where the toxic action occurs.
Arterial ammonia levels are usually high, although encephalopathy can certainly be present with a normal ammonia level. The presence of high levels of glutamine in the cerebrospinal fluid may help distinguish hepatic encephalopathy from other causes of coma. Electroencephalography is more sensitive than clinical evaluation in detecting minor involvement. The changes are nonspecific and consist of slower mean frequencies. Studies performed at different times can be compared to assess the effects of therapy.
Acute encephalopathy is treated by controlling precipitating factors, halting all dietary protein intake, cleansing the bowel with purgatives and enemas, and administering antibiotics (neomycin or ampicillin) or lactulose. Neomycin may be given orally or by gastric tube (two to four times daily) or rectally as an enema (1% solution one or two times daily). At least 1600 kcal of carbohydrate should be provided daily, along with therapeutic amounts of vitamins. Blood volume must be maintained to avoid prerenal azotemia. After the patient responds to initial therapy, dietary protein may be started at 20 g/d and increased by increments of 10-20 g every 2-5 days as tolerated.
Chronic encephalopathy is treated by restriction of dietary protein, avoidance of constipation, and elimination of sedatives, diuretics, and tranquilizers. To avoid protein depletion, protein intake must not be chronically reduced below 50 g/d. Vegetable protein in the diet is tolerated better than animal protein. Lactulose, a disaccharide unaffected by intestinal enzymes, is the drug of choice for long-term control. When given orally (20-30 g three or four times daily), it reaches the colon, where it stimulates bacterial anabolism (which increases ammonia uptake) and inhibits bacterial enzymes (which decreases the generation of nitrogenous toxins). Its effect is independent of colonic pH. A related compound outside the United States, lactitol (β-galactoside sorbitol), is also effective and appears to work faster. As a powder, it is easier to use than liquid lactulose. Intermittent courses of oral neomycin or metronidazole may be given if lactulose therapy and preventive measures are inadequate.
F Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008;57:1156.
F Hepatic encephalopathy 2012. Clin Liver Dis 2012;16:301.
Hepatic abscesses may be bacterial, parasitic, or fungal in origin. In the United States, pyogenic abscesses are the most common, followed by amebic abscesses (see Chapter 8). Unless otherwise indicated, the remarks in this section refer to bacterial abscesses.
Cases are about evenly divided between those with a single abscess and those with multiple abscesses. About 90% of right lobe abscesses are solitary, while only 10% of left lobe abscesses are solitary.
In most cases, the development of a hepatic abscess follows a suppurative process elsewhere in the body. Many abscesses are due to direct spread from biliary infections such as empyema of the gallbladder or protracted cholangitis. Abdominal infections such as appendicitis or diverticulitis may spread through the portal vein to involve the liver with abscess formation. About 40% of patients have an underlying malignancy. Other cases develop after generalized sepsis from bacterial endocarditis, renal infection, or pneumonitis. In 25% of cases, no antecedent infection can be documented (cryptogenic abscesses). Rare causes include secondary bacterial infection of an amebic abscess, hydatid cyst, or congenital hepatic cyst.
In most cases, the organism is of enteric origin.
Escherichia coli, Klebsiella pneumoniae, bacteroides, enterococci (eg, Streptococcus faecalis), anaerobic streptococci (eg, Peptostreptococcus), and microaerophilic streptococci are most common. Staphylococci, hemolytic streptococci, or other gram-positive organisms are usually found if the primary infection is bacterial endocarditis or pneumonitis.
When liver abscess develops in the course of another intra-abdominal infection such as diverticulitis, it is accompanied by increasing toxicity, higher fever, jaundice, and a generally deteriorating clinical picture. Right upper quadrant pain and chills may appear.
In other cases, the diagnosis is much less obvious, since the illness develops insidiously in a previously healthy person. In these, the first symptoms are usually malaise and fatigue, followed after several weeks by fever. Epigastric or right upper quadrant pain is present in about half of cases. The pain may be aggravated by motion or may be referred to the right shoulder.
The course of fever is often erratic, and spikes to 40-41°C are common. Chills are present in about 25% of cases. The liver is usually enlarged and may be tender to palpation. If tenderness is severe, the condition may be confused with cholecystitis.
Jaundice is unusual in solitary abscesses unless the patient’s condition is worsening. Jaundice is often present in patients with multiple abscesses and primary disease in the biliary tree and in general is a bad prognostic sign.
Leukocytosis is present in most cases and is usually over 15,000/μL. A small group of patients, usually the most seriously ill, may fail to develop leukocytosis. Anemia is present in most. The average hematocrit is 33%.
