In recent years, there has been an increase in the number of pediatric patients evaluated for liver transplantation ^(1,2). As in adults, these patients frequently have portal hypertension resulting in variceal hemorrhage. When such bleeding proves refractory to medical management, patients have traditionally undergone surgical portosystemic shunting with an operative mortality of 15% in elective cases and over 60% in the emergent setting ⁽³⁾. In addition, alteration of the extrahepatic vascular anatomy and the creation of intrabdominal adhesions increases the technical complexity of subsequent transplant surgery^(4,6). More recently, the transjugular intrahepatic portosystemic shunt (TIPS) procedure has been established as a safe and effective alternative to surgical shunting in adults ⁽⁵⁾. Herein we report three cases of children awaiting liver transplantation in whom TIPS procedures were successfully performed for refractory variceal bleeding.

The first patient was a six year old girl with a history of familial cholestasis, cirrhosis, and portal hypertension with esophageal varices. The patient was a transplant candidate who had several prior episodes of variceal bleeding. The most recent, occuring one month prior to this admission, was controlled with sclerotherapy.

She was admitted for an elective TIPS procedure to control recurrent variceal hemorrhage and serve as a bridge to liver transplantion. Admission laboratory data included a prothrombin time of 11.6, total bilirubin of 2.5, albumin of 3.4, hematocrit of 33.4, and a creatinine of 0.7. The left portal vein was accessed from a subxyphoid approach under direct ultrasound guidance with a 21 gauge Chiba needle and an 0.018 inch guide wire was placed to provide a radiopaque marker for the intrahepatic portal vein puncture. The internal jugular vein was accessed with a micro puncture set (Cook Inc., Bloomington, IN) under direct ultrasound guidance, and an 0.035 in. wire was advanced into the IVC and a 10 Fr. sheath was placed. The left hepatic vein was selected with a 5 Fr. multipurpose catheter after failure to access either the right or middle hepatic veins. A long 21 gauge Hawkins needle (Cook) directed through a standard Colapinto needle (Cook) was used to puncture the left portal vein (Fig. 1). When access was obtained, a 0.016 inch Microvena wire was advanced into the portal vein over which a 5 Frcatheter was placed. The parenchymal tract was predilated with a 6 mm angioplasty balloon, and a 68 mm length Wallstent (Schneider Inc., Minneapolis, MN) was deployed and dilated to 8 mm. Because the Wallstent did not entirely bridge the parenchymal tract, a second 42 mm length Wallstent was deployed and dilated to 8 mm to complete the shunt.

The portal to systemic gradient at the beginning of the procedure was 18 mmHg. The final gradient was only 3 mmHg. The distal end of the first Wallstent was suboptimally located deep into the main portal vein, near the portal confluence. Because of the possible negative impact on the future liver transplant, the patient was returned to the angiography suite on the second day and the distal shunt was dilated successfully with 8 mm, 10 mm, and 12 mm angioplasty balloons. Only minimal change in the position of the distal portion of the Wallstent was noted but the proximal end shortened significantly, creating a gap between the two Wallstents within the parenchymal liver tract. This was bridged by a new 68 mm Wallstent that was dilated to 8 mm. The procedure was terminated at this point and a 4 mmHg portosystemic gradient existed at the conclusion of the procedure. There were no significant postprocedural complications and the patient remained stable until transplantation 2 weeks later.

The second patient was a 7 year old girl with a past medical history of end stage polycystic kidney disease who had had a renal transplant 3.5 years prior to admission. The patient had associated congenital hepatic fibrosis with known portal hypertension and esophageal varices and had had one episode of variceal hemorrhage that was successfully treated with endoscopic sclerotherapy 3 months prior to this admission. She was evaluated and placed on the liver transplant list at that time.

The patient had a febrile illness and 1 day after admission had melanotic stools and was transferred to the pediatric intensive care unit. Endoscopy revealed a bleeding varix, which was treated with sclerotherapy. Admission laboratory data included a prothrombin time of 11.6, hematocrit of 33.9, total bilirubin of 2.5, albumin of 3.4, and creatinine of 0.7. The following day, she had massive Upper Gastrointestinal bleeding not responsive to intravenous vasopressin and somatostatin and received 5 units of Packed Red Blood Cells, 4 units of fresh frozen plasma, and 12 units of platelets. The patient was intubated for airway protection. A surgical shunt was briefly considered but, after consultation with interventional radiology, a TIPS procedure was attempted.

