To investigate the interventional treatment method of hepatic venous obstruction type Buga syndrome (BCS). Methods Retrospective analysis of clinical data of 69 patients with hepatic venous obstruction type BCS who underwent interventional treatment at Anhui Provincial Hospital from December 2010 to December 2012 was performed to observe the changes in opening hepatic vein pressure and patients’ clinical symptoms and to assess the asymptomatic survival rate after treatment. Telephone and outpatient follow-ups were used, and the follow-up period was up to July 2013.
Results: 66 patients were successfully treated with interventional therapy, of which 41 patients underwent balloon dilation alone, 6 patients underwent balloon dilation + stent placement, 14 patients underwent balloon dilation + thrombolytic therapy, and 5 patients underwent balloon dilation + thrombolytic therapy + stent placement. The difference was statistically significant (t=9.73, P<0.05). Among the successfully treated patients, 61 had complete postoperative symptom relief and the other 5 had partial symptom relief.
All 66 cases were followed up for 6-24 months, with a median follow-up time of 15 months. During the follow-up period, a total of 10 patients developed BCS-related symptoms again due to the treatment of vascular obstruction, 7 cases were successfully treated with revision therapy, and the remaining 3 cases failed. The asymptomatic survival rates were 76.4% and 92.3% after the first intervention and revision treatment, respectively. Conclusion Interventional treatment of hepatic venous obstruction BCS has a high technical success rate, a low recurrence rate, and a high short- to medium-term asymptomatic survival rate.
Budd-Chiari syndrome (BCS) is a clinical syndrome of portal and/or inferior vena cava hypertension caused by obstruction of the hepatic veins and/or the inferior vena cava above its opening. Depending on the site of obstruction, BCS can be divided into BCS with hepatic vein obstruction, BCS with inferior vena cava obstruction, and BCS with a combination of inferior vena cava and hepatic vein involvement.
At present, interventional treatment for inferior vena cava obstruction has become more mature, but there are still some controversies about the interventional treatment and its efficacy for patients with hepatic venous obstruction BCS. In this study, we retrospectively analyzed the clinical data of 69 patients with hepatic venous obstruction BCS from December 2010 to December 2012, and discussed the interventional treatment methods for hepatic venous obstruction BCS.
1. Data and methods
1.1 General information
In this group, 69 patients with BCS, 38 males and 31 females, aged (38±8) years (17-64), had BCS-related symptoms for (77±72) months; the common symptoms and signs were mainly symptoms of portal hypertension such as abdominal distension, poor appetite, abdominal pain, ascites, hepatomegaly, splenomegaly and liver injury. All patients in this group were diagnosed with BCS by magnetic resonance imaging (Figure 1) and Doppler ultrasound and met the following inclusion criteria.
1.2 Inclusion criteria
Patients with BCS whose hepatic vein obstruction and inferior vena cava flow were confirmed by angiography were included in this study. Patients who had been treated for BCS before admission and patients with secondary BCS due to various etiologies such as tumor were also excluded.
1.3 Interventional treatment
1.3.1 Opening the hepatic vein via the jugular and femoral vein routes: Inferior vena cava angiography was first performed via the jugular and/or femoral vein routes, and the opening of the hepatic vein was explored according to the results of preoperative imaging and inferior vena cava angiography.
For patients with hepatic vein lumen stenosis, a 5F Cobra catheter and an ultra-slip guidewire are used to explore the stenotic hepatic vein openings; for patients with hepatic vein occlusion, a single-curved catheter and a homemade single-curved steel needle are used to directly puncture the main trunk, branches, and traffic branches of the hepatic vein. After successful exploration, embedded imaging and manometry tubes were performed to measure the intrahepatic venous pressure and assess the obstruction of the main hepatic vein and its branches. After the assessment is completed, balloon dilation and stent placement are then performed for treatment.
1.3.2 Open the hepatic vein by the percutaneous transhepatic combined with inferior vena cava route: use ultrasound-guided percutaneous puncture of the hepatic vein, after successful puncture, introduce the guidewire, pass the obstructed segment of the hepatic vein, lead the guidewire out of the internal jugular vein or femoral vein route, and then perform retrograde opening treatment by the inferior vena cava route;.
