Prehepatic Portal Hypertension Research Articles

Outcomes of meso-Rex bypass for prehepatic portal hypertension in pediatric patients

Portal hypertension in pediatric patients is often associated with prehepatic portal hypertension (PHPH), frequently linked to thrombosis and cavernomatous degeneration of the portal vein (CDVP). This study evaluates the efficacy of the MesoRexBypass (MRB) in managing PHPH and associated thrombosis. MethodsA retrospective prognostic cohort design was employed to analyze the clinical outcomes of nine pediatric patients who underwent MRB between 2020 and 2022. Clinical and surgical variables were examined, including graft type, surgical time, and complications. Postoperative follow-up confirmed MRB functionality. ResultsThe MRB proved highly successful, with improved clinical parameters observed in all patients. Significant reductions in gastrointestinal bleeding, esophageal varices, and hypertensive gastropathy were observed postoperatively. Thrombocytopenia and liver enzyme levels showed substantial improvement, indicating enhanced liver function and amelioration of hypersplenism. The MRB's adaptability was demonstrated using autologous grafts and various graft sources.One patient experienced shunt thrombosis, another experienced minor gastrointestinal bleeding, and another died. The MRB exhibited a high success rate and few complications. ConclusionThe MRB is an effective and versatile surgical technique for managing PHPH in pediatric patients. This study emphasizes its promising outcomes and suggests its potential for enhancing treatment approaches and quality of life in this patient population. Further research with larger cohorts is needed to strengthen the evidence presented. The MRB holds promise as a valuable addition to the management of PHPH in children. Level of Evidence IV.

Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats.

Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.

THU-361 - The pan-PPAR agonist lanifibranor decreases portal pressure in models of both hepatic and prehepatic portal hypertension

THU-361 - The pan-PPAR agonist lanifibranor decreases portal pressure in models of both hepatic and prehepatic portal hypertension

A model of prehepatic portal hypertension in rats


 
 
 during the study, the methodology of the prehepatic portal hypertension (PPH) develop- ment model in Wistar rats was set, using partial portal vein ligation (PPVL). It was followed by the anal- ysis of model stability and its prolongation over time using the indicator of the portal vein constriction rate (PVCR) and the portohepatic perfusion (PHP) dependence on it. It was found that in 4-week-old rats with a body weight of 99.6 ± 2.0 g there was no mortality in PPVL at 53.45%; the reduction of PHP was critical at 69.13% of PPVL; in a group of 6-week-old rats with a body weight of 155 ± 3.5 g, where the median PPVL was 58.67 (95% CI 56.3-59.82) after PPVL, there was no mortality. At the same time, a delay in the physical development of rats was noted in comparison with the control subgroup and the subgroup with false ligation. Parenchymal and vessel changes were registered on serial ultrasound examination.
 
 

Prevalence and clinical characteristics of advanced portal vein thrombosis in cirrhotic patients with gastroesophageal variceal hemorrhage.

Portal venous thrombosis (PVT) in cirrhotic patients is usually asymptomatic and diagnosed incidentally. In this study we aimed to investigate the prevalence and characteristics of advanced PVT in cirrhotic patients with a recent episode of gastroesophageal variceal hemorrhage (GVH). Cirrhotic patients with recent GVH at one month before their admission for further treatment to prevent rebleeding were retrospectively recruited. Hepatic venous pressure gradient (HVPG) measurements, contrast-enhanced computed tomography (CT) scan of the portal vein system, and endoscopy were performed. PVT was diagnosed by CT examination and classified as none, mild and advanced. Of the 356 patients enrolled, 80 (22.5%) had advanced PVT. Elevated levels of white blood cells (WBC) and serum D-dimer were observed in advanced PVT patients compared with those with no or mild PVT. Moreover, HVPG was lower in patients with advanced PVT, with fewer patients having HVPG exceeding 12 mmHg, while grade III esophageal varices and varices with red signs were more prevalent. Multivariate analysis showed that WBC count (odds ratio [OR] 1.401, 95% confidence interval [CI] 1.171-1.676, P < 0.001), D-dimer level (OR 1.228, 95% CI 1.117-1.361, P < 0.001), HVPG (OR 0.942, 95% CI 0.900-0.987, P = 0.011), and grade III esophageal varices (OR 4.243, 95% CI 1.420-12.684, P = 0.010) were associated with advanced PVT. Advanced PVT, which is associated with a more severe hypercoagulable and inflammatory status, causes severe prehepatic portal hypertension in cirrhotic patients with GVH.

