Hematologic Disorders

Hematologic diseases that cause vascular thrombosis are the most common conditions that predispose to BCS in North America and Western Europe. Of disorders with thrombotic tendencies, polycythemia rubra vera is the most frequent, constituting 8.5% of the cases of BCS in the collected series of Parker (1959) and 10.4% of the cases in the collected series of Mitchell and colleagues (1982). In our series of 77 cases of BCS, 31% had polycythemia rubra vera, which is associated with BCS in some distinctly different ways compared with the classic disease. For one thing, it is found in young adults, rather than in middle-aged and elderly patients, and it is responsive to treatment with hydroxyurea or anagrelide, which should be started as soon as the disease is discovered and should be continued for life. In our experience, the disease runs a benign course if treated. Finally, polycythemia rubra vera associated with BCS is compatible with a long life, if it is treated with hydroxyurea.

Paroxysmal nocturnal hemoglobinuria is another hematologic disorder associated with BCS (Hartmann et al, 1980; Hoekstra et al, 2009; Liebowitz & Hartmann, 1981; Valla et al, 1987). It was responsible for 6.7% of the cases in the collected series of Mitchell and colleagues (1982) and 12% of the cases in the series of Valla and colleagues (1987). In all of the hematologic disorders associated with hepatic vein thrombosis, but particularly in paroxysmal nocturnal hemoglobinuria, thrombosis of other blood vessels outside of the liver has sometimes been observed. These cases of multiple sites of thrombosis have involved the portal, splenic, and superior mesenteric veins; pelvic veins; deep calf veins; splanchnic arteries; pulmonary artery; coronary arteries; and cerebral arteries (Peytremann et al, 1972).

As hematologic diagnosis has become progressively more sophisticated, many other thrombogenic conditions have been identified in BCS, including other myeloproliferative states—such as essential thrombocythemia, primary erythrocytosis, and myelofibrosis—and thrombophilic states, such as protein C deficiency, protein S deficiency, antithrombin III deficiency, and antiphospholipid syndrome with lupus anticoagulant or anticardiolipin antibodies or both (Bertina et al, 1994; Boughton, 1991; Dahlback, 1995; Dahlback et al, 1993; Espinosa et al, 2001; Koster et al, 1993; Mahmoud et al, 1995; Menon et al, 2004; Pelletier et al, 1994; Svensson & Dahlback, 1994; Valla, 2003; Vandenbroucke et al, 1994). Subjects with the factor V Leiden mutation, which leads to activated protein C resistance, have a 5-fold to 10-fold increase in the risk of thrombosis if they are heterozygotic and a 50-fold to 100-fold increase if they are homozygotic (Dahlback, 1995; Deltenre et al, 2001; Janssen et al, 2000). More recent evidence indicates that multiple prothrombotic factors acting concurrently are involved in a substantial percentage of patients with BCS (Denninger et al, 2000; Janssen et al, 2000). Rarely, hematologic malignancies, such as acute leukemia and lymphoma, have been associated with BCS.

In 2005, identification of the underlying cause of BCS was enhanced by the discovery of a very reliable and noninvasive marker for chronic myeloproliferative disorders. The marker is the gain-of-function mutation V617F of the JAK2 gene (Baxter et al, 2005; James et al, 2005; Jelinek et al, 2005; Jones et al, 2005; Kralovics et al, 2005; Levine et al, 2005; Steensma et al, 2005; Zhao et al, 2005). By combining identification of this marker with results of bone marrow histology and clonality assay, over 50% of the cases of BCS have been found to be due to an underlying chronic myeloproliferative disorder (Primignani et al, 2006).

It cannot be overemphasized that every patient found to have BCS should undergo a thorough hematologic evaluation. The workup that we perform is an expansion of the workup proposed by Mahmoud and Elias (1996) and others (Hirschberg et al, 2000; Valla, 2009) and is shown in Box 77.2. With these studies, it should be possible to diagnose all of the predisposing thrombogenic hematologic disorders known to be associated with BCS. If an evaluation such as this is done uniformly, it is highly likely that the incidence of idiopathic BCS will continue to decline.

Oral Contraceptives

An increased incidence of thromboembolic phenomena involving various blood vessels and organs in women taking oral contraceptives has been well established. The first case of BCS associated with use of oral contraceptives was reported by Ecker and McKittrick (1966), 5 years after these drugs became available commercially. Since then, more than 200 cases of BCS in patients taking oral contraceptive have been described (Janssen et al, 2000; Lewis et al, 1983; Maddrey, 1987; Valla et al, 1986; Zafrani et al, 1983), and the increasing overall incidence of BCS in recent years has been attributed partly to the widespread use of these agents. In the collective review reported by Mitchell and colleagues (1982), use of oral contraceptives was believed to be responsible for 9.4% of the cases of BCS during the period 1960 to 1980. Valla and associates (1986) reported that the relative risk of hepatic vein thrombosis among oral contraceptive users was close to that of stroke, myocardial infarction, and venous thromboembolism. In our series of 77 cases of BCS, 23% of patients gave a history of oral contraceptive use. The incidence is even higher if the denominator consists only of the number of women in each series. In our series, 49% of the 37 women with BCS used oral contraceptives.

Some authors have proposed that oral contraceptives are not a primary cause of BCS but contribute to thrombosis only if there is an underlying hematologic disorder (Valla et al, 1986). In our series, no hematologic disease was identified in users of oral contraceptives, but until relatively recently, our patients did not undergo the extensive hematologic workup shown in Box 77.2. The duration of usage of oral contraceptives before the diagnosis of BCS has ranged from 2 weeks to 10 years. In addition to causing BCS, oral contraceptives have been linked to other liver disorders, including VOD, portal vein thrombosis, cholestasis, hepatocellular adenoma, focal nodular hyperplasia, and possibly hepatocellular carcinoma and angiosarcoma (Zafrani et al, 1983).

Pregnancy and Postpartum

BCS has been observed in women during pregnancy and, more commonly, during the postpartum period. The first case of BCS reported by Chiari (1899) occurred in a woman who developed the disorder after childbirth. In the collective review by Mitchell and colleagues (1982), 9.9% of the cases of BCS occurred during pregnancy or postpartum, and in a series of 105 patients with BCS observed from 1963 through 1978, Khuroo and Datta (1980) reported 16 cases (15.2%) of BCS after pregnancy; 8 of the patients died, and 7 were lost to follow-up after discharge from the hospital. The hypercoagulable state that is known to occur during pregnancy is presumed to be responsible for the association of BCS with this condition, although only 1 of our 77 cases of BCS occurred during pregnancy or postpartum.

Malignant Neoplasms

Malignant neoplasms were responsible for 13.4% of the collected cases of BCS reported by Parker (1959), 8.8% of the collected cases reported by Mitchell and colleagues (1982), and 12% of the cases reported by Powell-Jackson and colleagues (1982). Because we do not operate on patients with BCS caused by cancer, none of our 77 patients had malignant neoplasms. Occlusion of the suprahepatic IVC by invasive tumors has been the cause of BCS in many cases. The most common cancers associated with BCS are hepatocellular carcinoma, renal cell carcinoma, adrenal carcinoma, and leiomyosarcoma of the IVC. Other malignancies that rarely have caused BCS include carcinomas of the lung, pancreas, and stomach; melanoma; reticulum cell sarcoma; adrenal sarcoma; and sarcoma of the right atrium.

Infections

Infections involving the liver were believed responsible for 3% of the collected cases of BCS reviewed by Parker (1959), 9.9% of the collected cases reported by Mitchell and colleagues (1982), and none of the cases in sizable series reported in more recent years, including our own series. The most common infections associated with BCS are those caused by parasites, particularly amebic liver abscess, hydatid disease, and schistosomiasis (see Chapters 67 and 68). Syphilitic gumma of the liver accounted for 1.8% of the cases in Parker’s review but has not been reported as a cause of BCS in recent years. Aspergillosis involving the hepatic veins and IVC has been a rare cause of BCS. In India, Victor and colleagues (1994) provided evidence that filariasis can cause BCS.

Trauma

Abdominal trauma has uncommonly predisposed to the development of BCS. Trauma was responsible for 1.2% of the collected cases of BCS reported by Parker (1959) and 2.4% of the collected cases reviewed by Mitchell and colleagues (1982). Blunt and penetrating trauma have been implicated in occasional cases of BCS.

Connective Tissue Disorders

Occasional cases of BCS have been reported in association with various connective tissue and autoimmune diseases, most of which are known to have thrombotic tendencies. Included among these are Behçet disease, Sjögren syndrome, mixed connective tissue disease, sarcoidosis, and rheumatoid arthritis. Numerous cases of BCS in patients with Behçet disease, including five of our own, have been described (Bazraktar et al, 1997; Orloff & Orloff, 1999).

Membranous Obstruction of the Vena Cava

More than 600 cases of BCS resulting from MOVC have been reported from Japan (Hirooka & Kimura, 1970; Kimura et al, 1972; Okuda, 2002; Ono et al, 1983; Taneja et al, 1979; Yamamoto et al, 1968), China (Wang, 1989; Wang et al, 1989; Wu et al, 1990) and other parts of Asia, India (Khuroo & Datta, 1980), and South Africa (Semson, 1982). In the United States and Europe, MOVC is rare. A congenital cause of this condition has been proposed, but evidence strongly suggests it represents the end result of acquired thrombosis (Kage et al, 1992; Okuda 2002; Okuda et al, 1995).

MOVC usually runs a chronic course over many years, and most patients will have developed extensive hepatic fibrosis and cirrhosis and portal hypertension by the time they come to medical attention. An increased incidence of hepatocellular carcinoma has been observed in association with MOVC (Okuda, 2002; Semson, 1982). The therapeutic implications of this condition and other forms of IVC occlusion are distinctly different from those of occlusion confined to the major hepatic veins.

Miscellaneous Rare Conditions

Other conditions that have been rarely associated with BCS include inflammatory bowel disease, hepatic torsion after partial resection of the liver, lipoid nephrosis, and protein-losing enteropathy.

Budd-Chiari Syndrome

The liver receives about one fourth of the cardiac output via its dual afferent blood supply, the portal vein and hepatic artery. After perfusing the sinusoids, the blood is returned to the heart through the hepatic veins and IVC. Obstruction to the egress of blood from the liver at any point along the outflow route results in numerous serious hemodynamic and morphologic alterations. There is a marked increase in intrahepatic pressure, which is reflected by a similar increase in portal pressure. The increased intrahepatic pressure causes extravasation of plasma from the liver sinusoids and lymphatics with formation of ascites. Obstruction to the egress of blood from the liver also results in dilation of the sinusoids and intense centrilobular congestion of the hepatic parenchyma, which is greatest around the terminal hepatic venules (central veins; Fig. 77.1). Ischemia, pressure necrosis, and atrophy of the parenchymal cells in the center of the liver lobule are apparent. With persistence of the obstruction, the necrotic parenchyma is replaced by fibrous tissue and regenerating nodules of liver tissue. The end result is cirrhosis of the type associated with chronic congestive heart failure. The rapidity with which cirrhosis develops is related to the severity of outflow obstruction, but it is not unusual for cirrhosis to occur within a matter of months (Parker, 1959).

