Extrahepatic Portal Vein Research Articles

Early partial portal venous contrast enhancement in canine CT‐Angiography

Early partial portal vein contrast enhancement (EPoVE) during the late arterial phase is seen in CT angiography of dogs. Previously, it has been a finding attributed to arterioportal vascular anomalies. However, EPoVE may be a normal feature of venous return from abdominal organs. This prospective, descriptive study investigated the origin of EPoVE using four-dimensional CT (4D-CT). Sixteen dogs undergoing 4D-CT for disease of the cranial abdomen were prospectively collected. Regions of interest were placed in the hepatic artery (HA), gastroduodenal vein (GV), extrahepatic portal vein (EHPV) cranial and caudal to the GV, and splenic vein (SV) caudal to its EHPV entry. Times to earliest, partial, full, and maximal vascular enhancement were recorded. A mixed model analysis of variance was used to compare time-to-contrast enhancement between vessels. The number, origin, and time of EPoVE were recorded if visible. A total of 24 EPoVE areas were observed in all dogs. Most dogs had either one (10/16) or two (5/16) areas of EPoVE. The origin of EPoVE was identified in 14 of 24 areas: the GV in five areas, cranial mesenteric vein in four areas, pancreatic branch of SV in three areas, and SV in two areas. The time-to-contrast-enhancement was significantly different for the individual veins compared to the HA. EPoVE during the late arterial phase is a common phenomenon of early portal venous drainage of abdominal organs; it should not be interpreted as pathognomonic for arterioportal vascular anomalies, which should be diagnosed based on additional criteria.

Surgical Management of Portal Biliopathy – A Prospective Analysis.

Background: Portal biliopathy denotes intrahepatic and extra hepatic biliary ductal abnormalities in portal hypertension. It is usually associated with extra hepatic portal vein obstruction (EHPVO). These patients are also prone to develop obstructive jaundice as a result of strictures and/or choledocholithiasis. Surgical management of obstructive jaundice in such patients becomes difficult in the presence of these collaterals. The aim of the study is to prospectively analyze the approach to management of patients with Symptomatic portal biliopathy. Subjects and Methods: The study was conducted at Narayana Medical College & Hospital, Chintareddy Palem, Nellore, Andhra Pradesh on surgical management of the patients of EHPVO with portal biliopathy presenting to the surgical clinic of this tertiary referral center between November 2016 and October 2017. The data was analyzed for presentation, clinical features, imaging and results of surgical management. Results: During the study period, total of 44 patients of EHPVO were referred for surgical management. Of these 14 patients (9 males, mean age 34.6 years) were diagnosed to have portal biliopathy. Ten patients had prior history of variceal bleed which was managed endoscopically. Jaundice was the most common symptom followed by right upper quadrant pain and recurrent cholangitis. Four patients had prior unsuccessful endoscopic management. ERCP/ MRCP was used for delineation of the biliary tree, which showed irregularity (14 patients), dominant strictures (8 patients), filling defects (5 patients), and intrahepatic biliary dilatation (7 patients). Proximal splenorenal shunt (PSRS) was performed in 13 patients. While in 1 patient peroperatively liver was found to be grossly nodular, hence gastro-esophageal devascularization with simultaneous biliary drainage was done. Of the 13 patients who underwent PSRS, all patients were intensively followed for 4-6 weeks with history and liver function tests. After 6 weeks, five patients showed clinical as well as biochemical improvement and they are being followed up regularly. Eight patients had persistent symptoms and abnormal liver function tests. These were the patients with dominant stricture and choledocholithiasis. Of these, 6 patients underwent Roux-en-Y hepaticojejunostomy. The average blood transfusion requirement at second surgery was 1 unit. Postoperative complications were minimal with no mortality. One patient and was lost to follow up and the remaining one is awaiting second surgery (RYHJ). Over a follow up of 3-28 months the patients are asymptomatic and well. Conclusion: Portal biliopathy with symptomatic biliary obstruction needs intervention. Surgical decompressive shunt followed by biliary drainage is the best possible treatment. While for most of the early biliary changes shunt alone is effective, patients with dominant stricture will need a biliary diversion which can be safely performed following Porto systemic shunt without increase in morbidity or mortality.

