Author Affiliations: Department of Thyroid Surgery (Su AP and Zhu JQ) and Department of Hepatobiliopancreatic Surgery (Zhang ZD and Tian BL), West China Hospital, Sichuan University, Chengdu 610041, China

Corresponding Author: Zhao-Da Zhang, MD, Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China (Tel/Fax: +86-28-85423822; Email: zhaodazhang@yeah.net)

 

© 2017, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(16)60129-7

Published online September 13, 2016.

 

 

Contributors: TBL designed the study. SAP conducted the majority of study and wrote the manuscript. ZZD and TBL revised the manuscript. ZZD and ZJQ offered suggestions for this work. ZZD is the guarantor.

Funding: None.

Ethical approval: Not needed.

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: Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascularization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB.

 

METHODS: The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014.

 

RESULTS: A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were observed in the TIPS group than those in the OSED group. During the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED.

 

CONCLUSION: For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.

 

(Hepatobiliary Pancreat Dis Int 2017;16:169-175)

 

KEY WORDS: liver cirrhosis; portal hypertension; recurrent variceal bleeding; transjugular intrahepatic portosystemic shunt; open splenectomy and esophagogastric devascularization

 

Portal hypertension secondary to liver cirrhosis results in two severe complications: esophagogastric variceal bleeding and hypersplenism. The former is the most common cause of death (approximately 30%) in this population. Furthermore, recurrent bleeding occurs in over 70% of patients with a history of variceal bleeding.^[1] The general consensus is that these patients should accept further treatment to prevent rebleeding. Surgical interventions play a key role in the treatment process. Liver transplantation has been regarded as the most effective treatment for cirrhotic patients with portal hypertension and recurrent variceal bleeding (PHRVB). However, organ shortage and high medical costs greatly limit its clinical application. Various interventions have been advocated to treat PHRVB, such as open splenectomy with esophagogastric devascularization (OSED), transjugular intrahepatic portosystemic shunt (TIPS), distal splenorenal shunt, and balloon-occluded retrograde transvenous obliteration.^[2-5]

 

OSED and TIPS are widely used in the treatment of PHRVB. The former is more commonly used in China, whereas the latter is more frequently used in Western countries.^[6] OSED is an effective treatment for PHRVB because the two severe complications can be solved simultaneously.^{[7, 8]} Nevertheless, several complications occur after OSED, including portal vein thrombosis, serious gastric mucosal damage, and delayed gastric emptying. TIPS has played an important role in the treatment of PHRVB since its introduction into clinical practice in 1988.^[9] TIPS is commonly recommended for patients with bleeding that is refractory to pharmacological and endoscopic control. With the development of techniques and stents, TIPS has generally been recognized as the first-line therapy for PHRVB, with an estimated technical success rate of 93%-100%.^{[10, 11]} However, some recent studies showed higher incidences of rebleeding, reintervention for the stenosis of stents, and hepatic encephalopathy for patients with TIPS as compared with other surgical interventions.^{[10, 11]}

 

To date, the effectiveness of TIPS and OSED for the treatment of PHRVB has not been compared. Therefore, we conducted a retrospective study to determine whether TIPS is superior to OSED in the treatment of PHRVB and the prevention of rebleeding.

 

 

The data were retrospectively collected from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone OSED at the Department of Hepatobiliopancreatic Surgery and TIPS at the Department of Gastroenterology of West China Hospital between January 1, 2010 and October 31, 2014. All patients were diagnosed with liver cirrhosis by biopsy or clinical manifestation, physical examination, laboratory examination, and imaging examination. All participants were diagnosed with portal hypertension and esophagogastric varices by endoscopy, which was confirmed during TIPS or OSED. In our institution, the indications of TIPS were a history of recurrent variceal bleeding and/or refractory ascites. Partial splenic embolization was performed based on hypersplenism and severe thrombocytopenia and/or leukopenia, which was also determined by surgeons. The indications of OSED were as follows: (1) recurrent esophagogastric variceal bleeding history; (2) moderate or severe esophagogastric varices (esophagogastric varices are graded according to the standards of the Chinese Digestive Endoscopy Society in Kunming on March 1, 2000);^[12] (3) hypersplenism and severe thrombocytopenia and/or leukopenia; (4) liver function in the Child-Pugh A or B class, with general conditions and important organ functions satisfying the indications for open surgery. The exclusion criteria included combination with liver cancer, pre-existing thrombosis in the portal vein system or ascites before operation, patients undergoing TIPS or OSED in the Child-Pugh C class or without variceal bleeding, and acute bleeding with emergency TIPS or OSED (within 72 hours). The indications for blood transfusion were hemoglobin at <70 g/L during acute bleeding and hemoglobin at <60 g/L during chronic blood loss. The study was approved by the local ethics committee. Informed consent was obtained from each patient.