Simulation of prehepatic portal hypertension and impact of hepatic deportalization on its tissue

Objective. On the prehepatic portal hypertension pattern, created by partial ligature of venae portae in rats, to estimate the impact of partial hepatic deportalization on its tissue.&#x0D; Materials and methods. The investigation was conducted on 35 male rats of a Wistar line, aged 4–6 weeks. In 15 laboratory animals the partial ligature of vena porta with formation of stenosis was conducted, and in 15 –false ligature, while the control group consisted of 5 intact laboratory animals.&#x0D; Results. There were revealed certain connections between conduction of partial ligature of vena porta and critical (lethal) lowering of portohepatic perfusion.&#x0D; The model of prehepatic portal hypertension, using partial ligature of vena porta, leading to partial lowering of portohepatic perfusion with development of cavernous transformation of vena porta and dystrophic changes in hepatocytes with further fibrous changes in hepatic parenchyma, was applied.&#x0D; Conclusion. The portal vein narrowing grade in range 52 – 59% constitutes the optimal one for the prehepatic portal hypertension formation with development of zonal adipose parenchymatous hepatic dystrophy and the balloon degeneration of hepatocytes with further development of fibroses in rats of a Wistar line aged 4 – 6 weeks.

Short and Long Term Effects of Splenectomy on Memory B Cell Level in Children

Introduction: Splenectomy has long been used to treat benign hematological abnormalities such as immune thrombocytopenia (ITP), some hemolytic anemias- especially hereditary spherocytosis and thalassemia, and prehepatic portal hypertension. The discovery that splenectomized individuals are more vulnerable to encapsulated organism infection has been attributed to the spleen's lack of filtration and the development of anticarbohydrate antibodies. Recent research in such splenectomized patients suggests that the lack of this specific anticarbohydrate antibody in these participants is attributable to a decreased number of Memory B cells (a subgroup of B lymphocytes in charge of T-independent responses). Traditional vaccinations, which are given to splenectomized patients to protect them from being infected by encapsulated organisms, can only act in the presence of both the spleen and its functioning marginal zone. As a Result, the study will look at the level of memory B cells in the blood after three months and 1-year post-splenectomy.&#x0D; Aim of the study: The objective of the study was to observe the short- and long-term effects of splenectomy on memory B cells in children. Methods: This prospective case-control study was conducted at the Pediatric Surgery Department of Bangabandhu Sheikh Mujib Medical University, Bangladesh. The study duration was one year, from July 2015 to August 2016. A total of 26 children were selected through a purposive sampling technique for this study, where the control group consisted of 10 children, and the case group consisted of 16 splenectomized children.&#x0D; Result: Among the case group participants, 56.25% were from the oldest age group of 12-15 years, and 37.5% were from the age group of 8-11-years. Male prevalence was high in both the control and the case group. Beta thalassemia was the primary indication for splenectomy for 81.25% of case group patients. Mean B lymphocyte was 39700.2 in the control group, 3655.3 at the 3-month follow-up of case group participants, and 3381.7 for those who had follow-up1-year after splenectomy. The mean amount of IgM memory B cells in the control group was 17.92%; at the 3-month follow-up of the case, it was 18.96%, and at the 1-year follow-up, it was 4.34%.&#x0D; Conclusion: In post-splenectomy individuals, immunological constitutions in memory B cells do not support a T-independent response and, therefore, vaccination.&#x0D; TAJ 2022; 35: No-1: 39-44

A Sri Lankan child with hypersplenism secondary to pre-hepatic portal hypertension, successfully managed with partial splenic artery embolization: a case report and review of the literature

