Author Affiliations: Organ Transplantation Center, Department of Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China (Li YN, Miao XY, Qi HZ, Hu W, Si ZZ, Li JQ, Li T and He ZJ)

Corresponding Author: Zhi-Jun He, MD, PhD, Department of Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China (Tel/Fax: +86-731-85292101; Email: hezhijun@hotmail.com)

 

© 2015, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(15)60337-X

Published online January 19, 2015.

 

 

Acknowledgement: We thank Mr. Willard Lee Lumpp and Prof. Jian Zhang for their help in word modifying.

Contributors: HZJ proposed the study. LYN and HZJ performed research and wrote the first draft. LYN and MXY collected and analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. HZJ is the guarantor.

Funding: None.

Ethical approval: The study protocol was approved by the Human Ethics Review Committee of the Second Xiangya Hospital, Central South University and was in compliance with the Declaration of Helsinki.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

BACKGROUND: Portal hypertension is one of the most important clinical conditions that cause intraoperative intensive hemorrhage in cirrhotic patients undergoing liver transplantation. Pre-transplant portal decompression may reduce the intraoperative bleeding during liver transplantation.

 

METHODS: Splenic artery trunk embolization (SATE) was performed one month prior to liver transplantation. Platelet count, prealbumin, international normalized ratio, and blood flow in the portal vein and hepatic artery were monitored before and one month after SATE. The measurements above were collected on admission and before surgery in the non-SATE patients, who served as controls. We also recorded the intraoperative blood loss, operating time, required transfusion, post-transplant ascites, and complications within three months after operation in all patients.

 

RESULTS: SATE significantly reduced portal venous blood flow, increased hepatic arterial blood flow, normalized platelet count, and improved prealbumin and international normalized ratio in the patients before liver transplantation. Compared to the non-SATE patients, the pre-transplant SATE significantly decreased the operating time, intraoperative bleeding, post-transplant ascites and severe surgical complications.

 

CONCLUSION: Pre-transplant SATE decreases portal pressure, improves liver function reserve, and reduces the surgical risk of liver transplantation effectively in patients with severe portal hypertension.

 

(Hepatobiliary Pancreat Dis Int 2015;14:263-268)

 

KEY WORDS: liver cirrhosis; liver transplantation; portal hypertension; damage control surgery

Patients with end-stage liver diseases usually have severe portal hypertension and need to be treated with liver transplantation. Thrombocytopenia, perihepatic extensive expansion of varicose vein plexus and blood coagulation dysfunction, which are caused by portal hypertension and liver decompensation, often lead to massive bleeding during liver transplantation and significantly affect the safety of the operation.^[1] Preoperative portal decompression is critical to improve the safety of liver transplantation. In Asia, to reduce the intraoperative bleeding risk, surgeons often performed mesocaval shunt surgery one month before biliary surgery for patients with complicated calculus of the bile duct and portal hypertension.^{[2, 3]} One month interval between the two stage surgeries allowed the close of perihepatic collateral circulation by portal decompression, which was believed to reduce the intraoperative bleeding. However, the portal decompression caused by shunt surgery could reduce the hepatic portal blood flow which damages the liver function and induces hepatic encephalopathy.^{[4, 5]} As a safe non-surgical technique, splenic artery embolization has also been used in the treatment of portal hypertension.^[6] It not only reduces portal vein blood flow and alleviates thrombocytopenia, but also increases hepatic arterial blood flow which benefits liver function.^[7-9] We have successfully used splenic artery trunk embolization (SATE) to treat cirrhotic patients with variceal bleeding of portal hypertension since 2005, and found that SATE improves the liver function in these patients (unpublished data). The results suggested that SATE also improves preoperative status and surgical safety in liver transplant patients with minimal side effects. The present study aimed to analyze the effect of SATE on reducing the intraoperative bleeding in liver recipients with severe portal hypertension.

 

 

The patients with end-stage liver cirrhosis, severe portal hypertension, but without a history of abdominal surgery and on the waiting list for liver transplantation were divided into two groups, SATE group and non-SATE controls. The patients were informed in detail of the research plan including the benefits of SATE and its possible complications. SATE was performed under abdominal angiography. Metallic coils or vascular plug were placed in the area adjacent to the root of the splenic artery to produce total embolization of the splenic artery trunk and avoid the acute splenic infarction.^[10] The study protocol was approved by the Human Ethics Review Committee of the Second Xiangya Hospital, Central South University and was in compliance with the Declaration of Helsinki. A signed consent form was obtained from each subject.

 

Between June 2008 and August 2013, 92 patients received liver transplantation in our transplant center. Among them, 35 patients who met the inclusion criteria were enrolled in this study. Sixteen patients agreed to receive pre-transplant SATE and their interval between SATE and liver transplantation was more than one month (SATE group), while the other 19 patients refused (non-SATE group).