 

The TIPS and OSED procedures performed in our institution were in accordance with the methods described by Zhou et al^[13] and Zhe et al.^[14] A Palmaz stent (Johnson & Johnson, Warren, NJ, USA), Wallstent (Schneider, Minneapolis, MN, USA) or Wallgraft stent (Boston Scientific, Galway, Ireland) with the diameter of 8-10 mm was used during TIPS. Portal venous pressure was measured through the water column. The portal vein gradient target was about 16.2 mmHg (22 cmH₂O).

 

For postoperative management, prophylactic wide-spectrum antibiotics were administered to all patients. Lactulose (10 mL, three times per day) was regularly provided to each patient by oral administration for 3 days after successful TIPS implantation. No further use of lactulose was approved unless the patient was diagnosed with hepatic encephalopathy. Anticoagulant therapy with the injection of low-molecular-weight heparin calcium (1.0 mL, once a day) was initiated if there was no evidence of bleeding at 2 days after TIPS implantation or OSED. Aspirin was orally provided if platelet was >500×10⁹/L after TIPS and OSED. Aspirin was also used post-discharge to prevent in-stent stenosis and thrombosis of the portal vein system. Every patient accepted similar dietary recommendations to prevent hepatic encephalopathy.

 

All the included patients were followed up either until the last scheduled follow-up examination or death. Follow-up was conducted in the outpatient department in the 1st, 3rd, 6th, and 12th month after discharge and annually thereafter. During the follow-up periods, patients who developed variceal bleeding were immediately subjected to endoscopy and ultrasound or computed tomography scanning. Otherwise, these procedures were performed during each of the follow-up periods. Recurrent esophagogastric variceal bleeding was defined as any episode of endoscopically confirmed esophagogastric variceal bleeding that occurred after the first treatment. Episodes of bleeding caused by anticoagulant therapy or other portal hypertension-unrelated lesions were excluded. Hepatic encephalopathy was defined by the assessment of mental status and the measurement of serum ammonia levels, according to the final report of the 1998 Working Party at the 11th World Congresses of Gastroenterology in Vienna.^[15]

 

The data concerning patient demographics (age, gender, body mass index, comorbidities, smoking history, endoscopic treatment history, OSED history, cause of cirrhosis, Child-Pugh class, and results of endoscopy and laboratory examination) and postoperative factors (laboratory examination, length of postoperative hospital stay, hospital mortality, and short- and long-term complications) were retrieved. Postoperative laboratory examinations were conducted on each patient before hospital discharge. Short-term complications were defined as complications within 30 days after surgery, and long-term complications were defined as complications after 30 days after TIPS or OSED.

 

All results were presented as the mean±standard deviation (SD). Statistical analysis was performed by SPSS computer software (version 19.0). Statistical comparison was performed between the TIPS group and OSED group by the χ² test and Student’s t test. Student’s t test was used to compare all values before and after TIPS and OSED. A P<0.05 was considered statistically significant.

 

 

Among the 479 analyzed patients, 196 received TIPS and 283 underwent OSED. Table 1 shows a comparison of the baseline demographics of patients in both groups. No significant differences were observed between the two groups in terms of age, gender, body mass index, smoking history, endoscopic treatment history, comorbidities, etiology of liver cirrhosis, Child-Pugh class, and results of endoscopy and laboratory examination. Nine patients (4.6%) in the TIPS group had an OSED history for the treatment of portal hypertension.