Maternal-fetal outcome in pregnancies complicated with non-cirrhotic portal hypertension: experience from a Tertiary Centre in South India.

To assess the maternal and perinatal outcomes of pregnant women with non-cirrhotic portal hypertension (NCPH). This was an observational study done by retrieving the records of pregnant women with non-cirrhotic portal hypertension admitted to a tertiary hospital in South India, over a 9-year study period. Data regarding the clinical course, complications during pregnancy, labor, and delivery details were reviewed. We also compared the outcomes among women with non-cirrhotic portal fibrosis (NCPF) with extrahepatic portal vein obstruction (EHPVO). During the study period, portal hypertension was noted in 0.07%(n = 108) of the pregnancies and 74.1% of them had NCPH. The diagnosis was made for the first time in 54.7% of them when presented with pancytopenia or splenomegaly. Variceal bleeding complicated 25% of the pregnancies in women with NCPH pregnancies, with three among them having a massive bleed. Eighteen among them underwent endoscopy following bleeding; variceal banding procedure was performed in nine of them without any complications. Preterm birth was the most common (20.6%) obstetric complication. There was one maternal death from severe sepsis, acute kidney injury, and disseminated intravascular coagulation, following a massive variceal bleed. Obstetric outcomes and medical complications were similar in women with NCPF and EHPVO. Perinatal loss was comparable in both the groups (14.3% vs. 9.6%, p = 0.417) CONCLUSION: Multidisciplinary team approach, with optimal and timely intervention with intensive monitoring, can reduce the morbidity and help achieve an optimal maternal-perinatal outcome in pregnancies complicated with portal hypertension.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. Between January 2012 and December 2019 (96months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8mmHg (range: 0-15mmHg). The mean hepatic venous pressure gradient was 3.6±2.6mmHg (range: 0-9mmHg) in the presence of HV-HV collaterals and 5.9±4.2mmHg (range: 1-15mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47mmHg (range: 0-15mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7mmHg (range: 0-9mmHg) in the presence of HV-HV collaterals and 10.3±4.1mmHg (range: 5-15mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75days (range: 0-8days). The mean wedge portosystemic gradient was 4.5±3.1mmHg (range: 2-9mmHg) and the mean portosystemic gradient was 14.5±3.7mmHg (range: 12-20mmHg) (P=0.006). HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Splenectomy with proximal spleno-left portal shunt for extrahepatic portal vein obstruction in children

PurposeTo report our initial experience with splenectomy and proximal spleno-left portal shunt as an alternative to the standard Rex shunt, when not applicable, in children with Extrahepatic Portal Vein Obstruction (EHPVO). MethodsPatients from March 2015 till September 2018, with EHPVO not suitable for Rex shunt or whose caregivers refused to consent for Internal Jugular Vein (IJV) dissection were assessed and prepared for splenectomy with proximal spleno-left portal shunt. The operative technique includes splenectomy, freeing of the splenic vein from the pancreatic bed till its junction with the inferior mesenteric vein, and then anastomosis with the intrahepatic left portal vein at the Rex recess. A distal lieno-renal shunt was performed in one patient and was excluded from the study. ResultsA total of 14 patients (mean age: 4.6 years) underwent splenectomy with proximal spleno-left portal shunt during the study period. The mean operative time was 246 min, while the mean postoperative hospital stay was 4.1 days. The patients' follow up period ranged from 6 to 42 months (median: 19.6 months). Only two patients had a single attack of variceal bleeding, 2 and 2.5 months postoperative respectively, and required endoscopic management with no further bleeding episodes. While the rest of patients showed an improvement of their variceal grades after the surgery. ConclusionSplenectomy with proximal spleno-left portal shunt seems to be a valuable alternative to the standard Rex shunt in treatment of children with EHPVO unsuitable for or following unsuccessful Rex shunt. Level of evidenceIV

Diagnostic challenges in non-cirrhotic portal hypertension - porto sinusoidal vascular disease.

