Original Report. AJR:178, May Received January 19, 2000; accepted after revision November 1, Géneral Leclerc, 92118, Clichy, France.

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1 lban L. Denys 1,2 Salah D. Qanadli 3 François Durand 4 Valerie Vilgrain 1 Olivier Farges 5 Jacques elghiti 5 Pascal Lacombe 3 Yves Menu 1 Received January 19, 2000; accepted after revision November 1, Department of Radiology, Hôpital eaujon, 100 lvd. du Géneral Leclerc, 92118, Clichy, France. 2 Present address: Department of Radiology and Interventional Radiology, CHUV 1011 Lausanne, Switzerland. ddress correspondence to. L Denys. 3 Department of Radiology, Hôpital mbroise Paré, 9 ve. Charles de Gaulle, oulogne, France. 4 Department of Hepatology, Hôpital eaujon, Clichy, France. 5 Department of Digestive Surgery, Hôpital eaujon, Clichy, France. JR 2002;178: X/02/ merican Roentgen Ray Society Original Report Feasibility and Effectiveness of Using Coronary Stents in the Treatment of Hepatic rtery Stenoses fter Orthotopic Liver Transplantation: Preliminary Report OJECTIVE. Our aim is to evaluate the feasibility, efficacy, and patency of using coronary stents for the treatment of hepatic artery stenosis after liver transplantation. CONCLUSION. Hepatic artery stenosis after liver transplantation can be treated using coronary stents. The low rate of complication, high technical success, and 1-year patency rates are encouraging. L iver graft ischemia caused by hepatic artery thrombosis is associated with a high incidence of mortality and morbidity. rterial thrombosis in the early postoperative period frequently results in graft failure and carries a mortality as high as 50% [1]. Little is known about therapy for hepatic artery stenosis after orthotopic liver transplantation. This entity may cause graft dysfunction and doubles the rate of biliary complications [2]. bbasoglu et al. [2] reported encouraging results when stenoses were revised either surgically by reanastomosis of vein graft interposition or by endovascular techniques. In their series, normal liver function was observed in 67% of patients after revision. One report in the cardiology literature showed the superiority of vascular stenting over balloon angioplasty alone in patients with coronary artery stenosis after cardiac transplantations [3]. This series reported that stents offered lower complication and restenosis rates than balloon angioplasty. Cardiac allograft vasculopathy is believed to be related to immunologic disorders, because it has also been observed that rejection plays a role in hepatic artery complication after orthotopic liver transplantation [2]. Even if the pathogenesis of hepatic artery stenosis seems to have a more multifactorial origin, encouraging results in coronary artery stenosis prompt us to use this technique for hepatic artery stenosis. Our aim was to evaluate prospectively in a nonselected population of consecutive patients the feasibility, patency, and efficacy of using coronary stents to treat hepatic arterial graft stenosis with a 1-year follow-up. Materials and Methods Ninety-nine patients received orthotopic liver transplantation in our institution from January 1998 to June Doppler studies were performed daily in the first week after transplantation, weekly during hospital stay, and routinely when any abnormalities were depicted on blood liver tests after this period. We evaluated the right and left hepatic arteries and measured the resistive index (maximal systolic velocity end diastolic velocity / maximal systolic velocity) and systolic ascending time. Values considered indicative of hepatic artery stenosis were a resistive index less than 0.5, systolic ascending time greater than 10 msec [4, 5], or both. If Doppler values were abnormal, the patient was referred for angiography. From the population of 99 patients, 13 patients (13.1%) were suspected of having hepatic artery stenosis on Doppler sonographic studies at days after surgery (mean, 94 days). Ten patients JR:178, May