BackgroundHypersplenism, one of the major complications of portal hypertension, is traditionally treated by splenectomy. However, partial splenic artery embolization is an evolving minimally invasive intervention to treat these patients effectively.Case presentationA 13-year-old girl was referred for further evaluation of isolated splenomegaly with pancytopenia. She did not have bleeding manifestations or features of anemia. She never had hematemesis or melena. On examination, she was pale. Abdominal examination revealed massive splenomegaly of 10 cm below the costal margin without hepatomegaly. Rest of the examination was unremarkable. Her investigations revealed a white cell count of 1700/mm3 (neutrophils 9.8% and lymphocytes 88.7%), hemoglobin 9.5 g/dL and platelet count 42,000/mm3. Blood picture showed pancytopenia without abnormal cells. Her reticulocyte count was 1.9%. Complete liver profile was normal. Abdominal ultrasonography revealed massive splenomegaly with the oblique length of 17 cm and normal echogenic liver with normal size. Cavernous transformation of portal vein with portal hypertension was evident. Mesenteric angiogram showed portal vein thrombosis and markedly tortuous splenic artery. Anti-nuclear antibodies and double-stranded DNA were negative. Ham test and urine for hemosiderin were negative. Clauss fibrinogen assay was normal. Hemoglobin high performance liquid chromatography for hemoglobin subtypes was normal. Anti-phospholipid antibodies were negative. JAK2 V617F mutation was not identified. Diagnosis of pre hepatic portal hypertension was made. Her upper gastrointestinal endoscopy was normal. Partial splenic artery coil embolization was done by interventional radiology team. Vaccines against capsulated organisms were given. Post-procedure contrast abdominal computed tomography revealed infarction of approximately 70% of the spleen and blood counts were improved. Index case is in the follow up for 3 years. She is on penicillin prophylaxis with regular blood count and annual upper gastrointestinal endoscopy monitoring.ConclusionsMinimally invasive interventions such as partial splenic artery embolization should be considered in managing the patients with hypersplenism secondary to portal hypertension.

ЭФФЕКТИВНОСТЬ СПЛЕНОРЕНАЛЬНОГО ШУНТИРОВАНИЯ В ЛЕЧЕНИИ ДОПЕЧЕНОЧНОЙ ФОРМЫ ПОРТАЛЬНОЙ ГИПЕРТЕНЗИИ У ДЕТЕЙ

Objective. To evaluate the results of treatment of prehepatic portal hypertension (PPH) in children by method of side-to-side splenorenal bypass. Methods. A retrospective, monocentric analysis of 114 patients with prehepatic portal hypertension was carried out in the period from 2000 to 2018. The age of the patients was from 6 months up to 18 years, the average age 10,1±3,8 years (M±σ). All patients underwent side-to-side splenorenal shunt. In the postoperative period, on the 7&lt;sup&gt;th&lt;/sup&gt; day, ultrasound examination of the abdominal organs with Doppler sonography (US) was performed to assess the volume of the spleen, the rate of portohepatic perfusion, the rate of blood flow along the side-to-side splenorenal shunt, as well as to assess its diameter. Control US was performed after the 1&lt;sup&gt;st&lt;/sup&gt;, 3&lt;sup&gt;rd&lt;/sup&gt;, 6&lt;sup&gt;th&lt;/sup&gt;, 12&lt;sup&gt;th&lt;/sup&gt; months; to assess the regression of esophageal and gastric varicose veins, the control esophagogastroduodenoscopy (EYD) was performed after 3&lt;sup&gt;rd&lt;/sup&gt; , 6&lt;sup&gt;th&lt;/sup&gt;, 12&lt;sup&gt;th&lt;/sup&gt; months and then once a year. Subsequently, the control examination of the patients was carried out once a year. The follow-up was 2-18 years. Results. Out of 114 patients who underwent side - to - side splenorenal shunt, 5 (4,4%) patients had recurrent bleeding from the esophageal variceal vein at the follow-up period (2-18 years). One patient had intra-abdominal arrosive bleeding from side-to-side splenorenal shunt provoked by severe postoperative pancreatitis. The average diameter of the shunt was 12±1.9 mm. The spleen volume decreased by 39.7±10.3%. Portohepatic perfusion reduced by 39% in comparison with the indicators before surgery. The blood flow rate along the side -to-side splenorenal shunt was 2403±557.3 ml/min. in 95,4% of patients the regression of variceal vein was noted. Hypersplenism syndrome was arrested in 73.6% of children. Conclusion. Side -to- side splenorenal shunt is considered to be an effective method of portal decompression with the effectiveness inpreventingboth esophageal and gastricvariceal veins bleeding in 95,4% of patients. What this paper adds The results of treatment of the prehepatic portal hypertension by method of side-to-side splenorenal shunt have been firstly analyzed, and the effect of this variant of portosystemic shunt on portohepatic perfusion has been assessed. It has been established that this option of shunt is effective for the portal system decompression and occupies an intermediate position between selective and total variant of portosystemic shunt.

