Intrahepatic Portal Hypertension Research Articles

Subcutaneous therapy for portal hypertension: PHIN-214, a partial vasopressin receptor 1A agonist

Cirrhosis is a liver disease that leads to increased intrahepatic resistance, portal hypertension (PH), and splanchnic hyperemia resulting in ascites, variceal bleeding, and hepatorenal syndrome. Terlipressin, a prodrug that converts to a short half-life vasopressin receptor 1 A (V1a) full agonist [8-Lys]-Vasopressin (LVP), is an intravenous treatment for PH complications, but hyponatremia and ischemic side effects require close monitoring. We developed PHIN-214 which converts into PHIN-156, a more biologically stable V1a partial agonist. PHIN-214 enables once-daily subcutaneous administration without causing ischemia or tissue necrosis and has a 10-fold higher therapeutic index than terlipressin in healthy rats. As V1a partial agonists, PHIN-214 and PHIN-156 exhibited maximum activities of 28 % and 42 % of Arginine vasopressin (AVP), respectively. The potency of PHIN-156 and LVP relative to AVP is comparable for V1a (5.20 and 1.65 nM, respectively) and V1b (102 and 115 nM, respectively) receptors. However, the EC50 of PHIN-156 to the V2 receptor was 26-fold higher than that of LVP, indicating reduced potential for dilutional hyponatremia via V2 agonism compared to terlipressin/LVP. No significant off-target binding to 87 toxicologically relevant receptors were observed when evaluated in vitro at 10 µM concentration. In bile duct ligated rats with PH, subcutaneous PHIN-214 reduced portal pressure by 13.4 % ± 3.4 in 4 h. These collective findings suggest that PHIN-214 could be a novel pharmacological treatment for patients with PH, potentially administered outside of hospital settings, providing a safe and convenient alternative for managing PH and its complications.

Biliary sepsis complication with congenital hepatic fibrosis: an unexpected outcome

BackgroundCHF (Congenital hepatic fibrosis) is a rare hereditary disease characterized by periportal fibrosis and ductal plate malformation. Little is known about the clinical presentations and outcome in CHF patients with an extraordinary complication with biliary sepsis.Case summaryOur case described a 23-year-old female diagnosed as CHF combined with biliary sepsis. Her blood culture was positive for KP (Klebsiella pneumoniae), and with a high level of CA19-9 (> 1200.00 U/ml, ref: <37.00 U/ml). Meanwhile, her imaging examinations showed intrahepatic bile duct dilatation, portal hypertension, splenomegaly, and renal cysts. Liver pathology revealed periportal fibrosis and irregularly shaped proliferating bile ducts. Whole-exome sequencing identified two heterozygous missense variants c.3860T > G (p. V1287G) and c.9059T > C (p. L3020P) in PKHD1 gene. After biliary sepsis relieved, her liver function test was normal, and imaging examination results showed no significant difference with the results harvested during her biliary sepsis occurred.ConclusionThe diagnosis of CHF complicated with biliary sepsis in the patient was made. Severely biliary sepsis due to KP infection may not inevitably aggravate congential liver abnormality in young patients. Our case provides a good reference for timely treatment of CHF patients with biliary sepsis.

A Narrative Review on Non-Cirrohotic Portal Hypertension: Not All Portal Hypertensions Mean Cirrhosis.

Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.

Focused panel sequencing points to genetic predisposition in non-cirrhotic intrahepatic portal hypertension patients in India.

Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme-a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolismand withfamilial NCIPH. Eighty-four Indian patients with liver biopsy-proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.

The genetics of portal hypertension: Recent developments and the road ahead.