FIGURE 77.1 Photomicrographs of preoperative liver biopsy specimens obtained from Budd-Chiari syndrome (BCS) patients 4 (A) and 5 (B) in our series, showing a typical picture of BCS consisting of intense centrilobular congestion and necrosis with widespread loss of hepatocytes. A thrombosed hepatic vein is seen in the center in A (×50).

(From Orloff MJ, Johansen KH, 1978: Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results. Ann Surg 188:494-512.)

The reversibility of liver damage in BCS is a direct function of the extent and duration of hepatic venous outflow obstruction. Early in the course of the disease, relief of the obstruction can be expected to result in reversal of the parenchymal and hemodynamic abnormalities. Late in the course, the damage to the hepatic parenchyma becomes irreversible; hence the timing of therapy has profound implications with regard to prognosis.

Three major hepatic veins—the right, left, and middle—conduct blood into the IVC from the bulk of the hepatic parenchyma. The left and middle hepatic veins usually form a common trunk just before joining the IVC, and several small hepatic veins enter directly into the retrohepatic IVC and drain the caudate lobe and small central regions of the right and left lobes of the liver. Our BCS experience indicates that all three major hepatic veins usually are occluded, although occasionally the occlusion is limited to one or two of the major veins. The small hepatic veins that join the retrohepatic IVC, particularly the veins draining the caudate lobe, often are spared.

In most cases of BCS, occlusion of the hepatic veins is caused by thrombosis (Parker, 1959). The thrombus undergoes organization and ultimately is converted to fibrous tissue that permanently occludes the veins. Although recanalization of the occluded veins sometimes occurs, it rarely results in effective new outflow channels. Retrograde propagation of the thrombus into smaller hepatic veins is commonly found. Prograde propagation of the thrombus from the hepatic veins into the IVC, with partial or complete occlusion of the IVC, sometimes occurs and markedly changes the therapeutic approach and prognosis. It is important to determine by imaging studies that include angiography and pressure measurements whether the IVC has become involved in the occlusive process.

MOVC has been reported to be the most common cause of BCS in Japan (Hirooka & Kimura, 1970; Kimura et al, 1972; Okuda et al, 1995; Ono et al, 1983; Taneja et al, 1979; Yamamoto et al, 1968), India (Khuroo & Datta, 1980), China (Wang, 1989; Wang et al, 1989, 2005; Wu et al, 1990), and in the Bantu population of South Africa (Semson, 1982). The “membrane” varies from very thin to several centimeters thick and usually contains fibrous tissue, smooth muscle, and elastic tissue. The location and extent of the membrane vary considerably, and in some cases a long segment of IVC has been replaced by fibrous tissue. Occlusion of one or more of the major hepatic veins often has been associated with membranous obstruction of the IVC. Although some experienced authors have proposed a congenital cause (Hirooka & Kimura, 1970; Kimura et al, 1972; Ono et al, 1983; Semson, 1982; Taneja et al, 1979), a strong argument has been made that suggests MOVC is the end result of thrombosis of the IVC, often occurring early in life (Okuda et al, 2002). Most of the cases have run a chronic course before discovery, and when first seen by a physician, patients have had extensive hepatic fibrosis or cirrhosis with portal hypertension and all of its manifestations. The therapeutic considerations in patients with MOVC differ from those in patients with BCS caused by obstruction of the hepatic veins.

Venoocclusive Disease

VOD of the liver, more recently called sinusoidal obstruction syndrome, may mimic BCS clinically, because both conditions involve hepatic venous outflow obstruction. VOD involves the sinusoids and the central and sublobular hepatic veins within the liver, however, rather than the hepatic veins (Kumar et al, 2003; Shulman et al, 1987, 1994). The underlying process in VOD is subendothelial sclerosis of the hepatic veins and sinusoids secondary to endothelial injury caused by a toxic agent, such as a pyrrolizidine alkaloid, antineoplastic drug, radiation, or a stem cell transplant. Thrombosis of the small hepatic veins may occur after damage to the venous intima. Electron microscopic studies of liver biopsy specimens obtained from children with VOD caused by pyrrolizidine poisoning showed marked endothelial damage in the sinusoids and subterminal and terminal hepatic veins in all zones of the liver, with extravasation of erythrocytes into the space of Disse and narrowing of the lumen where the sinusoid entered the central vein (Brooks et al, 1970).

Similar to BCS, hemorrhagic necrosis of the liver parenchyma around the centrilobular veins occurs early in the course of VOD. Extensive occlusion of the small hepatic veins ultimately leads to diffuse fibrosis and cirrhosis. Patients with VOD caused by chronic pyrrolizidine poisoning often have well-established cirrhosis when first seen by a physician. VOD that develops as a complication of therapy for another condition—such as occurs during cancer chemotherapy, radiation therapy, or bone marrow transplantation—usually is detected early in the course of the disease.

Symptoms

Findings on Physical Examination (Signs)

Hepatic Angiography and Pressures

The diagnostic study of greatest value in BCS, particularly if surgical therapy is contemplated and venous pressure measurements are required, is angiographic examination of the IVC and hepatic veins with pressure measurements (Clain et al, 1967; Kreel et al, 1967; Redman, 1975; Tavill et al, 1975). This study usually is combined with hepatic and superior mesenteric arteriography and indirect portography. In BCS confined to the hepatic veins, the IVC is patent, and IVC pressure is relatively normal for subjects with ascites (Fig. 77.2). Patency of the IVC is a prerequisite for portacaval shunt (PCS) and is a crucial finding (see Chapter 76A, Chapter 76B, Chapter 76C, Chapter 76D, Chapter 76E ). In some patients, the IVC is moderately compressed in its retrohepatic course by the enlarged liver and, in particular, by a hypertrophied caudate lobe (Fig. 77.3). This finding usually is not clinically significant (Clain et al, 1967; Kreel et al, 1967; Redman, 1975; Tavill et al, 1975).

FIGURE 77.2 Inferior venacavogram in Budd-Chiari syndrome patient 3 in our series, showing a widely patent inferior vena cava; pressure was 62 mm saline.

(From Orloff MJ, Johansen KH, 1978: Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results. Ann Surg 188:494-512.)

FIGURE 77.3 Inferior venacavogram in Budd-Chiari syndrome patient 6 in our series, showing a patent inferior vena cava with side-to-side compression in its retrohepatic course by the enlarged liver. IVC pressure at this time was 102 mm saline.

(From Orloff MJ, Johansen KH, 1978: Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results. Ann Surg 188:494-512.)

The most important angiographic finding is the demonstration by hepatic venography of occlusion or marked narrowing of the major hepatic veins. Sometimes it is not possible to find patent orifices of any of the hepatic veins, which is indirect evidence that all of the major hepatic veins are occluded. Usually it is possible, however, to enter at least one major hepatic vein and to show the presence of a thrombus or of narrowing and distortion of the vein (Fig. 77.4A). Injection of dye in the wedged position often shows a characteristic spiderweb pattern of small hepatic venous collaterals connecting to portal or systemic veins (see Fig. 77.4B). Wedged hepatic vein pressure (WHVP) usually is markedly elevated, which reflects the obstruction to hepatic venous outflow. In patients with hepatic vein occlusion alone, IVC pressure is substantially lower than WHVP.

FIGURE 77.4 Hepatic venogram in Budd-Chiari syndrome patient 2 in our series. A, Filling defects (thrombi) in the right hepatic vein occupy much of the lumen. B, Typical spiderweb pattern of small venous collaterals shown by injection of dye with the catheter in the wedged position.

(From Orloff MJ, Johansen KH, 1978: Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results. Ann Surg 188:494-512.)

In our series of 77 patients, angiographic studies showed occlusion of the hepatic veins alone in 51 patients and occlusion of both the hepatic veins and IVC in 26 patients. In all of our patients with hepatic vein occlusion alone, all three major hepatic veins were occluded.

A spiderweb pattern was observed in 48 patients (62%). WHVP was markedly elevated in all patients in whom it was measured. In the 51 patients with thrombosis confined to the hepatic veins, the IVC was patent, with relatively normal pressures for patients with ascites, ranging from 62 to 160 mm saline (Table 77.3). Many patients had moderate compression of the retrohepatic IVC by the enlarged liver, but invariably WHVP was substantially higher than IVC pressure—a crucial finding. In contrast, in the 26 patients with IVC occlusion, IVC pressure and WHVP were similar. All patients had stretched and attenuated hepatic artery branches within the liver and a patent portal vein (PV).

Table 77.3 Results of Diagnostic Studies in 77 Patients with Budd-Chiari Syndrome Treated by the Authors

IVC, inferior vena cava; WHVP, wedged hepatic venous pressure

An additional advantage of hepatic venography is that it facilitates performing a transjugular liver biopsy. Some investigators have stated that “at present, there is almost no place for direct or retrograde venography for the sole purpose of making a diagnosis of BCS” (Valla, 2009; Janssen et al, 2003). We hasten to point out that our use of hepatic venography was an essential guide to surgical therapy, not simply a means of making the diagnosis of BCS, as others have agreed (Kamath, 2006; Erdon, 2007).

Liver Biopsy

Percutaneous or transjugular needle liver biopsy yields histologic findings characteristic of BCS early in the course of the disease; along with hepatic angiography, it provides conclusive diagnostic information (Tang et al, 2001). The diagnostic features are quite spectacular and include intense centrilobular congestion combined with centrilobular loss of parenchyma and necrosis (see Fig. 77.1). Mild to moderate fibrosis of the liver parenchyma is found in many patients. As the disease evolves and becomes chronic, cirrhosis of the cardiac type develops. Cirrhosis has been observed within months of the onset of symptoms. Only two other conditions, constrictive pericarditis and congestive heart failure, produce a histologic picture similar to that seen in the acute stage of BCS. Both of these cardiac disorders can be eliminated easily from consideration by appropriate studies.

In our series, percutaneous or transjugular needle liver biopsy was done preoperatively in 73 of 77 patients, and open wedge liver biopsy was done at operation in all 77 patients (see Table 77.3). All patients had intense centrilobular congestion along with centrilobular hepatocellular loss and necrosis. Of the 65 patients in our series who were referred sufficiently early to undergo surgical portal decompression, 39 (60%) had fibrosis of the liver at an early point in the illness. In three patients, the fibrosis had progressed to cirrhosis. All 12 patients who were considered candidates for liver transplantation had advanced cirrhosis (see Chapter 97A).

Hepatic Scintiscanning

Scintiscans of the liver (see Chapter 15) with technetium 99m-sulfur colloid or other colloidal radionuclides show the nonspecific abnormalities of decreased and nonhomogeneous hepatic uptake of radiocolloid, increased uptake of radiocolloid by the spleen and bone marrow, and hepatosplenomegaly. Central localization of radiocolloid in the liver, the so-called central hot spot, has been reported to be of diagnostic importance (Fig. 77.5; Meindok & Langer, 1976; Tavill et al, 1975). It is seen when the thrombotic process spares the small hepatic veins that drain the caudate lobe and central areas of the right and left lobes directly into the IVC, so that these areas of the liver remain healthy and even hypertrophy. The central hot spot was observed in only 19 (25%) of the 77 patients with BCS in our series.

