What is portal vein hypertension?

Portal Hypertension: Definition and Pathophysiology

Portal hypertension is a pathological increase in portal venous pressure defined by a hepatic venous pressure gradient (HVPG) above 5 mmHg, with clinically significant portal hypertension (CSPH) occurring at HVPG ≥10 mmHg—the threshold at which life-threatening complications develop. 1

Fundamental Pathophysiology

Portal hypertension develops through a dual mechanism following the hydraulic equivalent of Ohm's law where "Pressure = Resistance × Flow":

• Increased intrahepatic resistance (the primary driver) consists of a structural component (70%) from fibrous tissue, vascular distortion from regenerative nodules, and microthrombi, plus a functional component (30%) from endothelial dysfunction with reduced nitric oxide bioavailability 1

• Increased portal blood flow occurs as the disease progresses, with splanchnic vasodilation contributing to elevated portal pressure 2, 3

• Activated hepatic stellate cells alter sinusoidal blood flow after activation, contributing significantly to increased intrahepatic resistance 2

Hemodynamic Classification

The severity stratification based on HVPG measurements is critical for prognosis and management:

• Normal HVPG: 1-5 mmHg 4, 1
• Portal hypertension: HVPG >5 mmHg 1
• Clinically significant portal hypertension (CSPH): HVPG ≥10 mmHg—the threshold where complications such as esophageal varices and ascites develop 4, 1
• High mortality threshold: HVPG ≥16 mmHg, independently associated with death in both compensated and decompensated cirrhosis 4, 1

Etiology

Cirrhosis from any chronic liver disease is the predominant cause of portal hypertension, accounting for the majority of cases. 5

Common causes include:

• Chronic viral hepatitis B/C 2
• Alcoholic liver disease 2
• Non-alcoholic steatohepatitis 2
• Autoimmune hepatitis 2
• Primary biliary cirrhosis (which can develop portal hypertension early, even before established cirrhosis) 5

Non-cirrhotic causes include:

• Idiopathic non-cirrhotic portal hypertension (INCPH), characterized by portal hypertension with patent portal/hepatic veins but without cirrhosis on biopsy 2
• Extrahepatic portal vein obstruction/thrombosis 2, 1
• Congenital liver fibrosis, sarcoidosis, and schistosomiasis 2

Life-Threatening Complications

Portal hypertension is the most important cause of morbidity and mortality in patients with cirrhosis, leading to:

• Variceal bleeding: 30-day mortality of 20%, with bleeding risk as high as 30% within 2 years of medium/large varices developing 4, 3
• Ascites: Reduces 5-year survival from 80% in compensated cirrhosis to 50% when ascites appears; refractory ascites has 1-year mortality of 20-50% 4, 1
• Hepatorenal syndrome (HRS): A grave complication of refractory ascites triggered by arterial vasodilation in splanchnic circulation, with Type 1 showing progressive severe renal decline 4
• Hepatic encephalopathy: Develops from portosystemic shunting 2, 4
• Spontaneous bacterial peritonitis: Complicates ascites 3

Diagnostic Approach

HVPG measurement is the gold standard for diagnosing and quantifying portal hypertension. 1, 5

Non-invasive alternatives include:

• Transient elastography (liver stiffness measurement): CSPH is highly unlikely at LSM ≤15 kPa and likely present at LSM ≥25 kPa, with 90-96% sensitivity and 48-50% specificity at 15 kPa cutoff 2, 1
• Blood-based tests (APRI score): 56% sensitivity and 68% specificity 1
• Doppler ultrasound: First-line investigation for extrahepatic portal vein obstruction 1

A critical caveat: Patients with INCPH are often radiologically misclassified as cirrhotic since ultrasound demonstrates liver surface nodularity and portal vein wall thickening; a clue for INCPH is low liver stiffness (<12 kPa) despite signs of portal hypertension 2

Prognostic Significance

HVPG is considered the single best predictor of outcome available to clinicians:

• In compensated cirrhosis, HVPG ≥10 mmHg predicts higher risk of clinical decompensation 2, 1
• HVPG ≥16 mmHg is strongly associated with increased mortality 2, 1
• HVPG reduction of ≥10% after therapy or to <12 mmHg correlates with considerable reduction in variceal bleeding risk and reduced portal hypertension-related decompensations 4, 1

Clinical Presentation Patterns

Compensated cirrhosis (mostly asymptomatic with good prognosis):

• Splenomegaly/hypersplenism 2
• Incidental finding of varices on screening 2
• Normal liver function in most cases 2

Decompensated cirrhosis (heralded by complications):

• Variceal bleeding (most common presentation in some populations) 2, 6
• Ascites (most frequent decompensating event) 6
• Hepatic encephalopathy 6
• Hepatorenal syndrome 4

Surgical Implications

CSPH (HVPG >10 mmHg) and Child-Pugh class B cirrhosis represent absolute contraindications to major liver resections (>2 segments), as portal hypertension is a major predictor of post-hepatectomy liver failure, perioperative mortality, and long-term survival. 4