S2372 Hemostatic Powder and Over-the-Scope Clip for Duodenal Variceal Bleeding

Introduction: Duodenal varices are rare and have an estimated prevalence of 0.4% in patients with portal hypertension who undergo upper endoscopy. Bleeding from duodenal varices does not commonly occur; when it does it is usually massive and fatal. There is a paucity of guidelines and consensus on the management of bleeding duodenal varices. We report the alternative use of hemostatic powder and over-the-scope clip (OTSC) to achieve hemostasis in a case of duodenal variceal hemorrhage due to prehepatic portal hypertension caused by portal vein thrombosis. Case Description/Methods: A 56-year-old transgender woman with no prior history of liver disease presented with acute hematemesis. She had been taking estrogen hormone therapy. Her INR and liver chemistries on admission were within normal limits. Esophagogastroduodenoscopy (EGD) revealed no active bleeding, but varices with a red spot in the second portion of the duodenum. No endoscopic intervention was performed. CT venography demonstrated portal vein thrombosis and prominent abdominal venous collateral vessels. The patient was referred to interventional radiology for placement of a transjugular intrahepatic portosystemic shunt (TIPS). The next day she had recurrent hematemesis and melena. Repeat EGD revealed bleeding duodenal varices. Three through-the-scope clips were placed, and hemostatic powder (TC-325) was used to achieve hemostasis. Several days later, the patient had another episode of bleeding, and EGD revealed displacement of prior hemostatic clips and bleeding from the same site in the duodenum. An OTSC (Padlock) was deployed, achieving complete hemostasis. The patient underwent successful TIPS placement, had no further recurrence of bleeding, and was eventually discharged home. Discussion: Current treatment modalities for bleeding duodenal varices include medications, endoscopic band ligation, injection sclerotherapy, TIPS, balloon-occluded retrograde transvenous obliteration (BRTO), and surgery. There have not been reports of hemostatic powder or OTSC used to control bleeding from duodenal varices to date. Our case demonstrates that hemostatic powder and OTSC can be effectively used to achieve hemostasis as a “bridge” until definitive therapy can be performed. Further studies are needed to evaluate the safety and effectiveness of these two treatments.Figure 1.: A) EGD revealed varices with a red spot in the second portion of the duodenum. B) Repeat EGD showed bleeding duodenal varices. C) Through-the-scope clips and hemostatic powder were applied to bleeding duodenal varices. D) OTSC was deployed for hemostasis.

THE USE OF ENDOSCOPIC LIGATION AND PORTO-SYSTEMIC SHUNTING IN THE TREATMENT STAGE OF CHILDREN WITH PORTAL HYPERTENSION

&#x0D; &#x0D; &#x0D; The bleeding from esophageal and gastric varices is one of the most dangerous complications in children with prehepatic portal hypertension (PH). The literature sources systematization shows that the question of choosing the variceal bleeding prevention optimal method and timing remains debatable in children. The main purpose of our study was to determine the opti- mal management for the variceal bleeding pre- ventive treatment in children with prehepatic PH. The obtained results indicate that the optimal option of the variceal bleeding prophylactic treatment may be a combination of endoscopic and surgical treatment methods in children with prehepatic PH.&#x0D; &#x0D; &#x0D;

