Portal Hypertension & Varices

DEFINITION

PH is elevated pressure within the portal venous system.
Normal portal pressure is ~<10mmHg
Portal hypertension typically >12mmHg

Portal Systems

A portal system is a venous system with 2 sets of capillaries joined by a vein.
Hepatic venous portal system is valveless venous system

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EPIDEMIOLOGY

Varies by cause
  

AETIOLOGY

Pathogenesis
Classified as:
Prehepatic
Hepatic
Post-Hepatic
Or more practically, as pre-sinusoidal or post-sinusoidal.
- Pre-sinusoidal normally has normal hepatocellular function (hence, eg, pts won't develop liver failure in context of variceal bleeding)
- hepatic or sinusoidal is by far the most common cause of PH
Can be differentiated based on wedge pressure measured by a catheter introduced into superior or inferior cava.

Aetiologies
Pre-Sinusoidal
(Liver function usually maintained unless inflammation extends beyond portal tracts)
Congenital absence of portal vein or abnormality
Portal vein thrombosis and causes
- eg. sepsis, splenectomy, pancreatitis, hypercoagulable states.
--> varices
Splenic or SMA thrombosis also
Idiopathic Portal Hypertension
Schistosomiasis
- common worldwide; causes obstruction to portal venules
Nodular regenerative hyperplasia
Primary biliary cirrhosis (prior to cirrhosis)

Sinusoidal
Non-cirrhotic portal fibrosis
Cirrhosis and causes
- worldwide, viral hepatitis is a key cause.
Sarcoidosis
[Any disease that distorts the sinusoids can lead to PH e.g. scarring of liver]
Pressure is transmitted upstream and throughout the portal system.
- viral hepatitis is the most common cause worldwide.

Post-sinusoidal
Budd-Chiari syndrome
Hepatic vein thrombosis
Tumours
Constrictive pericarditis
Trucuspid valve incompetence; chronic venous congestion

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BIOLOGICAL BEHAVIOUR

Pathophysiology


PH
70% of liver blood comes from vein; 30% from artery
Portal venous pressure should be compared to the vena cava; the 'portal pressure gradient'.
- can be measured by liver vein catheterization with wedging of the catheter in a hepatic vein.
Gradient <10 normal; >10 = PH
- at >10 often ascites will develop
- at >12, varices may develop.
- at >20, high mortality associated with bleeding.
Portal pressure distributed throughout portal system and collateral circulation develops.

Consequences

i) changes in portal pressure
ii) autonomic effects
iii) liver metabolism effects.
iv) release of cytokines affecting circulation

Vicious cycles
1. There is an active contraction of myofibroblasts and vascular smooth muscle cells in portal veins to compensate
--> this is counterproductive attempt to increase liver flow).
- vascular tone is a result of balance between endogenous vasoconstrictors (endothelin, leukotrienes, angiotensin II) and vasodilators (NO, prostacyclin).
--> due to low liver blood flow, mediators released favor vasoconstrictor imbalance, worsening PH.

2. In splanchnic circ, NO is plentifully released as a response to PH, leading to splanchnic vasodilation, further increasing portal pressure.
- meanwhile, peripheral vasodilation causes water and salt retention; accumulation of salt and water further increases splanchnic circulation and ascites
Increased circulating blood volume manifested by hyperdynamic CO (increased SV)
- despite this compensation, renal compromise may occur secondary to low effective perfusion pressure; hepatorenal syndrome.

Complications / Manifestations
Usually PH made in the context of its complications
Varices
- most serious complication.
- mortality of 20% mortality, and 60% rebleed rate within 2y if untreated.
Ascites
- PH implicated; associated with blood pooling in splanchnic circulation
- retention of water
- sodium and fluid accumulation in peritoneal cavity
Hypersplenism
- and trapping of platelets and WCs
--> thrombocytopaenia in a pt with liver disease strongly suggests PH.
Liver Failure (follows variceal bleeds)
Hepatorenal syndrome (follows variceal bleeds)

Surgery
Associated with high mortality from cirrhosis.
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MANIFESTATIONS

Symptoms

Patients without complications have few if any symptoms.
Diagnosis usually made in context of one of the above complications.

