Extra Hepatic Portal Venous Obstruction in Children: Approach and Management Mediscope

Portal hypertension in children is not uncommon and extra hepatic portal venous obstruction (EHPVO) constitute about 75% of portal hypertension. Several risk factors predispose to development of EHPVO such as neonatal sepsis, umbilical catheterization, severe dehydration, abdominal trauma or surgery etc. Common presentations are haematemesis and splenomegaly. Acute variceal bleeding is a medical emergency. Liver function is normal in extrahepatic portal hypertension unless there is portal bilopathy. High index of suspicion is the key of early diagnosis. portal vein confirm extra hepatic portal venous obstruction (EHPVO) in presence of thrombus and/or cavernoma. Adequate management including endotherapy, pharmacotherapy and/or surgery is an important key for better outcome.


Incidence:
PVT is responsible for 5%-10% of all cases of portal hypertension in western countries. About 40% are attributed to PVT in developing countries. In children, EHPVO accounts for 80% cases of PHT. After cirrhosis (upto 64.1%), EHPVO is the most common cause of portal hypertension globally. In the Indian subcontinent, 20%-30% of all variceal bleeds are due to EHPVO. 6,7 Etiology: The etiology of EHPVO is diverse and risk factors are usually detected in less than half of patients. Common local causes are: omphalitis, portal vein phlebitis, umbilical vein catheterization (UVC), pancreatitis, liver abscess, surgery around portal vein (splenectomy, cholecystectomy, Billroth-II procedure), and malignancies (pancreatic, hepatic, or duodenal). [8][9][10] Systemic causes include diarrheal illnesses, abdominal sepsis, and nephrotic syndrome. 11,12 A combination of local and systemic factors is seen in 19-64% of patients. 10 Congenital anomalies have been reported in 30% of children with EHPVO-more often in those without history of omphalitis-the commonest ones were cardiovascular and urinary tract abnormalities, others had Turner's syndrome, cleft lip and palate, coloboma, external ear, and limb deformities. 11,13 Finally, idiopathic cases constitute around 13-28% of adults and 26-62% of children with EHPVO. 8

Pathophysiology:
According to the unifying hypothesis, a major thrombotic event occurring at a young age involves main PV resulting in EHPVO, whereas repeated microthrombotic events later in life involve small or medium branches of PV leading to Idiopathic portal hypertension (IPH). Dual theory explains development of IPH secondary to increased splenic blood flow secondary to high inducible nitric oxide synthase (iNOS) and intrahepatic obstruction.8 Endothelial-mesenchymal transition (EndMT) theory says that vascular endothelial cells of portal venules acquire myofibroblastic features leading to collagen synthesis and subsequent occlusion of small PV branches. 14 Pathologically, there is cavernomatous transformation of the PV � a cluster of varying sized vessels replacing PV that are arranged haphazardly within connective tissue support at the liver hilum. These collaterals may extend for a variable length inside and outside the liver. Architectural pattern of liver is well preserved. Mild periportal fibrosis may be seen. 8,15 Clinical presentation: EHPVO has a bimodal age of presentationthose secondary to UVC, omphalitis, or perinatal events usually manifest early (within 3 years), whereas those following intraabdominal infections or idiopathic ones manifest late (8 years) or sometimes into early adulthood.8 Variceal bleed (49-85%) and splenomegaly (63-88%) are the commonest presentations in children. Mean ages of first bleeding episode are around 3.8-5.2 years. [16][17][18][19][20][21][22][23][24] In developing country, the diagnosis is mostly delayed up to a mean age of 6.3-9.3 years till the children have a mean number of 1.8-3.1 bleeding episodes before presentation. 16,25,26 Ascites is present in 4% of children and is often transient, related to the bleeding episode, growth failure, and hypoalbuminemia. 19,27 Investigations: Liver function test (LFT): Usually normal. Elevations of alkaline phosphatase and gamma-glutamyl transpeptidase are seen with development of portal biliopathy, while hypoalbuminemia may be seen during bleed episodes particularly in the setting of growth failure. 8,15 Endoscopy: Esophageal varices (fig 1), gastric varices, anorectal varices. It is seen that EHPVO children have greater proportion of high risk varices than the cirrhotic etiologies (70 vs 32%), esophageal varices are seen in 85-94% and two-thirds have large varices with red colour signs.28 Doppler ultrasonography of portal vein: PV thrombosis and portal vein cavernoma (sensitivity and specificity of >95%). 8,15 Contrast-enhanced CT and CT angiogram: Cavernomatous transformation of portal vein with splenomegaly, collaterals, and/or no opacification of intrahepatic portal vein in chronic EHPVO.29 MRCP for portal biliopathy (fig 4). 29 Liver biopsy: Normal but not mandatory. 29