The right internal jugular vein was accessed under direct sonographic guidance, and a 10 Fr. sheath was placed. The right hepatic vein was selected using a 5 Fr. multipurpose catheter. The right common femoral artery was then accessed with a micropuncture set, and a 4 Fr. SOS catheter was utilized to select the superior mesenteric artery. A digital superior mesenteric arteriogram confirmed patency of the superior mesenteric, main portal, right portal, and left portal veins. This also served as an anatomic landmark for portal vein access. A standard Colapinto needle was used, and several attempts at accessing the right portal vein were unsuccessful. The middle hepatic vein was then accessed and the Colapinto needle used to puncture the left portal vein. The tract was predilated with an 8 mm angioplasty balloon. A single 60 mm length by 8 mm diameter Wallstent was deployed and dilated to 8 mm, with ideal positioning of the stent, the distal tip just within the main portal vein and the proximal end located within the middle hepatic vein(Fig. 2).

Because the patient was actively bleeding at the time of procedure, the coronary vein was selectively catheterized with a 5 Fr. Cobra catheter and embolized with four 5 mm embolization coils (Cook). The pre-TIPS portal vein pressure was 41 mmHg and the hepatic vein pressure was 15 mmHg. The post-TIPS portal vein pressure was 27 mmHg and the right atrial pressure 18 mmHg, for a portosystemic gradient of 9 mmHg. Over the course of the next 48 hr, the patient's clinical state dramatically improved, with no evidence of further significant hemorrhage. The patient was extubated and discharged several days after the TIPS procedure. The stent developed a stenosis 5 months after placement that responded to balloon angioplasty. This was detected by increasing splenomegaly and recurrent varices on endoscopy. She remained asymptomatic until her transplant 8 months after the TIPS.

The third patient was an 11 year old girl with end stage liver disease secondary to biliary atresia with portal hypertension, mild coagulopathy, and hypersplenism, who was admitted for a liver transplant evaluation. Admission laboratory findings included total protein of 7.0, albumin of 3.7, direct bilirubin of 3.2, platelets of 45,000, prothrombin time of 15.9, and a hematocrit of 26. She had UGI bleeding six days after admission, with approximately 750 ml bloody emesis. Endoscopy revealed bleeding gastroesophageal varices, and sclerotherapy was performed. She continued to bleed and a TIPS was attempted.

Superior mesenteric angiography revealed patent superior mesenteric and portal veins, with filling of large gastroesophageal varices. Splenic angiography revealed a separate splenic artery origin from the aorta and several splenic artery branch aneurysms. The venous phase demonstrated large gastric varices that subsequently filled what was believed to be a spontaneous splenorenal shunt. TIPS was first attempted from a right hepatic vein approach but was unsuccessful despite multiple passes with a standard Colapinto needle. During the procedure, fluoroscopy revealed the development of pulmonary edema secondary to volume overload from prior fluid resuscitation, and the procedure was terminated. A TIPS was again attempted 12 hr later and, after several unsuccessful attempts from a right hepatic vein approach, access was obtained from a middle hepatic to left portal vein puncture. The tract was predilated and an 8 mm by 60 mm Wallstent placed without difficulty.

The pre-TIPS portal vein pressure was 38 mmHg. The post-TIPS portal vein pressure was 24 mmHg and the right atrial pressure 12 mmHg, for a portosystemic gradient of 12 mmHg. A post-TIPS portogram revealed preferential flow through the stent, with no significant filling of varices. She had no immediate post-TIPS complications and remained stable until 4 days after the procedure, at which time she had recurrent mild UGI bleeding. The TIPS was reevaluated and the shunt patent with a gradient of only 6 mmHg. However, there was persistent filling of gastric varices through the competitive shunt. Interestingly, the patient was noted to have an azygous continuation of the IVC on the follow-up examination. The varices were embolized with coils, and this effectively thrombosed the competitive shunt. She remained stable and received a liver transplant 24 hr after the TIPS revision.

The application of reduced and living-related donors has partially addressed the donor organ shortage. However, pediatric patients frequently wait for long periods prior to their liver transplant⁽²⁾. While endoscopic therapy is the primary therapy for variceal bleeding, refractory variceal hemorrhage remains a problem for the 10-15% of patients who do not respond to sclerotherapy⁽⁶⁾. Emergency transplantation is difficult in this setting because of the increased morbidity and mortality as well as the unavailability of suitable donor organs ^(1,7). TIPS is indicated in these situations as a bridge to transplantation.

The efficacy and safety of TIPS for treatment of variceal bleeding has been documented in several reported series. Laberge and colleagues reported 100 patients treated with the TIPS procedure and the Wallstent endoprothesis. Technical success was achieved in 96 of 100 patients. Acute variceal hemorrhage was controlled in 29 of 30 patients. An additional 64 of the 100 patients were treated on an elective basis for recurrent variceal bleeding. Variceal bleeding recurred in 10 of these 94 patients. Of the 96 patients who underwent a successful TIPS procedure, 26 had died, 22 had undergone liver transplant, and the remaining 48 patients had survived an average of 7.6 months ⁽⁷⁾. Freedman et al. attempted a TIPS for recurrent variceal hemorrhage in 24 patients. They achieved a 92% technical success rate with only one post-TIPS episode of recurrent bleeding⁽⁸⁾. Rossle et al. achieved a technical success of 93% using the Palmaz stent, with an 8% 6 month and a 18% 1 year incidence of rebleeding ⁽⁹⁾.

