Using Transjugular Intrahepatic Portosystemic Shunts to Control Variceal Bleeding before Liver Transplantation Ernest J. Ring, MD; John R. Lake, MD; John P. Roberts, MD; Roy L. Gordon, MD; Jeanne M. LaBerge, MD; Alexandra E. Read, MD; Martina R. Sterneck, MD; and Nancy L. Ascher, MD
• Objective: To determine the safety and efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in controlling bleeding from esophageal varices in patients awaiting liver transplantation. • Design: Prospective, uncontrolled trial. • Setting: University medical center with an active liver transplant program. • Patients: Thirteen patients referred for liver transplantation with either active variceal hemorrhage or recurrent variceal hemorrhage despite sclerotherapy; four patients had been previously treated with surgical portosystemic shunts. • Intervention: An intrahepatic portosystemic shunt created via a transjugular approach to the hepatic veins using expandable, flexible metallic stents. • Measurements: Portal pressures before and after the creation of the shunt, the direction of portal blood flow at differing diameters of the shunts, procedurerelated complications, and outcome in terms of survival, liver transplantation, and recurrent variceal bleeding. • Main Results: The transjugular intrahepatic portosystemic shunt was placed successfully in 13 patients, and bleeding was controlled acutely in all 13. After the procedure, the mean portal pressure decreased from 34 ± 8.9 cm H 2 0 to 22.4 ± 5.4 cm H 2 0 (P < 0.001). No complications were associated with the procedure; however, two patients died of causes unrelated to the procedure. Seven patients subsequently underwent liver transplantation and are doing well, and three patients are being managed conservatively. Bleeding recurred in one patient 102 days after the procedure secondary to shunt occlusion caused by neointimal proliferation. • Conclusion: Placement of a transjugular intrahepatic portosystemic shunt is apparently safe and effective therapy for variceal hemorrhage in patients referred for liver transplantation.
1 he management of patients with variceal hemorrhage has changed considerably over the past few years. Sclerotherapy has become the primary treatment for active variceal hemorrhage as well as for prevention of future variceal bleeding. Emergency shunt operations are now mainly reserved for the 10% to 15% of patients who do not respond to endoscopic treatment or who are bleeding from inaccessible gastric or intestinal varices (1, 2). Unfortunately, this approach has done little to improve the survival of patients with advanced liver disease. Fewer than 50% of patients with Child class C disease who bleed from varices survive 30 days, regardless of whether they undergo portosystemic shunt surgery or sclerotherapy, and only a few from each group are still alive at 1 year (3). Moreover, orthotopic liver transplantation has become an increasingly routine treatment for patients with end-stage liver disease. Long-term survival rates of more than 70% are now widely reported and appear to be no different for patients with variceal bleeding (4, 5). However, the limited availability of donor organs generally precludes emergency transplantation for acute hemorrhage, and if sclerotherapy fails to control the bleeding, then portosystemic shunts are done in these high-risk patients. Because conventional portacaval shunts add to the technical difficulty and operative blood loss of subsequent transplant surgery, most transplant surgeons recommend alternative procedures, such as mesocaval shunts, for patients who might eventually undergo transplantation. Placement of transjugular intrahepatic portosystemic shunts (TIPS) using expandable metallic stents has recently been described; portal decompression is achieved through a percutaneously established shunt between the hepatic and portal veins within the liver (6, 7). We have previously described our first patient with variceal bleeding who was treated by TIPS placement followed by elective liver transplantation (8). In this article, we describe our preliminary experience with TIPS as a way to control refractory variceal bleeding hemorrhage before liver transplantation. Methods Patients
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Our series included 13 patients with refractory variceal bleeding who were admitted to the Liver Transplantation Service, University of California, San Francisco, between June 1990 and May 1991 and who underwent TIPS placement portal decompression. Patients were considered to have failed sclerotherapy if bleeding could not be acutely controlled with endoscopic sclerotherapy (six patients) or more than two episodes
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of rebleeding requiring transfusion occurred during a 2-week period (seven patients). Patients underwent a mean of six sessions of sclerotherapy before TIPS placement. All patients who met these criteria underwent the TIPS procedure. During that time interval, two additional patients underwent TIPS for variceal bleeding, but they were not candidates for liver transplantation and were therefore not included in the series. Our study patients included seven men and six women. Their mean age was 46 years. Nine of the patients had Laennec cirrhosis; four had postnecrotic cirrhosis. Four patients had been previously treated with surgical portosystemic shunts that were functionally ineffective or occluded. Eleven of the patients were classified as having Child C disease and 2 patients as having Child B disease by the Child-Pugh modified scoring system (9). The mean Child-Pugh score was 10.7 ± 1.2. Average pre-procedure laboratory values included a serum bilirubin level of 60 ± 38 /xmol/L, a serum albumin level of 27 ± 5 g/L, and a prothrombin time of 16.5 ± 3.1 seconds. Clinically apparent ascites was present in nine patients; encephalopathy was present in six patients. Each patient was fully evaluated before the procedure and was accepted as a candidate for liver transplantation. The protocol for patient selection and the method used for the TIPS were approved by the Committee on Human Research, University of California, San Francisco. Procedure After informed consent was obtained from the patient or his or her next of kin, the patient was brought to the interventional radiology suite for the procedure. The right side of the neck was prepared with a sterile solution and isolated using sterile drapes. The right internal jugular vein was percutaneously punctured, and an angiographic catheter and guidewire were manipulated under fluoroscopic guidance through the superior vena cava, right atrium, and inferior vena cava into the middle or right hepatic vein. The catheter was then exchanged for an angiographic sheath with a hemostasis valve. The sheath was 40 cm in length and 3 mm in diameter. A Colapinto transjugular needle (Cook Inc., Bloomington, Indiana) (3.0-mm catheter with a beveled needle that was 1.7 mm in diameter) was advanced through the sheath and directed out of the hepatic vein anteriorly through the liver parenchyma toward the right portal vein. In the first three patients, the portal vein puncture was guided fluoroscopically by directing the needle toward a 0.9-mm catheter that had been previously placed transhepatically into the portal vein. In the subsequent patients, transhepatic portal vein catheterization was not done; in