Management:
Control and prophylaxis of variceal bleed: Treatment option includes vasoconstrictor drugs (octreotide), endotherapy-endoscopic sclerotherapy and endoscopic variceal ligation and propranolol. Octreotide used to control active variceal bleeding, 1-2 micro gm/kg stat at bolus dose followed by 1-2 micro gm/kg/hour at maintenance dose for 3-5 days. Band ligation followed by sclerotherapy may be a better alternative to sclerotherapy alone in children and used for both control of active variceal bleeding and prophylaxis. Endoscopic sclerotherapy (EST) ( fig. 2) and endoscopic variceal ligation (EVL) ( fig. 3) both are highly effective in controlling acute variceal bleeding in over 90% of cases along with eradication of variceal bleeding. Propranolol given for primary and secondary prophylaxis of variceal bleeding at a dose of 1-5 mg/kg/day to achieve 25% reduction in pulse rate. Propranolol must be withheld during bleeding episode. 11,19,30 Role of surgery: Meso-Rex shunt or Mesenterico-left portal vein bypass (MLPVB), decompresses superior mesenteric vein into left branch of PV (LPV) via an autologous graft, is the surgical shunt of choice in EHPVO. It restores hepatic portal blood flow in the closest possible physiological manner, and in a long run protects liver from parenchymal extinction. [31][32][33] Role of radiological intervention: Transjugular intrahepatic portosystemic shunt (TIPSS) -feasible in a non-cirrhotic PVT. Indications are: PHT complications (recurrent bleed, refractory ascites) getting difficult to manage medically, or need of anticoagulation in the presence of large varices. 34,35 Shunt reduction or closure is done by using coils or balloon occluded trans-venous obliteration. 35

Role of anti-coagulation:
In EHPVO with prothrombotic state as a cause, anti-coagulant can be started taking into consideration the risk of bleeding from the varices. 8

Management of portal biliopathy:
Endoscopic decompression is favoured for symptomatic PB (like jaundice, cholangitis, choledocholithiasis, or biliary stricture). However, in the long run, most of these patients require a shunt surgery. Biliary diversion procedures are rarely needed in case the symptoms of biliary obstruction persist after shunt. 8,[36][37][38] Portal vein thrombosis and liver transplant: Portal vein thrombosis is seen in 2%-6% post-transplantat Patient. 39,40 Portal vein thrombosis in pre-transplant was considered as an absolute contraindication for liver transplantation. With the advancement in the treatment options, portal vein thrombosis can represent itself as an indication for liver transplant. 41,42 The first successful liver transplant in patients with portal vein thrombosis was reported by Shaw. 43 Follow Up: Regular 6 monthly follow-up of all patients with EHPVO is mandatory to look for spleen size, growth, quality of life, school performance, development of jaundice, decompensation, portal biliopathy (PB), and hepato pulmonary syndrome, and to assess their laboratory values and imaging for PVT and PB. 8

Conclusion:
EHPVO is a childhood disorder causing PHT, where the etiology is either perinatal or early childhood vascular insult. The diagnosis is relatively easy if a high index of suspicion is kept. The management is mostly endoscopic with a good long-term outcome. 8