1.3.3 For combined hepatic vein thrombosis, a 5F thrombolytic catheter is placed in the hepatic vein via the jugular vein route for local thrombolytic therapy. Urokinase (100,000 U/dose, 4-6 times a day) was injected through the catheter for thrombolytic therapy; at the same time, low molecular heparin sodium (5000 U/dose, 2 times a day) was injected subcutaneously for anticoagulation therapy. The catheter position was adjusted according to the dissolution of the thrombus, so that the lateral orifice segment of the catheter was located within the thrombus. When the thrombus is completely dissolved and there is no change in the thrombus on the second consecutive review, the hepatic vein is opened via intervention.
1.3.4 Transjugular intrahepatic portosystemic shunt (TIPS) treatment: the hepatic vein, inferior vena cava and indirect portal vein are firstly imaged during the procedure, and if the main hepatic vein cannot be imaged, the hepatic vein can be imaged through the collateral hepatic vein or ultrasound-guided percutaneous hepatic penetration. According to the imaging results, the puncture point of hepatic vein or inferior vena cava and the needle entry point of portal vein puncture are selected.
1.4 Diagnostic and efficacy judgment criteria [S1]
Amount of ascites: MRI and/or ultrasonography showed limited ascites such as subdiaphragm, liver and kidney, spleen and kidney or cysto-rectal space as small amount of ascites; ascites seen diffusely distributed in the middle and lower abdomen and lateral abdomen, between intestinal tubes and around parenchymal organs as moderate amount of ascites; all of the whole abdominal cavity showed ascites filled with intestinal tubes floating or fixed among them as large amount of ascites. [S2] Angioplasty success criteria: after interventional opening treatment, blood flow is smooth and transmural pressure difference ≤ 100pxH2O is successful for opening treatment.
1.5 Follow up
Telephone and outpatient follow-ups were used, with regular follow-ups in the 1st to 4th week after treatment, in the 2nd and 3rd month, and every 3 months after 3 months, and the follow-up cut-off time was July 2013, or when the patients died and were lost to follow-up.
1.5 Statistical analysis
SPSS 16.0 statistical software was applied for analysis, using qualitative data expressed as number (percentage) and quantitative data expressed as mean ± standard deviation. The comparison of venous pressure difference before and after treatment was performed by paired sample t-test. The comparison of abdominal water volume before and after treatment (rank data) was performed using the Wilcoxon W rank sum test. The Kaplan-Meier method was used to calculate the survival rate of patients and the difference in survival rate between groups. p<0.05< span=""> was considered a statistically significant difference, and all statistical analyses were performed using SPSS 16.0 statistical software.
2, Results
2.1 Treatment situation
The first opening treatment was successful in 63 patients; the other 6 patients with BCS with hepatic vein obstruction failed the first opening treatment due to extensive occlusion of the hepatic vein, 2 of them had more severe symptoms and underwent TIPS treatment, 1 patient was successfully treated and the symptoms were relieved after surgery, the other 1 died of liver failure after surgery, the remaining 4 patients with BCS with mild symptoms were treated conservatively with internal medicine, and 3 patients had the second opening treatment after half a year The cumulative technical success rate of opening treatment was 95.7% (66/69). None of the patients had serious complications such as pericardial tamponade and vascular rupture.
The opening routes of the 66 successful patients were: 43 cases via jugular vein, 14 cases via femoral vein, and 9 cases via percutaneous transhepatic puncture. The opening treatment vessels were: one main hepatic vein in 35 cases, two or more main hepatic veins in 13 cases, parietal hepatic vein in 7 cases, and main hepatic vein + parietal hepatic vein in 11 cases. The treatment methods were: balloon dilation alone in 41 cases, balloon dilation + stent placement in 6 cases, balloon dilation + thrombolysis in 14 cases, balloon dilation + thrombolysis + stent placement in 5 cases.
2.2 Interventional efficacy
The hepatic vein pressure before and after opening treatment in BCS patients was (47±9) cm H2O and (23±7) cm H2O, respectively, and the difference was statistically significant (t=9.73, P<0.05< span="">). After successful interventional opening treatment in this group of patients, 61 cases had complete remission of symptoms and 5 cases had partial remission of symptoms. At the time of admission, 3 patients had a small amount of ascites, 20 had a moderate amount of ascites, and 43 had a large amount of ascites. At the time of discharge, all patients were free of ascites except 13 patients with a small amount of ascites, and the difference between the amount of ascites at admission and discharge was statistically significant (Z=10.38, P<0.05< span="">).
