Portal Hypertension in children: approach and evaluation

 

PORTAL HYPERTENSION in Children

Q1: What is portal hypertension? portal venous pressure > 12 mm Hg    or portal pressure gradient (between IVC and portal vein) >5 mm Hg  Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG) [the difference between the wedged (WHVP) and the free hepatic venous pressures] Pressure = Flow x Resistance (Resistance increases due to active myofibroblast or vascular smooth muscle cells in intrahepatic veins; and overall liver disease;  Flow  increases due to splanchnic arteriolar dilatation by release of endogenous vasodilators) (portal veins start and end as capillaries and no valves; please vide the picture on porto-caval anastomosis sites)

Q2: What are the 3 key components of portal hypertension? Splenomegaly Ascites Varix (Esophageal varices/ Gastro-esophageal varices/ Isolated gastric varices/ Rectal varices)

Q3: What are the causes of portal hypertension?  [Here is a list of causes of portal hypertension. For details of each entity, please view the table below.] Pre-sinusoidal EHPVO (extrahepatic portal venous obstruction) NCPF (non cirrhotic portal fibrosis) CHF (congenital hepatic fibrosis) Schistosomiasis  Myeloproliferative  Sinusoidal CLD (chronic liver disease) Post-sinusoidal VOD (veno-occlusive disease)  BCS (budd-Chiari syndrome)  CP (Constrictive pericarditis)  TR (Tricuspid regurgitation)

Q3: What are the complications of portal hypertension: Hepatopulmonary syndrome (HPS) Portopulmonary syndrome (PPS) Portal biliopathy Minimal hepatic encephalopathy (MHE) Hypersplenism Growth failure

Q4: What are the risk factors for development of EHPVO, NCPF, BCS? Hypercoagulable states Protein C deficiency Protein S deficiency Antithrombin III deficiency Factor V Leiden mutation MTHFR mutation Prothrombin mutation Myeloproliferative disorders Paroxysmal nocturnal hemoglobinuria Antiphospholipid syndrome (APLA) Nephrotic syndrome Cancer Pregnancy Use of oral contraceptives Intra-abdominal causes: umbilical vein catheterisation Intra-abdominal infection, appendicitis Chronic pancreatitis- splenic vein thrombosis Diarrhoea, endotoxin absorption  Intra abdominal surgery Peritoneal dialysis Endoscopic sclerotherapy Inflammatory bowel disease (IBD) Behcet syndrome Tumoral invasion: Hepatocellular carcinoma, Renal-cell carcinoma, Adrenal carcinoma Idiopathic

Q5: How to work up a case of portal hypertension? For etiological evaluation:  USG abdomen and Doppler of Hepatic vein, IVC CT Portal Venogram (usually prior to surgical operation) Fibroscan of liver Liver function tests LFT For varix assessment: Upper GI Endoscopy-- find the grade of varix and decide on prophylaxis (eg. Propranolol, Serial endoscopic program)  Associated underlying etiology evaluation:  Thrombophilia work up, Protein C, S, MTHFR, F-V LM etc For complication evaluation: Check SpO2, PaO2 if cyanosed or  suspected Hepatopulmonary syndrome (HPS) Hypersplenism- check CBC or blood counts Growth parameters evaluation Check LFT for suspected portal biliopathy

