Risk Factors for Hepatic Venous Outflow Obstruction in Piggyback Liver Transplantation: The Role of Recipient’s Pattern of Hepatic Veins Drainage into the Inferior Vena Cava

Background

The technique of orthotopic liver transplantation often has physiologic disturbance associated with the hepatectomy of the recipient’s inferior vena cava (IVC). To overcome this problem, “piggyback liver transplantation” (PBLT), a technique involving the direct anastomosis of the recipient’s hepatic veins with the donor’s IVC without the removal of the recipient’s IVC, was described by Calne in 1968 and Tzakis in 1989 [1,2].

In orthotopic liver transplantation, hepatic venous outflow obstruction (HVOO) is uncommon, as a suprahepatic cava-caval anastomosis was performed. With the use of PBLT, however, the occurrence of HVOO has increased. HVOO is a rare but lethal complication related with PBLT, and the reported that the incidences range between 1.5% and 4.6%, leading to a mortality rate of up to 23% [3–5].

In standard PBLT, to fashion an orifice for the direct anastomosis with the suprahepatic vena cava of the graft, the venoplasty of the recipient’s major hepatic veins (HVs) is performed based on the patterns of hepatic veins (HVs) drainage into the IVC (drainage pattern) [2]. Different types of venoplasty may influence the anatomical relationship between the venous outflow and graft location within the recipient liver fossa, leading to the twisting or compression of the anastomosis, which are considered as major factors for HVOO [6–8]. Thus, we speculated that the recipient’s drainage pattern affects the venous outflow reconstruction; therefore, hepatic venous outflow obstruction (HVOO) in standard in PBLT. The aim of this retrospective study was to evaluate the role of drainage pattern in HVOO.

Material and Methods

STUDY DESIGN:

A retrospective multicenter study of 202 patients who received PBLT from 2000 to 2016 was conducted. None of the patients had thrombotic tendencies, such as Budd-Chiari syndrome. The indications for PBLT in these patients included hepatocellular diseases such as hepatitis B or C virus-associated liver cirrhosis in 125 cases, hepatocellular carcinoma in 65 cases, and liver metabolic disease in 12 cases. Based on the experience of Tzakis [2], all of the patients had favorable circumstances in which the large HVs are relatively normal and accessible, or at least have small cirrhotic livers.

The patients were divided into 3 groups based on the drainage patterns by preoperative 3D reconstruction. In Group A (n=136), the left and middle HVs formed a common trunk before draining into the IVC; in Group B (n=52), the right and middle HVs formed a common trunk before draining into the IVC; and in Group C (n=14), the left, middle and right HVs formed a common trunk before draining into the IVC. Table 1 compares demographic and surgical data from the groups: sex, age, angle ∠AOB between the reconstructed outflow and IVC in cross-section of 3D image (∠AOB), graft-to-recipient weight ratio (GRWR), with or without HV ligation, caliber of HV anastomosis, length of reconstructed outflow (LRO), ratio between LRO and ∠AOB (LRO/∠AOB ratio), and HVOO incidence. The measurement for ∠AOB and LRO is described in this article’s section “Evaluation for the level of twisting or compression of the reconstructed outflow”. The risk factors of HVOO were analyzed using multivariate analyses. All of the donors had experienced either brain death or cardiac death. The main causes of donor death were head trauma, intracerebral hemorrhage, and cerebral thrombosis. The study was conducted according to the Helsinki Declaration of 1975 and was approved by our Institutional Review Board. All patients provided written the informed consent for use of clinical data collected from their medical records.

EVALUATION FOR LEVEL OF TWISTING OR COMPRESSION OF THE RECONSTRUCTED VENOUS OUTFLOW:

The twisting or compression of the reconstructed venous outflow due to graft location within the recipient’s liver fossa were considered as 2 major reasons for HVOO [6–8]. ∠AOB, a plane angle between the recipient’s common trunk of HVs and IVC in cross-section, was drawn using a three-dimensional reconstruction of the recipient’s liver, created using the IQQA®-Liver analysis system (EDDA Technology, NJ). We placed the vertex “O” on the center of the IVC, the side “OA” in the direction of common trunk of the recipient’s HVs and the side “OB” in the direction of largest transverse diameter of IVC. In our study, the venous outflow reconstruction was performed by the end-to-end anastomosis of the common trunk formed by the recipient’s HVs and the graft’s IVC according to Tzakis’s description [2], Therefore, the angle ∠AOB was used to assess the level of the venous outflow twisting (Figure 1). During the operation, LRO was the distance between the 2 confluences of recipient and graft’s suprahepatic veins. Patients with longer LRO but smaller size of ∠AOB were more likely to have HVOO due to venous outflow compression. Thus, LRO/∠AOB ratio was used to assess the level of the venous outflow compression.

TECHNICAL PROCEDURE OF VENOUS OUTFLOW RECONSTRUCTION IN DIFFERENT GROUPS:

All of the recipients received end-to-end anastomosis of the recipient’s venoplasty of the HVs’ common trunk and the graft’s suprahepatic IVC for venous outflow reconstruction in standard PBLT [2]. In Group A, we ligated the right HV and performed venoplasty comprising the left and middle HVs before the end-to-end anastomosis. In Group B, patients received ligation of the left HV and venoplasty comprising the left and middle HVs followed by end-to-end anastomosis. Group C patients received venoplasty comprising the right, middle, and left HVs with end-to-end anastomosed with the donor’s IVC (Figure 2).