Portal hypertension (PH), defined as a pathological increase in the portal vein pressure, has different aetiologies and causes. Intrahepatic PH is mostly secondary to the presence of underlying liver disease leading to cirrhosis, characterized by parenchymal changes with deregulated accumulation of extracellular matrix and vascular abnormalities; liver sinusoidal endothelial cells and hepatic stellate cells are key players in PH progression, able to influence each other. However, PH may also develop independently of parenchymal damage, as occur in portosinusoidal vascular disorder (PSVD), a group of clinical and histological entities characterized by portal vasculature dysfunctions. In this particular group of disorders, the pathophysiology of PH is still poorly understood. In the last years, several genetic studies, based on genome-wide association studies or whole-exome sequencing analysis, have highlighted the importance of genetic heritability in PH pathogenesis, both in cirrhotic and non-cirrhotic cases. The common PNPLA3 p.I148M variant, one of the main determinants of the susceptibility to steatotic liver disease, has also been associated with decompensation in patients with PH. Genetic variations at loci influencing coagulation, mainly the ABO locus, may directly contribute to the pathogenesis of PH. Rare genetic variants have been associated with familiar cases of progressive PSVD. In this review, we summarize the recent knowledges on genetic variants predisposing to PH development, contributing to better understand the role of genetic factors in PH pathogenesis.

Fatty liver and celiac disease: Why worry?

Celiac disease (CD) is a chronic inflammatory intestinal disorder mediated by the ingestion of gluten in genetically susceptible individuals. Liver involvement in CD has been widely described, and active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, fatty liver in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. Non-alcoholic fatty liver disease is estimated to affect approximately 25% of the world's adult population and is the world's leading cause of chronic liver disease. In view of both diseases' global significance, and to their correlation, this study reviews the available literature on fatty liver and CD and verifies particularities of the clinical setting.

Noninvasive diagnosis of liver fibrosis in schistosomiasis japonica: Opportunities and challenges

Noninvasive diagnosis of liver fibrosis in schistosomiasis japonica: Opportunities and challenges

S1736 Gallbladder Adenocarcinoma Ascites Masquerading as Intrahepatic Portal Hypertension

S1736 Gallbladder Adenocarcinoma Ascites Masquerading as Intrahepatic Portal Hypertension

First Clinical Experience of Venous Reconstruction With Autologous Vascular Prosthesis From the Sickle Ligament of the Liver With Partial Portosystemic Bypass Surgery

Aim of study. Presentation of our own first clinical experience of venous reconstruction in portosystemic bypass surgery with the use of autologous vascular prostheses of the falciform ligament of the liver in the splenorenal position in a patient with portal hypertension syndrome in the outcome of liver cirrhosis of viral etiology.Material and methods. Clinical observation of a patient born in 1978 with a diagnosis of cirrhosis of the liver of viral etiology (HCV) Child-Pugh A (6). MELD 10 points. Inactive phase. Intrahepatic portal hypertension syndrome. Esophageal varices grade III according to A. G. Scherzinger, gastric varices type I (GOV1) according to Sarin. Condition after repeated recurrent esophageal-gastric bleeding. Due to the high risk of another bleeding, as a secondary prevention of esophageal-gastric bleeding, partial splenorenal anastomosis of “H” - type was performed with the use of an autologous vascular prosthesis of the falciform ligament of the liver in the splenorenal position.Results. A flap measuring 60.0x20.0 mm was cut from the falciform ligament of the patient’s liver. From the latter, after adjusting the size of the graft to the individual needs of the patient, an autologous conduit was formed. It was used as an insert in the formation of an “H” - type splenorenal anastomosis with the imposition of two end-to-side anastomoses between the splenic vein and one end of the conduit and between the left renal vein and the other end of the conduit. The patency of the anastomosis was checked using intraoperative sonography. In a satisfactory condition, the patient was discharged for outpatient follow-up treatment at the place of residence. At the moment of writing the article, the follow-up period was 8 months. The bleeding did not recur. No varicose veins were found in the esophagus and stomach during control endoscopic examinations. The patency of the splenorenal shunt was confirmed by ultrasound dopplerography.Conclusion. The first clinical experience of venous reconstruction with portosystemic bypass surgery using as a possible replacement of autologous vascular prostheses of the falciform ligament of the liver in the splenorenal position in a patient with portal hypertension syndrome in the outcome of cirrhosis of the liver of viral etiology gives hope for the possibility of further successful testing of this method of splenorenal bypass surgery to reduce the risk of bleeding from varicose veins.