Non-cirrhotic portal hypertension consists of a group of diseases characterized by signs and complications of portal hypertension, which differ from cirrhosis through histological alterations, hemodynamic characterization and, clinical outcome. Because of the similarities in clinical presentation and imaging signs, frequently these patients, and particularly those with porto-sinusoidal vascular disease (PSVD), are misdiagnosed as having liver cirrhosis and thus raising difficulties in their diagnosis. The most challenging differentiation to be considered is between PSVD and cirrhosis and, although not pathognomonic, liver biopsy is still the standard of diagnosis. Although they still require extended validation before being broadly used, new non-invasive methods for the diagnosis of porto-sinusoidal vascular disease, like transient elastography, contrast-enhanced ultrasound or metabolomic profiling, have shown promising results. Another issue is the differentiation between PSVD and chronic extrahepatic portal vein obstruction, especially now when it is known that 40% of patients suffering from PSVD develop portal vein thrombosis. In this particular case, once the portal vein thrombosis occurred, the diagnosis of PSVD is impossible according to the current guidelines. Moreover, so far, the differentiation between PSVD and sinusoidal obstruction syndrome has not been clear so far in particular circumstances. In this review we highlighted the diagnostic challenges regarding the PSVD, as well as the current techniques used in the evaluation of these patients.

Surgical Portosystemic Shunts: History, Evolution, and Current Applications

AbstractMechanical obstruction, thrombus, intrinsic liver disease causing fibrosis or cirrhosis, or an outflow obstruction at the level of the sinusoids or hepatic venous obstruction can cause an increase in pressure or resistance, or both, leading to portal hypertension (PH). Portosystemic shunts (PSS) are usually performed to relieve the congestion that inevitably occurs in the setting of PH. Since their introduction, surgical PSS were often the treatment of choice to prevent recurrent bleeding in patients with clinically significant PH. Development of novel pharmacological therapies, continuous improvement of endoscopic approaches, the introduction of transjugular intrahepatic portosystemic shunt, and advancements in transplantation has provided an evolution in the approach for PH and has precipitated the steady decrease in the proportion of patients needing surgical shunts. Despite this, PSS remain important tools in the surgeon's armamentarium, as they are often employed in the pediatric population with extrahepatic portal vein obstruction and are frequently being used for portal inflow modulation to achieve better portal hemodynamics in resections and transplantation. This has become of great relevance to decrease the risk of small-for-size syndrome and portal hyperperfusion in liver transplantation, and to decrease the risk of posthepatectomy liver dysfunction after major resections in hepatobiliary surgery.

Sonographic Evaluation of a Unique Meso-Rex Shunt: A Case Study

Portal hypertension is a result of an increase in intrahepatic resistance in the main portal vein. The Meso-Rex shunt is used to bypass the obstructed portal vein and restore the venous flow into the liver. This procedure alleviates the need for a hepatic transplant. The Meso-Rex shunt has proven to be an effective treatment for extrahepatic portal vein obstruction, thus saving children from a complete transplant. There are variants to this bypass surgery, and sonography is commonly used to assess the condition pre- and postoperatively. In this case, the shunt was uniquely different from the typical Meso-Rex bypass surgery. Particular vasculature made it imperative for the sonographer to review the prior sonograms and review the chart information before preforming the examination. It should also be noted that sonographers must adapt the protocols to give the utmost treatment.

Pediatric living donor liver transplantation with non-anatomical portal vein reconstruction in idiopathic extrahepatic portal vein thrombosis

A 13-year-old boy had a history of recurrent hematemesis and melena since the age of 2 years. Owing to recurrent bleeding, he had undergone several endoscopic ligation procedures and had received regular blood transfusions over the last 7 years. Doppler ultrasonography showed extrahepatic portal vein thrombosis, while the hepatic vein was not visualized. Abdominal computed tomography confirmed cavernous transformation in the liver hilum. Liver biopsy revealed fibrosis. A diagnosis of extrahepatic portal vein obstruction (EHPVO) with portal hypertension was established. Living donor liver transplantation (LDLT) was performed owing to recurrent gastrointestinal bleeding and liver fibrosis. The liver graft was obtained from the patient's father, utilizing segments 2, 3, and 4 (graft-to-recipient weight ratio: 0.84%). Portal vein reconstruction using native internal jugular vein and external iliac vein was achieved with non-anatomical anastomosis due to the lack of availability of sizable superior mesenteric vein. The postoperative course was uneventful. We successfully performed LDLT with unusual portal vein reconstruction in a patient with EHPVO. Multiple interposition grafts were used to obtain adequate inflow from the splenorenal shunt. LDLT remains the last resort in such cases as other surgical procedures (such as Meso-Rex bypass) are not feasible.

