Gastro 53 Liver - Portal Hypertension EHPVO and NCPF

Portal pressure higher than 5 mm Hg

• Baveno V workshop consensus statement defined EHPVO as
• - EHPVO is defined by obstruction of extrahepatic portal vein with or without the involvement of intrahepatic portal vein and does not include isolated thrombosis of splenic vein or SMV.
• - EHPVO is characterized by features of recent thrombosis or portal HTN with portal cavernoma as a sequel of portal vein obstruction.
• - Presence of cirrhosis or malignancy should be stated.

• Note  - 
• Portal HTN is the commonest cause of upper GI bleeding in children EHPVO is the most common cause of portal HTN in children.

• 1. Infection
• - Omphalitis, neonatal umbilical sepsis,
• - Intraabdominal infection, post umbilical catherization

• 2. Trauma or surgery
• - Umbilical vein cannulation
• - Abdominal surgery
• - Abdominal trauma

• 3. Congenital anomaly
• - Valve in portal vein
• - Portal vein stenosis, atresia or agenesis

• 4. Hypercoagulable state -  
• - Deficiency of protein-C, protein-S, anti-thrombin III
• - Polycythemia vera
• - Dehydration

5. Idiopathic

• Portal venous changes
• - Usually entire length of portal vein is occluded with extension into the splenic vein and sometimes to SMV.
• - On gross examination, original portal vein is difficult to identify as it is usually replaced by cluster of variable sized vessels arranged haphazardly in a connective tissue support, called as portal cavernoma. In case of shorter duration, cavernoma may not be there.

• Liver changes
• - Liver is normal and architecture pattern is preserved.

• Recent or acute EHPVO
• - Abdominal pain
• - Ascites
• - Fever

• Chronic EHPVO
• 1. Variceal bleeding
• - Esophageal varices > Gastric varices > Rectal varices
• - Risk factors – esophagitis, drug ingestion (NSAIDS), febrile illness
• 2. Splenomegaly
• - Size of spleen increases with age
• - Massive splenomegaly – anemia, thrombocytopenia, leucopenia
• 3. Pain abdomen
• - Due to splenomegaly
• - Continuous pain may indicate splenic infarct or extensive venous thrombosis.

• 1. Portal biliopathy
• - Abnormalities of the extrahepatic and intrahepatic bile ducts in patients with portal HTN.
• - These include compression by paracholedochal collaterals on the bile ducts resulting in displacement, narrowing, stricture, angulation, dilatations and irregularity of bile ducts. [@ DANISH] 
• - Extrinsic compression, ischemia and combination of both have been proposed to be the possible mechanism.
• - May lead to obstructive jaundice, choledocholithiasis, and cholelithiasis.

• 2. Ectopic varices
• - Gall bladder varices
• - Rectal varices

• 3. Gastropathy and colopathy
• - Congested mucosa at different parts of GI tract – present as acute or occult GI bleeding.

• 4. Hypersplenism
• – thrombocytopenia, leucopenia, anemia

• 5. Special issues in children
• - Growth retardation – Malabsorption due to portal hypertensive enteropathy, increased bleeding frequency
• - Mental function and encephalopathy – hyperammonia as a result of porto-systemic shunting.

• It is the splenic hyperactivity with increased blood cell destruction. Diagnostic criteria are:
• - Splenomegaly
• - Pancytopenia
• - Normal bone marrow (Primary) or Hypercellular bone marrow (secondary)
• - Reversibility by splenectomy.

Child with upper GI bleeding + Splenomegaly with no features of chronic liver disease – most likely EHPVO.

• 1. USG –
• Portal vein and branches are invisible and replaced by multiple tortuous collateral veins – cavernomatous transformation of portal vein.
• Portal vein thrombosis may be observed as an echogenic lesion within the vessel.
• Liver pathology (size and echogenicity) and portal biliopathy which may be intrahepatic bile duct dilatation due to compression of CBD by cavernoma.

2. Doppler USG – Hemodynamic status of portal system, it is the diagnostic method of choice.

3. CECT – Display varices and parenchymal hepatic abnormalities.

4. CT  portogram - show portal vein replaced by multiple collaterals

4. Endoscopy – to detect status of varices.

5. ERCP, MRCP – to detect presence of portal biliopathy.

• 1. Prophylaxis
• - Reduce risk of initial bleeding – Primary prophylaxis
• - Reduce risk of rebleeding – Secondary prophylaxis
• Propranolol is used in dose of 2mg/kg/day in 2 divided doses. Heart rate is monitored and dosage is adjusted to prevent fall of heart rate more than 20% of baseline or absolute heart rate below 60/min.