2 Denys et al. (76%) were clinically asymptomatic, including two patients with elevated bilirubin and alkaline phosphatase levels. Two patients had jaundice with (n = 1) or without (n = 1) biliary dilatation. One patient had severe itching of unknown origin without jaundice. Liver biopsy performed in eight patients showed signs evocative of cholangitis in three patients and signs of cholestasis in four patients. In one patient, cholestasis was associated with centrilobular necrosis; biopsy showed recurrent C virus hepatitis. The nine men and four women with hepatic artery stenosis ranged in age from 28 to 63 years, with a mean age (± SD) of 48 ± 11 years. Orthotopic liver transplantation had been performed in these patients for hepatocellular carcinoma (n = 5), post hepatitis C cirrhosis (n = 1), primary sclerosing cholangitis (n = 1), primary (n = 1) or secondary (n = 1) biliary cirrhosis, hepatic amyloidosis (n = 1), alcoholic cirrhosis (n = 1), udd-chiari syndrome (n = 1), or acute and Delta viral fulminant hepatitis (n = 1). Vascular reconstruction had been performed using standard techniques: The main hepatic artery was anastomosed to the main hepatic artery in 10 patients (associated with vascular reconstruction of the left hepatic artery in two patients). right hepatic artery bypass graft was used in two patients, and an infrarenal aorta bypass graft was used in the remaining patient. Patients had received immunosuppressive treatment with different combinations of drugs, including aziatropine, tacrolimus, cyclosporine, and prednisone. In agreement with the transplantation team, we decided to attempt an endovascular treatment using coronary stents in patients with hepatic artery stenosis. ecause we would be using the stents in an offlabel application, we obtained oral informed consent from all patients. This study was not submitted for institutional review board approval. fter selective angiography of celiac trunk and hepatic artery via the femoral approach, we placed a 6-French sheath at the origin of the feeding vessel (celiac trunk [n = 10], superior mesenteric artery [n = 2], aorta [n = 1]) without crossing the stenosis with the sheath. The stenosis was crossed with a inch guidewire (PT Graphics; oston Scientific, oston, M). NIR coronary stents (Scimedoston Scientific, La Garenne Colombes, France) were implanted in 10 patients (Fig. 1), GianturcoRoubin coronary stents (Cook, jaeverskov, Denmark) were implanted in two patients, and VE coronary stents (Medtronic, Kerkrade, The Netherlands) were implanted in one patient. Sizes of stents were determined on the basis of automatic measurement of vessel size using the sheath diame- Fig year-old man with abnormal findings on hepatic artery Doppler study., Hepatic artery angiogram shows stenosis located in graft hepatic artery beyond anastomosis (arrow)., ngiogram obtained after placement of NIR stent (Scimed-oston Scientific, La Garenne Colombes, France) of 5 mm in diameter shows stenosis (arrow) has been reduced. C, ngiogram obtained at 1-year follow-up shows no recurrence of stenosis. C 1176 JR:178, May 2002

3 Coronary Stents in the Treatment of Hepatic rtery Stenoses ter as a reference. Patients received 5000 U of heparin during the procedure; after the procedure, they were put on long-term antiplatelet therapy (100 mg of aspirin daily). Follow-up during the first year was achieved by repeated clinical evaluation, monthly Doppler sonographic examination, and liver function tests. ngiography was performed systematically in all patients at 3 months and 1 year after stent placement. Stent patency was evaluated according to the Kaplan-Meier method. For the evaluation of stent patency, restenosis was considered when 50% of the lumen diameter was reduced. Results Stent Placement Procedure Stenoses were located at the arterial anastomosis in six patients (long stenosis, 1 cm), in the graft artery downstream anasto- mosis in five patients (short stenosis, <1 cm), and in the feeding hepatic artery in one patient. In one patient, stenosis was located only in a right hepatic branch with a patent left hepatic arterial branch. In all 13 patients, stents were successfully implanted in a single procedure. We used one stent in eight patients, two stents in four patients, and three stents in one patient. The diameters of stents implanted ranged from 3.5 to 5.5 mm (mean diameter, 4.4 mm). During stent placement, repeated balloon inflations were needed to fully expand the GianturcoRoubin stents (Fig. 2). We observed one stent thrombosis at 1 day after stent placement in a patient who had undergone transplantation because of end-stage udd-chiari syndrome resulting from poly- cythemia vera. She had a severe stenosis of the feeding hepatic artery 2 cm upstream of the anastomosis. The right hepatic branch was thrombosed and two branches were patent: one for segment IV and one for the left lobe. The first stent implanted on a preanastomotic stenosis was too short (9 mm), and it migrated to a segment IV branch, where it was successfully deployed. second, longer stent (16 mm) was then successfully placed over the anastomotic stenosis. The patient underwent long-term anticoagulant treatment with heparin. t day 1, no arterial signal was found in the right or left lobe. ngiography showed thrombosis of all intrahepatic branches with a patent proximal stent. Doppler measurements normalized immediately after stent placement in all patients except this one. C D Fig year-old man with suspected ischemic cholangitis., Celiac angiogram reveals anastomotic stricture (arrow)., ngiogram obtained after placement of Gianturco-Roubin stent (Cook, jaeverskov, Denmark) shows spasm over stent that is almost occlusing artery. C, ngiogram obtained after repeated balloon dilations had been performed shows stent is now fully opened. D, ngiogram obtained at 1-year follow-up shows no restenosis and artery is widely patent. JR:178, May