these cases, external ultrasound was used to guide the vein-tovein puncture. After the right portal vein branch was entered, a 0.9-mm guidewire was passed through the needle and manipulated across the main portal vein into the splenic or mesenteric vein. The inner 1.7-mm needle was then removed and a straight 1.7-mm catheter was advanced over the guidewire into the portal vein. The initial baseline portal pressure was measured directly through the catheter, and portal venography was done. The 1.7-mm angiographic catheter was then exchanged for an 8-mm angioplasty balloon catheter that was inflated in the tract between the hepatic and portal veins. The 3-mm catheter and the balloon catheter were then removed and a 2.3-mm Wallstent catheter (Schneider, Minneapolis, Minnesota) was introduced. Depending on the distance between the veins, either a 42-mm or a 68-mm self-expanding metallic stent (Wallstent, Schneider, Minneapolis, Minn.) was used for the shunt. The stent was positioned so that it began to open in the main portal vein just proximal to the bifurcation. It was deployed from there through the parenchymal tract toward the hepatic vein. After the stent was deployed and detached from the introducer catheter, the unconstrained segment of stent within the portal vein opened to its full 10-mm diameter. The segment constrained by the liver parenchyma was distended with an 8-mm angioplasty balloon. Contrast medium was then injected to determine whether the cephalad end of the stent extended into the hepatic vein. If the stent did not reach the lumen of the hepatic vein, a second stent was introduced and partially overlapped within the first to bridge the additional distance. Measurement of the portal vein pressure and portal venography were then repeated. If the postshunt portal venogram showed continued evidence of hepatofugal flow and filling of varices, then the intraparenchymal segment of the stent was expanded to its maximum diameter with a 10-mm angioplasty balloon, and portal venography and pressure measurements were repeated. The catheters were then removed from the jugular vein. All patients were monitored in an intensive care unit for 24 hours and then followed according to the standard pretransplant protocol at the University of California, San Francisco. Follow-up included monthly outpatient clinical and laboratory evaluations. Duplex ultrasound examinations were done at 3-month intervals in patients who did not undergo early transplantation. Alcoholic patients who had been sober for fewer than 3 months were required to attend a 28-day inpatient alcohol treatment program and to participate in a weekly outpatient support group.
Table 1. Clinical Characteristics and Follow-up Results in Patients Who Underwent the Transjugular Intrahepatic Shunt Procedure* Patient
Diagnosis
Control of Bleeding ShortLongterm term
Portal Vein Pressure Before After TIPS TIPSt
Follow-up
Improved Control of Ascites
Shunt Patency
d
cm H20 1 2 3 4 5 6 7 8 9 10 11 12 13
Crytogenic cirrhosis ALD ALD ALD ALD ALD ALD ALD ALD Autoimmune hepatitis Crytogenic cirrhosis HBV ALD
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes
28 21 31 34 32 30 37 40 33 55
16 19 19 23 18 21 29 32 19 28
Yes Yes Yes Yes Yes Yes Yes No No
Did not have transplantation Did not have transplantation Did not have transplantation Did not have transplantation Had transplantation Had transplantation Had transplantation Had transplantation Had transplantation Had transplantation Had transplantation Died Died
268 264 219 143 102 and 4$ 27 23 20 4 4 3 2 5
* ALD = alcoholic liver disease; HBV = hepatitis B virus; TIPS = transjugular intrahepatic portosystemic shunt. t Average decrease was 12 cm H 2 0 . Average pressure before TIPS was 34 cm H 2 0 , and average pressure after TIPS was 22 cm H 2 0 . X Patient 5 had two shunts placed.
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Statistics Results are expressed as mean ± SD. Results Clinical characteristics and follow-up results of patients undergoing TIPS are summarized in Table 1. The TIPS procedure was successful in all 13 patients, and no procedure-related complications occurred. The three TIPS procedures guided by preliminary transhepatic portal vein catheterization were done in a mean time of 163 ± 23 minutes. The subsequent ten procedures guided only by external ultrasound were done in a mean time of 121 ± 29 minutes. Portal pressure decreased from an initial average of 34.1 ± 8.9 cm H 2 0 to 22.4 ± 5.4 cm H 2 0 after the TIPS procedure (P < 0.001). In eight cases, the immediate postshunt portal venogram showed the complete elimination of flow into the varices with the stent expanded to 8 mm (Figure 1). In the other 5 patients, hepatofugal flow in the coronary vein was eliminated by expanding the stent to 10 mm. After TIPS placement, gastrointestinal bleeding ceased in all six patients who were actively bleeding when the procedure began. Only one of these patients has had further gastrointestinal bleeding, which occurred 102 days after the shunt was placed. Arterial portography done at that time showed an absence of flow through the shunt. The portal vein and its branches
were patent. The shunt was catheterized by a transjugular approach revealing a narrow irregular lumen. After balloon dilation, a second stent was deployed inside the original, with re-establishment of shunt patency. After this procedure, bleeding stopped and the patient underwent liver transplantation 4 days later. No immediate complications were noted after the TIPS procedure. Specifically, inadvertent puncture of the gallbladder, colon, or other viscus was not observed, and no bleeding complications occurred. Two patients died within 30 days after the procedure; in neither case was death related to the TIPS procedure or to hepatic failure. One patient died of respiratory failure and sepsis related to aspiration pneumonia that occurred during a previous attempt at endoscopic sclerotherapy. The other patient died of sepsis and renal failure as a late consequence of spontaneous bacterial peritonitis that was diagnosed before the procedure. Seven of the patients underwent liver transplantation after the TIPS procedure (3, 4, 4, 20, 23, 27, and 106 days, respectively). These patients have all been discharged from the hospital and are doing well (mean follow-up, 190 days). Two patients who were initially considered to be candidates for transplantation have improved clinically, and the previous indications for transplantation (refractory ascites and variceal hemorrhage) are no longer present; two patients are no longer considered transplant candidates because of renewed alcohol abuse. In the 8 patients in whom follow-up was
Figure 1. Diversion of portal flow through an 8-mm transjugular intrahepatic portosystemic shunt. Left Panel. Contrast medium was initially injected into both the hepatic vein (open arrows) and portal vein in order to estimate the length of parenchymal tract to be stented. Both the right and left branches of the portal vein are opacified. Portal pressure was 32 cm H 2 0 . Right Panel. Because the Wallstent is designed to self-expand up to 10 mm, the unconstrained segments of stent within the portal vein (open arrow) and hepatic vein (closed arrow) open to the stent's maximum diameter. The parenchymal segment of the stent was expanded to 8 mm with an angioplasty balloon. Repeat portal venography showed that portal flow had been totally diverted through the stent. Portal pressure was reduced to 18 cm H 2 0 . 306
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Figure 2. Histologic examination of a transjugular intrahepatic portosystemic shunt 20 days after insertion. The shunt lumen is round and smooth, and the stent's wires (arrows) are incorporated in a developing neointima.