Patient 3 had recurrent variceal bleeding despite a patent shunt and a portosystemic gradient of 6 mmHg. This was secondary to a competitive high-flow shunt through gastric varices draining into an enlarged azygous vein. Bleeding was controlled by embolization of the varices that effectively occluded the competitive shunt. In general, we will embolize the coronary vein if the patient is actively bleeding. Embolization of spontaneous splenorenal shunts may increase the chance of recurrent variceal bleeding if the TIPS becomes occluded. It is only when they are being supplied by gastric varices that these competitive shunts increase the risk of recurrent hemorrhage⁽¹⁰⁾.

The puncture of the portal vein remains the single most difficult step in performing the TIPS procedure. The most frequent access in the adult population is from the the right hepatic vein to the right portal vein; accessing the left portal vein is very uncommon. It is notable that the only successful approach in these 3 pediatric patients was via a left portal vein puncture. Methods of increasing the success rate of portal vein access have included ultrasound guidance, road mapping of the portal vein with wedged or occlusion balloon hepatic venography or mesenteric angiography, recanalization of the umbilical vein, transhepatic placement of wires or catheters in the portal system, and percutaneous placement of radiopaque coils adjacent to portal vein branches. We have found digital portal vein road mapping to be the safest and most reproducible technique.

A major complication of TIPS has been the occurrence of hepatic encephalopathy ⁽⁶⁾. This occurs in 10-24% of patients after the procedure but tends to be mild and easily controlled with medical therapy. Somberg noted a 24% incidence of hepatic encephalopathy. A majority occurred within the first month and 78% were controlled with lactulose alone⁽¹¹⁾. The incidence and severity of encephalopathy is likely influenced by the stent diameter and preservation of partial hepatic perfusion-and thus the portosystemic pressure gradient^{(6, 10)}. Patients over the age of 60 have been noted to have a significantly higher incidence of encephalopathy (30%) when compared with younger patients (10%) ^{(6, 17)}. Therefore, encephalopathy after TIPS in pediatric patients may be less of a theoretical concern. The Wallstents were dilated to 8 mm in all of our pediatric cases, achieving satisfactory portosystemic gradients of 6-12 mmHg without an episode of encephalopathy. Prophylactic lactulose therapy was not instituted in our patient population.

Stent placement has significant implications for the liver transplant procedure because if the stent is deployed within the main portal vein or superior mesenteric vein, or extends into the right atrium, this can significantly alter the complexity of the liver transplant⁽¹²⁾. Patient 1 had suboptimal placement, with the stent extending to the portal vein confluence. The patient received her transplant shortly after the TIPS. The stent was easily extracted because it had not become incorporated into the vein wall. Endothelialization can occur rapidly and is usually complete by 4 weeks ⁽⁶⁾.

Shunt monitoring with duplex ultrasound is critical because of the high incidence (50-75%) of shunt restenosis ^{(6, 13)}. Patient 2 developed a stenosis at 5 months post-TIPS that required a shunt revision; this demonstrates that children are subject to neointimal hyperplasia similar to that seen in adults. An interval decrease in the shunt velocity or slow flow (< 100 cm/sec) has been shown in adults to correlate with restenosis ^{(6, 17, 18)}. In patient 2 shunt malfunction was initially suspected because physical examination revealed increasing splenomegaly and recurrent varices were documented at endoscopy. Duplex sonography of the TIPS showed a midshunt velocity that had decreased to 80 cm/sec. After shunt revision with balloon angioplasty, the midshunt velocity increased to 150 cm/sec.

In the adult population, TIPS can be used to buy time for liver transplantation, decrease portal hypertension, decrease ascites, improve nutrition, and not infrequently eliminate entirely the need for a new liver⁽⁶⁾. When compared with surgical shunts, the TIPS procedure has decreased operative time, transfusion requirements, and ICU and hospital days. It is a less invasive, less expensive, and a faster procedure^{(14, 15)}.

The youngest reported patient to receive a TIPS was thirteen years of age⁽¹⁶⁾. These cases indicate that the TIPS procedure is technically feasible in very small children. The limits of the technology have yet to be determined. TIPS can be performed with the current adult Colapinto needle set or with a modification using a 21 gauge needle placed coaxially through the Colapinto needle. The recent availability of a variety of lengths and diameters of the Wallstent device will increase the feasibility of placing intrahepatic stents in a wide range of pediatric patients. The proliferation of pediatric transplant programs will no doubt increase the number of referrals for this innovative procedure.