4 Denys et al. Midterm Patency fter a mean (±SD) follow-up of 720 ± 190 days, two patients had died of septic conditions unrelated to the procedure, one at 4 months and one at 1 year after the procedure. ngiographic follow-up was done at 3 months in all but one patient, and it was repeated at 1 year in all but four of the 11 surviving patients: one patient did not undergo repeated angiography because he was followed up in another institution; three others refused 1-year angiography because their liver function test results and clinical findings were normal. Of the three patients who refused angiography at 1 year, two had undergone angiography with normal findings at 3 months and a Doppler study with normal findings and identical Doppler values at 3 months and at 1 year. They were considered in our statistical evaluation as having a patent stent at 1 year. The third patient had abnormal Doppler sonographic values at 1 year, although the artery had been dilated at 3 months; this patient was considered as having a recurrent intrastent restenosis for purposes of the Kaplan-Meier study. Four patients developed intrastent restenoses. ll had abnormal Doppler sonographic results. Three restenoses appeared at 3 months and were dilated successfully in two patients. The restenosis in the third patient was not redilated, because the stent was implanted in a tortuous Fig. 3. Kaplan-Meier curves estimate primary and secondary stent patency. and, Graphs indicate primary () and secondary () stent patency found in our follow-up at 3, 6, and 12 months of 13 patients whose hepatic artery stenoses after liver transplantation were treated with coronary stents. artery and the patient had normal findings on the liver function test. In the fourth patient, intrastent restenosis appeared at 1 year as a result of intimal hyperplasia and was not treated because of the stent was in a tortuous artery and because the patient had normal clinical and liver function test findings. nother patient developed a new stenosis 1 cm upstream of the stent. She simultaneously developed an anastomotic biliary stenosis. oth were treated by surgery. Pathologic study of the artery found a periarterial neuroma compressing the arterial lumen. t this point of our study, seven patients are doing well with normal clinical and liver function test findings. Three patients developed acute rejection during follow-up that was treated successfully without complication. One patient with ischemic cholangitis is in stable condition. Of six patients with histologic biliary tree lesions including cholestasis and cholangitis, three were stabilized, two developed biliary anastomotic stenoses that were successfully treated by surgery or percutaneous stenting, and one continued to have diffuse intrahepatic ischemic cholangitis while the arterial stent was patent. In the other patients, no biliary complication after correction of arterial stenosis occurred. Seven patients have normal Doppler values, and four patients have abnormal ones. These four patients included the one with thrombosed arteries, two patients with stenosed arteries, and one with a suspected recurrent stenosis after dilated intrastent restenosis. The Kaplan-Meier curve of patency shows cumulated primary stent patency at 3, 6, and 12 months of 68%, 62%, and 53%, respectively, with a standard deviation of 14% for a confidence interval of 95% (Fig. 3). Secondary stent patency at 3, 6, and 12 months was 84%, 77%, and 60%, respectively, with a standard deviation of 22% (Fig. 3). Discussion Hepatic artery thrombosis is a well-known complication of liver transplantation. In the early postoperative period, it may result in graft failure and may carry a mortality rate as high as 50% [1, 6]. Consequences of hepatic artery stenosis have been reported [2, 4, 7]. Most patients with hepatic artery stenoses present with abnormal findings on a liver function test. Compared with a control group, patients with hepatic artery stenosis are twice as likely to have biliary complications that have substantial impact on both graft and patient survival [2]. The same study found that patients with corrected hepatic artery stenosis had the same 4-year actuarial graft and patient survival rates as patients in the control group [2]. s a consequence, it is logical to treat such patients to prevent biliary complication and graft dysfunction JR:178, May 2002