sufficient to evaluate their mental status more than 14 days after the TIPS, there was no clinical evidence of encephalopathy. For patients who survived and did not undergo immediate transplantation, the mean time to discharge after the procedure was 4 days (range, 2 to 9 days). Before the TIPS procedure, nine patients had clinically evident ascites that was considered to be refractory to diuretic therapy. All patients experienced a diuresis after the procedure, and the four survivors who did not undergo transplantation currently do not have ascites according to ultrasound examinations. Three of the four transplant recipients who had ascites before TIPS placement had minimal ascites at the time of transplantation. In the explant livers from the seven transplant recipients, the segment that included the shunt and adjacent hepatic and portal veins was removed and fixed in formalin. The metal wires of the stents were then carefully removed using a dissecting microscope, and specimens were sectioned for histologic examination. In specimens obtained 4 days after the TIPS procedure, the shunt lumen was widely patent but had an irregular contour with blunt parenchymal mounds protruding between the stent's struts. Areas of hemorrhage were found in the adjacent parenchyma, with poorly organized thrombus present along some of the wires. The three specimens obtained between 20 and 27 days after TIPS placement showed a very round, smooth lumen, with the stent wires incorporated in a developing neointimal lining (Figure 2). A layer of flattened cells was present along the luminal surface, and immature collagen was present around the stent wires and along the hepatic parenchymal interface. The shunt removed after 106 days showed encasement of the initial stent within a densely collagenized neointima. Poorly organized thrombus was attached to some of the wires of the second stent that had been placed 4 days before transplantation when the original shunt occluded. No thrombus was found in the segment between the stents, suggesting that the first shunt had occluded from excessive neointimal proliferation.
Additional longer-term follow-up is available for four patients (4.5 to 8.5 months after the TIPS procedure). None of these patients has had further episodes of gastrointestinal bleeding. Duplex color flow scans or angiograms in these patients have shown shunt patency with rapid flow through the shunt lumen. Subsequently, routine follow-up endoscopy was not done, catheterization procedures were not repeated, and late changes in portal pressure were not evaluated.
Discussion Portal decompression through a percutaneously established communication between the hepatic and portal veins was first described by Rosch and colleagues (10) in 1969. Subsequently, several attempts have been made to expand the venous connection to a diameter that would be adequate for portal decompression. In 1982, Colapinto and colleagues (11) first reported the use of percutaneous intrahepatic shunts in humans. These investigators used angioplasty balloon catheters and repeated dilatation to establish a large transparenchymal channel. Although these shunts were effective in lowering portal pressure, they tended to occlude rapidly because of elastic recoil in the adjacent hepatic parenchyma. Palmaz and colleagues (12) and Hershey and colleagues (13) used expandable metallic vascular stents to create intrahepatic shunts in animals and showed that a neointimal lining formed within the stent in just a few weeks. Palmaz and colleagues (14) found that expandable metallic intrahepatic shunts placed in dogs with experimentally induced portal hypertension remained patent through 48 weeks. Richter and colleagues (6) successfully created intrahepatic shunts in 10 of 14 patients using the Palmaz balloon-expandable stent (Johnson & Johnson Interventional Systems, Warren, New Jersey). The procedures were technically difficult and required many hours to perform. In some cases, the TIPS procedure was done over 2 days; a transhepatic and a transjugular catheter
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were introduced on day 1, and the shunt was created on day 2. The methods used for TIPS placement in our series included several technical modifications that were intended to improve the efficiency of the procedure so that it could be completed more rapidly. Use of external ultrasound guidance for the portal vein puncture in the last 10 patients not only reduced the procedure time but also eliminated any possible risk for bleeding from the transhepatic catheter entry site. The needle used for the portal vein puncture in these procedures is very rigid, which allows the needle tip to be rotated and its course controlled by external manipulation even through very hard cirrhotic parenchyma. Because the needle is comparable in diameter to the catheters used subsequently, once the needle track is established, there is relatively little resistance to the passage of these catheters. The large lumen of this needle allows the passage of relatively rigid 0.035-inch guidewires that provide further support for the introduction of the catheters. Finally, the shunts were created using the Wallstent, which has the thinnest profile of all the available expandable metallic stents. Unlike other stents that require an outer sheath for introduction, the Wallstent is attached to its introducer catheter and passes into the portal vein directly over a guidewire. This stent is also more flexible than other expandable metallic stents and maintains a cylindrical shape even when positioned around very acute angles. This permits a successful shunt from almost any point of entry into the portal venous system and allows much more leeway in the location of the portal vein puncture. The time required to do the procedures in our series was generally between 2 and 3 hours. Because these cases represent our first attempts at performing this procedure, it is likely that with additional experience and further technical improvements, the procedure time will be further reduced. The ability to decompress the portal venous system rapidly and without general anesthesia makes the TIPS procedure a practical option even for high-risk patients with active bleeding. The average absolute reduction in portal pressure achieved after the TIPS procedure in our series was 12 cm H 2 0 , which is less than the typical pressure reduction achieved with direct portacaval anastomoses; however, this reduction is similar to the decreases reported by Sarfeh, Rypins, and colleagues (15, 16) for 8- and 10-mm mesocaval grafts, which is not surprising because the grafts used by these investigators were the same size as the expanded diameter of the metallic stents used for the shunts in our patients. Similarly, these investigators reported that only 9% of their patients developed encephalopathy, which is consistent with the fact that none of our patients have thus far developed this complication. The effect of previous portacaval shunt surgery on the outcome of liver transplantation remains controversial. There appears to be increased operative blood loss, increased rates of reoperation, and, possibly, increased late (> 1 year) mortality (17). Thus, most transplant surgeons do recommend avoiding portacaval anastomoses because of the adhesions produced in the portahepatis (15). Because TIPS are totally intrahepatic, they 308
