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ORIGINAL ARTICLE
Year : 2015  |  Volume : 20  |  Issue : 3  |  Page : 121-126
 

Vascular complications in biliary atresia patients undergoing living donor liver transplantation: Analysis of 110 patients over 10 years


1 Associate Consultant, Surgical Gastroenterology, Hepatobiliary Surgery and Liver Transplant, Apollo Hospitals, Ahmedabad, India; Department of Liver Transplant, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2 Department of Liver Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Date of Web Publication18-Jun-2015

Correspondence Address:
Dr. Bhavin Vasavada
Associate Consultant, Surgical Gastroenterology, Hepatobiliary Surgery and Liver Transplant, Apollo Hospitals, Ahmedabad, 380054, India

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9261.154651

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   Abstract 

Introduction: Vascular complications are very common in pediatric living donor liver transplants. We present our experience in vascular complications in biliary atresia patients undergoing liver transplantation. Materials and Methods: All the patients who have undergone living donor liver transplant for biliary atresia from January 2003 to March 2013 were retrospectively analyzed. P value < 0.05 was considered to be statistically significant. Results: Total 110 patients have undergone living donor liver transplantation for biliary atresia between January 2003 and March 2013. There were 56 males and 54 females. Median age at transplant was 13.5 months. Eleven were primary transplants and 99 were post KASAI procedure. One hundred left lateral, four left lobe, and four right lobe grafts were used. Twenty-two patients developed vascular complications. Twelve patients developed hepatic artery thrombosis. Eleven patients of hepatic artery thrombosis were managed with redo hepatic artery anastomosis and one patient managed with radial artery interposition graft. Five patients developed portal vein stenosis and were managed by portal vein stenting. Five patients developed portal vein thrombosis and portal vein thrombectomy and re-anastomosis were done. One patient developed stenosis at the site of venous anastomosis and was managed by stenting. One patient developed both hepatic artery thrombosis and portal vein thrombosis and eventually succumbed to these complications. Out of five cases who died in this study, two had vascular complications. Graft/recipient weight ratio (GRWR) greater than 2.5 was significantly associated with vascular complications (P = 0.017). Conclusion: Vascular complications are frequently seen in liver transplantation for biliary atresia. Large for size grafts, weight less than 10 kg, age less than 1 year, and prolonged warm ischemia time is significantly associated with vascular complications.


Keywords: Biliary atresia, liver transplantation, live donor liver transplantation, vascular complications, hepatic artery thrombosis


How to cite this article:
Vasavada B, Chen CL. Vascular complications in biliary atresia patients undergoing living donor liver transplantation: Analysis of 110 patients over 10 years. J Indian Assoc Pediatr Surg 2015;20:121-6

How to cite this URL:
Vasavada B, Chen CL. Vascular complications in biliary atresia patients undergoing living donor liver transplantation: Analysis of 110 patients over 10 years. J Indian Assoc Pediatr Surg [serial online] 2015 [cited 2019 Nov 15];20:121-6. Available from: http://www.jiaps.com/text.asp?2015/20/3/121/154651



   Introduction Top


Vascular complications are major cause of morbidity and mortality in case of liver transplantation. [1] They are more common after liver transplantation in pediatric patients. [2] Biliary atresia is the most common indication for liver transplants in children, and this disorder is associated with some congenital vascular anomalies in 10 to 27% of patients. [3] We present our experience on vascular complications in living donor liver transplantation for biliary atresia patients.


   Materials and Methods Top


Children who have undergone living donor liver transplant for biliary atresia from January 2003 to March 2013 at Chang Gung memorial hospital, Kaohsiung, Taiwan were analyzed retrospectively. Conventional ultrasonography (US) and color Doppler US were performed as screening methods to detect vascular and biliary complications post-LT. All patients underwent Doppler US using an Acuson 128 scanner (Acuson, Mountain View, Calif, United States) with 7.0 or 4.0 MHZ transducer at operation, daily for the first 2 postoperative weeks, and when necessary thereafter.

Factors such as age, sex, recipient weight, graft weight, graft/recipient weight ratio (GRWR), operative blood loss, portal vein size mismatch, number of arterial anastomosis, donor recipient arterial size mismatch, hepatic venous anastomosis technique, cold ischemia and warm ischemia time, duration of anhepatic phase, GRWR, type of graft, duration of surgery, primary transplant, timing of KASAI procedure were analyzed. We do not generally use reduced segment graft. We use microsurgical technique for arterial anastomosis. Since 2005, we use microsurgical technique for biliary anastomosis also. Portal vein stenosis was defined as stenosis greater then 50% of the total diameter.

Categorical variables were analyzed with chi square test and continuous variables with Mann Whitney U test. P value < 0.05 was considered as statistically significant. We considered median for comparisons whenever the distribution was skewed. Statistical analysis was performed using statistical package of social sciences (SPSS) version 21 (IBM).