Оцінка ендоскопічних та хірургічних методів лікування допечінкової форми портальної гіпертензії у дітей

Оцінка ендоскопічних та хірургічних методів лікування допечінкової форми портальної гіпертензії у дітей

Infected Extrahepatic Splanchnic Venous Stent(-Grafts): Clinical Presentation, Imaging, and Treatment in Three Patients

This brief report describes 3 patients with infected extrahepatic splanchnic venous stents or stent grafts. These devices had been placed to treat prehepatic portal hypertension 4 wk, 3 mo, and 31 mo, respectively, before readmission for fever. Blood cultures and fluorine-18 fludeoxyglucose positron emission tomography/CT were positive in all. With systemic antibiotic treatment, 2 patients showed a clinical recovery. In the third patient, antibiotic treatment failed. Therefore, the infected stent graft was surgically removed and a splenorenal shunt was created. No recurrent splanchnic venous infection was observed in these 3 patients.

3026 Rare Complication of Chronic Pancreatitis: Chronic Portal Vein Thrombus Causing Pre-Hepatic Portal Hypertension

INTRODUCTION: Portal vein thrombosis (PVT) is an uncommon complication of chronic pancreatitis. PVT more commonly occurs as a complication of acute pancreatitis and is an indicator of severity of disease. Patients with chronic pancreatitis can develop a pre-hepatic portal hypertension (HTN) in the setting of PVT. These patients are at risk for variceal hemorrhage. Early identification and management is critical. CASE DESCRIPTION/METHODS: A 34 year old female with a history of familial hypertriglyceridemia leading to necrotizing pancreatitis complicated by PVT in the past presented with sudden onset dizziness. She was documented to have a history of liver cirrhosis. On presentation to the outside hospital (OSH), patient was hypotensive and was noted to have a 5 g drop in Hb compared to baseline. She was transferred to the ICU and required support with blood transfusions and vasopressors. EGD at OSH demonstrated grade 1 non-bleeding esophageal varices and portal hypertensive gastropathy. Patient was transferred to our institution for TIPS evaluation. On presentation to our institution, patient remained hemodynamically stable. Examination was consistent with ascites and a R sided pleural effusion, which was confirmed by imaging. She underwent a work-up for chronic liver disease, which was negative. Her ascitic fluid volume was insufficient for paracentesis. Thoracentesis was performed with removal of 1.4 L of transudate consistent with hepatic hydrothorax. Her course was complicated by worsening jaundice. She subsequently underwent liver biopsy with hepatic venogram and pressure gradients. Biopsy did not show evidence of cirrhosis and hepatic venogram was consistent with pre-hepatic portal HTN. MRCP demonstrated dilated common bile duct and main pancreatic ducts. ERCP demonstrated stenosis in the main bile duct, which was treated with plastic stent placement. Following endoscopic intervention, patient's jaundice dramatically improved. TIPS was deferred given patient's history of PVT as well as limited efficacy in the absence of cirrhosis. DISCUSSION: Among reported cases of pre-hepatic portal HTN, chronic PVT secondary to chronic pancreatitis is rare. More commonly, splenic vein thrombus is described, resulting in a sinistral portal HTN with a predominance of gastric varices. Therapeutic considerations for pre-hepatic portal HTN are mainly focused on the prevention of variceal hemorrhage. Medical and endoscopic therapy is the standard of care. TIPS is an option for refractory cases.