All patients were given oral warfarin (initial dose 5 mg) anticoagulation therapy for 12 months after intervention, and coagulation function was reviewed regularly, and warfarin dosage was adjusted according to the test results. The prothrombin time was maintained at 20-25s.
2.3 Follow-up
All 66 patients were followed up for (6-24) months, with a median follow-up time of 15 months. The asymptomatic survival rates at 6, 12 and 24 months after the first intervention were: 97.0%, 92.2% and 76.4%, respectively; the asymptomatic survival rates at 6, 12 and 24 months after the modified intervention were: 98.4%, 98.4% and 92.3%, respectively. The difference in asymptomatic survival rate after the first intervention for BCS patients with different interventional methods was not statistically significant, χ2=3.082, P>0.05. See Figure 6, Table 1. 10 patients had symptoms related to BCS due to treatment of vascular obstruction again during the follow-up period, and all of them underwent interventional opening treatment again, of which 7 cases had successful revision treatment and 3 cases had treatment failure (one of them died of liver function (one of them died of liver failure).
3. Discussion
The clinical characteristics and etiology of BCS patients in China and western countries are very different, and the etiology of BCS in western countries is mostly various thrombosis-related diseases, while BCS in China is mostly caused by intimal occlusion of hepatic veins and/or inferior vena cava, which is not highly correlated with thrombosis-related diseases [2,5,7]. Both the lesion characteristics of BCS patients and their treatment methods also vary greatly from region to region due to differences in the etiology of BCS in different regions.
In Western countries, TIPS or even liver transplantation is often used for BCS patients, whereas in China, most BCS patients are treated with angioplasty to recanalize the obstructed vessels. In the past, it was thought that most BCS patients in China were due to inferior vena cava obstruction, but with advances in imaging equipment and techniques, recent studies have shown that only a very small number of BCS patients in China have simple inferior vena cava involvement, while the vast majority of BCS patients have hepatic vein involvement or both inferior vena cava and hepatic vein involvement. Therefore, how to treat hepatic vein obstruction in BCS patients has become a new clinical challenge.
3.1 Selection of the opening route
The most reasonable treatment for hepatic venous obstruction in BCS is to open the obstructed hepatic vein, because this can rebuild the physiological channel of hepatic venous return and fundamentally restore the structure and function of the liver. Currently, the most commonly used interventional methods for opening hepatic vein obstruction include transjugular or femoral vein approach and percutaneous transhepatic puncture combined with inferior vena cava approach.
The majority of patients with hepatic venous obstruction in BCS have stenosis of the hepatic vein opening or membrane occlusion of the hepatic vein resulting in proximal obstruction of the hepatic vein [11], and interventional opening of the obstruction via the jugular or femoral vein route is preferred. The use of transjugular venous access to the hepatic vein is relatively simple, has a relatively high success rate, and avoids the risk of percutaneous transhepatic puncture leading to abdominal hemorrhage.
For patients who fail to open the hepatic vein through the jugular vein, the femoral vein route can be used, but it is relatively difficult to open the hepatic vein through the femoral vein route because of the long distance, but for some of the collateral hepatic veins intersecting the inferior vena cava at an obtuse angle, the femoral vein route is more suitable for opening treatment. For patients with failed BCS via jugular and femoral vein routes, percutaneous transhepatic puncture combined with inferior vena cava route can be used to open the hepatic vein if the amount of ascites is small.
For patients with moderate or large amount of combined ascites, conservative medical treatment such as diuresis should be given first, and then the hepatic vein should be opened by percutaneous transhepatic route combined with intervention when the amount of ascites is low.
3.2 Selection of hepatic vein opening
When patients with hepatic vein obstruction BCS are treated with interventional opening, the first consideration should be to open the obstructed main hepatic vein. The right hepatic vein, which drains a large area of the liver and has a small angle with the inferior vena cava, is more suitable for opening treatment. If all three main hepatic veins of BCS patients are occluded lesions, opening treatment of the right hepatic vein can be attempted first.