NON-CIRRHOTIC PORTAL FIBROSIS CAUSING PORTAL HYPERTENSION

Portal hypertension is more prevalent in patients with liver cirrhosis and occurs infrequently in those without liver cirrhosis. Non-cirrhotic portal brosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are the two most common causes of non-cirrhotic portal hypertension. Unlike EHPVO, NCPF does not cause thrombosis of the extrahepatic portal vein. Sclerosis of the portal vein's medium and small branches occurs in NCPF. In NCPF, the hepatic venous pressure gradient (HVPG) is normal, in contrast to cirrhosis, where it is increased. Additionally, NCPF is referred to as non-cirrhotic intrahepatic portal hypertension (NCIPH), idiopathic portal hypertension, hepatoportal sclerosis, and benign intrahepatic portal hypertension. It is a disease with an unknown etiology that primarily affects middle-aged males and females and manifests as hematemesis and massive splenomegaly

Use of laparocentesis in the treatment of ascites in patients with liver cirrhosis

Ascites occurs in about 60 % of patients with cirrhosis within 10 years of diagnosis. Laparocentesis is the preferred first-line therapy in patients with cirrhosis and massive tense ascites, allowing more than 5–6 liters of ascitic fluid to be removed at one time. The search for informative prognostic factors and the development of a method for predicting unfavorable outcomes of repeated laparocenteses in patients with ascites are relevant to timely refer this contingent of patients to perform TIPS.The purpose of the study was to develop and evaluate the diagnostic significance of a model for determining the probability of unfavorable outcomes of laparocentesis in patients with ascites on the background of liver cirrhosis.The results of treatment of 99 patients with the ascitic syndrome associated with intrahepatic portal hypertension were studied. The multiple regression analysis using the binary response logit model was carried out to calculate the prediction models. The analysis of the treatment results of patients with liver cirrhosis and ascites by the laparocentesis method revealed a number of factors that influence the onset of an unfavorable outcome. 2 models with the inclusion of initial variables are the most promising for forecasting. Model A includes: patient weight, serum-ascites total protein gradient, hyponatremia; model B: MELD-Na score, serum-ascitic total protein gradient, patient weight. The developed prediction method is highly informative, effective, easily applicable, and can be widely used in clinical practice.The ability to predict an unfavorable outcome in patients with portal hypertension and ascites after laparocentesis allows for a personalized approach in the process of timely selection of more effective, but also more expensive treatment methods, such as TIPS, which will help us to increase the therapy effectiveness and the survival of this cohort of patients.

P-118 NONINVASIVE PARAMETERS OF PREDICTORS OF ESOPHAGEAL VARICES (EV) IN CHILDREN WITH INTRAHEPATIC PORTAL HYPERTENSION

Children with portal hypertension (PH) are at risk for variceal bleeding. The standard test for screening varices is endoscopy, an invasive method. Evaluate noninvasive parameters of predictors of esophageal varices (EV) in children with intrahepatic portal hypertension. This cross-sectional study included 168 children with no history of GI bleeding who underwent the first screening endoscopy for EV (mean age: 8.3+-4.7 years). Patients were classified into two groups: G1: Child-Pugh A and G2: Child-Pugh B and C. The noninvasive methods assessed were: 1) platelet count; 2) spleen size; 3) spleen size z score; 4) platelet count/spleen size ratio; 5) platelet count and spleen size z score ratio; 6) platelet count and equivalent adult spleen size ratio; 7) APRI; 8) CPR; 9) Risk score and 10) King's variceal prediction score. Continuous variables were expressed as the median and interquartile range (25%-75%) and compared using the Mann-Whitney test. The distribution of variables was analyzed through the chi-square test, with Fisher exact test, 2tailed. ROC curve analysis was used to calculate diagnostic accuracy as areas under the curve (AUROC); 95%confidence intervals (CI). The significance was considered when P<0.05. The incidence rate of EV was: G1 49.4% (44/89) and G2 64.6% (51/79) (OR 1.86-95% CI 1.001-3.47). The significant predictor of EV for G1was the Risk score: OR 0.813 (95% CI 0.723-0.903) and for G2, platelet count/spleen size z score: OR 0.849 (95% CI 0.756-0.943). The noninvasive predictors of EV varied according to the severity of the disease. The Risk Score forecasted EV in children Child A. Platelets/spleen size predicted EV in children Child B and C.

