Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is a serious complication of hepatic vena cava Budd-Chiari syndrome(HVC-BCS)that significantly reduces the survival time of patients.Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system.Methods:The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed.Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups.Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical,tumor,and etiological characteristics on the total survival time of patients,and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model.The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index.Results:Multivariate analysis showed that serum albumin level<34 g/L[hazard ratio(HR)=4.207,95%confidence interval(CI):1.816-8.932,P=0.001],maximum tumor diameter>7 cm(HR=8.623,95%CI:3.771-19.715,P<0.001),and inferior vena cava stenosis(HR=3.612,95%CI:1.646-7.928,P=0.001)were independent predictors of survival.A prognostic scoring system was developed according to the above-mentioned independent predictors,and patients were classified into grades A,B,C and D.Significant differences in survival were found among the four groups.Conclusions:This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC,which is helpful for clinical evaluation of patient prognosis.

A Budd-Chiari Syndrome Due to C Protein Deficiency: A Case Report at YaoundéGeneral Hospital (Cameroon)

Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.

Genetic investigation of the ubiquitin-protein ligase E3A gene as putative target in Angelman syndrome

BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.

Budd-Chiari syndrome in myeloproliferative neoplasms:A review of literature

Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPNs,i.e.,polycythemia vera,essential thrombocythemia and primary myelofibrosis,exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites,e.g.,portal,splanchnic or hepatic veins,the placenta or cerebral sinuses.The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury,stasis,elevated leukocyte adhesion,integrins,neutrophil extracellular traps,somatic mutations(e.g.,the V617F point mutation in the JAK2 gene),microparticles,circulating endothelial cells,and other factors,to name a few.Herein,we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs,with a particular focus on its epidemiology,pathogenesis,histopathology,risk factors,classification,clinical presentation,diagnosis,and management.

Fracture of inferior vena cava stent after endovascular treatment for Budd-Chiari syndrome:A case series and literature review

Budd-Chiari syndrome(BCS)is a rare condition characterized by hepatic venous outflow obstruction.Balloon angioplasty,with or without stenting,is the recommended first-line treatment modality in Asian countries.As a supplement to balloon angioplasty,expandable metallic Z-stent deployment can effectively improve long-term inferior vena cava(IVC)patency.Although stent placement is a standard and frequently performed treatment,very few IVC stent-related complications,such as stent fractures,have been reported.Here we present a case series and a comprehensive review of IVC stent fractures in patients with BCS.The most common characteristic of IVC stent fractures is a protrusion of the proximal segment of the IVC stent into the right atrium and its systolic and diastolic movements along with heart rhythms.Accurate stent deployment,large-diameter balloon dilation,patient breath-holding training,preferential selection of a triple stent,and the use of an internal jugular vein approach to stent deployment may ensure precise stent localization and avoid postoperative complications.

Budd-Chiari syndrome in children:Challenges and outcome

Budd-Chiari syndrome(BCS)is an uncommon disease of the liver,characterised by obstruction of the hepatic venous outflow tract.The etiological spectrum of BCS as well as venous obstruction pattern show wide geographical and demographic variations across the globe.Compared to adults with BCS,children have primary BCS as the predominant etiology,earlier clinical presentation,and hence better treatment outcome.Underlying prothrombotic conditions play a key role in the etiopathogenesis of BCS,though work-up for the same is often unyielding in children.Use of next-generation sequencing in addition to conventional tests for thrombophilia leads to better diagnostic yield.In recent years,advances in radiological endovascular intervention techniques have revolutionized the treatment and outcome of BCS.Various non-invasive markers of fibrosis like liver and splenic stiffness measurement are being increasingly used to assess treatment response.Elastography techniques provide a novel non-invasive tool for measuring liver and splenic stiffness.This article reviews the diagnostic and therapeutic advances and challenges in children with BCS.

Budd-Chiari syndrome:Etiology,pathogenesis and diagnosis

Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.