do not interfere with transplant operations. The stent was not encountered as the liver was removed in any of the patients in our series who underwent transplantation. However, during the introduction of the stent, special efforts should be made to avoid positioning it either too far into the main portal vein or out through the hepatic vein into the inferior vena cava where it could complicate the transplant operation. There appear to be few potential complications from intrahepatic portal vein shunting. The procedure, done through a jugular venipuncture, creates little risk for hemorrhage, even in patients with significant coagulopathies. Traversing a hepatic artery branch or biliary radical during the parenchymal puncture could conceivably cause hemobilia or arteriovenous fistula, but these complications have not yet occurred. Moreover, arterial injury is very unlikely because, when expanded, the metallic stent compresses and tamponades vessels within the parenchymal tract. Hemobilia should similarly be unlikely, unless there is associated biliary obstruction and dilated intrahepatic ducts. Because the puncture is entirely within the liver, even massive ascites poses no additional risks; however, in the presence of large-volume ascites and a small cirrhotic liver, special care should be taken to avoid inadvertently puncturing the capsule along the inferior surface of the liver. Our experience indicates that TIPS placement is a practical therapy for acute variceal hemorrhage and an effective bridge to transplantation. It is particularly useful in patients with alcoholic liver disease. The duration of function of the TIPS is sufficient to acquaint the patient with transplantation and, if necessary, to allow them to demonstrate compliance with an alcohol treatment program and to establish an adequate support system. The long-term benefit of TIPS placement remains to be demonstrated. Four of the patients who underwent the procedure are no longer being considered for transplantation. In three patients, clinical improvement after the TIPS decreased the need for transplantation; the other patient failed to comply with an alcohol treatment program. The durability of this method will become more clear as these and similar patients continue to be followed. Requests for Reprints: Ernest J. Ring, MD, University of California, San Francisco, Box 0628, San Francisco, CA 94143. Current Author Addresses: Drs. Ring, Gordon, and Laberge: University of California, San Francisco, Box 0628, San Francisco, CA 94143. Drs. Lake, Roberts, Sterneck, and Ascher: University of California, San Francisco, Box 0780, San Francisco, CA 94143. Dr. Read: Overlake Internal Medicine Associates, 1011 116th Avenue, NE, Bellevue, WA 98004.
References 1. Warren WD, Henderson JM, Millikan WJ, Galambos JT, Brooks WS, Riepe SP, et al. Distal splenorenal shunt versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Preliminary report of a prospective, randomized trial. Ann Surg. 1986;203:454-62. 2. The Copenhagen Esophageal Varices and Sclerotherapy Project. Sclerotherapy after first variceal hemorrhage in cirrhosis. A randomized multicenter trial. N Engl J Med. 1984;311:1594-600. 3. Cello JP, Grendel JH, Crass RA, Trunkey DD, Cobb EE, Heilbron DC, et al. Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and variceal hemorrhage. N Engl J Med. 1984;311:1589-94.
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4. Iwatsuki S, Starzyl TE, Todo S, Gordon RD, Tzakis AG, Marsh JW, et al. Liver transplantation in the treatment of bleeding esophageal varices. Surgery. 1988;104:697-705. 5. Crass RA, Keeffe EB, Pinson CW. Management of variceal hemorrhage in the potential liver transplant candidate. Am J Surg. 1989; 157:476-8. 6. Richter GM, Noeldge G, Roessle M, Siegerstetter V, Franke M, Palmaz JC, et al. Transjugular intrahepatic portosystemic stent shunt (TIPSS). Radiology. 1990;174:1027-30. 7. Zemel G, Katzen BT, Becker GJ, Benenati JF, Sallee DS. Percutaneous transjugular portosystemic shunt. JAMA. 1991;266:390-3. 8. Roberts JP, Ring E, Lake JR, Sterneck M, Ascher NL. Intrahepatic portocaval shunt for variceal hemorrhage prior to liver transplantation. Transplantation. 1991;52:160-2. 9. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;560:646-9. 10. Rosch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portocaval shunt: an experimental study. Radiology. 1969;92:1112-4. 11. Colapinto RF, Stronell RD, Birch SJ, Langer B, Blendis LM, Greig
12.
13.
14.
15.
16. 17.
PD, et al. Creation of an intrahepatic portosystemic shunt with a Gruntzig balloon catheter. Can Med Assoc J. 1982;126:267-8. Palmaz JC, Sibbitt RR, Reuter SR, Garcia F, Tio FO. Expandable intrahepatic shunt stents: early experience in the dog. AJR Am J Roentgenol. 1985;145:821-5. Rosch J, Uchida BT, Putnam JS, Buschman RW, Law RD, Hershey AL. Experimental intrahepatic portocaval anastomosis: use of expandable Gianturco stents. Radiology. 1987;162:481-5. Palmaz JC, Garcia F, Sibbitt RR, Tio FO, Kopp DT, Schwesinger W, et al. Expandable intrahepatic portacaval shunt in dogs with chronic portal hypertension. AJR Am J Roentgenol. 1986;147:1251-4. Sarfeh U, Rypins EB, Raiszadeh M, Milne N, Conroy RM, Lyons KP. Serial measurement of portal hemodynamics after partial portal decompression. Surgery. 1986;100:52-8. Rypins EB, Sarfeh U. Small-diameter portacaval H-graft for variceal hemorrhage. Surg Clin North Am. 1990;70:395-404. Turrion VS, Mora NP, Cofer JB, Solomon H, Morris CA, Gonwa TA, et al. Retrospective evaluation of liver transplantation for cirrhosis: a comparative study of 100 patients with or without previous porto-systemic shunt. Transplant Proc. 1991;23:1570-1.