Serum bilirubin is usually normal except in patients with multiple abscesses or biliary obstruction or when hepatic failure has supervened. Alkaline phosphatase is often elevated even in the presence of a normal bilirubin.
X-ray changes present in the right lung in about one-third of cases consist of basilar atelectasis or pleural effusion. The right diaphragm may be elevated and less mobile than the left.
Plain films of the abdomen are usually normal or show only hepatomegaly. In a few patients, an air-fluid level in the region of the liver reveals the presence and location of the abscess. Distortion of the contour of the stomach on upper gastrointestinal series may be seen with large abscesses involving the left lobe.
Ultrasound and CT scans are the most useful diagnostic tests, providing accurate information regarding the presence, size, number, and location of abscesses within the liver. CT scans have the added advantage of being able to demonstrate abscesses or neoplasms elsewhere in the abdomen. The radioisotope liver scintiscan is able to demonstrate most liver abscesses but is nonspecific, gives little other useful information, and is therefore not helpful.
In many cases, early findings may be so vague that hepatic abscess is not even considered. The multiple other causes of malaise, weight loss, and anemia would enter into the differential diagnosis. With spiking fevers, one must consider all the causes of fever of unknown origin. Failure to entertain the idea of hepatic abscess and to obtain the necessary scans leads to most errors in diagnosis.
Once imaging tests have demonstrated the abscess, the responsible organisms must be identified. Amebiasis should be considered in cases of a solitary abscess. Compared with amebic abscesses, pyogenic liver abscesses are seen more often in patients older than 50 years and are associated with jaundice, pruritus, sepsis, a palpable mass, and elevated bilirubin and alkaline phosphatase levels. Patients with amebic abscesses more often have been to an endemic area and have abdominal pain and tenderness, diarrhea, hepatomegaly, and positive serologic tests for amebiasis.
Intrahepatic spread of infection may create multiple additional abscesses and is responsible for some failures after treatment of an apparently solitary abscess. As the untreated abscess expands, rupture may occur in the pleural or peritoneal cavity, usually with catastrophic results. Septicemia and septic shock are common terminal complications of diffuse hepatic infection. Hepatic failure may develop in addition to uncontrolled sepsis, or it may predominate over signs of infection.
Hemobilia may follow bleeding from the vascular wall into the abscess cavity. In this case, hepatic artery embolization or ligation may be required to control bleeding.
Antibiotics should be started promptly. Initial coverage, before culture results are available, should be adequate for E coli, K pneumoniae, bacteroides, enterococci, and yanaerobic streptococci and consequently would usually include an aminoglycoside, clindamycin or metronidazole, and ampicillin. The regimen may be modified later according to the results of cultures.
About 80% or more of patients with liver abscesses are adequately treated by drainage catheters inserted percutaneously under ultrasound or CT guidance. Whether the patient has a single abscess or multiple abscesses, this is usually the most appropriate initial therapy. The catheters can be removed in 1-2 weeks after output becomes nonpurulent and scant.
In about 40% of patients, the catheters do not drain well following initial placement and must be repositioned. The principal advantage of percutaneous drainage is lower morbidity compared to open drainage, although not necessarily lower mortality. It is easier to provide thorough drainage surgically, so when difficulties are encountered with percutaneous drainage, laparotomy should be performed promptly. Surgical intervention is more often necessary in cases of multiple, loculated collections or when the abscess cavity contains a large amount of necrotic debris. In such cases, open debridement should be considered early. Likewise, early surgical intervention is indicated for patients who are seriously ill (APACHE II score ≥ 15). Rarely, multiple abscesses are confined to a single lobe and can be cured by lobectomy. Biliary obstruction or other causes of sepsis must also be corrected.
The overall mortality rate of 15% is more closely related to the underlying disease than to any other factor. The mortality rate is about 40% in patients with malignant disease. Pleural effusion, leukocytosis over 20,000/μL, hypoalbuminemia, and polymicrobial infection correlate with a poor outcome. In the United States, whether the abscess is solitary or multiple no longer has a major influence on survival, but where benign biliary disease remains a major cause of this disease, multiple hepatic abscesses are associated with a worse prognosis. Death is rare in patients with a cryptogenic liver abscess.
et al.. CT appearance of pyogenic abscesses caused by Klebsiella pneumonia. Radiology 2011;260:129.
et al.. Hepatic cysts and liver abscess. Surg Clin North Am 2010;90:679.