Transjugular intrahepatic portosystemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome

AIM:To evaluate the feasibility of transjugular intrahepatic portosystemic shunt(TIPS)for severe jaundice secondary to acute Budd-Chiari syndrome(BCS).METHODS:From February 2009 to March 2013,37patients with severe jaundice secondary to acute BCS were treated.Sixteen patients without hepatic venule,hepatic veins(HV)obstruction underwent percutaneous angioplasty of the inferior vena cava(IVC)and/or HVs.Twenty-one patients with HV occlusion underwent TIPS.Serum bilirubin,liver function,demographic data and operative data of the two groups of patients were analyzed.RESULTS:Twenty-one patients underwent TIPS and the technical success rate was 100%,with no technical complications.Sixteen patients underwent recanalization of the IVC and/or HVs and the technical success rate was 100%.The mean procedure time for TIPS was 84.0±12.11 min and angioplasty was44.11±5.12 min(P<0.01).The mean portosystemic pressure in the TIPS group decreased significantly from 40.50±4.32 to 16.05±3.50 mm Hg(P<0.01).The mean portosystemic pressure gradient decreased significantly from 33.60±2.62 to 7.30±2.21 mm Hg(P<0.01).At 8 wk after the procedures,in the TIPS group,total bilirubin(TBIL)decreased significantly from 266.24±122.03 before surgery to 40.11±3.52μmol/L(P<0.01)and direct bilirubin(DBIL)decreased significantly from 194.22±69.82μmol/L to 29.82±3.10μmol/L(P<0.01).In the angioplasty group,bilirubin returned to the normal range,with TBIL decreased significantly from 258.22±72.71μmol/L to 13.33±3.54μmol/L(P<0.01)and DBIL from175.08±39.27 to 4.03±1.74μmol/L(P<0.01).Liver function improved faster than TBIL.After 2 wk,in the TIPS group,alanine aminotransferase(ALT)decreased significantly from 50.33±40.61 U/L to 28.67±7.02U/L(P<0.01)and aspartate aminotransferase(AST)from 49.46±34.33 U/L to 26.89±8.68 U/L(P<0.01).In the angioplasty group,ALT decreased significantly from 51.56±27.90 to 14.22±2.59μmol/L(P<0.01)and AST from 60.66±39.89μmol/L to 8.18±1.89μmol/L(P<0.01).After mean follow-up of 12.6 mo,there was no recurrence of jaundice in either group.CONCLUSION:Severe jaundice is not a contraindication for TIPS in patients with acute BCS and TIPS is appropriate for severe jaundice due to BCS.

Surgical treatment of Budd-Chiari syndrome:analysis of 221 cases

BACKGROUND:Budd-Chiari syndrome (B-CS) refers to post-hepatic portal hypertension and/or inferior vena cava hypertension caused by obstruction of blood flow at the portal cardinal hepatic vein.The treatments of B-CS include operations on pathological membrane lesions,shunting and combined operations.Studies have shown that China,Japan,India and South Africa have a high incidence of B-CS.In China,the Yellow River Basin in Henan,Shandong,Jiangsu and Anhui Provinces also have a high incidence,around 10 per 100 000.METHODS:The clinical data of 221 B-CS patients were analyzed retrospectively.We focused on pathological types,surgical methods,effectiveness and complications of treatment,and follow-up.RESULTS:Based on imaging findings such as color ultrasonography,angiography or magnetic resonance angiography,the 221 patients were divided into 3 types (five subtypes):type Ia (72 patients),type Ib (20),type II (72),type IIIa (33),and type IIIb (24).Surgical procedures included balloon membranotomy with or without stent (65 patients),improved splenopneumopexy (18),radical resection of membrane and thrombus (17),inferior vena cava bypass [29,with cavocaval transflow (13) and cavoatrial transflow (16)],mesocaval shunt (41),splenocaval shunt (25),splenoatrial shunt (12),splenojugular shunt (6),and combined methods (8).The complication rate was 9.05% (20/221) and the perioperative death rate was 2.26% (5/221).All of the patients were followed up from 6 months to 5 years.The success rate was 84.6% (187/221),and the recurrence rate was 8.9% (9/101) and 13.5% (13/96) after 1-and 5-year follow-up,respectively.CONCLUSION:The rational choice of surgical treatment based on B-CS pathological typing may increase the success rate and decrease the recurrence.