Need to Assess

1. Underlying liver disease
- clinical history and findings.
- e.g. jaundice, ascites, muscle wasting
- lab tests for grading.

2. Imaging studies
- liver uss, augmented by CT, MRI
- shape and size of liver, focal lesions suspicious for HCC
- assessment of venous and arterial liver anatomy
- portal vein patency and tributaries

3. Endoscopy
Varices and gastropathy.

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INVESTIGATIONS

Biochemistry

See also ascites

Haematology
Low platelets in cirrhotics is strongly suggestive

Imaging
Imaging focuses on liver morphology and vasculature.
USS +/- CT and MRI.

Endoscopy
Focused on varices and portal hypertensive gastropathy.
Size, extent and risk factor of varices are considered carefully in treatment decisions.
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MANAGEMENT

Evaluation

Assess underlying disease, imaging and endoscopy.
Grade severity of liver disease, as with Child-Turcotte-Pugh or MELD score.
Treat underlying cause.

Child Pugh
Total Serum Bilirubin
Bilirubin <35 mg/dl: 1 point
Bilirubin 35-52 mg/dl: 2 points
Bilirubin >52 mg/dl: 3 points
Serum Albumin
Albumin >3.5 g/dl: 1 point
Albumin 2.8 to 3.5 g/dl: 2 point
Albumin <2.8 g/dl: 3 point
INR
INR <1.70: 1 point
INR 1.71 to 2.20: 2 point
INR >2.20: 3 point
Ascites
No Ascites: 1 point
Ascites controlled medically: 2 point
Ascites poorly controlled: 3 point
Encephalopathy
No Encephalopathy: 1 point
Encephalopathy controlled medically: 2 point
Encephalopathy poorly controlled: 3 point

Conservative

PH alone does not constitute reason for transplant.
See management of complications.

Operative

Role of Transplant
Often is the ultimate treatment (depending on cause)
- but PH alone is not an indication for transplant
--> only done in context of liver decompensation or HCC. (limited supply and need for immunosuppression).

MELD Score

Calculates a score based on creatinine, bilirubin, INR
- validated; indicates how likely a pt with end-stage liver disease is to die with transplantation.
- highest MELD score = highest priority
Risk of bleeding relates to coagulopathy.

Risks
Bleeding may be harzardous for transplant in this context
- coagulopathy and varices in retroperitoneum
- ocreotide may help to reduce splanchnic hypertension.
Venovenous bypass may be needed to reduce anhepatic phase.
Graft function may be impaired by high flow through portal system post transplant.
- decrease portal pressure gradient with pharcologic therapy

Outcomes
Generally successful, though many have varices they don't usually bleed
Persistent hypersplenism may continue
Need to watch graft for problems from recurrent liver disease or rejection
- will reincite PH.


Medical Management of Varices
See also Varices notes

Prophylaxis
1. Pharmacotherapy
- beta blockers; reduce portal pressures
2. Endoscopy
- banding if large or beta-blocker intolerant.
3. Transplant
- only with advanced end stage disease ie other indications for transplant

Acute variceal bleeding
1. Pharmacotherapy
- beta-blockers
2. Endoscopy
- banding
3. TIPS
- 10% of people = not controlled or recurs, then TIPS may be indicated

Prevention of recurrent bleeding
1. Pharmacotherapy
- beta blockers
2. Endoscopy
- banding
--> these two steps control bleeding in 80%
3. Tips
4. Liver Transplant
5. Shunts = ~legacy.

Ascites and SBP
Ascites common sequela of PHTN
Rx fluid restriction and diuretics
Frusemide and spironolactone advised
If SBP suspected, tap and culture peritoneal fluid.
- some use prophylactic antibiotics.

Shunting Procedures
No longer a significant part of the management repertoire in portal hypertension.
Now better management with radiology, endoscopic, and liver transplantation.