1970 Spontaneous Page Kidney as a Cause of Gastric Variceal Bleed

INTRODUCTION: Gastric variceal bleeding occurs in 15–50% of patients with non-cirrhotic portal venous thrombosis but can also occur in cases of splenic vein thrombosis (SVT) due to the formation of isolated gastric varices (IGV). We present the first reported case of a page kidney causing splenic vein compression, thrombosis, and subsequent gastric variceal bleeding. CASE DESCRIPTION/METHODS: A 31-year-old stuntman presented with epigastric pain and worsening exertional dyspnea over 3 weeks. History was notable for melena and anemia with no reported ulcers on endoscopy. On admission, he had hemoglobin of 4.1 g/dl with severe iron deficiency and elevated reticulocyte count. There was no serologic evidence of hepatic or renal disease. A computed tomography (CT scan) of the abdomen revealed a large left-sided perirenal collection consistent with page kidney, splenomegaly and decreased caliber of the mid and distal splenic vein suggestive of nonocclusive SVT. His liver was normal. Initial endoscopy revealed an IGV type 1 and mild portal hypertensive gastropathy (Figure 1). CT angiography did not reveal a splenorenal shunt to pursue a balloon retrograde transvenous obliteration (BRTO). While admitted, he developed hematemesis and worsening anemia. Ultimately, underwent IR splenic vein stenting with a bare-metal stent and subsequent decompression of the gastric varices with brisk flow of the portal vasculature (Figure 2). DISCUSSION: Gastric varices are classified primarily by location with most involving the gastroesophageal junction due to portal hypertension. The incidence of bleeding is highest in IGV, typically associated with SVT. Common etiologies of SVT include pancreatitis, malignancy or trauma. Our case described an extrinsic splenic vein compression and subsequent thrombosis due to a sub-capsular renal hematoma possibly of unclear etiology. Treatment for GV often depends on local expertise, but commonly consists of cyanoacrylate injection, banding (especially in type 1 gastro-esophageal varices), transjugular intrahepatic portosystemic shunt (TIPS) placement, BRTO, and even splenectomy. More recently, in cases of IGV due to isolated SVT, splenic vein stenting has been increasingly utilized. In our case, TIPS would not address the pre-hepatic portal hypertension and cyanoacrylate was not available. Splenic vein stenting was thus chosen to decompress the IGV with excellent response seen on subsequent follow-up (Figure 1).

Tense Ascites as a Presentation of Protein S Deficiency in a 9-Year-Old Boy

Ascites is not a usual finding in prehepatic portal hypertension, including portal vein thrombosis, but when portal vein thrombosis is acute and massive, ascites can be a presenting feature. We report a 9-year-old boy with tense ascites and portal and superior mesenteric vein thrombosis. A 9-year-old boy was evaluated for tense ascites which led to umbilical hernia since one month before admission. He did not have any clinical or laboratory stigmata of parenchymal liver disease. Imaging studies showed superior mesenteric and portal vein thrombosis. In laboratory tests for pre-thrombotic states, he suffered from significant protein S deficiency. Thrombophilic states like protein S deficiency predispose patient to vascular thrombosis. This vascular thrombosis can be present with signs and symptoms related to their territories. Prevention of thrombosis and rethrombosis with anticoagulant therapy is recommended.

FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis

Pathological bacterial translocation (PBT) in cirrhosis is the hallmark of spontaneous bacterial infections, increasing mortality several-fold. Increased intestinal permeability is known to contribute to PBT in cirrhosis, although the role of the mucus layer has not been addressed in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined, but we hypothesize that the recently described gut-vascular barrier (GVB) is impaired in experimental portal hypertension, leading to increased accessibility of the vascular compartment for translocating bacteria. Cirrhosis was induced in mouse models using bile-duct ligation (BDL) and CCl4. Pre-hepatic portal-hypertension was induced by partial portal vein ligation (PPVL). Intestinal permeability was compared in these mice after GFP-Escherichia coli or different sized FITC-dextrans were injected into the intestine. Healthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-E. coli from the small intestine to the liver, whereas BDL and CCl4-induced cirrhotic mice demonstrate pathological translocation, which is not altered by prior thoracic-duct ligation. The mucus layer is reduced in thickness, with loss of goblet cells and Muc2-staining and expression in cirrhotic but not PPVL mice. These changes are associated with bacterial overgrowth in the inner mucus layer and pathological translocation of GFP-E. coli through the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran, but only slightly altered in PPVL mice. This pathological endothelial permeability and accessibility in cirrhotic mice is associated with augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB, whereas both FXR-agonists ameliorate gut to liver translocation of GFP-E. coli. Cirrhosis, but not portal hypertension per se, grossly impairs the endothelial and muco-epithelial barriers, promoting PBT to the portal-venous circulation. Both barriers appear to be FXR-modulated, with FXR-agonists reducing PBT via the portal-venous route. For intestinal bacteria to enter the systemic circulation, they must cross the mucus and epithelial layer, as well as the gut-vascular barrier. Cirrhosis disrupts all 3 of these barriers, giving bacteria access to the portal-venous circulation and thus, the gut-liver axis. Diminished luminal bile acid availability, cirrhosis and the associated reduction in farnesoid x receptor (FXR) signaling seem, at least partly, to mediate these changes, as FXR-agonists reduce bacterial translocation via the portal-venous route to the liver in cirrhosis.