Hepatocellular carcinoma in Budd-Chiari syndrome:A single center experience with long-term follow-up in South Korea

AIM:To evaluate long-term clinical course of BuddChiari syndrome(BCS) and predictive factors associated with the development of hepatocellular carcinoma(HCC) and survival.METHODS:We analyzed 67 patients with BCS between June 1988 and May 2008.The diagnosis of BCS was confirmed by hepatic venous outflow obstruction shown on abdominal ultrasound sonography,computed tomography,magnetic resonance imaging,or venography.The median follow-up period was 103 ± 156 [interquartile range(IQR)] mo.RESULTS:The median age of the patients was 47 ± 16(IQR) years.At diagnosis,54 patients had cirrhosis,25(37.3%) Child-Pugh class A,23(34.3%) Child-Pugh class B,and six(9.0%) patients Child-Pugh class C.During the follow-up period,HCC was developed in 17 patients,and the annual incidence of HCC in patients with BCS was 2.8%.Patients in HCC group(n = 17) had higher hepatic venous pressure gradient(HVPG) than those in non-HCC group(n = 50)(21 ± 12 mmHg vs 14 ± 7 mmHg,P = 0.019).The survival rate of BCS patients was 86.2% for 5 years,73.8% for 10 years,and 61.2% for 15 years.In patients with BCS and HCC,survival was 79% for 5 years,43.1% for 10 years,and 21.5% for 15 years.CONCLUSION:The incidence of HCC in patients with BCS was similar to that in patients with other etiologic cirrhosis in South Korea.The HVPG is expected to provide additional information for predicting HCC development in BCS patients.

Budd-Chiari syndrome in China: A 30-year retrospective study on survival from a single center

AIM To investigate 30-year treatment outcomes associated with Budd-Chiari syndrome(BCS) at a tertiary hospital in China.METHODS A total of 256 patients diagnosed with primary BCS at our tertiary hospital between November 1983 and September 2013 were followed and retrospectively studied. Cumulative survival rates and cumulative mortality rates of major causes were calculated by Kaplan-Meier analysis, and the independent predictors of survival were identified using a Cox regression model. RESULTS Thirty-four patients were untreated; however, 222 patients were treated by medicine, surgery, or interventional radiology. Forty-four patients were lost to follow-up; however, 212 patients were followed, 67 of whom died. The symptom remission rates of treated and untreated patients were 81.1%(107/132) and 46.2%(6/13), respectively(P = 0.009). The cumulative 1-, 5-, 10-, 20-, and 30-year survival rates of the treated patients were 93.5%, 81.6%, 75.2%, 64.7%, and 58.2%, respectively; however, the 1-, 5-, 10-, 20-, and 30-year survival rates of the untreated patients were 70.8%, 70.8%, 53.1%, 0%, and unavailable, respectively(P = 0.007). Independent predictors of survival for treated patients were gastroesophageal variceal bleeding(HR = 3.043, 95%CI: 1.363-6.791, P = 0.007) and restenosis(HR = 4.610, 95%CI: 1.916-11.091, P = 0.001). The cumulative 1-, 5-, 10-, 20-, and 30-year mortality rates for hepatocellular carcinoma were 0%, 2.6%, 3.5%, 8%, and 17.4%, respectively.CONCLUSION Long-term survival is satisfactory for treated Chinese patients with BCS. Hepatocellular carcinoma is a chronic complication and should be monitored with long-term follow-up.