5 Coronary Stents in the Treatment of Hepatic rtery Stenoses ecause the material used in endovascular stenting and angioplasty has dramatically improved in recent years, we decided in consensus with the transplantation team to attempt endovascular repair in all patients with hepatic artery stenosis instead of having them undergo surgical repair. We chose to use coronary stents rather than simple balloon angioplasty for two reasons: First, treatment of coronary artery lesions after heart transplantation has been shown to be dramatically improved by using stents rather than balloon angioplasty. Rates of restenosis and complications were less with stents than with balloon angioplasty; the rate of restenosis using stents was less than 24% in this aggressive disease [3]. t 1 year, only four of 13 patients developed restenosis in our series. Coronary allograft disease is related to immunologic disorders, whereas hepatic artery stenosis is multifactorial because patients may have not only immunologic disorders but also surgical microtraumatisms, vaso vasorum interruption, intimal flap, and intimal proliferation. The second reason we decided to use coronary stents was that balloon angioplasty was not accepted by our surgical team because of reported severe complications and variable rates of restenosis [8]. Very different rates of restenosis have been reported, from no restenosis to rates as high as 75% [2, 8 10]. Furthermore, follow-up was achieved only by Doppler sonography and not by angiography; a false-negative Doppler study may have underestimated the restenosis rate [4]. We expected that the use of stents would reduce the risk of arterial complications such as arterial rupture and dissections. In our limited experience, only one complication occurred and our rate of restenosis was acceptable. We used different kinds of coronary stents depending on lesion size and diameter and the type of stents available in our unit. We did not find differences from a technical point of view. However, we recommend against using the Gianturco-Roubin stent in this indication: We had difficulty fully opening it, because of its low radial force [11]. Even in very tortuous arteries, we did not encounter problems in bringing stents into the stenotic area. Six- French sheaths and coaxial systems were helpful. The ideal stent in this indication must have a good radial force and low profile and be flexible enough to be placed in angulated arteries. In conclusion, our findings are encouraging for a conservative endovascular approach for hepatic artery stenosis. Primary stenting of hepatic artery stenosis is feasible and offers a low complication rate with an acceptable 1-year patency rate. References 1. Langnas N, Marujo W, Stratta RJ, Wood RP, Shaw W Jr. Vascular complications after orthotopic liver transplantation. m J Surg 1991;161: bbasoglu O, Levy MF, Vodapally MS, et al. Hepatic artery stenosis after liver transplantation: incidence, presentation, treatment, and long term outcome. Transplantation 1997;63: Heublein, Pethig K, Maass C, Wahlers T, Haverich. Coronary artery stenting in cardiac allograft vascular disease. m Heart J 1997;134: Dodd GD III, Memel DS, Zajko, aron RL, Santaguida L. Hepatic artery stenosis and thrombosis in transplant recipients: Doppler diagnosis with resistive index and systolic acceleration time. Radiology 1994;192: Platt JF, Yutzy GG, ude RO, Ellis JH, Rubin JM. Use of Doppler sonography for revealing hepatic artery stenosis in liver transplant recipients. JR 1997;168: Griffith JF, John PR. Imaging of biliary complications following paediatric liver transplantation. Pediatr Radiol 1996;26: Orons PD, Sheng R, Zajko. Hepatic artery stenosis in liver transplant recipients: prevalence and cholangiographic appearance of associated biliary complications. JR 1995;165: Orons PD, Zajko, ron KM, Trecha GT, Selby RR, Fung JJ. Hepatic artery angioplasty after liver transplantation: experience in 21 allografts. J Vasc Interv Radiol 1995;6: bad J, Hidalgo EG, Cantarero JM, et al. Hepatic artery anastomotic stenosis after transplantation: treatment with percutaneous transluminal angioplasty. Radiology 1989;171: Mondragon RS, Karani J, Heaton ND, et al. The use of percutaneous transluminal angioplasty in hepatic artery stenosis after transplantation. Transplantation 1994;57: Vrints CJ, Cools F, osmans J, Claeys M, Snoeck JP. cute luminal gain after stenting: comparison of Gianturco-Roubin and Palmaz-Schatz stents. J Invasive Cardiol 1996;8: JR:178, May