Ramucirumab, A Second-Line Option For Patients With Hepatocellular Carcinoma: A Review Of The Evidence.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and predominantly develops in patients with liver cirrhosis. In patients with advanced disease, such as extra-hepatic extension or portal vein involvement, and with intermediate disease unsuitable for locoregional therapies, systemic therapy is recommended, if liver function and performance status are adequate. Following a decade of negative Phase III trials since the approval of sorafenib, more recently several drugs have proven efficacy both in first line versus sorafenib (lenvatinib) or in second line versus placebo (regorafenib, cabozantinib, ramucirumab). In this review, we summarize the preclinical and clinical evidence supporting the use of ramucirumab, a recombinant IgG1 monoclonal antibody that specifically binds to Vascular Endothelial Growth Factor receptor 2 (VEGFR-2), in HCC. Following the results of the REACH trial, that was negative in the overall study population but identified a subgroup that could benefit from ramucirumab treatment, the REACH-2 trial was a randomized, placebo-controlled trial, designed to assess ramucirumab as second line in patients with alpha-fetoprotein (AFP) ≥400 ng/mL. The results of REACH-2 were published in February 2019, leading to Food and Drug Administration and European Medicines Agency approval of the drug as second-line agent for advanced HCC (after sorafenib) in patients with AFP ≥400 ng/mL. For the first time in the history of systemic treatments for HCC, a predictive factor of efficacy was identified. In this review, we also discuss the potential clinical development of systemic treatments in HCC, focusing on combination therapies with immunotherapy (following the recent results of the combination of atezolizumab and bevacizumab in the IMbrave 150 clinical trial) and treatment sequences as a way to maximize survival benefit.

Long‐term Outcomes and Health Perceptions in Pediatric‐onset Portal Hypertension Complicated by Varices

Outcomes of pediatric-onset portal hypertension are poorly defined. We aimed to assess population-based long-term outcomes of pediatric-onset portal hypertension complicated by varices. All children with esophageal varices (n = 126) were identified from 14,144 single nationwide referral center endoscopy reports during 1987 to 2013, and followed up through national health care and death registers. A questionnaire was sent to survivors (n = 94) of whom 65 (69%) responded. Nineteen underlying disorders included biliary atresia (35%), extrahepatic portal vein obstruction (35%), autosomal recessive polycystic kidney disease (7%), and other disorders (23%). During median follow-up of 15.2 (range 0.5-43.1) years patients underwent median 9 (1-74) upper gastrointestinal endoscopies. Esophageal varices were first observed at a median age of 4.0 (0.3-18.2) years, 112 (89%) patients underwent median 6 (1-56) sclerotherapy/banding sessions, and 61 (48%) experienced median 2 (range 1-20) variceal bleeding episodes. Forty-eight surgical shunt procedures were performed to 41 (36%) patients and 38% underwent liver transplantation. Portal hypertensive biliopathy was diagnosed in 4 patients. Hepatopulmonary syndrome necessitated liver transplantation in 2 patients, hepatic encephalopathy in 2, and hepatorenal syndrome in 1. No patient died of variceal bleeding. Patient-reported perception of health on a scale of 1 to 10 was 9 (range 4-10), and 86% reported no current symptoms attributable to esophageal varices. Pediatric-onset portal hypertension is a heterogeneous disease with significant long-term morbidity, requiring multimodal approach with considerable resources and continuation of follow-up in adulthood. Although mortality to variceal bleeding was avoided, bleeding episodes recurred also in adulthood, while patient-reported health of long-term survivors was encouraging.