FIGURE 77.5 A-C, Scintiscan of liver in three cases of Budd-Chiari syndrome, showing central accumulation of radionuclide, the so-called central hot spot.

(From Mitchell MC, et al, 1982: Budd-Chiari syndrome: etiology, diagnosis and management. Medicine [Baltimore] 61:199-218.)

Computed Tomography

Computed tomography (CT; see Chapter 16) of the liver after injection of contrast agents has been shown to be of diagnostic value in BCS (Baert et al, 1983; Mathieu et al, 1987; Lupescu, 2008; Erdon, 2007; Kamath, 2006; Vogelzang et al, 1987). The findings include 1) absence of opacification of the hepatic veins, which in normal subjects usually can be shown clearly; 2) nonhomogeneous and delayed uptake of contrast material in the liver; 3) delayed emptying of contrast material from venous structures at the periphery of the liver; and 4) occlusion of the IVC in patients with IVC thrombosis. CT also shows ascites and hepatomegaly. We performed CT in 64 of our 77 patients and observed these abnormalities in all of them.

Ultrasonography

Real-time and Doppler duplex ultrasonography (US) of the liver have been shown to be of diagnostic value in BCS (Baert et al, 1983; Becker et al, 1986; Bolondi et al, 1991; Chaubal et al, 2006; Grant et al, 1989; Gupta et al, 1987; Hosoki et al, 1989; Powell-Jackson et al, 1986; Rossi et al, 1981; see Chapter 13). Findings include 1) absence of normal hepatic veins draining into the IVC with flat or reversed flow, 2) an abnormal intrahepatic network of comma-shaped venous structures, 3) thrombus in IVC and flat or reversed flow in patients with IVC thrombosis, and 4) enlargement of the caudate lobe. Ascites has been shown regularly. We observed these abnormalities in all 61 patients in whom US was performed in our series. We regularly used Doppler US as an initial screening tool, but we depended on angiography for a definitive diagnosis and guide to treatment.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI; see Chapter 17) is capable of showing patency or obstruction of the hepatic veins and is particularly effective in visualizing the entire length of the IVC. It has been reported to be useful in differentiating the acute form of BCS from the subacute and chronic forms (Noone et al, 2000; Kamath, 2006; Erdon, 2007; Lupescu et al, 2008). Because of the high cost of MRI, it is not a first-line diagnostic procedure in our program; none of our 66 patients underwent MRI.

Abnormal Liver Function Tests

Results of liver function tests are usually abnormal in BCS, although the type of abnormality varies and is nondiagnostic (see Table 77.3). All 24 patients in our series who had studies of injected bromosulfophthalein or indocyanine green dye clearance had marked retention of dye, ranging from 23% to 90% (normal <6%). All 77 patients had elevation of serum alkaline phosphatase, ranging from 138 to 458 IU (normal 25 to 85 IU). Of 77 patients, 74 had prolonged prothrombin time and partial thromboplastin time, and 96% had a marked decrease in serum albumin concentration (range, 2.1 to 2.8 g/dL); 69 patients (90%) had elevations of aspartate aminotransferase (range, 76 to 540 IU), and 39 (51%) had mild to moderate elevations of serum bilirubin (range, 3.8 to 6.8 mg/dL). These biochemical abnormalities are not specific to BCS, but they indicate significant hepatic dysfunction and are an important part of the diagnostic workup.

Ascitic Fluid Analysis

Analysis of ascitic fluid in patients with BCS is of little diagnostic value, because the results vary considerably (Mitchell et al, 1982; Tavill et al, 1975). Protein concentration has been reported to range from 0.5 to 4.9 g/dL.

Upper Gastrointestinal Radiographs

Barium contrast upper GI radiographs were obtained in 53 patients with BCS in our series. The results were normal in 31 patients but showed esophageal varices in 22 patients (42%); 13 of the 22 patients with varices had cirrhosis. In the chronic forms of BCS, esophageal varices can be shown regularly by radiography and confirmed by esophagogastroscopy. Currently, we infrequently perform contrast upper GI radiographs.

Esophagogastroscopy

Esophagogastroscopy (EG) was performed in 28 patients, 18 of whom (64%) were found to have esophageal varices (see Chapter 75A, Chapter 75B, Chapter 75C ).

Experimental Studies

The theoretical basis for the use of SSPCS to relieve BCS resulting from occlusion of the hepatic veins is provided by substantial evidence indicating that the valveless PV can be converted into an outflow tract by an in-continuity anastomosis with the systemic venous system to decompress the obstructed hepatic vascular bed (Britton & Shirey, 1962; Britton et al, 1967; Burchell et al, 1976; Long et al, 1960; Longmire et al, 1958; Moreno et al, 1967; Mulder & Murray, 1960; Murray & Mulder, 1961; Orloff et al, 1997; Orloff & Snyder, 1961; Tamaki et al, 1968; Warren & Muller, 1959). To test this hypothesis, we conducted an experimental evaluation of SSPCS in dogs with BCS (Orloff & Johansen, 1978). Our method of producing BCS in dogs consisted of ligation and division of all hepatic veins except the large left hepatic vein, which was loosely surrounded by an ameroid constrictor (Fig. 77.6; Orloff et al, 1963, 1965; Sweat et al, 1966). The lumen in the ameroid constrictor gradually narrowed as the hygroscopic casein plastic swelled centrally so that the remaining left hepatic vein was completely occluded within several weeks, and severe hepatic outflow block, portal hypertension, and massive, intractable ascites resulted. BCS was produced in 64 dogs, which were put into three treatment groups when ascites was massive: group I underwent sham laparotomy, group II underwent end-to-side PCS, and group III underwent SSPCS.

FIGURE 77.6 Our technique of induction of Budd-Chiari syndrome in dogs by ligation and division of all hepatic veins except the large left hepatic vein, which was surrounded by a hygroscopic, casein-plastic ameroid constrictor that gradually swelled centrally and occluded the vein.

(From Orloff MJ, Johansen KH, 1978: Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results. Ann Surg 188:494-512.)

Table 77.6 summarizes the results of our experimental study. All dogs rapidly re-formed ascites after either sham laparotomy or end-to-side PCS and died with massive ascites within 6 months. In striking contrast, only 1 of the 24 dogs in group III reaccumulated ascites after SSPCS, and 67% of these dogs survived in good health without ascites until the time of sacrifice 1 year postoperatively. Before hepatic vein ligation, the liver was normal in all dogs on gross and microscopic examinations. At the time of sham laparotomy or shunt, when BCS was well established, all livers were enlarged two to four times normal size and appeared congested and friable. Liver biopsy specimens at this time showed intense centrilobular congestion, necrosis of cells around the central veins, dilated lymphatics, and subcapsular edema (Fig. 77.7). In the dogs in group I, these gross and microscopic abnormalities were unchanged at the time of death, and substantial fibrosis was found in many of the liver biopsy specimens. Similarly, all of the dogs in group II had hepatomegaly at the time of death, and severe congestion, necrosis, and fibrosis were found in all liver biopsy specimens; although, in 38% of the animals, the microscopic picture was less severe than at the time of the end-to-side shunt operation. Only one dog with SSPCS in group III, the single animal with ascites, had an enlarged liver and microscopic findings of congestion and necrosis at the time of death. The other 23 dogs in group III had a liver that was normal in size and gross appearance at autopsy; liver biopsy specimens were normal in 35% of these dogs and showed minimal fibrosis in the remaining 65%.

FIGURE 77.7 Photomicrographs of liver biopsy specimens obtained from a dog. A, Before hepatic vein ligation, when the liver was normal. B, Just before portacaval shunt, when Budd-Chiari syndrome was well established, and ascites was massive. Intense congestion and necrosis of the hepatic parenchyma is evident in the biopsy specimen (×140).

(From Orloff MJ, Johansen KH, 1978: Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results. Ann Surg 188:494-512.)

Clinical Results of the Authors

On the basis of the results of our experimental studies, which showed SSPCS was effective in relieving BCS and reversing liver damage, we performed SSPCS in 39 patients with BCS caused by thrombosis of the hepatic veins without involvement of the IVC (Orloff & Girard, 1989; Orloff & Johansen, 1978; Orloff et al, 1992b, 2000); subjects were 21 women and 18 men, and ages ranged from 19 to 45 years. Of the 39 patients, 14 had polycythemia rubra vera, 11 had been taking oral contraceptives, 5 had Behçet disease, and 1 had protein C deficiency. In the remaining 8 patients, no condition predisposing to hepatic vein thrombosis was identified. Patients operated on before 1996 did not undergo the extensive hematologic workup shown in Box 77.2 that is currently performed. The symptoms, signs, results of diagnostic studies, and findings at operation are shown in Tables 77.2 to 77.5.

Tables 77.5 and 77.8 summarize the long-term results of SSPCS in our series. One patient underwent emergency operation, when the thrombosis of his hepatic veins suddenly extended into and occluded his previously patent IVC. An attempt to reverse a rapid downhill course by IVC thrombectomy and PCS was unsuccessful, and the patient died 6 days postoperatively with multiorgan failure and recurrence of IVC thrombosis. The remaining 38 patients (97%) recovered from the shunt operation and were long-term survivors. A striking feature of the early recovery period was a rapid gain in lean body weight that averaged 28 pounds in 3 months.

The 38 survivors of the shunt operation have been followed up for 5 to 37 years (mean follow-up 15 years). All survivors have been followed up for 5 years or more. One long-term death occurred in a patient with Behçet disease, who was relieved of BCS and ascites but died of diffuse vasculitis that caused hemorrhagic infarction of the colon 2 years postoperatively. The other 37 patients are currently alive, for an overall survival rate of 95%. All of the survivors have remained free of ascites without requiring diuretic therapy. Results of periodic liver function tests have been consistently normal except in the three patients who already had cirrhosis when they were referred to us. None of the patients has portosystemic encephalopathy, undoubtedly because they have good hepatic function. Hepatosplenomegaly has disappeared in all patients. Of the 38 survivors of SSPCS, 36 are employed or work full time at home. Of the 37 current survivors, 36 (97%) are leading productive lives of good quality.

One patient had recurrence of ascites 5 years after the shunt operation and was found to have developed marked narrowing of the IVC at the level of the previously occluded hepatic vein orifices. He was treated surgically with a bypass graft extending from below the area of obstruction in the IVC to the right atrium. Twenty-seven years after the bypass operation, the patient is free of ascites, and angiographic studies show a patent bypass graft with normal pressures in the IVC and PV.