 

TIPS and OSED were successfully performed in all the patients. In the TIPS group, the portal venous pressures before and after stenting were 26.2±0.8 mmHg (35.6±1.1 cmH₂O) and 16.7±1.0 mmHg (22.7±1.4 cmH₂O) (P=0.000), respectively. Partial splenic embolization was also simultaneously or subsequently performed in 33 patients (16.8%). In the OSED group, the mean operating time was 218.4±67.3 minutes and intraoperative blood loss was 285.2±206.1 mL. Intraoperative splenic blood salvage was applied in all the OSED patients. The allogenic blood transfusion rates were 25.0% (49/196) and 21.9% (62/283), respectively (P=0.430).

 

Table 2 reveals the short- and long-term complications after TIPS and OSED. For the short-term complications, both groups were comparable in terms of the incidence of ascites, portal vein thrombosis, rebleeding, and hyperpyrexia. Compared with the OSED group, the incidence of pleural effusion, splenic vein thrombosis and pulmonary infection were significantly lower in the TIPS group. However, the hepatic encephalopathy rate was significantly higher in the TIPS group than that in the OSED group (17.9% vs 3.2%, P=0.001). Pancreatic leakage and intestinal leakage developed in nine (3.2%) and five (1.8%) patients, respectively, of the OSED group. Intestinal obstruction also occurred in five (1.8%) OSED patients who required readmission. Five (2.6%) patients in the TIPS group had hemorrhage at the puncture points in the neck site. Five (2.6%) patients died of multiple organ dysfunction syndrome within 30 days after TIPS. Two (0.7%) patients died of abdominal hemorrhage within 30 days after OSED. The postoperative length of hospital stay was significantly shorter in the TIPS group than that in the OSED group (6.1±2.5 vs 9.7±4.9 days; P=0.001). However, TIPS was associated with higher hospital costs compared with OSED (63479.5±72937.9 vs 30920.1±9117.1 RMB; P=0.013). The mean follow-up times were 29.2±7.6 months in the TIPS group and 28.7±8.3 months in the OSED group. Among the long-term complications, significantly higher incidences of rebleeding (15.3% vs 4.6%) and hepatic encephalopathy (17.3% vs 3.9%) were observed in the TIPS group compared with the OSED group. The most common causes of rebleeding in the TIPS group were portal vein thrombosis and in-stent stenosis, which occurred in 44 and 37 patients, whereas portal vein thrombosis was the main cause of rebleeding in the OSED group. Twenty-nine patients with in-stent stenosis required reoperation for stent repatency. No significant differences were observed between the two groups in terms of portal vein thrombosis, splenic vein thrombosis, secondary liver cancer, and mortality. Four OSED patients with portal vein thrombosis were treated successfully with anticoagulant therapies. In the TIPS group, 17 patients died during the follow-up period. The causes of death included variceal rebleeding in eight patients, liver failure in five patients, and liver cancer in four patients. In the OSED group, 14 patients died of variceal rebleeding (n=9) and liver cancer (n=5).

 

Table 3 shows the changes in hematological parameters and liver function in patients with TIPS and OSED. In the TIPS group, significant differences were found between the pre- and postoperative white blood cell and liver function. In the OSED group, the hematological parameters, including the white blood cell, hemoglobin, and platelet levels, significantly increased after surgery and during long-term follow-up. No significant differences were noted between the pre- and last visit liver function in the two groups. Significant differences were observed between both groups during the last visit in terms of the preoperative hemoglobin, as well as the postoperative hemoglobin, ALT, AST, and albumin levels.

 

 

Portal hypertension is hemodynamically defined as a pathological increase in the portal pressure gradient;^[16] this common condition is secondary to liver cirrhosis and highly prevalent in China. Portal hypertension is the direct cause of esophagogastric variceal bleeding. Therefore, portal decompression can play a key role in the prevention and treatment of PHRVB. As shown in the current study, TIPS established large intrahepatic portosystemic anastomosis and effectively decreased the portal pressure.^{[10, 11, 17]} Although splenectomy contributed to a transient increase in the portal pressure, the intervention led to a long-term, stable reduction in the portal pressure because of a significant reduction in the splenic vein flow into the portal venous pressure.^[18] In addition, the main branches of the stomach coronary vein were divided during devascularization, which could greatly decrease the rebleeding rate.