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• Objective: To determine the safety and efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in controlling bleeding from esophageal varices in patients awaiting liver transplantation. • Design: Prospective, uncontrolled trial. • Setting: University medical center with an active liver transplant program. • Patients: Thirteen patients referred for liver transplantation with either active variceal hemorrhage or recurrent variceal hemorrhage despite sclerotherapy; four patients had been previously treated with surgical portosystemic shunts. • Intervention: An intrahepatic portosystemic shunt created via a transjugular approach to the hepatic veins using expandable, flexible metallic stents. • Measurements: Portal pressures before and after the creation of the shunt, the direction of portal blood flow at differing diameters of the shunts, procedurerelated complications, and outcome in terms of survival, liver transplantation, and recurrent variceal bleeding. • Main Results: The transjugular intrahepatic portosystemic shunt was placed successfully in 13 patients, and bleeding was controlled acutely in all 13. After the procedure, the mean portal pressure decreased from 34 ± 8.9 cm H 2 0 to 22.4 ± 5.4 cm H 2 0 (P < 0.001). No complications were associated with the procedure; however, two patients died of causes unrelated to the procedure. Seven patients subsequently underwent liver transplantation and are doing well, and three patients are being managed conservatively. Bleeding recurred in one patient 102 days after the procedure secondary to shunt occlusion caused by neointimal proliferation. • Conclusion: Placement of a transjugular intrahepatic portosystemic shunt is apparently safe and effective therapy for variceal hemorrhage in patients referred for liver transplantation.
1 he management of patients with variceal hemorrhage has changed considerably over the past few years. Sclerotherapy has become the primary treatment for active variceal hemorrhage as well as for prevention of future variceal bleeding. Emergency shunt operations are now mainly reserved for the 10% to 15% of patients who do not respond to endoscopic treatment or who are bleeding from inaccessible gastric or intestinal varices (1, 2). Unfortunately, this approach has done little to improve the survival of patients with advanced liver disease. Fewer than 50% of patients with Child class C disease who bleed from varices survive 30 days, regardless of whether they undergo portosystemic shunt surgery or sclerotherapy, and only a few from each group are still alive at 1 year (3). Moreover, orthotopic liver transplantation has become an increasingly routine treatment for patients with end-stage liver disease. Long-term survival rates of more than 70% are now widely reported and appear to be no different for patients with variceal bleeding (4, 5). However, the limited availability of donor organs generally precludes emergency transplantation for acute hemorrhage, and if sclerotherapy fails to control the bleeding, then portosystemic shunts are done in these high-risk patients. Because conventional portacaval shunts add to the technical difficulty and operative blood loss of subsequent transplant surgery, most transplant surgeons recommend alternative procedures, such as mesocaval shunts, for patients who might eventually undergo transplantation. Placement of transjugular intrahepatic portosystemic shunts (TIPS) using expandable metallic stents has recently been described; portal decompression is achieved through a percutaneously established shunt between the hepatic and portal veins within the liver (6, 7). We have previously described our first patient with variceal bleeding who was treated by TIPS placement followed by elective liver transplantation (8). In this article, we describe our preliminary experience with TIPS as a way to control refractory variceal bleeding hemorrhage before liver transplantation. Methods Patients
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Our series included 13 patients with refractory variceal bleeding who were admitted to the Liver Transplantation Service, University of California, San Francisco, between June 1990 and May 1991 and who underwent TIPS placement portal decompression. Patients were considered to have failed sclerotherapy if bleeding could not be acutely controlled with endoscopic sclerotherapy (six patients) or more than two episodes
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of rebleeding requiring transfusion occurred during a 2-week period (seven patients). Patients underwent a mean of six sessions of sclerotherapy before TIPS placement. All patients who met these criteria underwent the TIPS procedure. During that time interval, two additional patients underwent TIPS for variceal bleeding, but they were not candidates for liver transplantation and were therefore not included in the series. Our study patients included seven men and six women. Their mean age was 46 years. Nine of the patients had Laennec cirrhosis; four had postnecrotic cirrhosis. Four patients had been previously treated with surgical portosystemic shunts that were functionally ineffective or occluded. Eleven of the patients were classified as having Child C disease and 2 patients as having Child B disease by the Child-Pugh modified scoring system (9). The mean Child-Pugh score was 10.7 ± 1.2. Average pre-procedure laboratory values included a serum bilirubin level of 60 ± 38 /xmol/L, a serum albumin level of 27 ± 5 g/L, and a prothrombin time of 16.5 ± 3.1 seconds. Clinically apparent ascites was present in nine patients; encephalopathy was present in six patients. Each patient was fully evaluated before the procedure and was accepted as a candidate for liver transplantation. The protocol for patient selection and the method used for the TIPS were approved by the Committee on Human Research, University of California, San Francisco. Procedure After informed consent was obtained from the patient or his or her next of kin, the patient was brought to the interventional radiology suite for the procedure. The right side of the neck was prepared with a sterile solution and isolated using sterile drapes. The right internal jugular vein was percutaneously punctured, and an angiographic catheter and guidewire were manipulated under fluoroscopic guidance through the superior vena cava, right atrium, and inferior vena cava into the middle or right hepatic vein. The catheter was then exchanged for an angiographic sheath with a hemostasis valve. The sheath was 40 cm in length and 3 mm in diameter. A Colapinto transjugular needle (Cook Inc., Bloomington, Indiana) (3.0-mm catheter with a beveled needle that was 1.7 mm in diameter) was advanced through the sheath and directed out of the hepatic vein anteriorly through the liver parenchyma toward the right portal vein. In the first three patients, the portal vein puncture was guided fluoroscopically by directing the needle toward a 0.9-mm catheter that had been previously placed transhepatically into the portal vein. In the subsequent patients, transhepatic portal vein catheterization was not done; in