Long-acting Release Octreotide for Pediatric Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding (UGIB) secondary to portal hypertension (PHT), without endoscopic or surgical treatment options due to an ectopic or unidentified bleeding site or the patient's anatomic characteristics, is challenging in pediatric hepatology. The usual treatment in these cases includes intravenous Octreotide. Recently, the availability of long-acting release Octreo tide (OCT-LAR) for monthly intramuscular administration has become an interesting therapeutic alternative. To report the case of an infant with UGIB due to PHT who was successfully treated with OCT-LAR. Eight-month-old patient with repeated episodes of UGIB due to extrahepatic portal vein malformation, requiring blood transfusions, and intravenous octreotide infusions. As neither endoscopic nor surgical treatment were feasible, we decided to start IM OCT- LAR monthly. After ten months of treatment, the patient did not present bleeding episodes. No medication-related events were observed. We consider that this report could help in the management of similar pediatric patients with UGIB due to PHT without conventional therapeutic possibilities.

Spleen stiffness measurement as a non-invasive test to evaluate and monitor portal hypertension in children with extrahepatic portal vein obstruction.

The aim of the study was to test the feasibility of spleen stiffness measurement (SSM) by two-dimensional shear wave elastography (2D-SWE) and compare data on its diagnostic use with upper gastrointestinal endoscopy in children with extrahepatic portal hypertension (EHPH) before and after surgery. A total of 44 children were included in this study [34 children with EHPH (main group)] and 10 controls (7.57 ± 1.22years), who underwent ultrasonography including SSM by 2D-SWE. Patients in the main group also underwent upper gastrointestinal endoscopy (UGE) and CT angiography. The main group was divided into three subgroups: Group A: patients with EHPH without large spontaneous portosystemic shunts (n = 15); Group B: patients with EHPH with large spontaneous portosystemic shunts (n = 9); Group C: patients with EHPVO and after surgical portosystemic shunts (n = 10). According to UGE, children in group A had significantly higher grades of esophageal varices (EV) (2.3 ± 0.14; p < 0.001) compared to those in groups B and C. After surgical shunting procedures (in group C), the grade of EV declined to 0.37 ± 0.14. There was significant difference (p < 0.001) in the mean SS of children in group A (70 ± 4.64kPa) compared to those in group B (37.04 ± 4.62kPa) and group C (26.3 ± 2.9kPa). After surgery, SS decreased but remained elevated compared with controls (26.3 ± 2.9 vs 17.85 ± 1.3kPa; p = 0.016). The SS showed a small but significant correlation with grades of EV (r = 0.56, p = 0.002). The SS measured by 2D-SWE is feasible in children with EHPH and the results reflect the presence or degree of EV, thus elastography of spleen is useful in monitoring portal hypertension before and after shunt surgeries.

Role of noninvasive tools for prediction of clinically evident portal hypertension in children.

Noninvasive tools (NITs) for predicting varices in children with portal hypertension (PHTN) are infrequently used. Eighty-five consecutive, treatment-naïve children with PHTN and 97 controls were enrolled study from July 2017 to November 2018. Each case was evaluated by esophagogastroduodenoscopy (EGD) and various NITs: platelet spleen size Z (PSZ), clinical prediction rule (CPR), King's variceal prediction rule (KVaPS), Splenic stiffness (SSM) and liver stiffness measurement (LSM) by point shear wave elastrography (pSWE). Had PHTN due to extra hepatic portal vein obstruction (EHPVO) and 70% due to cirrhosis [chronic liver disease (CLD)]. Sixty-five percent of PHTN cases had varices. Children with varices had lower platelet counts, lower albumin and larger spleens. SSM and LSM were significantly higher in cases as compared with controls. SSM was significantly higher in cases with varices than those without. SSM and LSM, at cutoffs of 3.8 and 3.2 kPa, respectively, discriminated PHTN cases from controls with an area under the curve (AUROC) of 0.67 (0.59-0.74). Both SSM and LSM predicted varices in CLD, but in EHPVO, only SSM predicted varices. SSM of 5.2 and 12.8 kPa, in CLD and EHPVO subgroups, respectively, had AUROC of 0.73 and 0.94 for variceal prediction. Blood-based NITs performed better in the CLD subgroup: aspartate aminotransferase platelet ratio index, CPR and KVPS predicted severity of PHTN with AUROC of 0.81, 0.92 and 0.93, respectively. Blood-based NITs outperform elastography for prediction of PHTN/varices in children with CLD. SSM by pSWE is a better predictor of varices than LSM, especially in the EHPVO subgroup.