Liver biopsies and angiographic or US studies were performed periodically for 37 years after shunt in the 38 survivors, and the results are summarized in Table 77.8. Cirrhosis persisted in the three patients who already had cirrhosis by the time of the shunt operation, including the patient with Behçet disease. In 97% of the survivors, there was no longer any evidence of hepatic congestion or necrosis in the follow-up biopsy specimens, as shown in Figure 77.8. Mild to moderate fibrosis was found in 42% of the patients, but 50% had normal liver biopsy specimens. Angiography or US showed patency of the PCS and IVC, and pressure measurements showed a wide-open anastomosis with a gradient that ranged from 0 to 44 mm saline and averaged only 4 mm across the shunt. Two patients with polycythemia rubra vera developed thrombosis of the PCS 1 week and 3 months postoperatively. Both patients were operated on immediately, the shunt was taken down, fresh thrombus was removed from the PV, and the portacaval anastomosis was reconstructed with an H-graft of autologous internal jugular vein. Subsequently, both patients were maintained on anticoagulant therapy with warfarin. One patient has remained well for 28 years since revision of the shunt. The other patient developed recurrent shunt thrombosis and required liver transplantation (LT), but he is well 19 years after transplantation. It is now our policy to maintain all patients with a known coagulopathy on permanent anticoagulant therapy.

FIGURE 77.8 Photomicrographs of liver biopsy specimens obtained just before and 2 years after side-to-side portacaval shunt from Budd-Chiari syndrome patient 11. A, Before portacaval shunt (PCS), intense centrilobular congestion and necrosis with substantial fibrosis can be seen (×50). B and C, Two years after PCS, a normal liver architecture, a striking reversal of the pathologic process of Budd-Chiari syndrome, can be seen (B, ×80; C, ×160.)

Our experience with the surgical treatment of BCS differs from almost every other report of surgery for BCS in the following respects: 1) it involved unselected, consecutive patients with BCS who were referred to us and were treated at a single institution; 2) the patients were treated and studied prospectively, and our report is based on prospectively collected data, not on retrospective reviews of medical records with all the known shortcomings; 3) SSPCS was performed by a single senior faculty surgeon, whose experience included performance of more than 2500 SSPCS procedures; 4) follow-up was 100% and was performed regularly for more than 3 decades.

Our series is the single largest clinical experience reported to date involving the use of SSPCS in BCS confined to the hepatic veins. Our clinical experience confirmed our experimental observations regarding the efficacy of SSPCS in relieving hepatic venous outflow obstruction. All 39 of our patients in whom thrombosis remained localized to the hepatic veins survived the operation and remained free of ascites for years without requiring diuretic therapy, and the shunt remained permanently patent in all but one patient. All but three of the survivors were operated on early in the course of the disease, before liver damage was irreversible; in these patients hepatosplenomegaly disappeared, and liver function rapidly returned to normal. The results of serial liver biopsies performed for 5 to 37 years postoperatively are particularly encouraging, because they showed that the shunt had brought about substantial and long-term reversal of the striking pathologic lesions of BCS (see Fig. 77.8). SSPCS seems to be the most effective treatment of BCS confined to the hepatic veins. The long-term survival rate of the patients in our series has not been equaled by any other form of therapy, medical or surgical.

The single postoperative death in our series taught us a valuable lesson. When this 28-year-old man with polycythemia rubra vera was admitted to our hospital, clear clinical and angiographic evidence showed the occlusive process confined to the hepatic veins. During the 8-day course of his diagnostic workup, however, the thrombosis extended into the IVC, and his condition deteriorated dramatically. An emergency attempt at IVC thrombectomy and PCS failed. Extension of the thrombotic process from the hepatic veins into the IVC is a well-known event in BCS (Parker, 1959), and the potential for this devastating complication exists in every patient; therefore when the diagnosis of hepatic vein occlusion has been made, it seems unwise to delay operation.

SSPCS is indicated only in patients with BCS who have a patent IVC and an IVC pressure that is substantially lower than WHVP or portal pressure. Obstruction or occlusion of the IVC, manifested clinically by edema of the lower extremities and lower trunk and shown by angiography and IVC pressure measurements, is a contraindication to PCS. It is not unusual for patients with BCS caused by hepatic vein occlusion to have an elevated pressure in the IVC as a result of caval compression by an enlarged, congested liver or massive ascites or both. The absolute level of IVC pressure is not crucial to the effectiveness of SSPCS, as long as the portal pressure is substantially higher than caval pressure, and the IVC is shown to be patent. Others have reported relief of BCS by an in-continuity mesocaval shunt in patients with high IVC pressure but substantially higher portal pressure, showing that it is possible to decompress the liver as long as the differential is substantial between pressures in the PV and IVC (Vons et al, 1986). In our long-term follow-up studies after SSPCS, we have observed that compression of the IVC disappears with relief of hepatic congestion, and caval pressure returns to normal.

After SSPCS, the occlusive process in the hepatic veins extended into the adjacent IVC in only one of the 38 long-term survivors in our series. This untoward development occurred 5 years after the shunt operation and was treated successfully by a bypass graft from the IVC to the right atrium. It is possible that the infrequency of this complication is attributable to the PCS, which might inhibit propagation of the thrombus by increasing blood flow in the IVC and relieving stasis of blood in the liver.

The importance of performing SSPCS early in the course of BCS cannot be overemphasized. Hepatic venous outflow obstruction produces widespread destruction of the hepatic parenchyma by pressure necrosis and ischemia, and the liver damage becomes irreversible in a surprisingly short time: some patients have developed cirrhosis within 3 or 4 months of the onset of symptoms. Relieving ascites is far less important than decompressing the liver. Recently, groups of physicians that did not include surgeons have recommended a stepwise approach to treatment of BCS, beginning with a trial of anticoagulants, then angioplasty or thrombolysis and stenting, then transjugular intrahepatic portosystemic shunt (TIPS), and finally liver transplantation (Plessier & Valla, 2009; Janssen et al, 2003; de Franchis, 2005; Hoekstra & Janssen, 2008; DeLeve et al, 2009). The stepwise plan carries with it the danger of permitting liver damage to become advanced and irreversible.

Although a few patients have recovered spontaneously from BCS, most have not. The literature is replete with descriptions of patients who would have been suitable candidates for PCS but were treated nonoperatively and died. Our experience shows that it is imperative to perform SSPCS as soon as possible after the diagnosis of BCS has been made.

Clinical Results of Other Surgeons

Treatment by direct SSPCS or its hemodynamic equivalents—the portacaval interposition graft, mesocaval interposition graft, or splenorenal shunt—of BCS caused by occlusion of the hepatic veins has been reported in more than 300 patients by other surgeons (Ahn et al, 1987; Auvert & Farge, 1963; Bachet et al, 2007; Bismuth & Sherlock, 1991; Cameron et al, 1983; Dong et al, 2005; Eisenmenger & Nickel, 1960; Erlik et al, 1962; Fisher et al, 1999; Gentil-Kocher et al, 1988; Gibson, 1960; Hemming et al, 1996; Henderson et al, 1990; Hoyumpa et al, 1971; Huguet et al, 1979; Klein et al, 1990; Langer et al, 1975; Ludwick et al, 1967; Malt et al, 1978; McCarthy et al, 1985; Millikan et al, 1985; Montano-Loza et al, 2009; Murad et al, 2004; Noble, 1976; Panis et al, 1994; Pezzuoli et al, 1985; Powell-Jackson et al, 1982; Prandi et al, 1975; Schramek et al, 1974; Singhal et al, 2006; Slakey et al, 2001; Vons et al, 1986; Wang, 1989; Wu et al, 1990; Zeitoun et al, 1999). Many of the reports have involved descriptions of single cases. Some more recent retrospective multiinstitutional studies involving reviews of medical records have been based on analyses, as a single entity, of patients with widely different characteristics, such as the stage and type of BCS, time lapsed from diagnosis to treatment, site of hepatic venous outflow occlusion, and type of portosystemic shunt. Portacaval, mesocaval, splenorenal, mesoatrial, mesoinnominate, cavoatrial, portoatrial, and TIPS have been considered as a single entity termed a portosystemic shunt (Murad et al, 2004; Zeitoun et al, 1999). It is not possible to compare the results of these studies with our results, which were based on a prospective study of patients with BCS caused by hepatic vein thrombosis alone, all of whom underwent a direct SSPCS early in the course of their disease by a single surgeon at a single institution.

At institutions that have reported series of cases, success rates of portal decompression in BCS have been approximately 85% after direct SSPCS (Ahn et al, 1987; Bismuth & Sherlock, 1991; Hemming et al, 1996; McCarthy et al, 1985; Panis et al, 1994; Pezzuoli et al, 1985) and 67% after splenorenal shunt (Ahn et al, 1987; McCarthy et al, 1985; Millikan et al, 1985; Wang, 1989). Mesocaval or portacaval interposition grafts with autologous internal jugular vein have been reported in about 50 patients with BCS, most of them in France, with a success rate of 89% (Bismuth & Sherlock, 1991; Gentil-Kocher et al, 1988; McCarthy et al, 1985; Panis et al, 1994; Pezzuoli et al, 1985; Vons et al, 1986). Mesocaval or portacaval interposition grafts using synthetic materials, such as Dacron or polytetrafluoroethylene (Gore-Tex), have been successful in approximately 52% of 39 patients with BCS, which is the lowest success rate of the various in-continuity portal decompressive procedures (Ahn et al, 1987; Hemming et al, 1996; Henderson et al, 1990; Klein et al, 1990; McCarthy et al, 1985; Millikan et al, 1985; Pezzuoli et al, 1985; Wang, 1989). In our opinion, use of synthetic interposition portacaval or mesocaval grafts and the splenorenal shunt are inferior to direct SSPCS in the treatment of BCS, although all three shunts are hemodynamically similar. Occlusion of the shunt is a serious complication that may result in death: the splenorenal shunt and the synthetic interposition grafts have a substantial incidence of thrombosis, not only in BCS but also in other diseases that cause portal hypertension (Dowling, 1979; Hemming et al, 1996; Orloff, 1977, 1998; Orloff & Orloff, 1992); in contrast, the incidence of shunt occlusion in our series of more than 2500 direct SSPCS procedures—most of which have been followed up repeatedly by catheterization, angiography, or US—is 0.5%.

Four patients underwent end-to-side PCS for treatment of BCS. One patient had a favorable response during 1 year of follow-up (Marchal et al, 1974), but the other three died (Alpert, 1976; Brink & Botha, 1955; Langer et al, 1975). Because the hepatic side of the transected PV is ligated in an end-to-side PCS, the PV cannot function as an outflow tract to decompress the liver. It has been well established that in the presence of hepatic outflow block, the side-to-side anastomosis is substantially more effective than the end-to-side shunt in overcoming intrahepatic hypertension (Reynolds et al, 1962; Taylor & Myers, 1956; Warren & Muller, 1959).