these cases, external ultrasound was used to guide the vein-tovein puncture. After the right portal vein branch was entered, a 0.9-mm guidewire was passed through the needle and manipulated across the main portal vein into the splenic or mesenteric vein. The inner 1.7-mm needle was then removed and a straight 1.7-mm catheter was advanced over the guidewire into the portal vein. The initial baseline portal pressure was measured directly through the catheter, and portal venography was done. The 1.7-mm angiographic catheter was then exchanged for an 8-mm angioplasty balloon catheter that was inflated in the tract between the hepatic and portal veins. The 3-mm catheter and the balloon catheter were then removed and a 2.3-mm Wallstent catheter (Schneider, Minneapolis, Minnesota) was introduced. Depending on the distance between the veins, either a 42-mm or a 68-mm self-expanding metallic stent (Wallstent, Schneider, Minneapolis, Minn.) was used for the shunt. The stent was positioned so that it began to open in the main portal vein just proximal to the bifurcation. It was deployed from there through the parenchymal tract toward the hepatic vein. After the stent was deployed and detached from the introducer catheter, the unconstrained segment of stent within the portal vein opened to its full 10-mm diameter. The segment constrained by the liver parenchyma was distended with an 8-mm angioplasty balloon. Contrast medium was then injected to determine whether the cephalad end of the stent extended into the hepatic vein. If the stent did not reach the lumen of the hepatic vein, a second stent was introduced and partially overlapped within the first to bridge the additional distance. Measurement of the portal vein pressure and portal venography were then repeated. If the postshunt portal venogram showed continued evidence of hepatofugal flow and filling of varices, then the intraparenchymal segment of the stent was expanded to its maximum diameter with a 10-mm angioplasty balloon, and portal venography and pressure measurements were repeated. The catheters were then removed from the jugular vein. All patients were monitored in an intensive care unit for 24 hours and then followed according to the standard pretransplant protocol at the University of California, San Francisco. Follow-up included monthly outpatient clinical and laboratory evaluations. Duplex ultrasound examinations were done at 3-month intervals in patients who did not undergo early transplantation. Alcoholic patients who had been sober for fewer than 3 months were required to attend a 28-day inpatient alcohol treatment program and to participate in a weekly outpatient support group.
Table 1. Clinical Characteristics and Follow-up Results in Patients Who Underwent the Transjugular Intrahepatic Shunt Procedure* Patient
Diagnosis
Control of Bleeding ShortLongterm term
Portal Vein Pressure Before After TIPS TIPSt
Follow-up
Improved Control of Ascites
Shunt Patency
d
cm H20 1 2 3 4 5 6 7 8 9 10 11 12 13
Crytogenic cirrhosis ALD ALD ALD ALD ALD ALD ALD ALD Autoimmune hepatitis Crytogenic cirrhosis HBV ALD
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes
28 21 31 34 32 30 37 40 33 55
16 19 19 23 18 21 29 32 19 28
Yes Yes Yes Yes Yes Yes Yes No No
Did not have transplantation Did not have transplantation Did not have transplantation Did not have transplantation Had transplantation Had transplantation Had transplantation Had transplantation Had transplantation Had transplantation Had transplantation Died Died
268 264 219 143 102 and 4$ 27 23 20 4 4 3 2 5
* ALD = alcoholic liver disease; HBV = hepatitis B virus; TIPS = transjugular intrahepatic portosystemic shunt. t Average decrease was 12 cm H 2 0 . Average pressure before TIPS was 34 cm H 2 0 , and average pressure after TIPS was 22 cm H 2 0 . X Patient 5 had two shunts placed.
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Statistics Results are expressed as mean ± SD. Results Clinical characteristics and follow-up results of patients undergoing TIPS are summarized in Table 1. The TIPS procedure was successful in all 13 patients, and no procedure-related complications occurred. The three TIPS procedures guided by preliminary transhepatic portal vein catheterization were done in a mean time of 163 ± 23 minutes. The subsequent ten procedures guided only by external ultrasound were done in a mean time of 121 ± 29 minutes. Portal pressure decreased from an initial average of 34.1 ± 8.9 cm H 2 0 to 22.4 ± 5.4 cm H 2 0 after the TIPS procedure (P < 0.001). In eight cases, the immediate postshunt portal venogram showed the complete elimination of flow into the varices with the stent expanded to 8 mm (Figure 1). In the other 5 patients, hepatofugal flow in the coronary vein was eliminated by expanding the stent to 10 mm. After TIPS placement, gastrointestinal bleeding ceased in all six patients who were actively bleeding when the procedure began. Only one of these patients has had further gastrointestinal bleeding, which occurred 102 days after the shunt was placed. Arterial portography done at that time showed an absence of flow through the shunt. The portal vein and its branches
were patent. The shunt was catheterized by a transjugular approach revealing a narrow irregular lumen. After balloon dilation, a second stent was deployed inside the original, with re-establishment of shunt patency. After this procedure, bleeding stopped and the patient underwent liver transplantation 4 days later. No immediate complications were noted after the TIPS procedure. Specifically, inadvertent puncture of the gallbladder, colon, or other viscus was not observed, and no bleeding complications occurred. Two patients died within 30 days after the procedure; in neither case was death related to the TIPS procedure or to hepatic failure. One patient died of respiratory failure and sepsis related to aspiration pneumonia that occurred during a previous attempt at endoscopic sclerotherapy. The other patient died of sepsis and renal failure as a late consequence of spontaneous bacterial peritonitis that was diagnosed before the procedure. Seven of the patients underwent liver transplantation after the TIPS procedure (3, 4, 4, 20, 23, 27, and 106 days, respectively). These patients have all been discharged from the hospital and are doing well (mean follow-up, 190 days). Two patients who were initially considered to be candidates for transplantation have improved clinically, and the previous indications for transplantation (refractory ascites and variceal hemorrhage) are no longer present; two patients are no longer considered transplant candidates because of renewed alcohol abuse. In the 8 patients in whom follow-up was
Figure 1. Diversion of portal flow through an 8-mm transjugular intrahepatic portosystemic shunt. Left Panel. Contrast medium was initially injected into both the hepatic vein (open arrows) and portal vein in order to estimate the length of parenchymal tract to be stented. Both the right and left branches of the portal vein are opacified. Portal pressure was 32 cm H 2 0 . Right Panel. Because the Wallstent is designed to self-expand up to 10 mm, the unconstrained segments of stent within the portal vein (open arrow) and hepatic vein (closed arrow) open to the stent's maximum diameter. The parenchymal segment of the stent was expanded to 8 mm with an angioplasty balloon. Repeat portal venography showed that portal flow had been totally diverted through the stent. Portal pressure was reduced to 18 cm H 2 0 . 306
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Figure 2. Histologic examination of a transjugular intrahepatic portosystemic shunt 20 days after insertion. The shunt lumen is round and smooth, and the stent's wires (arrows) are incorporated in a developing neointima.