”Left gastric vein to inferior vena cava” bypass in patients with portal hypertension

Aim. To present the first Russian experience in the management of portal hypertension of various etiology by creating a selective portosystemic shunt between left gastric vein and inferior vena cava (leftgastric vein caval bypass).Material and methods. “Left gastric vein to inferior vena cava” bypass was performed in 6 patients with portal hypertension: 4 men and 2 women (mean age 40.4 years). The follow-up period ranged from 10 to 36 months.Results. “Left gastric vein to inferior vena cava” bypass was effective in the management of portal hypertension and its complications in 5 out of 6 patients. Complete eradication of esophagogastric varices and no variceal bleeding were observed in long-term period. These patients demonstrated no clinical or laboratory signs of hepatic encephalopathy and/or hepatic failure within the follow-up. One patient with thrombophilia and extrahepatic portal vein obstruction (factor V Leiden mutation) had thrombosis of the shunt and recurrent variceal bleeding in 6 months after surgery because of unauthorized abandonment of the anticoagulation.Conclusion. “Left gastric vein to inferior vena cava” bypass is an effective procedure for prevention of variceal bleeding (or recurrence) in patients with portal hypertension. The limitation of this technique is insufficient diameter of left gastric vein in many patients. This procedure has certain pathophysiological advantages over other types of portosystemic anastomoses due to highly selective nature of the shunt. Thus, this approach should be introduced into surgical treatment of these patients.

Biliary Atresia Patients With Successful Kasai Portoenterostomy Can Present With Features of Obliterative Portal Venopathy.

Study of liver explants of biliary atresia (BA) patients with successful Kasai portoenterostomy (KP). Pathology and medical records of BA liver explants from January 2009 to June 2018 with successful KP were reviewed along with appropriate controls. Fourteen out of 68 (20.6%) BA patients with LT had a successful KP. Median age at BA diagnosis, KP and LT was 60.5 days, 61 days, and 10 years, respectively, with conjugated bilirubin (c-bil) normalizing at 12.5 weeks after KP. Advanced fibrosis was diffuse in 2/14 (14.3%) explants, limited to periphery in 11/14 (78.6%) and absent in 1. Hilar partial nodular transformation (PNT) was seen in 11 explants (78.6%) and diffuse nodular regenerative hyperplasia (NRH) in 2 (14.3%). Areas of PNT and NRH showed diffuse portal sclerosis (100%), complete and incomplete portal vein (PV) stenosis (100%), PV herniation (100%), hypervascular portal tracts (20%), periportal abnormal vessels (100%), abundant lymphatic collaterals (100%), mild medial hepatic arterial hypertrophy (100%), and delicate fibrous septae (100%). Extrahepatic PVs showed variable luminal occlusion with mean PV intima to full thickness ratio of 0.6 +/- 0.11; significantly higher than age-matched noncirrhotic (n = 27, 0.08 +/- 0.09; P < 0.0001) and cirrhotic controls (n = 19, 0.34 +/- 0.2; P = 0.0015); and comparable to BA patients with failed KP (P = 0.82) and without KP (P = 0.04). BA patients with successful KP can present with obliterative portal venopathy (OPV). In the context of optimal bile drainage, portal hypertension may not be because of advanced parenchymal fibrosis but possibly because of OPV. Vascular abnormalities of the PV system should be investigated in BA patients.