• 2. Endoscopic Management of acute variceal bleeding
• - Endoscopic variceal ligation - Rapid eradication of varices with fewer sessions and fewer complications
•  
• Complications of endoscopic management - Retrosternal pain, fever, ulcer, stricture

• 3. Medical management of acute variceal bleeding
• - Vasopressin – splanchnic vasoconstriction that reduces blood flow in all splanchnic organs – reduces portal venous flow and decreases portal pressure.
• - Terlipressin – synthetic analogue of vasopressin, longer activity
• - Somatostatin – causes splanchnic vasoconstriction
• - Octreotide – somatostatin analogue, 1-2µgm/kg stat followed by 1-2µgm/kg/hr, when bleeding is controlled, dose is reduced by 50% every 12-24 hours.

• - Failure of endotherapy to control bleeding
• - Presence of gastric or ectopic varices (not amenable to endoscopic management)
• - Complications – portal biliopathy
• - Severe growth failure
• - Massive splenomegaly – hypersplenism
• - Poor follow up
• - Rare blood group

Depending on whether they completely decompress, compartmentalize, or partially decompress the portal venous circulation, portosystemic shunts can be classified as nonselective, selective, or partial.

• - Complete decompression of entire portal venous system by diverting total portal blood flow away from liver.
• - Effectively control variceal bleeding
• - Because of complete portal flow diversion, however, they are complicated by frequent postoperative encephalopathy and accelerated hepatic failure. 

• Types of non-selective shunts
• A) end-to-side fashion - end to side portacaval shunt (Eck fistula)
• B) side-to-side fashion - portacaval shunt, large diameter interposition shunts, and conventional splenorenal shunt. 

Presently, nonselective shunts are only rarely indicated. TIPS, also a nonselective shunt, is the preferred therapy for most situations in which nonselective shunts were previously used (e.g., patients with both variceal bleeding and medically intractable ascites). In general, a nonselective shunt is constructed only when a TIPS cannot be performed or when a TIPS fails.

Note - TIPS has no role in EHPVO.

• Advantage -  hypersplenism is eliminated by splenectomy
• Disadvantage - Because the smaller proximal rather than the larger distal end of the splenic vein is used, shunt thrombosis is more common after this procedure than after the distal splenorenal shunt.
• Low frequency of encephalopathy is probably a result of restoration of hepatic portal perfusion after shunt thrombosis developed

• - Divert the blood of gastro-esophageal splenic segment and maintain the blood flow in mesenteric segment
• - Lesser chance of post shunt encephalopathy
• - Types of selective shunts –
• a) Distal splenorenal shunt (Warren shunt)
• b) Inokuchi shunt 

• The distal splenorenal shunt consists of anastomosis of the distal end of the splenic vein to the left renal vein and interruption of all collateral vessels (e.g., coronary vein and gastroepiploic veins) that connect the superior mesenteric vein and gastrosplenic components of the splanchnic venous circulation
• This results in separation of the portal venous circulation into a decompressed gastrosplenic venous circuit and high-pressure superior mesenteric venous system that continues to perfuse the liver.
• Although the distal splenorenal shunt results in portal flow preservation in more than 85% of patients during the early postoperative interval,the high-pressure mesenteric venous system gradually collateralizes to the low-pressure shunt, resulting in loss of portal flow in approximately 50% of patients by 1 year

• Contraindications of Warren shunt -
• - Intractable ascitis
• - Prior splenectomy
• - A splenic vein diameter less than 7 mm is a relative contraindication to the procedure because the incidence of shunt thrombosis is high when a small diameter vein is used.
• 

Interposition of a vein graft between the left gastric (coronary) vein and IVC

• Interposition of jugular venous allograft between SMV and intrahepatic left portal vein – restores physiological hepatopetal flow. 
• Done in EHPVO 
• 