sufficient to evaluate their mental status more than 14 days after the TIPS, there was no clinical evidence of encephalopathy. For patients who survived and did not undergo immediate transplantation, the mean time to discharge after the procedure was 4 days (range, 2 to 9 days). Before the TIPS procedure, nine patients had clinically evident ascites that was considered to be refractory to diuretic therapy. All patients experienced a diuresis after the procedure, and the four survivors who did not undergo transplantation currently do not have ascites according to ultrasound examinations. Three of the four transplant recipients who had ascites before TIPS placement had minimal ascites at the time of transplantation. In the explant livers from the seven transplant recipients, the segment that included the shunt and adjacent hepatic and portal veins was removed and fixed in formalin. The metal wires of the stents were then carefully removed using a dissecting microscope, and specimens were sectioned for histologic examination. In specimens obtained 4 days after the TIPS procedure, the shunt lumen was widely patent but had an irregular contour with blunt parenchymal mounds protruding between the stent's struts. Areas of hemorrhage were found in the adjacent parenchyma, with poorly organized thrombus present along some of the wires. The three specimens obtained between 20 and 27 days after TIPS placement showed a very round, smooth lumen, with the stent wires incorporated in a developing neointimal lining (Figure 2). A layer of flattened cells was present along the luminal surface, and immature collagen was present around the stent wires and along the hepatic parenchymal interface. The shunt removed after 106 days showed encasement of the initial stent within a densely collagenized neointima. Poorly organized thrombus was attached to some of the wires of the second stent that had been placed 4 days before transplantation when the original shunt occluded. No thrombus was found in the segment between the stents, suggesting that the first shunt had occluded from excessive neointimal proliferation.
Additional longer-term follow-up is available for four patients (4.5 to 8.5 months after the TIPS procedure). None of these patients has had further episodes of gastrointestinal bleeding. Duplex color flow scans or angiograms in these patients have shown shunt patency with rapid flow through the shunt lumen. Subsequently, routine follow-up endoscopy was not done, catheterization procedures were not repeated, and late changes in portal pressure were not evaluated.
Discussion Portal decompression through a percutaneously established communication between the hepatic and portal veins was first described by Rosch and colleagues (10) in 1969. Subsequently, several attempts have been made to expand the venous connection to a diameter that would be adequate for portal decompression. In 1982, Colapinto and colleagues (11) first reported the use of percutaneous intrahepatic shunts in humans. These investigators used angioplasty balloon catheters and repeated dilatation to establish a large transparenchymal channel. Although these shunts were effective in lowering portal pressure, they tended to occlude rapidly because of elastic recoil in the adjacent hepatic parenchyma. Palmaz and colleagues (12) and Hershey and colleagues (13) used expandable metallic vascular stents to create intrahepatic shunts in animals and showed that a neointimal lining formed within the stent in just a few weeks. Palmaz and colleagues (14) found that expandable metallic intrahepatic shunts placed in dogs with experimentally induced portal hypertension remained patent through 48 weeks. Richter and colleagues (6) successfully created intrahepatic shunts in 10 of 14 patients using the Palmaz balloon-expandable stent (Johnson & Johnson Interventional Systems, Warren, New Jersey). The procedures were technically difficult and required many hours to perform. In some cases, the TIPS procedure was done over 2 days; a transhepatic and a transjugular catheter
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were introduced on day 1, and the shunt was created on day 2. The methods used for TIPS placement in our series included several technical modifications that were intended to improve the efficiency of the procedure so that it could be completed more rapidly. Use of external ultrasound guidance for the portal vein puncture in the last 10 patients not only reduced the procedure time but also eliminated any possible risk for bleeding from the transhepatic catheter entry site. The needle used for the portal vein puncture in these procedures is very rigid, which allows the needle tip to be rotated and its course controlled by external manipulation even through very hard cirrhotic parenchyma. Because the needle is comparable in diameter to the catheters used subsequently, once the needle track is established, there is relatively little resistance to the passage of these catheters. The large lumen of this needle allows the passage of relatively rigid 0.035-inch guidewires that provide further support for the introduction of the catheters. Finally, the shunts were created using the Wallstent, which has the thinnest profile of all the available expandable metallic stents. Unlike other stents that require an outer sheath for introduction, the Wallstent is attached to its introducer catheter and passes into the portal vein directly over a guidewire. This stent is also more flexible than other expandable metallic stents and maintains a cylindrical shape even when positioned around very acute angles. This permits a successful shunt from almost any point of entry into the portal venous system and allows much more leeway in the location of the portal vein puncture. The time required to do the procedures in our series was generally between 2 and 3 hours. Because these cases represent our first attempts at performing this procedure, it is likely that with additional experience and further technical improvements, the procedure time will be further reduced. The ability to decompress the portal venous system rapidly and without general anesthesia makes the TIPS procedure a practical option even for high-risk patients with active bleeding. The average absolute reduction in portal pressure achieved after the TIPS procedure in our series was 12 cm H 2 0 , which is less than the typical pressure reduction achieved with direct portacaval anastomoses; however, this reduction is similar to the decreases reported by Sarfeh, Rypins, and colleagues (15, 16) for 8- and 10-mm mesocaval grafts, which is not surprising because the grafts used by these investigators were the same size as the expanded diameter of the metallic stents used for the shunts in our patients. Similarly, these investigators reported that only 9% of their patients developed encephalopathy, which is consistent with the fact that none of our patients have thus far developed this complication. The effect of previous portacaval shunt surgery on the outcome of liver transplantation remains controversial. There appears to be increased operative blood loss, increased rates of reoperation, and, possibly, increased late (> 1 year) mortality (17). Thus, most transplant surgeons do recommend avoiding portacaval anastomoses because of the adhesions produced in the portahepatis (15). Because TIPS are totally intrahepatic, they 308