Effectiveness and safety of endoscopic treatment for duodenal variceal bleeding: a systematic review.

Duodenal varix is a rare condition that involves massive bleeding, diagnostic difficulties, and a high rate of rebleeding and mortality. The purpose of this study was to systematically review endoscopic treatment for duodenal variceal bleeding to evaluate its effectiveness and safety. We searched PubMed, Embase, Web of Science, and the Cochrane Library up to 21 November 2019. Ninety-two studies containing 156 patients were finally included, and individual data from 101 patients (mean age: 52.67 ± 13.82 years, male: 64.4%) were collected and further analyzed. We used an analysis of variance and χ2 or Fisher's exact tests to analyze individual data from 101 patients. The cause of duodenal variceal bleeding was cirrhosis-related intrahepatic portal hypertension (IPH) in 76.2% of patients. The overall rates of initial hemostasis and treatment success of endoscopic treatment for duodenal variceal bleeding were 89.1 and 81.2%, respectively. The median duration of follow-up was 4.5 (1.0, 12.0) months. The overall rates of rebleeding and mortality were 8.9 and 13.9%, respectively. Among a variety of endoscopic treatments available, only the initial hemostasis rate was significantly different between the endoscopic injection sclerotherapy and endoscopic tissue adhesive (ETA) groups (72.7 vs. 94.7%, P = 0.023); differences in treatment success, rebleeding, mortality, and adverse events were not statistically significant among the four groups. Endoscopic intervention is a feasible, well tolerated, and effective modality for the treatment of duodenal variceal bleeding. Among the variety of endoscopic treatments available, ETA with cyanoacrylate may be preferable for duodenal variceal bleeding.

Idiopathic refractory ascites after allogeneic stem cell transplantation: a previously unrecognized entity

At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)-related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients' median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.