If the diameter and drainage range of the opened hepatic vein are large enough, opening one hepatic vein can effectively treat the symptoms of portal hypertension in BCS patients, but if the opening difficulty is low or the diameter of the opened hepatic vein is small, the simultaneous opening of multiple main hepatic veins can be considered. If the obstructed segment of the main hepatic vein is long and the opening treatment fails, we can try to open the secondary hepatic vein to relieve the symptoms related to portal hypertension.
3.3 Selection of interventional treatment methods
After successful exploration of the obstructed hepatic vein, treatment should be selected according to the characteristics of the treated vascular lesion. For non-thrombotic obstructive lesions, balloon dilatation should be performed first, and the diameter of the balloon should be selected according to the diameter of the treated vessels, generally in the range of 12mm-20mm. If the thrombus is formed in the hepatic vein, thrombolytic therapy should be performed first, and then balloon dilation and stenting should be performed.
It is relatively difficult to open the hepatic vein with extensive obstruction, and the failure rate of opening treatment is high. For patients whose clinical symptoms are mild, they can be treated with conservative internal medicine first and then undergo 2-stage opening treatment after the formation of compensated intrahepatic side branches. transplantation.
3.4 Criteria for successful hepatic vein opening treatment
The success of angioplasty is usually evaluated according to the results of angiography, and it is generally considered that the opening treatment is successful when the vascular diameter of the lesion is restored to more than 70% of the normal vascular diameter at the time of angiographic review.
However, the lumen morphology of angiography is subjective and difficult to grasp as a criterion for successful treatment; compared with this, the transmural pressure difference is a more realistic response to the local hydrodynamic situation of the lumen after balloon dilatation of the vascular lesion, and is less affected by the functional state of the heart and the instantaneous pressure fluctuations after the opening of the vessel, while the transmural pressure difference is a quantitative index that can be measured intraoperatively with a manometry device and is easy to control.
In theory, if the stenosis disappears completely after dilatation, the value of transmural pressure difference should be very small. In our clinical work, we found that the transmural pressure difference ≤100pxH2O after angiogenesis treatment of obstructed hepatic veins, and the patient’s symptoms and signs can disappear completely after surgery. Therefore, it is more reliable to use the transmural pressure difference as the treatment success standard of angioplasty, but the specific value can be further studied and corrected in the future.
3.5 Efficacy of interventional treatment for hepatic vein type BCS
Ten patients (15.2%) in this group had recurrence of the treated vessel obstruction during the follow-up period using the above treatment strategy. All patients with recurrence were treated again with revision angioplasty, and 70% (7) of them were successfully treated. The 2-year asymptomatic survival rate for this group of patients at the end of follow-up was 92.3%. The difference in asymptomatic survival rates after intervention for BCS patients in this study was not statistically significant for each treatment, which may be related to the small sample size of patients with some treatments.
Also, this study was a selection of interventional treatments based on lesion characteristics of BCS patients rather than a case-randomized controlled study, and there was a large selection bias, so even if the postoperative asymptomatic survival rate of BCS patients with one interventional approach was higher than that of patients with other treatments, it did not indicate that the approach was superior to other treatments. Reocclusion of the treated vessel is one of the complications of interventional BCS and the underlying cause of recurrence of BCS-related symptoms.
Although some scholars believe that endovenous stenting may reduce the incidence of hepatic vein reocclusion, endovenous stenting is a permanent placement that increases the difficulty of corrective postoperative management once restenosis occurs, so patients with BCS should be treated with caution for hepatic vein stenting.
Some scholars believe that the use of overlapping stents for TIPS treatment can reduce the occurrence of in-stent restenosis due to regeneration of hepatocytes at the lesion, but restenosis after hepatic vein stenting is mostly due to fiber proliferation at the distal end of the stent, so it is not significant to use overlapping stents and maintain hepatic vein patency, and it affects the formation of compensatory side branches of the hepatic vein in patients with overlapping stents, so stenting in the hepatic vein is not recommended. Therefore, it is not advisable to use the overlapping stent when stenting the hepatic vein.
In conclusion, interventional treatment of hepatic venous obstruction BCS has a high technical success rate, a low recurrence rate, and a high short- and medium-term asymptomatic survival rate, but the long-term efficacy needs to be further investigated in follow-up studies.