Since our chapter on BCS was being prepared for the previous edition of this book 6 years ago, a number of reviews by nonsurgeons have been published (Janssen et al, 2003; Bachet et al, 2007; Plessier & Valla, 2008; Hoekstra & Janssen, 2008; Amarapurkar et al, 2008; DeLeve et al, 2009). These reviews, authored by physicians who had no personal experience with surgical treatment of BCS, were based on retrospective data collected from the literature, and they contained negative evaluations of the portosystemic shunt that were contrary to the results of our prospective studies. Examples of these negative evaluations that we believe are erroneous are: 1) “Overall perioperative mortality has been high, averaging 25%” (our perioperative mortality rate is 0%); 2) “The rate of shunt dysfunction due to early or late thrombosis or to late stenosis has reached 30% in series with long-term follow-up” (only 2 [5%] of our 38 patients developed thrombosis of the PCS 1 week and 3 months postoperatively, and this was permanently corrected by reoperation); 3) “Surgical portosystemic shunting … failed to show any impact on survival after adjustment for independent prognostic factors” (the survival rate in our series 5 years to 38 years postoperatively is 95%).

It is noteworthy that recent reviews, authored mainly by surgeons who have had personal experience with portosystemic shunts, have been supportive of the use and effectiveness of this important modality of the treatment in BCS (Menon et al, 2004; Klein, 2006; Zimmerman et al, 2006; Singhal et al, 2006; Montano-Loza et al, 2009).

Authors’ Technique of Side-to-Side Portacaval Shunt

We have performed more than 2500 SSPCS operations over 50 years. From this experience, we have concluded that it is possible, with the proper technique, to perform a satisfactory SSPCS in almost every patient who has a patent PV. Contrary to some statements in the literature, we have been able to perform SSPCS without difficulty in every patient with BCS on whom we have operated. We have performed shunt catheterization and angiography or US every 1 to 2 years in almost all of our patients since the 1970s, and we have observed a 99.5% long-term shunt patency rate. Our technique of SSPCS (Orloff, 1983; Orloff & Orloff 1992, 1994; Orloff et al, 2007) is illustrated in Figures 77.9 to 77.18. Important technical features of the operation are as follows:

FIGURE 77.9 Position of patient for side-to-side portacaval shunt.

FIGURE 77.10 Long right subcostal incision used for side-to-side portacaval shunt.

FIGURE 77.11 Exposure of the operative field for side-to-side portacaval shunt.

FIGURE 77.12 Circumferential isolation of the inferior vena cava between renal veins and liver in preparation for side-to-side portacaval anastomosis.

FIGURE 77.13 Exposure of portal vein in preparation for side-to-side portacaval anastomosis.

FIGURE 77.14 Mobilization of a long length of portal vein, including the segment behind the pancreas, in preparation for side-to-side portacaval anastomosis.

FIGURE 77.15 Measurement of pressures in the inferior vena cava (IVC) and portal vein (PV) with a saline (spinal) manometer by direct needle puncture before performance of portacaval anastomosis. All portal pressures are corrected by subtracting the IVC pressure from the portal pressure. Pressures in the IVC and PV are measured again after completion of the shunt. A, For all pressure measurements, the bottom of the manometer is positioned at the level of the IVC, which is marked on the skin surface of the body with a towel clip. B, IVC pressure. C, Free portal pressure. D, Hepatic occluded portal pressure, obtained on the hepatic side of a clamp occluding the portal vein. E, Splanchnic occluded portal pressure, obtained on the intestinal side of a clamp occluding the portal vein.

FIGURE 77.16 Side-to-side portacaval anastomosis. A, Placement of clamps on the inferior vena cava (IVC) and portal vein (PV). B, Strips of IVC and PV 2.5 cm in length have been excised. C, Placement of a posterior row of continuous 5-0 vascular suture from inside the lumina of IVC and PV.

FIGURE 77.17 Side-to-side portacaval anastomosis. Placement of anterior row of two continuous everting sutures of 5-0 vascular material.

FIGURE 77.18 Completed side-to-side portacaval anastomosis.

Figure 77.9 shows the position of the patient on the operating table, viewed from the patient’s right side. The patient is positioned with the right side elevated at an angle of 30 degrees to the table, and the table is “broken” at the level of the costal margin and at the knees to widen the space between the right costal margin and right iliac crest.

Figure 77.10 shows the incision. A long right subcostal incision extending from the xiphoid to well into the flank is made two fingerbreadths below the costal margin; we have used this incision in every operation over the course of 50 years. The skin is incised superficially with the scalpel, and the other layers are incised with electrocautery, which greatly reduces blood loss and shortens the operating time. When electrocautery is used, it is usually unnecessary to clamp any blood vessels with hemostats. The right rectus abdominis, external oblique, and transverses abdominis muscles are completely divided, and the medial 3 to 4 cm of the latissimus dorsi muscle is often incised. The peritoneum often contains many collateral blood vessels and is incised with the electrocautery to obtain immediate hemostasis.

Figure 77.11 shows the exposure of the operative field. The viscera are retracted by three Deaver retractors positioned at right angles to each other: the inferior retractor retracts the hepatic flexure of the colon toward the feet, the medial retractor displaces the duodenum medially, and the superior retractor retracts the liver and gallbladder toward the head. The posterior peritoneum overlying the IVC is incised with electrocautery by an extended Kocher maneuver just lateral to the descending duodenum, and the retractors are repositioned to retract the head of the pancreas medially and the right kidney caudally. Alternatively, a self-retaining retractor may be used in place of the three handheld Deaver retractors.

Figure 77.12 shows the isolation of the IVC: the anterior surface is cleared of fibroareolar tissue, and the IVC is isolated around its entire circumference, from the entrance of the right and left renal veins below to the point where it disappears behind the liver above. The IVC is surrounded with an umbilical tape. To accomplish the isolation, several tributaries may have to be ligated in continuity with fine silk ligatures and then divided. These include the right adrenal vein, one or two pairs of lumbar veins that enter on the posterior surface, and the caudal pair of small hepatic veins that enter on the anterior surface of the IVC directly from the liver. When the IVC has been mobilized completely, it can be lifted up toward the PV. Failure to isolate the IVC circumferentially is one major reason for the erroneous claim that SSPCS often cannot be performed, because the PV and IVC are too widely separated.

Figure 77.13 shows the exposure of the PV. The superior retractor is repositioned medially so that it retracts the liver and gallbladder at the point of entrance of the portal triad. The PV is located in the posterolateral aspect of the portal triad and is approached from behind. The fibrofatty tissue on the posterolateral aspect of the portal triad contains nerves, lymphatics, and lymph nodes and is divided by blunt and sharp dissection; this is a safe maneuver, because there are no portal venous tributaries on this aspect of the portal triad.

As soon as the surface of the PV is exposed, a vein retractor is inserted to retract the common bile duct and hepatic artery medially. The PV is mobilized circumferentially at its midportion and is surrounded with an umbilical tape. It is isolated up to its bifurcation in the liver hilum, and several tributaries on the medial aspect are ligated in continuity with fine silk and divided.

Figure 77.14 shows the mobilization of the PV behind the pancreas. Using the umbilical tape to pull the PV out of its bed, it is cleared to the point where it disappears behind the pancreas. The tough fibrofatty tissue that binds the PV to the pancreas must be divided. Several tributaries that enter the medial aspect of the PV and one tributary that enters the posterolateral aspect are divided, but it is usually unnecessary to divide the splenic vein. Wide mobilization of the PV is essential for performance of a side-to-side portacaval anastomosis. Failure to mobilize the PV behind the pancreas is a second major reason for difficulty in accomplishing an SSPCS. In some patients, it is necessary to divide a bit of the head of the pancreas to obtain adequate mobilization of the PV. Bleeding from the edges of the divided pancreas is controlled with suture ligatures. Division of a small amount of the pancreas is a helpful maneuver, and we have never observed postoperative complications, such as pancreatitis, from its performance.

Figure 77.15 shows the measurement of pressures in the IVC and PV before performing the portacaval anastomosis. The performance of an SSPCS is illustrated in Figures 77.16 to 77.18. After it is determined that the IVC and PV can be brought together without excessive tension, a Satinsky clamp is placed obliquely across a 5-cm segment of the anteromedial wall of the IVC in a direction that is parallel to the course of the overlying PV, and the IVC is elevated toward the PV. One 5-cm segment of the PV is isolated between two angled vascular clamps, and the PV is depressed toward the IVC, bringing the two vessels into apposition (see Fig. 77.16). One 2.5-cm long, thin strip of the IVC and one 2.5-cm strip of the PV are excised with the scissors (see Fig. 77.16B). It is important to excise a thin longitudinal segment of the wall of each vessel rather than simply to make an incision in each vessel. A retraction suture of 5-0 vascular suture material is placed in the lateral wall of the vena caval opening and is weighted by attachment to a hemostat to keep the vena caval orifice open. The clamps on the PV are momentarily released to flush out any clots, then the openings in both vessels are irrigated with heparinized saline.

The anastomosis is started with a posterior, continuous, over-and-over suture of 5-0 vascular suture material (see Fig. 77.16C). The posterior continuous suture is tied at each end of the anastomosis. The anterior row of sutures consists of an everting, continuous, horizontal mattress stitch of 5-0 vascular material started at each end of the anastomosis (see Fig. 77.17). The suture started at the superior end of the anastomosis is discontinued after three or four throws and is deliberately left loose so that the interior surface of the vessels can be visualized as the anastomosis is completed. In this way, inadvertent inclusion of the posterior wall in the anterior row of sutures is avoided. The suture started at the inferior end of the anastomosis is inserted with continuous tension until it meets the superior suture, at which point the superior suture is drawn tight, and the two sutures are tied to each other. Before drawing the superior suture tight, the clamps on the PV are momentarily released to flush out any clots, and the anastomosis is thoroughly irrigated with heparinized saline.

Figure 77.18 shows the finished anastomosis, upon completion of which a single interrupted tension suture is placed just beyond each end of the anastomosis to take tension off the anastomotic suture line. The clamp on the IVC is removed first, the clamp on the hepatic side of the PV is removed next, and finally the clamp on the intestinal side of the PV is removed. Bleeding from the anastomosis occurs infrequently, but it can be controlled by one or two well-placed interrupted sutures of 5-0 vascular suture material.

Pressures in the PV and IVC must be measured after the anastomosis is completed. Usually the pressures in the PV and IVC are similar after the shunt is in place. A pressure gradient of greater than 50 mm saline between the two vessels indicates that there is an obstruction in the anastomosis, even when no obstruction can be palpated. In such circumstances, the anastomosis should be opened to remove any clots, and if necessary, the entire anastomosis should be taken down and done again. It is essential that there be no more than a 50-mm saline gradient between the PV and IVC to achieve permanently adequate portal decompression and to avoid ultimate thrombosis of the shunt.

Mesoatrial Shunt

When BCS is caused by thrombosis of the IVC and of the hepatic veins, SSPCS and equivalent decompressive procedures are ineffective, because the high pressure in the infrahepatic IVC does not permit adequate decompression of the portal system and liver. Under such circumstances, a mesoatrial shunt has been advocated. Synthetic Dacron or Gore-Tex grafts ranging from 14 to 20 mm in diameter have been used in most cases and have been connected end-to-side to the superior mesenteric vein in the abdomen and the right atrium in the thorax.

