What is portal hypertension?

What is Portal Hypertension?

Portal hypertension is a pathological increase in portal pressure, defined as a hepatic venous pressure gradient (HVPG) above 5 mmHg, that develops from increased intrahepatic resistance combined with increased portal blood flow, leading to life-threatening complications including variceal bleeding, ascites, and hepatorenal syndrome. 1, 2

Pathophysiology

Portal hypertension develops through two fundamental mechanisms that work together:

Increased Intrahepatic Resistance

• Structural component (70%): Fibrous tissue deposition, vascular distortion from regenerative nodules, and microthrombi physically obstruct blood flow 2
• Functional component (30%): Endothelial dysfunction with reduced nitric oxide bioavailability causes active vasoconstriction within the liver 2
• Activated hepatic stellate cells further alter sinusoidal blood flow after activation 2

Increased Portal Blood Flow

• Splanchnic vasodilation occurs primarily through increased nitric oxide production, which is the main factor leading to increased splanchnic blood flow 1
• Hyperglucagonemia and neoangiogenesis further contribute to elevated splanchnic blood flow 1
• Systemic vasodilation manifests as arterial hypotension, activating neurohumoral systems (norepinephrine, angiotensin-2, anti-diuretic hormone) that cause sodium/water retention and increased cardiac output—creating a hyperdynamic circulatory state 1

This follows the hydraulic equivalent of Ohm's law: Pressure = Resistance × Flow 2

Diagnostic Thresholds and Clinical Significance

The severity of portal hypertension is classified by HVPG measurements:

• Normal HVPG: 1-5 mmHg 1, 2
• Portal hypertension: HVPG >5 mmHg 1, 2
• Mild portal hypertension: HVPG >5 but <10 mmHg 1, 2
• Clinically significant portal hypertension (CSPH): HVPG ≥10 mmHg—the threshold above which complications (varices, ascites, clinical decompensation) begin to appear 1, 2
• High bleeding risk: HVPG >12 mmHg identifies patients at risk for variceal hemorrhage 1
• High mortality threshold: HVPG ≥16 mmHg is independently associated with increased mortality in both compensated and decompensated cirrhosis 2, 3

Gold Standard Measurement

HVPG is measured through hepatic vein catheterization using a balloon catheter, calculating the difference between wedged (occluded) hepatic venous pressure and free hepatic venous pressure 1, 2

Critical caveat: HVPG measures sinusoidal pressure and does not provide useful data in prehepatic or presinusoidal portal hypertension (portal vein thrombosis, schistosomiasis) where wedged pressure remains normal 1

Clinical Consequences and Prognosis

Portal hypertension is the most important cause of morbidity and mortality in cirrhosis patients, with 30-day mortality of 20% after variceal bleeding 3

Impact on Survival

• Compensated cirrhosis: 80% 5-year survival 3
• When ascites develops: Survival drops to 50% at 5 years 3
• Refractory ascites: 1-year mortality ranges from 20-50% 3

Major Complications

• Variceal bleeding: Controlled in up to 85% with combination vasoactive agents plus endoscopic therapy 3
• Ascites: Most common complication of portal hypertension 2
• Hepatorenal syndrome: Frequent and grave complication triggered by arterial vasodilation in splanchnic circulation 3
• Hepatic encephalopathy: Results from portosystemic shunting 3

Non-Invasive Assessment

While HVPG is the gold standard, non-invasive alternatives exist:

• Transient elastography (liver stiffness measurement): Sensitivity 90-96%, specificity 48-50% at 15 kPa cutoff 2
• APRI score: 56% sensitivity, 68% specificity 2
• Doppler ultrasound: First-line for extrahepatic portal vein obstruction 2

Important pitfall: Patients with idiopathic non-cirrhotic portal hypertension are often radiologically misclassified as cirrhotic, but a clue is low liver stiffness (<12 kPa) despite signs of portal hypertension 2

Therapeutic Implications

Pharmacologic Targets

Non-selective beta-blockers (propranolol, nadolol, carvedilol) reduce portal pressure through:

• β-1 blockade: Decreases cardiac output 1
• β-2 blockade: Causes splanchnic vasoconstriction through unopposed α-adrenergic activity (this is the more important mechanism) 1
• Carvedilol's additional benefit: Anti-α1 adrenergic activity causes intrahepatic vasodilation 1

Hemodynamic Response Goals

• HVPG reduction ≥20% from baseline or to <12 mmHg: Virtually eliminates variceal bleeding risk 3, 4
• HVPG reduction ≥10%: Associated with decreased risk of first variceal hemorrhage in compensated cirrhosis 2
• Responders have markedly decreased risk of bleeding/rebleeding, ascites, spontaneous bacterial peritonitis, and improved survival 4

Surgical Considerations

CSPH (HVPG >10 mmHg) and Child-Pugh class B cirrhosis represent absolute contraindications to major liver resections (>2 segments), as portal hypertension predicts post-hepatectomy liver failure, perioperative mortality, and reduced long-term survival 3