Our techniques of vascular reconstruction is described as under.

Arterial anastomosis

Arterial anastomosis was performed end to end with either polypropelene 8-0 or 9-0 interrupted sutures under operating microscope by micro-vascular surgeon.

Hepatic venous anastomosis

Triple venoplasty was performed on recipient vena cava side by creating single wide opening from right hepatic vein, middle hepatic vein and left hepatic vein to create single large outflow tract.

Left hepatic vein in case of left lateral or if there are separate openings of segment 2 and segment 3 veins, then if possible, we combine them by venoplasty and anastomosis is done with either 5-0, 6-0 polypropelene continuous suture.

Portal venous anastomosis

For portal vein anastomosis, we do branch patch venoplasty at the confluence of the native right and left PV whenever there is portal vein size mismatch and anastomose it end to end with polyporpelene 5-0 or 6-0 with growth factor kept. [4],[5]


   Results Top


Patients' characteristics

Total 110 patients have undergone living donor liver transplantation for biliary atresia between 2003 and 2013. There were 56 males and 54 females. Median age at transplant was 13.5 months. Eleven were primary transplant and 99 were post KASAI procedure. One hundred left lateral, four left lobe, and six right lobe grafts were used. Median age at Kaiser procedure was 60 days. Median PELD and CTP scores were 14 and 8, respectively. Median weight was 8.6 kg, median cold ischemia, warm ischemia, and anhepatic phase times were respectively 34, 42 and 69 minutes. Median graft weight was 290 gm. Median GRWR was 3.20.

Vascular complications

Twenty-two patients developed vascular complications. The overall vascular complications rate was 20%.

Hepatic artery thrombosis

Eleven patients developed hepatic artery thrombosis. Nine patients of hepatic artery thrombosis were managed with redo hepatic artery anastomosis and one patient managed with radial artery interposition graft. One patient also developed associated portal vein thrombosis. We performed double arterial anastomosis in 13 patients because of two graft arteries but none of them developed hepatic artery thrombosis.

Mean donor and recipient artery size was 2.5 mm. We defined donor and recipient artery mismatch as size difference more than 1 mm.

Total 10 patients had donor and recipient artery size mismatch, out of which two developed hepatic artery thrombosis. Discrepancy in donor and recipient artery size was not associated with hepatic artery thrombosis (P = 0.349).

Two patients out of 12 patients died in postoperative period. Hepatic artery thrombosis was significantly associated with over all mortality (P = 0.037). [Figure 1] shows Kaplan Meier curve and log-rank analysis.
Figure 1: Survival was significantly low in hepatic artery thrombosis group


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Factors like donor recipient artery size mismatch, age at KASAI procedure, intra operative blood loss, cold ischemia time, warm ischemia time, age at transplant, weight of patient, sex, pediatric end stage liver disease score (PELD), age at KASAI, were compared between hepatic artery thrombosis group and patients who did not developed hepatic artery thrombosis [Table 1]. Prolonged warm ischemia time was significantly associated with hepatic artery stenosis (P = 0.027). Pearson correlation coefficient was 0.280. Corelation was significant (P = 0.022, 2-tailed).
Table 1: Univariate analysis of hepatic artery thrombosis


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In hepatic artery stenosis group, one patient was re-explored for bowel perforation. One developed acute respiratory distress syndrome, same patient had associated hepatic vein stenosis and was stented for that and subsequently expired, and one had biopsy proven acute rejection. Overall complications were not significantly associated with hepatic artery thrombosis (P = 0.39).

Portal vein complications

Five patients developed portal vein stenosis and were managed by portal vein stenting. Five patients developed portal vein thrombosis and portal vein thrombectomy and re-anastomosis was done. One patient developed both hepatic artery thrombosis and portal vein thrombosis and eventually succumbed to these complications. Median age at transplant (P = 0.024), median weight (P = 0.022), and median GRWR (P = 0.018) were significantly different between patients who developed portal vein stenosis and patients who did not develop [Table 2]. There was no difference between survival rates between two groups [Figure 2].
Figure 2: Patients who developed portal vein complications did not differ significantly from patients who did not develop portal vein stenosis


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Table 2: Univariate analysis of portal vein complications


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Hepatic venous stenosis

As described above the patient with hepatic venous stenosis expired due to associated acute respiratory distress syndrome (ARDS).