We performed mesoatrial shunting in eight patients with BCS caused by thrombosis of the IVC and the hepatic veins. A 16-mm ring-reinforced Gore-Tex prosthesis was used. The operation was performed through a midline laparotomy and a median sternotomy. The superior mesenteric vein was isolated circumferentially for a distance of about 3 cm in the root of the small bowel mesentery, and the pericardium was opened to expose the lateral wall of the right atrium. The graft was anastomosed to the side of the superior mesenteric vein with continuous 5-0 vascular suture, tunneled through the root of the transverse mesocolon and greater omentum, then passed anterior to the stomach and left lobe of the liver into the mediastinum through an opening made in the anterior diaphragm. Finally, the prosthesis was anastomosed to the side of the right atrium with a continuous 5-0 vascular suture. To ensure wide-open anastomoses, an ellipse of the wall of the superior mesenteric vein and of the right atrium was excised before connecting the prosthesis.

Our results of mesoatrial shunting are shown in Tables 77.5, 77.7, and 77.8. A mesoatrial shunt reduced the mean gradient between the PV and right atrium from 211 to 78 mm saline. All eight patients survived the operation and left the hospital alive, although five (63%) of the eight patients subsequently developed thrombosis of the graft and died from liver failure. Three of the deaths occurred during the first postoperative year, one occurred in the second year, and one occurred in the fifth year. All five patients developed recurrence of ascites, and three developed portosystemic encephalopathy as their hepatic function deteriorated. The causes of BCS in the five patients whose mesoatrial shunt failed were oral contraceptives in one, polycythemia rubra vera in one, antithrombin III deficiency in one, and a postpartum state in one; the cause of the other one was unknown. These causes were no different from those found in the long-term survivors of portal decompression in our series. The patients whose mesoatrial shunt failed were not a higher risk group; they died because their mesoatrial shunt thrombosed 1 to 5 years after insertion, not because they were poorer risk patients to start with.

The three long-term survivors of the mesoatrial shunt (38%) have been followed up for 23 years, 21 years, and 21 years, respectively. Angiography and US have shown patency of their grafts. They are free of ascites, have normal liver function, and do not require diuretics; two of the three are gainfully employed. Serial liver biopsy specimens show residual congestion in one patient and moderate fibrosis in two. In one patient, the liver appears normal.

Several series of mesoatrial shunting that involve 5 or more patients have been reported in the literature, although the length of follow-up generally has been relatively short. Stringer and colleagues (1989) of London reported excellent results in 5 patients, but the follow-up period of 9 to 16 months was too short to warrant conclusions. Wang and colleagues (1989, 2005) of Beijing reported a survival rate of 61% and 50% at 5 and 10 years, respectively, in 70 patients, but his reports contain insufficient details to determine how many of the patients had patent and functioning grafts, how well the patients were followed, or the exact nature of the BCS that was being treated. Emre and colleagues (2000) of Istanbul reported an 85% survival rate of 13 patients during follow-up of 1 to 76 months, with one known thrombosed shunt. Behera and associates (2002) of Chandigarh, India, described 100% graft patency during 6 to 71 months of follow-up of 10 patients, with a survival rate of 90%. Khanna and colleagues (1991) of Chandigarh, India, reported a 62% survival rate of 13 patients during follow-up of 2 months to 7.5 years.

The results of Henderson and colleagues’ (1990) study of nine patients, of Klein and colleagues (Klein et al, 1990; Slakey et al, 2001) study of 15 patients, and of our own investigations of eight patients are representative of the experience with mesoatrial shunting in the United States. Survival rates ranged from 38% to 67%, and the percentage of patients with grafts that were patent and decompressing was only 33% to 60% during relatively short follow-up periods. Cameron and colleagues (1984; Klein et al, 1990) reported improved results with the use of an 8-cm external silicone rubber sleeve around a 16-mm ring-reinforced Gore-Tex prosthesis to prevent compression of the graft by the sternum. This innovation may reduce the frequency of graft thrombosis, but the results of mesoatrial shunting generally have been disappointing.

The high thrombosis rate of the mesoatrial shunt may be due to the fact that it is a relatively low-flow synthetic graft placed within the venous system. It does not decompress the obstructed IVC. To overcome these shortcomings, we worked in the experimental laboratory to devise a new operation for this form of BCS consisting of a combined SSPCS and cavoatrial shunt (CAS) through a Gore-Tex graft (Orloff et al, 1992a). This combined shunt was aimed at decompressing the hypertensive IVC and shunting the entire systemic venous flow from the lower two thirds of the body and the entire portal venous flow through the graft.

Experimental Studies

BCS was produced in rats by gradual occlusion of the suprahepatic IVC with an ameroid constrictor. As the hygroscopic casein plastic took up fluid and swelled centrally, the lumen in the ameroid gradually narrowed until, after 25 to 30 days, it completely occluded the IVC and produced severe hepatic outflow block, portal hypertension, and massive intractable ascites typical of BCS. One month after insertion of the ameroid constrictor around the IVC, when all rats had massive ascites, hepatomegaly, and portal hypertension, they were randomly divided into three groups (Fig. 77.19). Group I was composed of 16 control rats that underwent a sham thoracolaparotomy when BCS was well established. Group II consisted of 22 rats subjected to a mesoatrial shunt from the superior mesenteric vein to the right atrium with a 3-mm Gore-Tex graft inserted by microsurgical technique. Group III comprised 22 rats that underwent SSPCS combined with CAS from the IVC to the right atrium with a 3-mm Gore-Tex graft. Forty-four rats survived the operations and were studied.

FIGURE 77.19 Experimental groups of rats with Budd-Chiari syndrome produced by constriction of the inferior vena cava by an ameroid constrictor. Control sham laparotomy, mesoatrial shunt, and combined side-to-side portacaval (PC) shunt and cavoatrial (CA) shunt were compared.

(From Orloff MJ, et al, 1992: Treatment of Budd-Chiari syndrome due to inferior vena cava occlusion by combined portal and vena caval decompression. Am J Surg 163:137-143.)

Table 77.9 summarizes the results in the three groups of rats. All control rats that underwent sham thoracolaparotomy in group I rapidly reaccumulated ascites and died within 2 months. Nine of 16 rats with mesoatrial shunts in group II re-formed ascites and died within 2 months. All of these animals were found at autopsy to have thrombosis of the mesoatrial graft. In contrast, only 2 of 16 rats treated by combined SSPCS and CAS in group III developed CAS-graft thrombosis, re-formed ascites, and died. The remaining 14 rats in group III were found to have patent grafts and shunts when they were sacrificed after 3 months. Liver biopsy specimens in all rats were normal before IVC constriction, and after BCS was well established, they showed intense centrilobular congestion and moderate central necrosis. Severe pathologic changes persisted until death or sacrifice in all control rats in group I and in 11 of 16 rats with mesoatrial shunts in group II; however, combined SSPCS and CAS in group III reversed the liver pathology in 14 of 16 rats.

Our Clinical Results with Combined Side-to-Side Portacaval Shunt and Cavoatrial Shunt

On the basis of the encouraging results of our experimental studies, we have treated 18 seriously ill patients with BCS caused by IVC thrombosis with combined SSPCS and CAS using a 20-mm ring-reinforced Gore-Tex graft. The characteristics of the patients are summarized in Tables 77.4 and 77.5. The study included 12 men and 6 women, ranging in age from 25 to 37 years. All 18 patients were in good health before the onset of symptoms and signs, which consisted of marked ascites, edema of the lower extremities, hepatosplenomegaly, abdominal pain, weakness, and muscle wasting. The combined operation is depicted in Figure 77.20.

FIGURE 77.20 Combined side-to-side portacaval (PC) shunt and cavoatrial (CA) shunt using a 20-mm ring-reinforced Gore-Tex graft. The operation was done in 18 patients with Budd-Chiari syndrome secondary to inferior vena cava occlusion.

(From Orloff MJ, et al, 1992: Treatment of Budd-Chiari syndrome due to inferior vena cava occlusion by combined portal and vena caval decompression. Am J Surg 163:137-143.)

The procedure was performed through a long right subcostal incision for the PCS and then a medium sternotomy for the CAS. After completion of the SSPCS, a 20-mm diameter, ring-reinforced Gore-Tex graft was anastomosed to the side of the IVC at the level of the PCS. The graft was channeled anterior to the liver through an opening made in the right leaf of the diaphragm and was anastomosed to the side of the right atrium. Combined SSPCS and CAS reduced the mean gradient between the PV and right atrium from 196 mm saline to 23 mm saline. All 18 patients survived the combined shunt operation and are alive 5 to 25 years postoperatively (see Tables 77.7 and 77.8). Mean follow-up is 12 years. All patients are free of ascites, and none requires diuretics; hepatomegaly and splenomegaly are gone; and liver function tests results are normal in all survivors, with no instance of portosystemic encephalopathy. All survivors are gainfully employed or keeping house and leading productive lives of good quality.

Serial percutaneous liver biopsy specimens have shown normal architecture in 14 patients and mild fibrosis in four. Serial angiographic studies with pressure measurements and Doppler duplex US have shown patency and good function of SSPCS and CAS in all patients (Fig. 77.21). Recanalization of the IVC or hepatic veins has not occurred. Permanent anticoagulation with warfarin and low-dose acetylsalicylic acid (aspirin) has been maintained in all patients. In our program, combined SSPCS and CAS has replaced mesoatrial shunt as the preferred treatment for BCS caused by IVC obstruction.

FIGURE 77.21 Shunt catheterization and venogram showing patency of the portacaval shunt (PCS) and cavoatrial shunt (CAS) 1 year after performance of combined PCS and CAS in a patient with Budd-Chiari syndrome secondary to inferior vena cava occlusion. Serial angiographic studies showed patency and excellent function of the PCS and CAS in all patients.

(From Orloff MJ, et al, 1992: Treatment of Budd-Chiari syndrome due to inferior vena cava occlusion by combined portal and vena caval decompression. Am J Surg 163:137-143)

Transjugular Intrahepatic Portosystemic Shunt

TIPS (see Chapter 76E) is SSPCS inserted percutaneously under radiographic control. As such, it is based on the same rationale for relieving hepatic venous outflow obstruction and intrahepatic portal hypertension as the surgical SSPCS. The attractiveness of TIPS lies in the fact that it can be done without a major surgical abdominal operation in patients who have liver disease, who are often quite ill. Its major disadvantage is a substantial incidence of occlusion of the TIPS that may require repeated revisions and hospitalizations and often involves recurrence of symptoms. In some patients who have complete occlusion of the hepatic veins or complete occlusion of the IVC, an additional disadvantage is technical inability to insert the TIPS. Insertion of the TIPS by direct puncture of the retrohepatic IVC, which sometimes is the only way that the shunt can be created, may be associated with a substantial incidence of complications (Rössle et al, 2004).