Thrombin dynamics in children with liver disease or extrahepatic portal vein obstruction or shunt

IntroductionChanges in the coagulation profile in children with liver disease and extrahepatic portal vein obstruction or shunt result in both bleeding and thrombosis. Routine coagulation tests do not accurately predict bleeding risk, as they are not sensitive to changes in anticoagulant factors. The thrombin generation assay could be suitable for describing the overall balance of coagulation in children with liver disease. This study aims to characterise the mechanism of thrombin generation in this population, focusing on prothrombin conversion and thrombin inhibition. MethodsPatients were categorised as: severe (paediatric end stage liver disease score > 15) and mild disease, or portal vein obstruction or shunt. Age and gender matched healthy controls were used. The thrombin generation assay was performed in plasma samples from patients and controls with and without exogenous thrombomodulin and the results were further analysed with the computational thrombin dynamics method. ResultsA total of 42 patients (severe, n = 5; mild, n = 29, obstruction/shunt, n = 8) and 20 controls were included in this study. The total prothrombin conversion, thrombin-antithrombin formation and the thrombin decay capacity, in the presence and absence of thrombomodulin were reduced in children with severe liver disease. The rate of prothrombin conversion was increased and thrombin decay capacity was decreased in patients with portal vein obstruction or shunt compared to controls. ConclusionThis study demonstrates changes in the mechanism in thrombin generation seen in severe chronic liver disease. The changes vary in parenchymal versus non parenchymal liver disease and further study assessing the clinical significance of these variations in mechanism is required.

An analysis on the use of Warren’s distal splenorenal shunt surgery for the treatment of portal hypertension at the University Hospitals Leuven

Introduction Extrahepatic portal vein thrombosis (PVT) is the most common cause of portal hypertension (PH), particularly in children. PH-related manifestations include refractory variceal bleeding, splenomegaly and ascites. Albeit more rarely performed, the distal splenorenal shunt (Warren’s shunt) has proven to be effective in selectively decompressing the collateral circulation. The aim of our study was to describe our experience with the distal splenorenal shunt and to determine the long-term effect on PH-related side-effects. Methods Distal splenorenal shunt operations performed at our institution between 2000 and 2014 were reviewed for: age, male/female ratio, children/adults ratio, body mass index, indications, grade of PVT (Yerdel classification), maximal shunt-flow velocity, shunt patency and thrombosis, re-intervention for variceal bleeding and survival. Complications of PH (esophageal variceal bleeding and ascites) were compared pre- versus post-operatively (last follow-up). Paired student t-test and fisher’s exact were applied for pre- versus post-operative comparison. Results are reported as median [range]. Results Fourteen patients with PVT and refractory complications of PH underwent distal splenorenal shunt surgery. Age was 15 years [4.5–66]. Male/female ratio was 7/7. PVT -grade was 2 [1–4]. Follow-up was 3 [0.5–14]. All shunts were patent (100%) with no shunt thrombosis (0%) at last follow-up. There was no re-intervention for variceal bleeding (0%) and survival at last follow-up was 100%. Occurrence of esophageal variceal bleeding was higher pre-operatively (57%) than postoperatively (0%) (p = .0032) and also the incidence of ascites was higher pre-operatively (79%) than postoperatively (0%) (p < .0001). Conclusions Based on our experience, the distal splenorenal shunt can be considered a valuable surgical technique for PVT-induced PH, with excellent post-operative prevention of complications of PH.

Pathological abnormalities in splenic vasculature in non-cirrhotic portal hypertension: Its relevance in the management of portal hypertension.