• The objectives of partial and selective shunts are the same: effective decompression of varices, preservation of hepatic portal perfusion, and maintenance of some residual portal hypertension.
• A small-diameter interposition portacaval shunt using a PTFE graft, combined with ligation of the coronary vein and other collateral vessels. When the prosthetic graft is 10 mm or less in diameter, hepatic portal perfusion is preserved in most patients, at least during the early postoperative interval

• Sugiura-Futagawa operation - extensive esophagogastric devascularization that includes vagotomy, pyloroplasty, and splenectomy, as well as an esophageal transection
• Hasab Devascularization

• Portal biliopathy –
• o Presence of choledocholithiasis – endoscope sphincterotomy and stone removal
• o Strictures – Ballon dilatation and stent placement
• o If endoscopic failure – portosystemic shunt followed by biliary surgery

• Hypersplenism
• o Overwhelming sepsis may increase if child is <5 years. Vaccination against pneumococcus, H. influenzae and Meningococcus at least 10 days before splenectomy.

EHPVO and NCPF are together categorized as non-cirrhotic portal hypertension. These affect young patients who characteristically present with well tolerated upper GI bleed together with significant splenomegaly. The differentiating features are as follows:

• Clinical features:
• 1.The age at presentation for NCPF is usually the 3rd decade  (much older than EHPVO) though 7% of all NCPF patients may present before 15 years of age. 
• 2.Massive splenomegaly is a very prominent clinical feature of NCPF.
• 3.While most patients of NCPF tolerate upper GI bleed episodes well (like EHPVO), the nodular variety of NCPF (10% of all NCPF cases) is a subgroup which could present with derangement of liver function tests and liver decompensation following a bleed episode. 
• 4.On the other hand, symptomatic portal biliopathy is more common in EHPVO than NCPF because of the longer duration of disease and more of high pressure collaterals in the hepatoduodenal ligament in EHPVO.

• Radiological features:
• EHPVO: The main portal vein and/or its main branches are characteristically seen to be replaced by a cavernoma on imaging (Doppler/CT portovenogram/MR portovenogram).The direction of flow of blood in the collaterals is hepatopetal.
• NCPF: The main portal vein is dilated (> 13-14 mm); with thickened portal vein wall (>3 mm). The intrahepatic terminal branches of the portal vein (beyond the second order branches) are attenuated.
• Core liver biopsy would show preserved liver architecture with increased peri-venular fibrosis in the portal triads. ​
• Essentially, the diagnosis of NCPF is reached by excluding a portal cavernoma  or underlying chronic liver  disease (by etiological work up for CLD and liver biopsy).

[Note - normal portal vein diameter is <1cm]

• The hepatorenal syndrome is potential causes of acute kidney injury in patients with acute or chronic liver disease.
• Arterial vasodilatation in the splanchnic circulation, which is triggered by portal hypertension, appears to play a central role in the hemodynamic changes and the decline in renal function.
• The presumed mechanism is increased production or activity of vasodilators, mainly in the splanchnic circulation, with nitric oxide thought to be most important.
• As the hepatic disease becomes more severe, there is a progressive rise in cardiac output and fall in systemic vascular resistance; the latter change occurs despite local increases in renal and femoral vascular resistance that result in part from hypotension-induced activation of the renin-angiotensin and sympathetic nervous systems.

Types - Based upon the rapidity of the decline in kidney function

• •Type 1 – more serious type; it is defined as at least a twofold increase in serum creatinine  to a level greater than 2.5 mg/dL during a period of less than two weeks, a urine output less than 400 to 500 mL per day.
• •Type 2  – less severe than that observed with type 1 disease. The major clinical feature in patients with type 2 hepatorenal syndrome is ascites that is resistant to diuretics.

• Acute insults – bacterial infection, GI bleeding
• Rapid diuresis

• In patients with spontaneous bacterial peritonitis - administration of IV albumin (1.5 g/kg) at the time of diagnosis of infection and another dose of albumin (1 g/kg) on day 3 of antibiotic treatment .
• In selected patients with cirrhosis and ascites - chronic norfloxacin therapy (400 mg/day)

• Critically ill patients – treatment with norepinephrine in combination with albumin.
• Not critically ill patients – terlipressin with albumin. Where terlipressin is not available, initial treatment with a combination of midodrine, octreotide, and albumin
• Who fail to respond to medical therapy with the above regimens - TIPS
• If failure to above therapy – liver transplantation. Dialysis as a bridge to liver transplantation or liver recovery.