PORTAL HYPERTENSION (pHTN): Causes & evaluation
etiology	Pointers	Management (Mx)
PRE-SINUSOIDAL
Extra hepatic portal venous obstruction (EHPVO) (good livers but bad veins) m/c cause of pHTN in children in India	Age: 1st or 2nd decade, usually 5-6 yr age UGI Bleed: hematemesis, malena (usually about 80% children present with UGI bleed below 20 year age) Splenomegaly (commonly seen, mild<6cm/ moderate 6-10cm/ massive >10cm) Usually no Hepatomegaly/ cirrhosis/ ascites/ jaundice (as the liver gets another blood supply from Hepatic artery) Stunted growth (dt splenomegaly compressing the stomach leading to early satiety and deprivation of hepatotropic growth factors like insulin and glucagon) Look for complications like portal biliopathy etc Doppler PV: visible thrombus, portal cavernoma, proximal dilatation, tortuous portal vein, PV diameter >17mm, absence of respiratory phasicity, demonstration of collaterals like LGV>7mm, collaterals of >1.7 times the aortic calibre CT/MR  Portovenogram Predisposing factors evaluation (see risk factors)  ACUTE Portal vein thrombosis: usually due to septicemia and dehydration following severe diarrhoea leading to abdominal pain (due to small bowel ischemia and intestinal infarction causing acute abdomen), progressive ascites. mortality is often high.	Mx goal:  prevent bleeding (primary prophylaxis).  manage acute bleeding.  prevent recurrent bleed (secondary prophylaxis).  Mx strategies:  Serial endoscopic variceal management programme Propranolol prophylaxis Growth supplements Splenectomy/  Devascularization
Noncirrhotic portal fibrosis (NCPF)	clinical features same as EHPVO except for usual age of presentation adulthood (25-35yrs) obliterative portal venopathy, involves small and medium sized branches of portal vein.  USG & Doppler: main portal vein mostly spared, microthrombi in branches can be detected. nodularity in the liver may be detected due to nodular regenerative hyperplasia.  CT/MR  Portovenogram	Management is moreover similar to EHPVO
Schistosomiasis (Hepatosplenic form) Schistosoma mansoni &  Schistosoma japonicum second most common parasitemia worldwide (after Malaria) lay eggs in presinusoidal venules, leading to granulomatous inflammation	UGI bleeding Splenomegaly Hepatomegaly (usually left lobe) lack of typical physical changes of liver dysfunction like jaundice, spider nevi, palmar erythema, ascites, gynecomastia Repeated stool examinations Schistosoma mansoni eggs; schistosoma antibodies by serological test CBC: sometimes eosinophilia Liver biopsy: the fibrosis is restricted to the portal area, with preservation of the lobular architecture of the liver (c.f.  cirrhosis, fibrosis starts around portal tracts or hepatic veins and spreads forming bridges between hepatic and portal veins)	praziquantel 40 mg/kg Variceal banding TIPS for severe portal hypertension (take Liver biopsy for microbiological evaluation and histopathology) esophagogastric devascularization with splenectomy
Congenital Hepatic fibrosis (CHF) due to  deficiency of the terminal branches of the portal vein in the fibrotic portal zone.	Hepatomegaly (due to hepatic fibrosis) with stony hard consistency of liver.  Splenomegaly GI bleed (less common) associated with: ciliopathies that affect kidneys like polycystic kidney disease (PKD), nephronophthisis (NPHP) chronic tubulointerstitial disease Imaging like USG, MRI of liver and kidney Fibroscan Liver Biopsy: similar to cirrhosis (but clinically with preserved liver function) Genetic testing: clinical exome	symptomatic and supportive Management of complications Genetic counselling of parents
Myeloproliferative disease  Mechanism:  i. infiltration of portal zones with cells like RBC, platelets causing increased viscosity. ii. platelet dysfunction causing thrombosis. iii. cirrhosis of liver	Chronic symptoms- fever, bone pain, petechiae, repeated infections, Splenomegaly thrombosis may include various other parts of body including deep vein thrombosis (DVTs)  Bone marrow biopsy: diagnostic most of the time Clinical exome or mutation study (including JAK2 mutation) evaluate for: primary myelofibrosis, polycythemia vera, essential thrombocythemia, hypereosinophilic syndrome, Systemic mastocytosis and CML, Hodgkins	Manage portal hypertension with beta blocker and endoscopic variceal ligation Treat the underlying etiology (by oncologist or hematologist)
SINUSOIDAL
Chronic liver disease (CLD)/ Cirrhosis	look for Common causes like: Hep B, Hep C, Autoimmune hepatitis, Galactosemia, GSD, HFI, a1-AT deficiency, Wilson, Drug induced-Mtx, INH UGIB: hematemesis, malena Splenomegaly (may regress after large GI bleed- Smith Howard syndrome) Hepatomegaly/ cirrhosis/ ascites/ jaundice e/o CLD: palmar erythema, spider angioma, clubbing, edema USG Abdomen Fibroscan	Ascites Mx: Diuretics, low salt diet Varix Mx: endoscopy, beta blocker. Etiology Mx: like antivirals for HBV and HCV, Chelation for Wilsons, Immunosuppressants for autoimmune disease etc.
POST- SINUSOIDAL
Veno-occlusive disease (VOD) or  Hepatic sinusoidal obstruction syndrome (HSOS) It is nonthrombotic obliterative process	predisposing factors:  transplant, plant alkaloids (herbal tea), irradiation, drugs- immunosuppressants, anticancer drugs (cyclophosphamide) typically presents in the days or weeks after hematopoietic cell transplantation (HCT) with refractory thrombocytopenia, hepatomegaly, ascites, and jaundice, Doppler USG:  increased phasicity of portal veins with eventual development of portal flow reversal Liver biopsy: for definitive diagnosis (difficult to diagnose by imaging) Severity grading (in adult post HCT)  [based on: Time from emergence of first clinical symptoms to diagnosis ≤4 days/ Bilirubin:≥5 mg/dL, Doubling <48 hour/  Transaminases >5 times upper limit of normal/ Weight gain >5 percent/ Renal function ≥1.5 times baseline at transplant]	Supportive care: analgesia, diuretics Defibrotide may be tried High dose methylprednisolone (after screening for infections) TIPS Liver transplant
Budd-Chiari syndrome (BCS) or  Hepatic venous outflow tract obstruction (HVOTO) +- IVC obstruction	Usually triad of - Abdominal pain, Hepatomegaly, Ascites in acute/ fulminant form: nausea, vomiting, jaundice in chronic/ subacute form: splenomegaly, varix, abdominal vein dilatation [look for evidence of coagulopathy, encephalopathy and hepatorenal syndrome__indicates poor prognosis and warrants urgent relief of obstruction] USG Doppler (IOC) (Sn,Sp 85%): non-visualisation of HV Confirm by Hepatic venography: ‘Spider web pattern’  USG: Caudate lobe hypertrophy (GB edema may misdiagnosed as cholecystitis) Rule out cardiac causes: Abdomino-jugular reflux + Echo Liver Biopsy: nutmeg liver appearance (Zone 3 necrosis and congestion) Etiological work up: thrombotic/ APLA etc	Control ascites: restrict Na, Lasilactone LVP+Albumin with Lasix Anti-coagulant: Heparin (acute stage) Warfarin (target INR 2-2.5) Thrombolytic therapy Anticoagulant Screen for varices & b-blocker prophylaxis Ascites control: with diuretics Angioplasty TIPS Surgical Shunt: side to side portacaval, central splenorenal, mesocaval, (meso atrial if IVC block) Liver transplant
Constrictive pericarditis (CP) & Tricuspid regurgitation	can be suspected by cardiovascular system examination (Pulse, JVP, BP, precordial examination) Confirmed by echocardiography, CXR	manage with diuretics, cardiac remodelling agents etc treat the underlying etiology

For author information: sabyasachimistri@gmail.com

Dr Sabya, MD, Pediatrics, (AIIMS)