КЛИНИЧЕСКИЙ СЛУЧАЙ ЛЕЧЕНИЯ ПАЦИЕНТА С ПОРТАЛЬНОЙ ГИПЕРТЕНЗИЕЙ, РАЗВИВШЕЙСЯ НА ФОНЕ ТРОМБОЗА ВОРОТНОЙ ВЕНЫ

Non-cirrhotic causes of the development of portal hypertension make up about 10%. The factors leading to its development are the development of thrombosis in the portal vein system, occlusion due to pancreatitis, pancreatic tumors, and other causes. Acute bleeding from esophageal varices is a formidable complication of portal hypertension, regardless of its etiology. The tactics of treatment and prevention of bleeding from esophageal varices in patients with portal vein thrombosis generally corresponds to that for intrahepatic portal hypertension in liver cirrhosis with some additions. Aim. Presentation of the results of clinical observation of an open Hassab operation (esophagogastric devascularization without esophageal transection + splenectomy) in a patient with portal vein thrombosis complicated by portal hypertension and esophageal varices, as well as a short literary excursion on this issue. Materials and methods. The patient was admitted to the surgical department with thrombosis of the portal, splenic and superior mesenteric veins complicated by subhepatic portal hypertension with splenomegaly, varicose veins of the esophagus and stomach of the 2nd-3rd degrees, left-sided hydrothorax, moderate anemia. Direct anticoagulants, antibiotics, non-steroidal anti-inflammatory drugs, proton pump inhibitors were used. Given the risk of bleeding from varicose veins of the esophagus and stomach, as well as existing necrosis in the spleen, Hassab operation (esophagogastric devascularization in combination with splenectomy) was performed at the fourth level of surgical management. Results. Despite ongoing therapy with antiplatelet agents, in 2 months after the operation the patient developed thrombosis of the left subclavian and internal jugular veins as well as recurrent left-sided hydrothorax. Conservative therapy has been successful. Relapse of esophageal varices bleeding was diagnosed in a patient 4 years after surgery, conservative and endoscopic hemostasis being successful. Acute thrombophlebitis of the saphenous veins of the right lower leg was diagnosed in the patient 9 years after surgery, it having been treated conservatively. Acute adhesive intestinal obstruction developed 11 years after surgery, conservative therapy was successful. Currently, the patient is being followed at the outpatient department, his condition being satisfactory and hydroxycarbamide, antiplatelet agents and non-selective betablockers being taken by him on a regular basis takes. Based on this clinical observation, it seems difficult to judge the effect of Hassab operation on the course of the disease in the described patient. However, it is worth noting a persistent increase in the level of platelets in the general blood test in the postoperative period, which could contribute to the recurrence of venous thrombosis in the patient. Conclusions. According to the current scientifically based recommendations in the treatment of these patients priority should be given to conservative and minimally invasive endoscopic and interventional X-ray endovascular techniques.

Early detection and staging of chronic liver diseases with a protein MRI contrast agent

Early diagnosis and noninvasive detection of liver fibrosis and its heterogeneity remain as major unmet medical needs for stopping further disease progression toward severe clinical consequences. Here we report a collagen type I targeting protein-based contrast agent (ProCA32.collagen1) with strong collagen I affinity. ProCA32.collagen1 possesses high relaxivities per particle (r1 and r2) at both 1.4 and 7.0 T, which enables the robust detection of early-stage (Ishak stage 3 of 6) liver fibrosis and nonalcoholic steatohepatitis (Ishak stage 1 of 6 or 1 A Mild) in animal models via dual contrast modes. ProCA32.collagen1 also demonstrates vasculature changes associated with intrahepatic angiogenesis and portal hypertension during late-stage fibrosis, and heterogeneity via serial molecular imaging. ProCA32.collagen1 mitigates metal toxicity due to lower dosage and strong resistance to transmetallation and unprecedented metal selectivity for Gd3+ over physiological metal ions with strong translational potential in facilitating effective treatment to halt further chronic liver disease progression.

Non-Cirrhotic Intrahepatic Portal Hypertension Induced Pulmonary Arterial Hypertension: Is it More Prevalent than we Think?

Introduction Porto-Pulmonary Hypertension (PoPH) belongs to WHO group I, Pulmonary Arterial Hypertension (PAH). It has a prevalence of 0.5-5% and is potentially curable with liver transplant. Non-cirrhotic intrahepatic portal hypertension (NCIPH) is a rare cause of PoPH that shares clinical features of advanced right heart failure. Based on review of the literature and Pulmonary Hypertension (PH) registries, most studies report the prevalence of patients with the liver cirrhosis with little to no data on the incidence of PoPH amongst the non-cirrhotic patient population. In this report, we describe the two cases of “missed” NCIPH and PoPH who were diagnosed in our institution within the span of six months. Case Reports The first patient was a 36 year old African American female who carried an initial diagnosis of SLE and ITP. She was on combination therapy with prostacyclin and endothelin receptor antagonist for the treatment of PAH. Her recurrent epistaxis from thrombocytopenia was refractory to therapy with prednisone, Rituximab, Romiplostim requiring multiple PRBC transfusions. Abdominal imaging revealed splenomegaly while liver biopsy demonstrated Nodular Regenerative Hyperplasia (NRH) without cirrhosis. The second patient, a 44 year old Chinese female, was initially diagnosed with idiopathic PAH. She was also identified to have ITP and showed no significant response to dexamethasone. On hospital admission, both patients presented with large volume ascites, splenomegaly and dependent edema. While in the ICU, they underwent RHC with assessment of Hepatic Venous Pressure Gradient (HVPG) demonstrating severely elevated pressures at 14 mmHg (Normally ≤ 5 mmHg) (Table 1). Liver biopsy was performed during the same procedure without complications. The pathology was consistent with NCIPH. Summary Our report illustrates the importance of considering the diagnosis of NCIPH in patients with PH and refractory ITP, particularly in the setting of splenomegaly and lack of overt cirrhosis. Due to an estimated 50% of patients with NCIPH that go on to develop portal hypertension, it is important to consider this diagnosis when evaluating patients with PH as the treatment strategy differs from idiopathic and connective tissue disease-associated PAH. Given the limited risk of HVPG measurement as part of the evaluation of patients with PAH, our single center experience would suggest screening for NCIPH in select patients and embracing this etiology in the differential.

