Early Post-Operative Doppler Ultrasound as A Predictive Factor for Vascular Complications after Liver Transplantation

Objective: To evaluate the diagnostic accuracy of early postoperative Doppler ultrasound (DUS) for vascular thrombosis after liver transplantation and to evaluate its impact on clinical outcome.

Materials and Methods: This retrospective study examined 219 patients who underwent liver transplantation at a single reference institution. The results of early postoperative DUS were compared with angiographic, clinical and surgical data through a medical records review. The sensitivity and specificity of DUS for diagnosing vascular complications in the hepatic arteries and portal vein were calculated.

Results: DUS diagnosed vascular complications in 23 out of 210 included patients (10.9%). For the diagnosis of arterial and portal vein complications (stenosis/thrombosis), DUS showed respectively sensitivity of 75% and 90.9% and specificities of 96% and 100%. Overall mortality rate was 10.5% and patients who presented vascular alterations at early postoperative DUS presented a higher mortality (21.7%) rate than those with normal DUS (9.0%), although with no statistically significant difference (p=0.074).

Conclusion: DUS is a valuable tool for early vascular complication diagnosis, with high specificity rates for portal and arterial stenosis/thrombosis. Sensitivity rate in this series was lower for arterial complications.

Doppler Ultrasonography; Liver Transplantation; Treatment Outcome

Over the past 20 years, liver transplantation has proven to be an excellent therapeutic option for patients with advanced liver disease. Vascular complications are the major causes of morbidity and mortality after liver transplantation, mainly in living donor graft recipients. However, the early detection and treatment of these complications may reduce its impact [1,2].

Doppler ultrasound (DUS) is frequently the first imaging exam employed to evaluate vascular complications after liver transplantation, owing to its availability, low cost, and absence of complications. The exam is able to diagnose such vascular complications, including thrombosis and stenosis of the hepatic artery, portal vein, and hepatic veins [3-6]. Angiography is currently further recommended to confirm vascular complications.

The effectiveness of DUS in the diagnosis of vascular complications has been described previously. However, its results at early postoperative period varies, and its correlation with patients’ clinical evaluation is controversial [7-10]. For instance, transient high-resistance arterial waveform can be detected by early DUS in the absence of complications or may be the first sign of arterial stenosis. The early detection of vascular complications in patients undergoing hepatic transplantation can allow minimally invasive treatments (e.g., balloon angioplasty for hepatic artery stenosis) or new surgical procedures to be performed before biliary injury, severe liver failure and/or sepsis develops [11].

The present study aimed to correlate the findings of early postoperative DUS with the clinical and surgical outcome of liver transplantation, concerning vascular complications.

After approval of the institutional Ethics Review Board, we conducted a retrospective survey on the records of 219 patients who underwent liver transplantation between May 2001 and July 2007. At our institution, DUS is routinely performed within the first 12 hours after transplantation, and when clinically indicated after that period. Another DUS is performed just before the discharge of the hospital. A standard questionnaire was completed for patients with an early postoperative DUS, including epidemiological, clinical, laboratory, and surgical data, as well as the reports of the DUS and, if any, digital angiography results were avaiable. Nine patients were excluded because they did not have early postoperative DUS. Patients were followed for at least 1 year to assess outcomes and survival.

The DUS examinations after transplantation are standardized and evaluate: 1) hepatic parenchyma and biliary tracts; 2) the flow at hepatic artery, portal vein, and hepatic vein; and 3) extra-hepatic changes. Hepatic artery evaluation included the presence or absence of flow. Resistive index (RI) and peak systolic velocities of the hepatic artery were not systematically accessed at every first postoperative Doppler exam, since parenchyma edema, which is common in the early postoperative period, may alter it [12]. For portal vein, the presence or absence of flow was examined either at the hilus and intra-hepatic portal branches. For the hepatic veins, the presence or absence of flow and its waveform were examined. The exams had been performed by one out of three radiologists with at least 5 years practice in Doppler US and all images were reviewed to evaluate the exam quality before inclusion.

For patients with non invasive follow up, clinical outcome (e.g. signs and symptoms related to vascular complications, laboratory tests and sequential DUS) was used as gold standard. When indicated, digital angiography or surgical intervention was performed. Based on the mentioned criteria, the sensitivity, specificity, predictive value, and accuracy of the first postoperative DUS findings in the diagnosis of vascular complications, were calculated.