 

In the present study, among the patients with liver function in Child-Pugh A or B class, OSED was superior over TIPS in the treatment of PHRVB and in the prevention of rebleeding, which further confirmed that OSED could effectively control bleeding.^{[8, 19]} OSED also significantly increased the white blood cell and platelet counts. However, OSED demonstrated several disadvantages over TIPS, including a higher incidence of short-term complications with pleural effusion, splenic vein thrombosis, pulmonary infection, incisional infection, and a longer postoperative length of hospital stay. Meanwhile, TIPS had some disadvantages, which included high hospital cost and high incidence of hepatic encephalopathy and stent occlusion.

 

The incidence of hepatic encephalopathy after TIPS and OSED reported in the literatures varies from 30% to 55% and 0% to 1.4%, respectively.^{[6, 14, 20, 21]} Most incidences occurred in the early postoperative stage and were transient in nature. In our study, the hepatic encephalopathy rates were similar between the early and late postoperative stages. The incidences of hepatic encephalopathy after TIPS and OSED were 17.3% and 3.9%, respectively, during the long-term follow-up periods. Relatively lower rates of hepatic encephalopathy were observed in the TIPS group compared with that in other studies; this trend may be attributed to the hemodynamic stability and compensated liver function in these patients.^[22] Another probable reason was the smaller diameter of the shunt. The risk factors of hepatic encephalopathy reported in the literature mainly include increased age, pre-existing hepatic encephalopathy, and high Child-Pugh scores.^[23] Therefore, the management of these risk factors may decrease the incidence of hepatic encephalopathy after TIPS and OSED.

 

Stent occlusion is another common complication after TIPS. The rate of stent occlusion was reported to range from 30% to 70% with the use of bare stents in TIPS, whereas the postoperative patency rate reached 100% with the use of covered stents.^[24-26] Compared with bare stents, the covered stents did not increase the hepatic encephalopathy rate. The current study showed that 12 cases with covered stents had postoperative stent occlusion. However, all cases did not follow the instruction to take aspirin for anticoagulation after hospital discharge. One previous study^[27] revealed that trapidil and ticlopidine with initial heparin could reduce intimal proliferation. Early in-stent stenosis is mainly caused by thrombosis, which can be avoided by anticoagulation.^[28]

 

Thrombosis in the portal vein is a major complication after TIPS and OSED. Stent occlusion and splenectomy, which lead to decreased blood flow in the portal vein system, are important risk factors of portal vein thrombosis. In the current study, a lower incidence of acute thrombosis in the portal vein was observed in the TIPS group than that in the OSED group (6.6% vs 10.2%) within 30 days after operation, but the long-term incidence of portal vein thrombosis was higher in the TIPS group than that in the OSED group (22.4% vs 15.9%). Few studies have reported the incidence of portal vein thrombosis after TIPS. The incidence rate may be underestimated because some patients with portal vein thrombosis may not have symptoms. The reported incidence of portal vein thrombosis after OSED varied from 28% to 52%.^{[29, 30]} In our study, standard anticoagulation therapy may contribute to the lower incidence of portal vein thrombosis after OSED. Stent occlusion and portal vein thrombosis are the main causes of readmission and rebleeding; thus, regular Doppler ultrasound monitoring is required for the timely identification of stent occlusion and portal vein thrombosis, which can greatly decrease the readmission and rebleeding rates, as well as subsequent cost.

 

The most common cause of death among cirrhosis patients is recurrent bleeding. For the TIPS procedure, in-stent stenosis and portal vein thrombosis are two important causes of postoperative recurrent bleeding. For the OSED procedure, rebleeding always occurs because of the portal hyperdynamic state and non-inclusion of high esophageal branches of the stomach coronary vein. Variceal rebleeding was significantly more frequent, and the mortality rate was higher in patients who received TIPS as compared with OSED. Higher platelet counts may have also contributed to the lower rebleeding rate in the OSED group. The rebleeding rate in the TIPS patients in the present study (short-term, 6.1%; long-term, 15.3%) was similar to the rates in other comparable studies.^{[31, 32]} A study^[33] showed that the five- and ten-year recurrent bleeding rates of patients who received OSED were 6.2% and 13.3%, respectively, which were lower than those of patients who underwent TIPS.

 

In conclusion, for the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED for the treatment of PHRVB and the prevention of rebleeding.

 

 

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