Etiology and portal vein thrombosis in Budd-Chiari syndrome

AIM: To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome (BCS) patients prospectively. METHODS: A total of 75 patients (40 female, 35 male) who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively. Findings from on physical examination, ultrasonography, duplex ultrasonography and venography were analyzed. Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance, and anticardiolipin antibodies, antinuclear antibodies, and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit. RESULTS: At least one etiological factor was determined in 54 (72%) of the patients. The etiology could not be defined in 21 (28%) patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient. The most common cause was the web (16%), the second was Hydatid disease (11%), the third was Behcet’s disease (9%). Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them (82%). CONCLUSION: Behcet’s disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal veinthrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.

Selection of treatment modalities for Budd-Chiari Syndrome in China:A preliminary survey of published literature

AIM: To evaluate the frequency of use of various treatment modalities for Budd-Chiari syndrome (BCS) in China by conducting a preliminary survey of relevant literature.

Necessity and indications of invasive treatment for Budd-Chiari syndrome

BACKGROUND:The development of collaterals in Budd-Chiari syndrome has been described and these collaterals play an important role in the presentation of this disease.These collaterals are diagnostic and their use in management strategy has never been evaluated.This study aimed to investigate the indications,feasibility and necessity of invasive treatment for patients with Budd-Chiari syndrome and to determine whether such a strategy is necessary for optimal management.METHODS:Twenty-nine patients who had been treated at our unit were enrolled in this study.Based on physical and biochemical examination,and hemodynamic compensation by collaterals,18 patients underwent radiological intervention (group A),while the other 11 had no invasive treatment (group B).The related hemodynamic parameters were acquired when percutaneous angiography was performed.RESULTS:In group A,all patients underwent successfully inferior vena cava (IVC) balloon angioplasty with or without stenting.Four patients also underwent hepatic vein angioplasty.In these patients,the mean IVC pressure before and after treatment was statistically different (29.3±9.2 vs 15.1±4.6 mmHg,P<0.01).The mean IVC pressure was much lower in group B than in group A (12.9±2.4 vs 29.3±9.2 mmHg,P<0.01),but there was no difference from that of the patients after radiological treatment (12.9±2.4 vs 15.1±4.6 mmHg,P>0.05).Median follow-up was 32.3 months (mean 21.3 months;range 3-61 months).In the course of follow-up,the patients in group A survived with good systemic status except for re-stenosis in one patient who underwent re-canalization of the IVC.In group B,10 patients had good systemic status except one patient who had a meso-caval shunt because of deterioration.CONCLUSIONS:The rationale of 'early diagnosis and early treatment' is not suitable for all patients with Budd-Chiari syndrome.Satisfactory survival can be achieved in some patients without invasive treatment,who are completely compensated by rich collaterals.Nonetheless,a positive treatment procedure should be performed if the patient's situation worsens in the course of regular follow-up.

A caval homograft for Budd-Chiari syndrome due to inferior vena cava obstruction

Transjugular intrahepatic portosystemic shunt (TIPS) is the standard treatment of Budd-Chiari syndrome (BCS) non responsive to medical therapy. However, patients with inferior vena cava (IVC) obstruction proximal to the atrium do not benefit from TIPS and a surgical approach is mandatory. We report the case of BCS due to intrapericardial IVC obstruction. We describe a novel surgical approach using a fresh caval homograft. An attempt to balloon dilatation of the IVC obstruction was complicated by right atrial disruption with tamponade and ventricular fibrillation. Lately, the patient successfully underwent a reconstruction of the cavo-atrial continuity by the interposition of a fresh caval homograft, a novel surgical approach never described before for BCS. Further follow-up revealed progressive reduction and resolution of ascites, and overall clinical improvement. IVC obstruction near to the atrium can be surgically approached with a new technique consisting in inferior vena cava resection and replacement with a caval homograft.