 

To evaluate the effects of SATE on the blood flow of the portal vein and hepatic artery, Doppler ultrasound (Acuson, CA, USA) was used to measure the hemodynamic indices of the portal vein and hepatic artery by one investigator according to the standard protocol.^[11] This Doppler ultrasound was equipped with serial curvilinear transducers of 3.5 and 5 MHz and software for direct or automatic calculation of the hemodynamic parameters based on the spectral Doppler waveform. The patients were examined after overnight fast in a supine position. Portal venous time-averaged maximum velocity, hepatic arterial mean velocity, and the vessel diameter (D) of the portal vein and hepatic artery were measured by color Doppler ultrasound. The blood flow of portal vein and hepatic artery was calculated according to standardized formula (Blood flow=πD²×15×mean velocity, mL/min). The data on the platelet count, prealbumin, international normalized ratio (INR), and blood flow of both portal vein and hepatic artery were collected before the embolization and at one month after the embolization in the SATE patients. In the non-SATE patients, the data of the same parameters were collected on admission and before liver transplantation. The classic orthotopic liver transplantation without veno-venous bypass was performed in all patients. During the surgical procedure, the massive portal-systemic collateral circulation channels were found in 16 of the non-SATE patients and 15 of the SATE patients, and were treated with ligation or cutting-off to avoid the escape of portal inflow through collaterals.

 

The data on various surgical parameters such as intraoperative blood loss, operating time, required transfusion and postoperative ascites in the perioperative phase were collected. The data on the surgical complications within three months were also collected according to the Dindo-Clavien classification.^[12] We analyzed the data obtained from the two groups respectively to evaluate the effects of pre-transplant SATE on the surgical safety of liver transplantation.

 

Differences in the data between the SATE and non-SATE patients were analyzed using the Mann-Whitney U test, Chi-square test, and analysis of variance. The Wilcoxon's paired test was used to analyze the differences before and after SATE, and those from non-SATE patients on admission and before surgery, respectively. All statistical analyses were performed using SPSS software (Release 17.0.0, Polar Engineering and Consulting, Nikiski, AK, USA). A P value of <0.05 was considered statistically significant.

 

 

There were no significant differences between the patients with SATE and non-SATE in age, gender, underlying disease, the Child-Pugh scores and MELD scores on admission (Table 1). Esophageal gastric varices were found in all cases. Esophageal gastric variceal ligation or embolization was performed in 12 patients of the SATE group and 15 of the non-SATE group to prevent variceal bleeding during the waiting time. There were no significant differences in donor's age, waiting time, and in warm and cold ischemia time of the graft between the two groups (Table 1).

 

As confirmed by angiography, SATE led to an immediate increase of hepatic arterial blood flow and a sharp reduction of splenic blood flow (Fig. 1). Most of the SATE patients experienced a few days (range 3-7) of low-degree fever after the embolization which did not need treatment. No SATE-related severe complications, such as hemorrhage, vascular injury, portal vein thrombosis, and splenic necrosis or infection were found. SATE significantly reduced the portal venous blood flow (median 905.6 vs 582.6 mL/min, P<0.01) and increased the hepatic arterial blood flow (median 85.4 vs 499.1 mL/min, P<0.01) (Fig. 2). SATE also significantly increased the platelet count (median 36.0×10⁹ vs 96.0×10⁹/L, P<0.001), prealbumin (median 85.0 vs 104.5 mg/L, P<0.01), but decreased the INR (median 1.7 vs 1.6, P<0.05) (Figs. 3 and 4). No differences were found in the observed variables between the two groups on admission, and between on admission and before surgery in the non-SATE patients (Figs. 2-4).

 

Intraoperative blood loss was significantly decreased (4897.4±2046.5 vs 2541.8±1105.6 mL, P<0.05). The amount of transfused blood (concentration of red blood cells 20.9±7.8 vs 11.3±5.2 U, P<0.05), operating time (466.1±69.2 vs 370.6±50.5 min, P<0.05) and post-transplant ascites drainage (836.8±255.3 vs 249.4±102.7 mL/d, P<0.05) were significantly decreased in patients with SATE compared with those in patients with non-SATE (Table 2).

 

According to the Dindo-Clavien classification, no significant differences were found in grade I and II complications between the two groups. Ten patients with non-SATE had grade III complications. Among them, three patients had splenic artery steal syndrome associated graft liver dysfunction which was corrected by SATE. One patient developed abdominal infection and 2 patients who developed pneumothorax were treated by a catheter drainage. Four patients received additional surgical intervention because of a postoperative hemorrhage. Only 3 patients with SATE had grade III complications. Among them, one patient with pulmonary atelectasis was treated by bronchial cleaning under a fiber bronchoscope, and 2 patients with abdominal infection were treated with a percutaneous drainage. In 9 patients with non-SATE who had grade IV complications, 6 had single organ dysfunction, and 3 developed multiorgan dysfunction. Only two patients with SATE had single organ dysfunction. Two patients with non-SATE had grade V complication. These patients died from postoperative hemorrhage and infection. No patient with SATE had grade V complication. Statistical analysis showed that there was significant difference between the two groups in grade III and IV complications (P<0.05) (Table 2).