Overall vascular complications

If we look at the overall vascular complications, 22 patients developed vascular complications. Five patients died out of 110 in follow-up period. There was no difference in overall survival rates between patients who developed vascular complications and who did not [Figure 3].
Figure 3: There was no survival difference between patients who developed vascular complications and patients who did not


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On univariate analysis weight less then 10 kg, large for size graft (GRWR > 2.5), and warm ischemia time was associated with increased vascular complications [Table 3]. However, on multivariate logistic regression analysis, none of this independently predicted vascular complications.
Table 3: Univariate analysis of vascular complications


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   Discussion Top


Biliary atresia (BA) is the most common cause of chronic cholestasis in infants and children. [6] It is one of the commonest indications of liver transplantation in pediatric population. [3] KASAI portoenterostomy is recommended as the primary initial therapy for extra hepatic biliary atresia; however, majority of these patients will develop chronic liver disease, and almost all will require liver transplantation (LT) before reaching adulthood. Vascular complications after LDLT have been a major concern in pediatric LT, particularly in patients with BA. [2] In this study, we present our results of last 10 year with regard to vascular complications in living donor liver transplantation.

In our series, total vascular complication rate was 20%, which is similar to Seiders et al., showed over all vascular complication rate of 21% in their series of 157 pediatric living donor liver transplants. [7],[14] Hepatic artery complications, portal vein complications were seen in 10.9% and 9.1% patients, respectively, in our series. Seiders et al., described these rates to be 10% and 4% in their series. [7],[14] Vascular complications are much common in pediatric liver transplantation. Pareja et al., [8] in their study of 1,560 adult patients described hepatic artery thrombosis rate of 2.8%. In our series, we encountered hepatic artery thrombosis in 10.9% patients.

Hepatic artery thrombosis is known to be associated with high perioperative mortality with some series suggesting mortality up to 50%. [10],[11] Hepatic artery thrombosis was significantly associated with mortality in our series. Two out of 12 patients expired; however, those patients had associated portal vein thrombosis and hepatic vein stenosis. Rest of the patients could be saved due to timely intervention that shows that prompt diagnosis and timely intervention improves overall survival in this devastating post transplant complication. S. Sevmis et al., also stressed on importance of early diagnosis of this devastating complication. [9]

Jensen et al., described that Portal vein complications occur in 12% of pediatric liver transplantation. [12] In our series, portal vein complication rate was 9.1%. When portal vein thrombosis occurs early in postoperative period immediate management is necessary to prevent graft failure and mortality. [12] Five cases of portal vein thrombosis occurred in immediate postoperative period in our series and we re-explored those patients. All five patients were managed by thrombectomy and re-anastomosis. Only one patient with associated hepatic artery thrombosis died in our series. Warnaar et al., [14] also described that long-term patient and graft survival can be achieved in one-third patients following immediate thrombectomy.

Management of late portal vein complications is not well-defined. We generally prefer to stent the anastomosis if portal vein stenosis is >50%. Five patients with portal vein stenosis >50 % were diagnosed at least 2 months after liver transplantation. All patients were managed with stenting by interventional radiological methods. All five patients are at present complication free and doing well. In our series, portal vein complications were not associated with major morbidities. Only one patient with hepatic artery thrombosis died with associated acute respiratory distress syndrome. One patient developed pneumonia.

Only one patient in our series developed hepatic vein stenosis and was managed by stenting but he also developed hepatic artery thrombosis and died eventually.

Biliary complications are considered to be manifestation of late hepatic artery complications. [13] Total six patient among this 110 patients developed biliary complications with four bile leaks and two strictures at hepaticojejunostomy site. Only one patient with bile leak had associated portal vein stenosis. No patient with hepatic artery thrombosis developed biliary complications. However, there was no late hepatic artery thrombosis in our series.

Mazzaferro et al., [15] showed that arterial diameter <3 mm was associated with hepatic artery thrombosis. However, in our series, mean size of donor and recipient was 2.5 mm and arterial size, no of anastomosis or arterial size mismatch were not associated with hepatic artery thrombosis. We use microsurgical technique for both arterial and biliary anastomosis and this may suggest that routine use of microsurgical technique may help in preventing hepatic artery thrombosis. In our series, only increase in warm ischemia time was significantly associated with hepatic artery thrombosis. Farmer et al., also suggested that increase warm ischemia time was associated with worse graft survival. [16]

In our series, portal vein complications were significantly associated with lower recipient weight, high GRWR and lower recipient age, and overall vascular complications were significantly associated with large for size graft, weight less than 10 kg, and increased warm ischemia time. Langnas et al., also found that weight less than 10 kg was significantly associated with vascular thrombosis. [17] Moon et al., [18] showed large for size grafts were associated with portal vein complications. Kiuchi et al., [19] also showed that large for size grafts were associated with increased vascular complications and acute rejection.

There are certain limitations of this study being a retrospective study. Mortality was low (5) in this study so statistical analysis related to mortality may not be accurate.


   Conclusion Top


Vascular complications are commoner in pediatric liver transplantation than adult liver transplantation. However, early diagnosis and prompt management of vascular complications can prevent further morbidity and mortality. Smaller age, low recipient weight, large for size graft, and prolonged warm ischemia time may be associated with increased vascular complications.