BACKGROUNDPortal hypertension (PH) is associated with changes in vascular structure and function of the portosplenomesenteric system (PSMS). This is referred to as portal hypertensive vasculopathy. Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients. Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy. In view of this, it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH (NCPH).AIMTo investigate pathological abnormalities of splenic vein in patients with NCPH, and suggest its possible implications in the management of PH.METHODSA prospective observational study was performed on 116 patients with NCPH [Extrahepatic portal vein obstruction (EHPVO): 53 and non-cirrhotic portal fibrosis (NCPF): 63] who underwent proximal splenorenal shunt (PSRS), interposition shunt or splenectomy with devascularization in JIPMER, Pondicherry, India, a tertiary level referral center, between 2011-2016. All patients were evaluated by Doppler study of PSMS, computed tomography porto-venogram and upper gastrointestinal endoscopy. An acoustic resonance forced impulse (ARFI) scan and abdomen ultrasound were done for all cases to exclude cirrhosis. Intraoperative and histopathological assessment of the harvested splenic vein was performed in all. The study group was divided into delayed and early presentation based on the median duration of symptoms (i.e. 108 mo).RESULTSThe study group comprising of 116 patients [77 (66%) females and 39 (34%) males] with NCPH had a median age of 22 years. Median duration of symptoms was 108 mo. The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding (hematemesis and melena). The ARFI scan revealed a median score of 1.2 (1.0-1.8) m/s for EHPVO and 1.5 (0.9-2.8) m/s for NCPF. PSRS was performed in 84 patients (two of whom underwent interposition PSRS using a 10 mm Dacron graft); splenoadrenal shunt in 9; interposition mesocaval shunt in 5; interposition 1st jejunal to caval shunt in 1 patient and devascularization with splenectomy in 17 patients. Median pre-splenectomy portal pressure was 25 (range: 15-51) mm Hg. In 77% cases, the splenic vein was abnormal upon intraoperative assessment. Under macroscopic examination, wall thickening was observed in 108 (93%), venous thrombosis in 32 (28%) and vein wall calcification in 27 (23%) cases. Upon examination under a surgical magnification loupe, 21 (18%) patients had intimal defects in the splenic vein. Histopathological examination of veins was abnormal in all cases. Medial hypertrophy was noted in nearly all patients (107/116), while intimal fibrosis was seen in 30%. Ninety one percent of patients with intimal fibrosis also had venous thrombosis. Vein wall calcification was found in 22%, all of whom had intimal fibrosis and venous thrombosis. The proportion of patients with pathological abnormalities in the splenic vein were significantly greater in the delayed presentation group as compared to the early presentation group.CONCLUSIONPathological changes in the splenic vein similar to those in cirrhotic patients with PH are noted in NCPH. We recommend that PH in NCPH be treated as systemic and pulmonary hypertension equivalent in the gastrointestinal tract, and that early aggressive therapy be initiated to reduce portal pressure and hemodynamic stress to avoid potential lethal effects.

Transsplenic portal vein recanalization and direct intrahepatic portosystemic shunt placement to optimize liver transplantation

BackgroundPercutaneous trans-splenic portal vein recanalization (PVR) has been reported for facilitation of transjugular intrahepatic portosystemic shunts (TIPS), however has not been applied to patients undergoing direct intrahepatic portosystemic shunt (DIPS). We report the utilization of trans-splenic-PVR with DIPS creation in a patient with chronic portal and hepatic vein occlusions undergoing liver transplantation evaluation.Case presentationA 48-year-old male with decompensated alcoholic cirrhosis complicated by refractory ascites, hepatic encephalopathy, and variceal bleeding underwent CT that demonstrated chronic occlusion of the hepatic veins (HV), extrahepatic portal vein (PV), and superior mesenteric vein (SMV). Due to failed attempts at TIPS at outside institutions, interventional radiology was consulted for portal vein recanalization (PVR) with TIPS to treat the portal hypertension and ascites and also facilitate an end-to-end PV anastomosis at transplantation. After an initial hepatic venogram confirmed chronic HV occlusion, a DIPS with trans-splenic PVR was planned. The splenic vein was accessed under sonographic guidance using a micropuncture set and subsequently upsized to a 6 French sheath over a stiff guidewire. A splenic venogram via this access confirmed occlusion of the PV with drainage of the splenic vein (SV) through gastric varices. The thrombosed PV was then recanalized and angioplastied to restore PV flow via the transsplenic approach. A transjugular liver access kit with a modified 21-gauge needle was advanced into the IVC through the internal jugular vein (IJV) sheath and directed towards the target snare in PV. The needle was used to subsequently puncture the PV through the caudate lobe and facilitate placement of a wire into the SV. The initial portosystemic gradient (PSG) was 20 mmHg. The IJV sheath was advanced through the hepatic parenchymal tract into the main-PV and a stent-graft was placed across the main PV and into the IVC. A portal venogram demonstrated brisk blood flow through the DIPS, resolution of varices and a PSG of 8 mmHg. One month after the procedure, the patient had a significant reduction in ascites and MELD-NA score. Patient is currently listed and awaiting transplantation.ConclusionsIn the setting of chronically occluded portal and hepatic veins, trans-splenic PVR DIPS may serve as an effective bridge to liver transplantation by facilitating an end to end portal vein anastomosis.