Between 1995 and 2004, there were many reports of TIPS treatment of BCS, each involving a few patients (Blum et al, 1995; Cejna et al, 2002; Ganger et al, 1999; Huber et al, 1997; Mancuso et al, 2003; Michl et al, 1999; Perello et al, 2002; Rogopoulos et al, 1995; Rössle et al, 1998; Uhl et al, 1996). The largest and longest reported experience with TIPS in BCS during that period was that of Rössle and colleagues (2004) at the University Hospital of Freiburg, Germany, who described their experience with 35 patients—11 acute, 13 subacute, and 11 chronic—who were followed up for a mean of 37 (± 29) months. Shunt failure occurred in 7 patients (20%): 2 were technical failures, 2 required LT (1 died), and 3 died after TIPS. Excluding the 2 patients who required LT but including the 2 who could not have TIPS for technical reasons, the 5-year survival rate was 74%. TIPS occlusion requiring revision occurred in 19 (58%) of 33 patients. One patient required 10 revisions during a follow-up period of 53 months.

Results reported by others were not as good as those of the Freiburg group. Mancuso and associates (2003) described a series of 15 patients, with 5 deaths and 1 technical failure—a 40% negative outcome. Cejna and colleagues (2002) reported a series of 8 patients; 2 (25%) died 2 weeks after TIPS, 1 developed TIPS occlusion requiring LT, and 3 others required two to seven revisions for TIPS stenosis. Only 2 (25%) of 8 of the initial series of patients had revision-free TIPS patency. Perello and colleagues (2002) reported a series of 13 patients in which there were three shunt failures (23%). The failures included 1 death, 1 TIPS thrombosis that necessitated a surgical shunt, and 1 patient that required LT. Of the remaining 10 patients, 7 (70%) developed TIPS occlusion. In 5 of these, TIPS dysfunction had not been corrected.

Since 2004, use of TIPS in BCS has increased substantially, mainly in Europe, in part as a result of the availability of polytetrafluoroethylene (PTFE)-covered stents. Most of the reports have involved retrospective reviews of small numbers of cases followed up for short periods of time. In 2006, Rössle and colleagues reported results of TIPS with PTFE-covered stents in 112 patients, 17 of whom had BCS. Of these, 12 patients were lost to follow-up, and 16 developed TIPS failure. The 1-year TIPS failure rate was 10%, 22 patients died, and 3 underwent LT. The mortality rate without and with the patients lost to follow-up was 20% and 30%, respectively. The authors concluded that the TIPS procedure was improved by the PTFE-covered stent.

Other recent reports of TIPS treatment of BCS include a 124 patients (Murad et al, 2008 [16 patients]; Garcia-Pagan et al, 2008; Eapen et al, 2006 [30 patients]; Plessier et al, 2006 [20 patients]; Gandini et al, 2006 [13 patients]; Hernandez-Guera et al, 2004 [25 patients]; Attwell et al, 2004 [17 patients]). Garcia-Pagan and colleagues (2008) conducted a retrospective review of 124 BCS patients treated with TIPS in six European centers between 1993 and 2006. It is noteworthy that 147 of 221 patients with BCS were eligible for TIPS, but 14 were excluded for technical contraindications, and attempts at TIPS failed in an additional nine patients. Thus, in a population of patients with BCS, only 60% actually underwent TIPS. Twenty-two patients had complications associated with the TIPS procedure, and 2 died as a result. Sixty-one (41%) of the 124 patients had TIPS dysfunction during follow-up that required restenting in 35, angioplasty in 20, and thrombolysis in 6. Portosystemic encephalopathy developed in 21% of patients within 1 year. During follow-up, 16 patients died (13%), and 8 required LT (6.5%). Actuarial LT-free survival rates at 1, 5, and 10 years were 88%, 78%, and 69%, respectively.

Surprisingly, Garcia-Pagan and colleagues drew the following conclusions: 1) “Our results show that overall TIPS is an extremely effective therapy for patients with severe BCS in whom medical treatment has failed.” 2) “However, treatment with TIPS resulted in excellent long-term survival.” 3) “In conclusion, in experienced hands, TIPS is an extremely useful therapy for most BCS patients in whom medical treatment or recanalization fails. It may improve survival and should therefore be considered the treatment of choice.”

The survival rate of surgical portosystemic shunt in our series is shown in Table 77.7. In patients with acute and subacute BCS resulting from occlusion of the hepatic veins, operative mortality after SSPCS has been 3%, and 5-year survival has been 97%. In patients with BCS secondary to IVC occlusion treated by combined SSPCS and CAS, the 5-year survival has been 100%. All of the patients have been relieved of the symptoms of BCS, and readmission to the hospital has been infrequently necessary. These results are superior to the best reported results of TIPS in comparable patients. Without doubt, the long-term health care costs of TIPS are substantially higher than the costs of surgical therapy.

Liver Transplantation

LT (see Chapter 97A, Chapter 97B, Chapter 97C, Chapter 97D, Chapter 97E ) is a radical, drastic treatment for BCS, but it is effective when a patient’s life is at stake, and no other form of therapy would work. LT is not in competition with SSPCS or any other type of treatment. It is useful in far advanced, decompensated liver disease, when it is too late to accomplish survival with portal decompression procedures.

It is imperative that the indications for the use of LT in BCS be established and clearly understood. The indications that we adhere to are as follows:

Using these indications, 12 of our patients have been approved and listed for LT. Their characteristics are shown in Table 77.10. In 10 of the 12 patients, an underlying thrombogenic hematologic disorder was identified. The time lapse from clinical onset of BCS to LT was much longer than in our patients who were treated by SSPCS, ranging from 11 to 21 months and averaging 15.9 months. These patients had a chronic form of BCS. The indication for LT was cirrhosis with progressive liver failure in 11 patients whose severe hepatic decompensation precluded consideration of SSPCS, and thrombosis of a PCS with recurrence of clinical manifestations of BCS was the indication in one patient. In 11 of our patients, thrombosis was confined to the hepatic veins, and in one patient, the hepatic veins and suprahepatic IVC were occluded. All but one patient, the one with an occluded PCS, had a patent PV.

Table 77.10 Characteristics of 12 Patients Approved and Listed for Liver Transplantation for Budd-Chiari Syndrome

BCS, Budd-Chiari syndrome

Table 77.11 shows the clinical findings in our 12 patients. All patients had massive ascites, jaundice, severe muscle wasting, hepatomegaly, splenomegaly, and dilated collateral veins on the abdominal wall. Encephalopathy had occurred in 50%, and one or more episodes of bleeding varices had occurred in 58%. All patients had cirrhosis on preoperative liver biopsy and in the recipient liver removed at LT. This was a group with advanced, decompensated liver disease. All of them were Child-Turcotte-Pugh (CTP) class C (Child & Turcotte, 1964) determined by the quantitative scoring method of Campbell and colleagues (1973).

Table 77.11 Preoperative Clinical Findings in 12 Patients Approved and Listed for Liver Transplantation for Budd-Chiari Syndrome

Table 77.12 shows the results of preoperative liver function tests. Serum bilirubin was substantially elevated, and serum albumin was markedly depressed in every patient. Prothrombin activity was invariably low, resulting in a mean international normalized ratio of 2.0. Aspartate aminotransferase and serum alkaline phosphatase were significantly elevated. Liver function test results were highly abnormal and reflected serious hepatic failure.

Table 77.12 Preoperative Liver Function Tests in 12 Patients Approved and Listed for Liver Transplantation for Budd-Chiari Syndrome

Table 77.13 shows the survival rate of the 12 patients who were approved and listed for LT. Three patients died of liver failure while awaiting LT during periods of 4 to 10 months. Two patients died during the immediate period after LT, one from relentless graft rejection and one from sepsis with multisystem organ failure. A third patient died 9 months postoperatively of liver failure, but no patients were lost after the first year. The 1- and 5-year survival rates were 50%. If the three patients who died before LT could be accomplished are excluded, the actual 1-year and 5-year survival rates of the patients who underwent LT are 67%. The 5-year survival rate is comparable to the reported survival rate of LT in CTP class C patients who do not have BCS.

Table 77.13 Long-Term Results of Liver Transplantation for Budd-Chiari Syndrome in 12 Patients Approved and Listed for Orthotopic Liver Transplantation

BCS, Budd-Chiari syndrome; OLT, orthotopic liver transplantation

The six long-term survivors of LT have been followed up for more than 5 years and have had a life of good quality (see Table 77.13). Five are working full time, and BCS has not recurred in any. All survivors were placed on anticoagulant therapy postoperatively and are receiving lifelong maintenance warfarin and aspirin treatment.

Experience with Liver Transplantation in Budd-Chiari Syndrome Reported in the Literature

To date, the English literature contains reports of more than 1000 patients with BCS who have undergone LT, and Table 77.14 summarizes these reports. The largest number of case reports have come from reviews of 248 patients registered in the European Liver Transplantation Registry and 510 patients registered in the United Network for Organ Sharing (UNOS) Liver Standard Transplant Analysis and Research files. All of the reports were based on retrospective reviews of medical records. No prospective studies of LT in BCS have been done.

Table 77.14 Indications for Liver Transplantation in 15 Retrospective Series of Budd-Chiari Syndrome Reported in the Literature

BCS, Budd-Chiari syndrome; IVC, inferior vena cava; OLT, orthotopic liver transplantation; PSS, portosystemic shunt; TIPS, transjugular intrahepatic portosystemic shunting; UNOS, United Network for Organ Sharing.

As shown in Table 77.14, the indications for LT varied greatly, and it cannot be said that LT was done in patients who had 1 year or less to live because of cirrhosis with progressive liver failure. In several series (Jamieson et al, 1991; Melear et al, 2002; Ringe et al, 1995; Segev et al, 2007), the indications were not clearly stated. Ulrich and colleagues (2008) reported 12% of the 39 patients were CTP class A, and 57% were class B, obviously not in liver failure. The report of Halff and colleagues (1990) stated, “The decrease in synthetic function was not as severe as in many other causes of end-stage liver disease.” Every series had some patients who underwent LT because of a failed portosystemic shunt. In the registry review of Mentha and associates (2006), 49 of the 248 patients had failure of a portosystemic shunt (Campbell et al, 1988; Krom et al, 1984).

Table 77.15 shows the survival statistics in the reported series. All of the studies suffer from the fact that follow-up of many of the patients was short, sometimes less than 1 year. A substantial variation in patient selection was apparent from one series to the next, particularly with regard to severity of liver disease, so that they cannot be compared with each other. The early mortality rate in series that had 10 or more patients ranged from 5% to 36% and averaged 15%. The 5-year survival rate, when it was reported, ranged from 45% to 95% and averaged 71%. Segev and colleagues (2007) in their UNOS registry review reported that since introduction in 2002 of the Model for End-Stage Liver Disease (MELD) scoring system for organ allocation by disease severity, 3-year patient survival has increased from 72.6% to 84.9%, and 3-year graft survival has increased from 64.5% to 80.6%.