TIPS Notes
Effective across spectrum of causes of PH

Indications
:

1. Variceal bleeding; as per algorithm

2. Recurrent ascites
- TIPS is very effective in control, but risks generally outweigh benefits; highly selective.

3. Hepatic hydrothorax
- 500ml+ of pleural fluid accumulation with ascites
- in <10% of cirrhotics, due to peritoneal fluid entering chest
- same points as for TIPS, not routine; highly selective

4. Hepatorenal syndrome
- a bad prognostic sign; late stages of haemodynamic change resulting from cirrhosis
- alterations in vasoactive hormones cause renal arterial vasoconstriction and intrarenal arteriovenous communications
--> renal hypoperfusion and renal failure.
- TIPS is possible but not very safe due to contrast load and hemodnamic changes

5. Hepatopulmonary Syndrome
- intrapulmonary vasodilation and multiple right to left shunts; impaired gas exchange
- TIPS cannot be recommended as little evidence; but possible in highly selected cases as bridge to surgery

6. Budd-Chiari
- hepatic venous ouflow obstruction, results in cirrhosis and PH
- treated with hepatic balloon angioplasty, liver transplant if fulminant; then TIPS can be a bridge to surgery
- may permenantly stabilize liver in some pts, obviating need for transplant

7. Portal Gastropathy
- diffuse dilatation of gastric veins; inflamed and fragile gastric mucosa can bleed.
- TIPS may normalize portal pressure, reducing this risk.
- only if not responsive to more conservative therapies.

Technique

1. Proper pt work up reduces complications
- Imaging of patent portal vein and relative orientation of hepatic veins
--> plan efficient access
- Hydrate for renal function
- Prophylactic ABs +/- lactulose
Be cognizant of risks, esp 30d mortality, which ranges from <5% to 50% for emergent procedures in pts with advanced liver disease.

2. Access through R Int Jug with vascular sheath

3. Assessment of Pressures
- must ensure R atrial pressure not elevated else blood shunted to an already overburdened heart.
- 20mmHg R pressure dangerous.  16 mmHg borderline; don't do unless variceal bleeding and needs life saving therapy.
- delineate portal venous system by injection of CO2 via hepatic vein catheter; not nephrotoxic

4. Place Shunt
- cannulate R portal vein from R hepatic vein
- sheath advanced across tract over needle; contrast injected to ensure correct location.
- balloon used to predilate tract.
- portal pressure checked and shunt only placed if benefit suggested by ratio
- (then bail out and instead embolize varices

5. Evaluate shunt
- us. 8-10mm stent to allow sufficient flow but prevent encephalopathy
- final portal venogram documents flow and lack of variceal filling

TIPS: Special Issues

Budd-Chiari: very challenging due to thrombosis; classic spider vein appearance.
- may necessetate IVC placement
Parallel TIPS: if symptoms not alleviated from a previous TIPs
- can place a second parallel
Transumbilical or Direct Portal Access
-When access to portal vein challenging due to anatomy can use these methods to conduit into L portal vein.
- opacified portal system, providing a TIPS target
TIPS Reversal: occasionally necessary
- when overzealous shunting causes liver failure or encephalopathy
- options are decrease shunting or shut down the TIPS
- reduce by second stent inside first, e.g. hourglass shape.

TIPS: Outcomes
Most effective option for treating varices
- rebleeding rate is low; 4%
- cessation of bleeding almost immediate after TIPS
Very effective for ascites when used; reduces risk 50-80%
Improves survival and transplant free survival compared to other options
Improves renal function in 62% of hepatorenal syndrome pts.

Complications
Liver failure 2%
Encephalopathy 10% (unless already decompensated; then 50%)
Bleeding 4%
Sepsis 4%, (use prophylactic ABs)
Renal failure (contrast, dehydration).
Mortality 10-30%, mainly in advanced liver disease patients.

Follow-up
USS surveillance
Recurrent variceal bleeding suggests TIPS occlusion.
10% reintervention rate

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REFERENCES
Tjandra, Clunie, Thomas
Cameron 10th