Statistical analyses were performed using SPSS for Windows, version 12.0 (SPSS Inc. Chicago, Illinois). Frequency analysis was performed to characterize the sample. The following tests were used to compare variables: chi-square test when both variables were categorical, and Student's t-test and Mann-Whitney test when one of the variables was continuous with and without normal distribution, respectively. P value was considered statistically significant when equal to or less than 0.05.

Patient demographics

Vascular complications on DUS and follow-up

Hepatic arterial flow evaluation

Portal vein flow evaluation

Hepatic veins flow evaluation

Outcome

The diagnosis of vascular complications after liver transplantation is usually achieved by DUS use in the early postoperative period. Vascular complications, which often go unnoticed during the early postoperative period, are the most important technical problem following liver transplantation [13]. The present study confirmed the findings of other papers, which observed that children and grafts from living donors have a higher risk of developing these complications, which are associated with high morbidity and decreased survival rates [14,15]. Recently, Lee et al. also found that abnormal DUS findings on postoperative days 1 and 2 was an independent risk factor for vascular complications requiring intervention [16].

The frequency of vascular complications on this study was similar to results published in literature. According to Machado et al., arterial thrombosis is the most commonly identified postoperative vascular complication, and occurs in 15-20% of children and 4-12% of adult patients [17]. Tamsel et al. described portal vein complications in 1-12.5% of liver transplantations and hepatic vein complications are seen in 0-3% [18].

Early postoperative DUS had a sensitivity of 75% and specificity of 96.6% in the diagnosis of arterial complications. Using the similar diagnostic criteria, other authors showed a sensibility between 67 and 92% and a specificity of 73-97% [12,18,19]. Despite the limitations of this retrospective study, including the operator-dependent nature of DUS and the fact that different examiners performed tests, DUS had sensitivity and specificity values, similar to the values described in the literature. Diagnosis of arterial thrombosis by DUS had a higher positive predictive value when arterial flow was absent at both hilus and intrahepatic branches.

At our population, there were 8 false-positive and 2 false-negative results for arterial thrombosis. False-positive results has been described as common as in the present study and may be related to disproportion of the diameters of the recipient and graft vessels, kinking of the anastomoted hepatic artery, slowing of flow and small size of hepatic artery [2,12,18]. False-negative results are more important because they can delay diagnosis and treatment and may be related to thrombosis of distal parenchymal branches of the hepatic artery [18].

We observed a high sensitivity and specificity of early DUS for the diagnosis of portal vein complications after liver transplantation (91% and 100% respectively), which was also described by other authors [18,20].

Our results showed a poor correlation between DUS and follow-up data for the identification of hepatic vein complications. Hepatic vein obstruction occurs more commonly on later postoperative period (>1 week), and thus early postoperative DUS have a low sensibility to predict this complication [21,22]. In addition, DUS findings should be interpreted with caution in the immediate postoperative period because reduced hepatic vein pulsatilibity, which is the most important parameter for the diagnosis of hepatic vein obstruction, may be observed during this time and resolves spontaneously after a few days [20].

DUS is a valuable tool for screening arterial and portal thrombosis in the early postoperative period. Early detection of vascular complications by DUS can enable their immediate treatment and quick resolution, thereby reducing the mortality and improving prognosis for patients undergoing liver transplantation.

1. Wozney P, Zajko AB, Bron KM, Point S, Starzl TE (1986) Vascular complications after liver transplantation: a 5-year experience. AJR Am J Roentgenol 147: 657-663.


2. Nolten A, Sproat IA (1996) Hepatic artery thrombosis after liver transplantation: temporal accuracy of diagnosis with duplex US and the syndrome of impending thrombosis. Radiology 198: 553-559.


3. Someda H, Moriyasu F, Fujimoto M, Hamato N, Nabeshima M, et al. (1995) Vascular complications in living related liver transplantation detected with intraoperative and postoperative Doppler US. J Hepatol 22: 623-632.


4. De Gaetano AM, Cotroneo AR, Maresca G, Di Stasi C, Evangelisti R, et al. (2000) Color Doppler sonography in the diagnosis and monitoring of arterial complications after liver transplantation. J Clin Ultrasound 28: 373-380.