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.

Pediatric Hepatobiliary Interventions in the Setting of Intrahepatic Vascular Malformations, Portal Hypertension, and Liver Transplant

Within the broad spectrum of pediatric hepatobiliary disorders, hepatic vascular malformations, portal hypertension, and hepatic transplant interventions pose numerous challenges. The role of interventional radiology within each of these conditions is discussed herein, beginning with endovascular management of high flow hepatic vascular malformations. Next, while becoming less common in adult populations, surgical portoportal and portosystemic shunts remain prevalent in many pediatric centers. Shunt anatomy is reviewed along with endovascular management techniques for shunt dysfunction. Next, the growing experience with pediatric transjugular intrahepatic portosystemic shunt placement is reviewed along with tips for success in pediatric patients. Finally, pediatric hepatic transplant interventions are discussed with technical notes pertinent to split liver anatomy.

Idiopathic Portal Hypertension Related Refractory Ascites (IPHRA) after Allogeneic Stem Cell Transplant

Background At our center, we observed a series of patients who developed transudative refractory ascites secondary to non-cirrhotic non-veno-occlusive disease (NC-nVOD) portal hypertension after allogeneic transplant (allo-SCT). The natural history, pathogenesis and etiology of this phenomenon is not well characterized nor well studied in the literature. Objectives To study and analyze the clinical characteristics and outcome of myeloid and lymphoid malignancy patients who developed IPHRA post allo-HCT. Methods In this retrospective study, we analyzed age>18 myeloid and lymphoid malignancy patients who developed IPHRA post allo-HCT. IPHRA was defined as NC-nVOD intrahepatic portal hypertension (serum ascites albumin gradient ≥ 1.1 or hepatic venous pressure gradient (HVPG) >5) and related refractory ascites in the absence of pre and post-hepatic etiologies of portal hypertension. Results We identified 24 patients who developed IPHRA post allo-HCT from our database. Median age at the time of allo-HCT was 52 yrs (range, 23-67). 23/24 did not have elevated LFT (Transaminases> 2.5 ULN/Bilirubin>1.5 ULN) before allo-HCT. Median time to development of IPHRA after allo-HCT was 95 days (range, 21-576 days). A median number of paracentesis that these patients had was 2 (range, 1-11); 5 had an intraperitoneal catheter placed, and 2 had TIPS to decrease the portal pressure. Portal pressures were measured in 15 patients, 9 had moderate portal hypertension (HVPG 5-10), and 6 had severe portal hypertension (HVPG >10). Liver biopsy was done in 20 patients, and for 3 patients we had autopsy results available. None of the patients met either the histological or clinical criteria of VOD or cirrhosis. 19 patients (79 %) died, and the median survival after development of IPHRA was 5.2 months (range, 0.7-49). The most common cause of death were complications of ascites/liver failure (n=7, 37%), and infectious causes (n=7, 37%). Conclusion IPHRA is an unrecognized fatal entity post-allo-HCT and has a high mortality rate. Further investigation is necessary to establish prognostic criteria for patients at risk of this serious complication.