Changing spectrum of Budd-Chiari syndrome in India with special reference to non-surgical treatment

AIM： To evaluate patterns of obstruction, etiological spectrum and non-surgical treatment in patients with Budd-Chiari syndrome in India. METHODS： Forty-nine consecutive cases of Budd- Chiari syndrome （BCS） were prospectively evaluated. All patients with refractory ascites or deteriorating liver function were, depending on morphology of inferior vena cava （IVC） and/or hepatic vein （HV） obstruction, triaged for radiological intervention, in addition to anticoagulation therapy. Asymptomatic patients, patients with diuretic-responsive ascites and stable liver function, and patients unwilling for surgical intervention were treated symptomatically with anticoagulation. RESULTS： Mean duration of symptoms was 41.5 ± 11.2 （range = 1-240） too. HV thrombosis （HVT） was present in 29 （59.1%）, IVC thrombosis in eight （16.3%）, membranous obstruction of IVC in two （4%） and both IVC-HV thrombosis in 10 （20.4%） cases. Of 35 cases tested for hypercoagulability, 27 （77.1%） were positive for one or more hypercoagulable states. Radiological intervention was technically successful in 37/38 （97.3%）： IVC stenting in seven （18.9%）, IVC balloon angioplasty in two （5.4%）, combined IVC-HV stenting in two （5.4%）, HV stenting in 11 （29.7%）, transjugular intrahepatic portosystemic shunt （TIPS） in 13 （35.1%） and combined TIPS-IVC stenting in two （5.4%）. Complications encountered in follow-up： death in five, re-stenosis of the stent in five （17.1%）, hepatic encephalopathy in two and hepatocellular carcinoma in one patient. Of nine patients treated medically, two showed complete resolution of HVT. CONCLUSION： IN our series, HVT was the predominant cause of BCS. In the last five years with the availability of sophisticated tests for hypercoagulability, etiologies were defined in 85.7% of cases. Non-surgical management was successful in most cases.

Transjugular intrahepatic portosystemic shunt for Budd-Chiari syndrome:A comprehensive review

Budd-Chiari syndrome(BCS)is a relatively rare clinical condition with a wide range of symptomatology,caused by the obstruction of the hepatic venous outflow.If left untreated,it has got an high mortality rate.Its management is based on a step-wise approach,depending on the clinical presentation,and includes different treatment from anticoagulation therapy up to Interventional Radiology techniques,such as transjugular intrahepatic portosystemic shunt(TIPS).TIPS is today considered a safe and highly effective treatment and should be recommended for BCS patients,including those awaiting orthotopic liver transplantation.In this review the pathophysiology,diagnosis and treatment options of BCS are presented,with a special focus on published data regarding the techniques and outcomes of TIPS for the treatment of BCS.Moreover,unresolved issues and future research will be discussed.

Budd-Chiari syndrome management:Lights and shadows

Budd-Chiari syndrome (BCS) is a rare disease whose management should follow a step by step strategy.Anticoagulation and medical therapy should be the first line treatment.Revascularization or TIPS are indicated in case of no response to medical therapy.OLT should be indicated as a rescue therapy and anticoagulation be started soon after OLT.However,no clear indica-tion can actually be given about the timing of different treatments.Moreover,there is some concern about treatment of some subgroup of patients,especially regarding the risk of recurrence after liver transplanta-tion.The topic of this paper is to critically review the actual knowledge of BCS management.

Imaging and interventions in Budd-Chiari syndrome

Budd-Chiari syndrome(BCS) consists of a group of disorders with obstruction of hepatic venous outflow leading to increased hepatic sinusoidal pressure and portal hypertension.Clinically,two forms of disease(acute and chronic) are recognized.Mostly the patients present with ascites,hepatomegaly,and portal hypertension.In acute disease the liver is enlarged with thrombosed hepatic veins(HV) and ascites,whereas in the chronic form of the disease there may be membranous occlusion of HV and/or the inferior vena cava(IVC),or there may be short or long segment fibrotic constriction of HV or the suprahepatic IVC.Due to advances in radiological interventional techniques and hardware,there have been changes in the management protocol of BCS with surgery being offered to patients not suitable for radiological interventions or having acute liver failure requiring liver transplantation.The present article gives an insight into various imaging findings and interventional techniques employed in the management of BCS.