do not interfere with transplant operations. The stent was not encountered as the liver was removed in any of the patients in our series who underwent transplantation. However, during the introduction of the stent, special efforts should be made to avoid positioning it either too far into the main portal vein or out through the hepatic vein into the inferior vena cava where it could complicate the transplant operation. There appear to be few potential complications from intrahepatic portal vein shunting. The procedure, done through a jugular venipuncture, creates little risk for hemorrhage, even in patients with significant coagulopathies. Traversing a hepatic artery branch or biliary radical during the parenchymal puncture could conceivably cause hemobilia or arteriovenous fistula, but these complications have not yet occurred. Moreover, arterial injury is very unlikely because, when expanded, the metallic stent compresses and tamponades vessels within the parenchymal tract. Hemobilia should similarly be unlikely, unless there is associated biliary obstruction and dilated intrahepatic ducts. Because the puncture is entirely within the liver, even massive ascites poses no additional risks; however, in the presence of large-volume ascites and a small cirrhotic liver, special care should be taken to avoid inadvertently puncturing the capsule along the inferior surface of the liver. Our experience indicates that TIPS placement is a practical therapy for acute variceal hemorrhage and an effective bridge to transplantation. It is particularly useful in patients with alcoholic liver disease. The duration of function of the TIPS is sufficient to acquaint the patient with transplantation and, if necessary, to allow them to demonstrate compliance with an alcohol treatment program and to establish an adequate support system. The long-term benefit of TIPS placement remains to be demonstrated. Four of the patients who underwent the procedure are no longer being considered for transplantation. In three patients, clinical improvement after the TIPS decreased the need for transplantation; the other patient failed to comply with an alcohol treatment program. The durability of this method will become more clear as these and similar patients continue to be followed. Requests for Reprints: Ernest J. Ring, MD, University of California, San Francisco, Box 0628, San Francisco, CA 94143. Current Author Addresses: Drs. Ring, Gordon, and Laberge: University of California, San Francisco, Box 0628, San Francisco, CA 94143. Drs. Lake, Roberts, Sterneck, and Ascher: University of California, San Francisco, Box 0780, San Francisco, CA 94143. Dr. Read: Overlake Internal Medicine Associates, 1011 116th Avenue, NE, Bellevue, WA 98004.
References 1. Warren WD, Henderson JM, Millikan WJ, Galambos JT, Brooks WS, Riepe SP, et al. Distal splenorenal shunt versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Preliminary report of a prospective, randomized trial. Ann Surg. 1986;203:454-62. 2. The Copenhagen Esophageal Varices and Sclerotherapy Project. Sclerotherapy after first variceal hemorrhage in cirrhosis. A randomized multicenter trial. N Engl J Med. 1984;311:1594-600. 3. Cello JP, Grendel JH, Crass RA, Trunkey DD, Cobb EE, Heilbron DC, et al. Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and variceal hemorrhage. N Engl J Med. 1984;311:1589-94.
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4. Iwatsuki S, Starzyl TE, Todo S, Gordon RD, Tzakis AG, Marsh JW, et al. Liver transplantation in the treatment of bleeding esophageal varices. Surgery. 1988;104:697-705. 5. Crass RA, Keeffe EB, Pinson CW. Management of variceal hemorrhage in the potential liver transplant candidate. Am J Surg. 1989; 157:476-8. 6. Richter GM, Noeldge G, Roessle M, Siegerstetter V, Franke M, Palmaz JC, et al. Transjugular intrahepatic portosystemic stent shunt (TIPSS). Radiology. 1990;174:1027-30. 7. Zemel G, Katzen BT, Becker GJ, Benenati JF, Sallee DS. Percutaneous transjugular portosystemic shunt. JAMA. 1991;266:390-3. 8. Roberts JP, Ring E, Lake JR, Sterneck M, Ascher NL. Intrahepatic portocaval shunt for variceal hemorrhage prior to liver transplantation. Transplantation. 1991;52:160-2. 9. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;560:646-9. 10. Rosch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portocaval shunt: an experimental study. Radiology. 1969;92:1112-4. 11. Colapinto RF, Stronell RD, Birch SJ, Langer B, Blendis LM, Greig
12.
13.
14.
15.
16. 17.
PD, et al. Creation of an intrahepatic portosystemic shunt with a Gruntzig balloon catheter. Can Med Assoc J. 1982;126:267-8. Palmaz JC, Sibbitt RR, Reuter SR, Garcia F, Tio FO. Expandable intrahepatic shunt stents: early experience in the dog. AJR Am J Roentgenol. 1985;145:821-5. Rosch J, Uchida BT, Putnam JS, Buschman RW, Law RD, Hershey AL. Experimental intrahepatic portocaval anastomosis: use of expandable Gianturco stents. Radiology. 1987;162:481-5. Palmaz JC, Garcia F, Sibbitt RR, Tio FO, Kopp DT, Schwesinger W, et al. Expandable intrahepatic portacaval shunt in dogs with chronic portal hypertension. AJR Am J Roentgenol. 1986;147:1251-4. Sarfeh U, Rypins EB, Raiszadeh M, Milne N, Conroy RM, Lyons KP. Serial measurement of portal hemodynamics after partial portal decompression. Surgery. 1986;100:52-8. Rypins EB, Sarfeh U. Small-diameter portacaval H-graft for variceal hemorrhage. Surg Clin North Am. 1990;70:395-404. Turrion VS, Mora NP, Cofer JB, Solomon H, Morris CA, Gonwa TA, et al. Retrospective evaluation of liver transplantation for cirrhosis: a comparative study of 100 patients with or without previous porto-systemic shunt. Transplant Proc. 1991;23:1570-1.
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