Most of the series did not report the results of pathologic examination of the liver removed from the patient with BCS. The reports of Ringe and colleagues (1995) on 43 patients, Halff and colleagues (1990) on 32 patients, Sakai and Wall (1991, 1994) on 11 patients, and Srinivasan and associates (2002) on 19 patients described the findings in the host liver, however, and confirmed the clinical impression that many patients underwent LT without having decompensated liver disease. Only 17 of the 43 patients of Ringe and colleagues (1995) had cirrhosis; the others had congestion alone (14 patients) and fibrosis alone, lesions that are found in the early stages of BCS. Similarly, in the report of Halff and colleagues (1990), none of the 32 patients had cirrhosis, and Sakai and Wall (1994) reported that 3 of 11 of their patients had central congestion and necrosis but no fibrosis or cirrhosis.

An important concern about LT in BCS is recurrence of BCS in the transplanted liver (Bahr et al, 2003; Goldstein et al, 1991). Table 77.16 shows the incidence of recurrent BCS in the liver allograft. Some investigators reported no recurrence of BCS, whereas others (Knoop et al, 1994a, 1994b; Halff et al, 1990; Cruz et al, 2005) reported substantial recurrence rates of 13% to 27% despite treatment with anticoagulants. Most series have shown a substantial incidence of posttransplant thrombosis in other splanchnic blood vessels, particularly in the PV (range, 9% to 40%), often with disastrous consequences. The frequent development of thrombosis makes it mandatory that patients receive early and lifelong anticoagulation therapy after LT. At the same time, it should be recognized that anticoagulation sometimes fails to prevent thrombosis.

One of the potential benefits of LT in certain thrombogenic disorders, such as antithrombin III deficiency and protein-C deficiency, is correction of the underlying defect by transplantation of a liver from a normal donor. It has been suggested that LT is preferable to SSPCS in the treatment of BCS, because if SSPCS fails, the risk of performing subsequent LT is increased. It has been proposed that mesocaval shunt is preferable to SSPCS, because it is advantageous to avoid dissection of the hepatic hilum, should subsequent LT be required (McMaster, 1994; Bismuth & Sherlock, 1991; Slakey et al, 2001). In our experience, patients with BCS treated by SSPCS infrequently require LT. Of 57 patients with BCS whom we treated by SSPCS, only 1 (2%) subsequently required LT during long-term follow-up. In our experience with more than 2500 PCS procedures in patients with cirrhosis, the long-term shunt patency rate has been 99.5%.

Additionally, at least 10 more recent studies have shown that previous portosystemic shunt, regardless of type, had no influence on the outcome of LT (Aboujaoude et al, 1991; Bismuth et al, 1990; Boillot et al, 1991; Iwatsuki et al, 1988; Langnas et al, 1992; Mazzaferro et al, 1990; Minegaux et al, 1994; Turrion et al, 1991). Aboujaoude and colleagues (1991) emphasized that thrombosis of a portosystemic shunt may seriously compromise performance of LT; long-term shunt patency should therefore be the main factor that determines the type of shunt selected for the potential LT candidate, a point that is all the more true in patients with BCS. Direct PCS has had a thrombosis rate of 0.5% or less in all of our studies, compared with occlusion rates of 24% to 53% reported in the literature for mesocaval interposition shunts using synthetic grafts (Fletcher et al, 1981; Hemming et al, 1996; Smith et al, 1980; Terpstra et al, 1987). Mesocaval interposition shunts using autologous internal jugular vein grafts, which have been used widely in France, have shown patency rates comparable to direct SSPCS (Bismuth & Sherlock, 1991; Gentil-Kocher et al, 1988; Vons et al, 1986).

A second important indication for LT is failure of a portosystemic shunt, usually because of thrombosis, with persistence or recurrence of clinical manifestations of BCS. In experienced hands, and with the routine, long-term use of anticoagulation therapy after portosystemic shunt, this should be a rare indication—but the literature indicates that such is not the case.

The third and fourth indications for orthotopic liver transplantation (OLT) in BCS are rare, and we have not encountered such cases, although they have been reported without many details in the literature. These are unshuntable patients with portal hypertension resulting from thrombosis of the portal venous system, provided that there are patent blood vessels available to vascularize the liver allograft, and acute fulminant hepatic failure (Sakai & Wall, 1994).

It is important to emphasize that SSPCS and LT are not competing forms of treatment. SSPCS is the appropriate treatment in the early and middle stages of BCS, when portal decompression would sustain life by reversing or stabilizing the liver disease. OLT is the appropriate treatment in the late stages of BCS, when the liver disease is no longer reversible, and when stabilization of progressive hepatic decompensation is impossible. Most patients who are candidates for LT should be in CTP class C.

In considering treatment of BCS by LT, it is important to take into account the downside of such therapy, namely 1) insufficient donor livers to treat the many patients who need LT; 2) long periods on the waiting list during which, as was true in our patients, more than one third of the patients die; 3) the unpredictable availability of donor organs; 4) the need for and consequences of lifelong immunosuppression; and 5) the high cost of LT, which our data show is almost five times the cost of portosystemic shunt.

Surgical Removal of Venous Obstruction

Senning (1981, 1983) reported a direct method of removing obstruction of the IVC and hepatic veins in patients with chronic BCS. The operation is performed with cardiopulmonary bypass and involves opening the suprahepatic IVC and right atrium, removing any vena caval thrombus, resecting the dorsocranial part of the liver containing the confluence of the occluded major hepatic veins, and reconstructing the hepatic outflow tract by suturing the right atrium to the liver capsule. Since his initial description, Senning (1987) and others (Pasic et al, 1993) have reported the results of the operation in 17 patients, 2 of whom (12%) died within 2 weeks of operation and 4 of whom died later. Actuarial 1-year and 3-year survival rates were 76% and 57%, LT was required for 2 patients, and 3 developed recurrent thrombosis. During follow-up of 7 months to 11 years, 10 (67%) of the 15 early survivors had prolonged relief of BCS.

Kawashima and colleagues (1991) reported success of the Senning operation in 5 of 7 patients during follow-up of 2 months to 5 years, and Nakao and colleagues (1988) described success in 2 patients followed up for 1 to 2 months. In a modification of the operation, Koja and associates (Koja et al, 1996; Kuniyoshi et al, 1998) described direct removal of the IVC obstruction under partial cardiopulmonary bypass in 32 patients with chronic BCS resulting from IVC obstruction of 1 to 42 years’ duration. Koja and associates (Koja et al, 1996; Kuniyoshi et al, 1998) reopened the IVC and occluded hepatic veins under direct vision without resecting the liver and reconstructed the hepatic outflow tract with a patch graft of autologous pericardium. Many of the patients had cirrhosis or severe fibrosis of the liver, and 29 of the 32 had esophageal varices. No operative deaths were reported. During 1.5 to 17 years of follow-up, there were four late deaths, and seven patients developed hepatocellular carcinoma. Survival rates at 5 and 10 years were 93.6% and 81%. In a follow-up to their earlier report, in 2009 Kuniyoshi and colleagues (Inafuku et al, 2009) reported their results from 1979 to 2008 in 53 patients. Overall mortality rate was 32%, and 14% of survivors developed total obstruction or severe stenosis of the reconstructed IVC, therefore it does not appear that radical open-end venectomy is the first-choice operation for IVC occlusion.

Percutaneous Transluminal Angioplasty

Use of percutaneous transluminal angioplasty has been reported in more than 300 patients with BCS (Anonymous, 1982; Baijal et al, 1996; Furui et al, 1990; Griffith et al, 1996; Jeans et al, 1983; Martin et al, 1990; Sato et al, 1990; Tyagi et al, 1996; Wu et al, 2002; Xu et al, 1996; Yamada et al, 1983, 1991; Yang et al, 1996; Li et al, 2009). Most of the patients had chronic liver disease of long duration, and many of them had obstruction of the IVC of the membranous or segmental types. The obstructed vein was dilated with one or more balloon catheters. In all cases, the pressure gradient that existed before balloon dilation was substantially reduced or eliminated at the time of dilation. Stenosis often recurred, however, and required repeated balloon dilations. Most of the patients have not had long-term follow-up, so it is difficult to evaluate the ultimate effectiveness of percutaneous transluminal angioplasty. Of the few patients who have been observed for several years, the long-term success rate is less than 50% (Griffith et al, 1996; Martin et al, 1990; Sato et al, 1990; Yamada et al, 1991), although Wu and associates (2002) reported restenosis in only one of 41 patients during follow-up of 32 (± 12) months.

The use of expandable metallic stents has been added to balloon angioplasty in an attempt to maintain prolonged patency of the IVC (Baijal et al, 1996; Furui et al, 1990; Sawada et al, 1991; Xu et al, 1996, 1999; Li et al, 2009). The follow-up period of the patients who have IVC stents is too short to evaluate the efficacy of this procedure. In our opinion, based on the available evidence, percutaneous transluminal angioplasty and placement of expandable metallic stents warrant consideration only in patients with chronic BCS resulting from stenosis of the IVC. Patients treated by transluminal angioplasty should have careful follow-up that includes venography and pressure measurements every few months to detect recurrent stenosis of the IVC.

Thoracic Transposition of the Spleen

Transposition of the spleen into the left pleural cavity to create collateral venous connections between portal and pulmonary systems has been used sporadically in the treatment of portal hypertension and, in addition, has been advocated for treatment of BCS secondary to occlusion of the IVC (Akita & Sakoda, 1980; Khuroo & Datta, 1980; Schrieber & Gonzalez, 1967; Strauch, 1970). The procedure involves displacing the spleen into an opening in the left diaphragm and suturing the left lower lobe of the lung to the spleen after removing the splenic capsule and abrading the surface of the lung. It is impossible to evaluate the effectiveness of this procedure because of the paucity of information in the few case reports. Akita and Sakoda (1980) of Japan reported the use of “splenopneumopexy” in 15 patients who had diseases that they called BCS. Although few details were given, it seems that most or all of the Japanese patients had a chronic disorder that consisted of cirrhosis and esophageal varices in addition to IVC obstruction. It is possible that many of the patients had the typical MOVC that accounts for most of the cases of BCS in Japan. Portal hypertension, determined by splenic pulp pressure measurements, persisted after splenopneumopexy in all patients. It is doubtful that thoracic transposition of the spleen can decompress the liver and portal system sufficiently to prevent or reverse liver damage in the crucial early stages of BCS caused by occlusion of the IVC.

Peritoneovenous Shunt

Peritoneovenous shunt is a device that relieves ascites by transferring fluid through a one-way valve from the peritoneal cavity into the superior vena cava. It has been advocated as primary treatment for BCS by LeVeen and colleagues (LeVeen et al, 1976). The peritoneovenous shunt may be useful as a palliative measure in patients in whom portal decompression is not feasible or has been tried and failed. The peritoneovenous shunt is not indicated as the primary treatment of most patients with BCS, however, because it does not decompress the obstructed hepatic vascular bed, and it has no effect on the ongoing liver damage. Use of this device early in the course of BCS may squander the opportunity to reverse the liver damage by therapy that effectively decompresses the liver. Long-term studies of peritoneovenous shunting in patients with BCS have not been reported, probably because most patients in whom this device has been used have died from their underlying disease. There is predictable evidence, however, that the liver disease progresses to cirrhosis in the face of a functioning peritoneovenous shunt (Cameron et al, 1983).