The role of surgical shunts in the treatment of pediatric portal hypertension

BackgroundPortal diversion by surgical shunt plays a major role in the treatment of medically refractory portal hypertension. We evaluate our center’s experience with surgical shunts for the treatment of pediatric portal hypertension. MethodsAll patients who underwent surgical shunt at a single institution from 2008 to 2017 were reviewed. The primary outcome was intervention-free shunt patency. ResultsIn this study, 34 pediatric patients underwent portal shunt creation. The median age was 7.7 years (interquartile range 4.3–12.0). Twenty-nine patients (85%) had prehepatic portal hypertension and 5 patients (15%) had intrahepatic portal hypertension. The primary manifestations of portal hypertension were esophageal varices (97%) and gastrointestinal bleeding (77%). Eighteen patients (53%) underwent meso-Rex bypass, 10 patients (29%) underwent splenorenal shunt, and 6 patients (18%) underwent mesocaval shunt. Outcomes were notable for minimal wound complications (9%), rebleeding events (12%), and mortality (3%). In the postoperative setting, 10 patients (29%) experienced a shunt complication (occlusion or stenosis), 4 of which occurred in the early postoperative period and required urgent intervention. The 1-year and 5-year “primary patency” patency rates were 71% and 66%, respectively. ConclusionChildren suffer significant morbidity from the sequelae of portal hypertension. Our experience reinforces the feasibility of surgical shunts as an effective treatment option associated with low rates of morbidity and mortality.

Management of betablocked patients after sustained virological response in hepatitis C cirrhosis.

BACKGROUNDCurrent guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option.AIMTo assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population.METHODSInclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after direct-acting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician.RESULTSSample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/µL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk.CONCLUSIONPortal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.

Safety and Efficacy of a Novel Shunt Surgery Combined with Foam Sclerotherapy of Varices for Prehepatic Portal Hypertension: A Pilot Study

OBJECTIVES:This pilot study investigated the safety and efficacy of a novel shunt surgery combined with foam sclerotherapy of varices in patients with prehepatic portal hypertension.METHODS:Twenty-seven patients who were diagnosed with prehepatic portal hypertension and underwent shunt surgeries were divided into three groups by surgery type: shunt surgery alone (Group A), shunt surgery and devascularization (Group B), and shunt surgery combined with foam sclerotherapy (Group C). Between-group differences in operation time, intraoperative blood loss, portal pressure decrease, postoperative complications, rebleeding rates, encephalopathy, mortality rates and remission of gastroesophageal varices were compared.RESULTS:Groups A, B and C had similar operation times, intraoperative bleeding, and portal pressure decrease. The remission rates of varices differed significantly (p<0.001): one patient in Group A and 6 patients in Group B had partial response, and all 9 patients in Group C had remission (2 complete, 7 partial). Two Group A patients and one Group B patient developed recurrent gastrointestinal bleeding postoperatively within 12 months. No postoperative recurrence or bleeding was observed in Group C, and no sclerotherapy-related complications were observed.CONCLUSIONS:Shunt surgery combined with foam sclerotherapy obliterates varices more effectively than shunt surgery alone does, decreasing the risk of postoperative rebleeding from residual gastroesophageal varices. This novel surgery is safe and effective with good short-term outcomes.