 
   References Top

1.
Khalaf H. Vascular complications after deceased and living donor liver transplantation: A single-center experience. Transplant Proc 2010;42:865-70.  Back to cited text no. 1
    
2.
Yilmaz A, Arikan C, Tumgor G, Kilic M, Aydogdu S. Vascular complications in living-related and deceased donation pediatric liver transplantation: Single center atexperience from Turkey. Pediatr Transplant 2007;11:160-4.  Back to cited text no. 2
    
3.
Lilly JR, Chandra RS. Surgical hazards of co-existing anomalies in biliary atresia. Surg Gynecol Obstet 1974;139:49-54.  Back to cited text no. 3
[PUBMED]    
4.
Saad S, Tanaka K, Inomata Y, Uemoto S, Ozaki N, Okajima H, et al. Portal vein reconstruction in pediatric liver transplantation from living donors. Ann Surg 1998;227:275-81.  Back to cited text no. 4
    
5.
de Magnée C, Bourdeaux C, De Dobbeleer F, Janssen M, Menten R, Clapuyt P, et al. Impact of pre-transplant liver hemodynamics and portal reconstruction techniques on post-transplant portal vein complications in pediatric liver transplantation: A retrospective analysis in 197 recipients. Ann Surg 2011;254:55-61.  Back to cited text no. 5
    
6.
Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C, Golmard JL, Auvert B. Prognosis of biliary atresia in the era of liver transplantation: French national study from 1986 to 1996. Hepatology 1999;30:606-11.  Back to cited text no. 6
    
7.
Sieders E, Peeters PM, TenVergert EM, de Jong KP, Porte RJ, Zwaveling JH, et al. Early vascular complications after pediatric liver transplantation. Liver Transpl 2000;6:326-32.  Back to cited text no. 7
    
8.
Pareja E, Cortes M, Navarro R, Sanjuan F, López R, Mir J. Vascular complications after orthotopic liver transplantation: Hepatic artery thrombosis. Transplant Proc 2010;42:2970-2.  Back to cited text no. 8
    
9.
Sevmis S, Karakayali H, Tutar NU, Boyvat F, Ozcay F, Torgay A, et al. Managment of early hepatic arterial thrombosis after pediatric living-donor liver transplantation. Transplant Proc 2011;43:605-8.  Back to cited text no. 9
    
10.
Langnas AN, Marujo W, Stratta RJ, Wood RP, Li SJ, Shaw BW. Hepatic allograft rescue following arterial thrombosis. Role of urgent revascularization. Transplanttion 1991;51:86-90.  Back to cited text no. 10
    
11.
Griffith JF, John PR. Imaging of biliary complications following paediatric liver transplantation. Pediatr Radiol 1996;26:388-94.  Back to cited text no. 11
    
12.
Jensen MK, Campbell KM, Alonso MH, Nathan JD, Ryckman FC, Tiao GM. Management and long-term consequences of portal vein thrombosis after liver transplantation in children. Liver Transpl 2013;19:315-21.  Back to cited text no. 12
    
13.
Margarit C, Hidalgo E, Lázaro JL, Murio E, Charco R, Balsells J. Biliary complications secondary to late hepatic artery thrombosis in adult liver transplant patients. Transpl Int 1998;11:S251-4.  Back to cited text no. 13
    
14.
Warnaar N, Polak WG, de Jong KP, de Boer MT, Verkade HJ, Sieders E, et al. Long-term results of urgent revascularization for hepatic artery thrombosis after pediatric liver transplantation. Liver Transpl 2010;16:847-55.  Back to cited text no. 14
    
15.
Mazzaferro V, Esquivel CO, Makowka L, Kahn D, Belle S, Kahn D, et al. Factors responsible for hepatic artery thrombosis after pediatric liver transplantation. Tranplant Proc 1989;21:2466-7.  Back to cited text no. 15
    
16.
Farmer DG, Venick RS, McDiarmid SV, Ghobrial RM, Gordon SA, Yersiz H, et al. Predictors of outcomes after pediatric liver transplantation: An analysis of more than 800 cases performed at a single institution. J Am Coll Surg 2007;204:904-14.  Back to cited text no. 16
    
17.
Langnas AN, Marujo W, Stratta RJ, Wood RP, Shaw BW Jr. Vascular complications after orthotopic liver transplantation. Am J Surg 1991;161:76-82.  Back to cited text no. 17
    
18.
Moon JI, Jung GO, Choi GS, Kim JM, Shin M, Kim EY, et al. Risk factors for portal vein complications after pediatric living donor liver transplantation with left-sided grafts. Transplant Proc 2010;42:871-5.  Back to cited text no. 18
    
19.
Kiuchi T, Kasahara M, Uryuhara K, Inomata Y, Uemoto S, Asonuma K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999;67:321-7.  Back to cited text no. 19
    


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