THE CLASSIFICATION AND DIAGNOSIS OF HVOO:

HVOO was classified into 3 types (intraoperative, postoperative acute, and chronic HVOO).

When the blood supply of the graft was recovered during the operation, the intraoperative HVOO should show signs of liver swelling, portal hypertension, and even hypotension resulting from insufficient venous return. If these signs were relieved by adjusting the position of the graft, intraoperative HVOO was diagnosed.

For the early diagnosis of postoperative HVOO, venous outflow was regularly examined by ultrasound twice per day from PBLT to postoperative day (POD) 14, and then once per day until POD 28, and then once or twice per week during the remaining hospitalization time.

Although Doppler ultrasound is considered more sensitive and accurate than computed tomography (CT) [5], CT has some value for detection of hyperplasia and/or fibrotic changes around the anastomoses resulting in HVOO, as well as avoiding unnecessary invasive venographies, particularly when the patient’s condition was suggestive for chronic HVOO.

Hepatic venography and manometry are the criterion standard for diagnosis of HVOO and are performed when HVOO is suspected according to these findings mentioned above. Finally, HVOO was confirmed if the venous outflow had a pressure gradient >3 mm Hg and/or the anastomotic stricture was >50%.

The postoperative acute HVOO was defined as occurrence within 1 month after the initial PBLT, and chronic HVOO was defined as that at 1 month or later after the initial PBLT.

STATISTICS:

All data were processed by SPSS 16.0. Results are expressed as mean ± standard error or percentages. Continuous variables were tested using one-way analysis of variance followed by least significant difference t test within groups. Categorical variables were compared by chi-square test followed by Bonferroni post hoc test within the 3 groups. Any variable that was observed as significant (p<0.05) by univariate analysis was considered as a candidate for multivariate analysis by multiple logistic regression models. Differences were considered statistically significant at p<0.05.

Results

PATIENT CHARACTERISTICS:

All of the patients were divided into 3 groups based on the recipient drainage pattern. The comparisons of patient demographics and surgical data within the 3 groups are summarized in Table 1. Overall, while it remained comparatively low in Group B (9.6%) and Group C (7.1%), the incidence of HVOO increased significantly in Group A (23.5%).

Among the 136 patients in Group A, HVOO occurred in 32 cases, including 28 cases with intraoperative HVOO and 4 cases with postoperative acute HVOO. In Group B, the overall occurrence of HVOO was 9.6% (5 of 52 patients). Among the 5 cases with HVOO, 2 cases were diagnosed as intraoperative HVOO and the others were postoperative HVOO. Group C had 14 patients in total, among who only 1 had postoperative chronic HVOO after PBLT.

No significant differences were observed within the 3 groups in the comparisons of sex ratio, age, GRWR, or caliber of HV anastomosis. Unlike Group C, all of the patients in Group A and B had right or left HV ligation. In Group A, the patients had a significantly larger size of ∠AOB (159.9±0.5°) than in the other groups (Group B 50.4±0.9°, Group C 93.2±0.8°, p=0.000). The LRO/∠AOB ratio in Group B (0.06±0.003) significantly increased compared with Group A (0.03±0.002) and Group B (0.04±0.007) (Table 1).

RISK FACTORS FOR HVOO:

Based on comparisons of patient characteristics, size of ∠AOB, LRO/∠AOB ratio, and with or without HV ligation, produced significant results and were considered for multivariate analysis. In multiple logistic regression models, size of ∠AOB and LRO/∠AOB ratio were both risk factors for HVOO (Table 2).

Discussion

LIMITATIONS:

Results of our study and some previous studies are not consistent with regard to the association between HVOO and the hyperplasia and/or fibrotic changes around the anastomoses [3,7,11,12]. However, we cannot conclude that these pathologic changes were not risk factors for HVOO, due to the retrospective nature of our study and the relatively small sample size of Group C. Although conflicting results were reported on cavo-caval side-to-side or end-to-side anastomosis for outflow reconstruction, it is clear that the best-performing techniques are using the stumps of the 3 major hepatic veins to avoid HVOO in PBLT [3,13–15]. In our study, we had the same opinion on the use of the stumps of the 3 major HVs. However, we cannot state that cavo-caval side-to-side or end-to-side anastomosis technique is more effective than the other 2 types of venoplasty for outflow reconstruction, due to the lack of comparative analysis. Cavo-caval side-to-side or end-to-side anastomosis needs a complete or partial clamp of IVC temporarily and cannot completely avoid the complications related to vascular anastomosis [14]. In fact, the relatively simpler intraoperative preventions described above in Groups A and B also contributed to reduced incidence of HVOO, particularly in Group B, whose HVOO incidence did not differ significantly from Group 3.

Conclusions

Our findings demonstrate a strong association between the drainage patterns and HVOO. The best choice for outflow reconstruction is Group C. The patients in Group A and B were likely to develop HVOO due to anastomosis twisting and compression, respectively. Prevention and treatment based on the patients’ drainage patterns were helpful for prevention and treatment of HVOO.