 

 

Severe intraoperative bleeding is a common consequence in cirrhotic patients with portal hypertension during liver surgery. Although the incidence of this complication was decreased along with the improvement of surgical techniques and equipments, intraoperative bleeding is still one of the important causes to induce severe complications and perioperative death in patients with liver transplantation.^[13-16] The patients with end-stage liver diseases usually suffer from severe cirrhosis with portal hypertension, multiple collateral vessels, splenomegaly and poor liver function. The high portal venous pressure and perihepatic multiple collateral vessels induced by portal hypertension can cause massive bleeding during hepatectomy.^[1] Coagulopathy caused by splenomegaly and hepatic decompensation often aggravates bleeding.^[1,13] Reducing the intraoperative bleeding during liver transplantation has been a major technical challenge for surgeons.

 

In Asia, intraoperative bleeding is reduced by a shunt surgery one month prior to biliary surgery in hepatolithiasis patients with portal hypertension.^{[2, 3, 17]} However, the pre-stage shunt surgery is not suitable for liver transplantation patients because the shunt surgery induces portal decompression by bypassing the portal venous blood flow, which can reduce the hepatic portal blood flow, influence the recovery of liver function adversely, and induce hepatic encephalopathy.^{[4, 5]} It is difficult for patients with Child-Pugh C stage liver function to tolerate a portacaval shunt surgery before liver transplantation. In spite of this, pre-stage portal decompression makes it possible to close perihepatic collateral circulation before liver surgery which is helpful to reduce intraoperative hemorrhage. This procedure can be applied to the liver transplantation in portal hypertension patients.

 

The splenic artery is an important supply of portal vein inflow especially in portal hypertension. SATE is usually used to treat thrombocytopenia and esophageal varicose vein hemorrhage caused by portal hypertension. Splenic arterial embolization can not only reduce portal venous blood flow and portal pressure, but also increase the blood supply of hepatic artery and improve the liver function.^[18-21] Therefore, SATE reduces the surgical risk factors, such as high portal venous pressure, perihepatic multiple collateral vessels, thrombocytopenia and liver dysfunction, in the liver transplant patients with portal hypertension. Umeda et al^[22] found that decreasing the portal pressure by blocking the splenic artery trunk on the preoperative day or ligaturing it intraoperatively reduced the bleeding risk in living donor liver transplantation. In our study, SATE was performed to reduce portal pressure one month prior to liver transplantation. The one-month interval between the embolization and liver transplantation allows the closure of perihepatic collateral vessels, normalization of thrombocytopenia and improvement of liver function, which are crucial to reduce the intraoperative bleeding of liver transplantation in portal hypertension patients. Although SATE indeed decreases portal venous blood flow, the increased hepatic arterial blood flow can significantly improve the liver function. In comparison with the intraoperative blood loss (6726±1048 mL) reported by Umeda et al,^[22] our data showed an improved effect (2541.8±1105.6 mL). This implies that SATE performed one month earlier is better than that performed perioperatively because one month is enough to close the perihepatic collateral vessels.

 

Compared with partial splenic embolization, the long-term therapeutic effect of SATE is not as good as expected due to the compensation of blood vessels around the spleen, but it has an obviously short-term therapeutic effect with less complications.^[23-26] The spleen can still have partial blood perfusion through the dorsal pancreatic artery and gastroomental artery after SATE. This slows down the splenic infarction.^[27] Our data showed that the patients could tolerate SATE without severe SATE-related complications.

 

Severe complications and perioperative death are greatly related to the intraoperative bleeding in liver transplantation.^{[1, 13-16]} In our study, the pre-transplant SATE significantly reduces the risk factors before liver transplantation. This treatment greatly reduces the intraoperative bleeding in liver recipients with portal hypertension so that the severe complications are also significantly decreased.

 

The study was not a randomized and double-blinded study. We used only patients who met design conditions and excluded those with disadvantage factors such as history of abdominal surgery. Moreover, the application of nonparametric statistical methods could reduce the adverse effects of small sample size on the results, and it was helpful for quick access to research results.

 

In conclusion, pre-transplant SATE decreases the portal pressure, normalizes thrombocytopenia, and improves the liver function and preoperative status. This procedure increases the safety of liver transplantation in the patients with end-stage liver diseases and severe portal hypertension.

 

 

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