5. Lee J, Ben-Ami T, Yousefzadeh D, Ramirez J, Funaki B, et al. (1996) Extrahepatic portal vein stenosis in recipients of living-donor allografts: Doppler sonography. AJR Am J Roentgenol 167: 85-90.


6. Ko EY, Kim TK, Kim PN, Kim AY, Ha HK, et al. (2003) Hepatic vein stenosis after living donor liver transplantation: evaluation with Doppler US. Radiology 229: 806-810.


7. García-Criado A, Gilabert R, Salmerón JM, Nicolau C, Vilana R, et al. (2003) Significance of and contributing factors for a high resistive index on Doppler sonography of the hepatic artery immediately after surgery: prognostic implications for liver transplant recipients. AJR Am J Roentgenol 181: 831-838.


8. García-Criado A, Gilabert R, Berzigotti A, Brú C (2009) Doppler ultrasound findings in the hepatic artery shortly after liver transplantation. AJR Am J Roentgenol 193: 128-135.


9. Uzochukwu LN, Bluth EI, Smetherman DH, Troxclair LA, Loss GE Jr, et al. (2005) Early postoperative hepatic sonography as a predictor of vascular and biliary complications in adult orthotopic liver transplant patients. AJR Am J Roentgenol 185: 1558-1570.


10. Kok T, Slooff MJ, Thijn CJ, Peeters PM, Verwer R, et al. (1998) Routine Doppler ultrasound for the detection of clinically unsuspected vascular complications in the early postoperative phase after orthotopic liver transplantation. TransplInt 11: 272-276.


11. Miraglia R, Maruzzelli L, Caruso S, Milazzo M, Marrone G, et al. (2009) Interventional radiology procedures in adult patients who underwent liver transplantation. World J Gastroenterol 15: 684-693.


12. Dodd GD 3rd, Memel DS, Zajko AB, Baron RL, Santaguida LA (1994) Hepatic artery stenosis and thrombosis in transplant recipients: Doppler diagnosis with resistive index and systolic acceleration time. Radiology 192: 657-661.


13. Varotti G, Grazi GL, Vetrone G, Ercolani G, Cescon M, et al. (2005) Causes of early acute graft failure after liver transplantation: analysis of a 17-year single-centre experience. Clin Transplant 19: 492-500.


14. Steinbrück K, Enne M, Fernandes R, Martinho JM, Balbi E, et al. (2011) Vascular complications after living donor liver transplantation: a Brazilian, single-center experience. Transplant Proc 43: 196-198.


15. Khalaf H1 (2010) Vascular complications after deceased and living donor liver transplantation: a single-center experience. Transplant Proc 42: 865-870.


16. Lee H, Lim CW, Yoo SH, Koo CH, Kwon WI, et al. (2014) The effect of Doppler ultrasound on early vascular interventions and clinical outcomes after liver transplantation. World J Surg 38: 3202-3209.


17. Machado MM, Zan ASCN, Oliveira IRS (1999) Ultrasonographic, anatomic and clinical features of the vascular complications involving the hepatic artery and portal vein in liver transplant recipients. Radiol Bras 32: 223.


18. Tamsel S, Demirpolat G, Killi R, Aydin U, Kilic M, et al. (2007) Vascular complications after liver transplantation: evaluation with Doppler US. Abdom Imaging 32: 339-347.


19. Platt JF, Yutzy GG, Bude RO, Ellis JH, Rubin JM (1997) Use of Doppler sonography for revealing hepatic artery stenosis in liver transplant recipients. AJR Am J Roentgenol 168: 473-476.


20. Chong WK, Beland JC, Weeks SM (2007) Sonographic evaluation of venous obstruction in liver transplants. AJR Am J Roentgenol 188: W515-521.


21. Hwang HJ, Kim KW, Jeong WK, Kim SY, Song GW, et al. (2009) Hepatic outflow obstruction at middle hepatic vein tributaries or inferior right hepatic veins after living donor liver transplantation with modified right lobe graft: comparison of CT and Doppler ultrasound. AJR Am J Roentgenol 193: 745-751.


22. Sommovilla J, Doyle MM, Vachharajani N, Saad N, Nadler M, et al. (2014) Hepatic venous outflow obstruction in pediatric liver transplantation: technical considerations in prevention, diagnosis, and management. Pediatr Transplant 18: 497-502.