What are the causes and management options for portal hypertension, including pre-hepatic, hepatic, and post-hepatic factors?

Portal Hypertension: Causes by Anatomic Location

Portal hypertension is classified anatomically into pre-hepatic, hepatic (intrahepatic), and post-hepatic causes based on the site of increased resistance to portal blood flow, with the hepatic/intrahepatic category further subdivided into presinusoidal, sinusoidal, and postsinusoidal locations. 1

Pre-Hepatic Causes

Portal vein thrombosis is the primary pre-hepatic cause of portal hypertension. 1

• In pre-hepatic portal hypertension, the obstruction occurs before blood reaches the liver parenchyma
• HVPG measurements show normal wedged pressure, normal free pressure, and normal gradient because the sinusoidal pressure remains unaffected 1
• Doppler ultrasound is the first-line investigation, with CT for confirmation 2
• Screening should be considered in patients with myeloproliferative disease and antiphospholipid syndrome 2

Hepatic (Intrahepatic) Causes

The hepatic causes are subdivided by the anatomic level of resistance:

Presinusoidal

• Schistosomiasis 1
• Idiopathic portal hypertension (idiopathic non-cirrhotic portal hypertension, INCPH) 1
• Cholestatic liver disease-related cirrhosis (early stages) 1
• Nodular regenerative hyperplasia and obliterative portal venopathy 1
• HVPG measurements show normal values in early stages, though in advanced presinusoidal disease the HVPG will eventually increase 1
• A diagnostic clue for INCPH is low liver stiffness (<12 kPa) despite signs of portal hypertension 2

Sinusoidal (Most Common)

Cirrhosis from any chronic liver disease is the predominant cause, accounting for the majority of portal hypertension cases. 3, 2

Specific etiologies include:

• Alcohol-related liver disease 1

• Chronic hepatitis C 1, 2

• Chronic hepatitis B 2

• Non-alcoholic steatohepatitis (NASH) 1, 2

• HVPG measurements show elevated wedged pressure, normal free pressure, and elevated gradient 1

• Portal hypertension develops through increased intrahepatic resistance (70% structural from fibrosis and vascular distortion, 30% functional from endothelial dysfunction) combined with increased portal blood flow 2

• Primary biliary cirrhosis can develop portal hypertension early, even before established cirrhosis, due to a potential pre-sinusoidal component where ductular proliferation and portal fibrosis impact hepatic vascular resistance 1, 3

Postsinusoidal

• Sinusoidal obstruction syndrome (hepatic veno-occlusive disease) 1
• HVPG measurements show elevated wedged pressure, normal free pressure, and elevated gradient 1

Post-Hepatic Causes

Right heart failure is the primary post-hepatic cause. 1

• The obstruction occurs in the hepatic veins or inferior vena cava after blood exits the liver
• HVPG measurements show elevated wedged pressure, elevated free pressure, and normal gradient because both pressures are equally elevated 1
• Budd-Chiari syndrome (hepatic vein thrombosis) represents another post-hepatic cause 1

Clinical Significance of Classification

The anatomic classification is critical because HVPG measurement (the gold standard for portal hypertension assessment) only accurately reflects sinusoidal pressure and does not provide useful data in pre-hepatic or presinusoidal portal hypertension. 1

• Normal HVPG is 1-5 mmHg, portal hypertension is >5 mmHg, clinically significant portal hypertension (CSPH) is ≥10 mmHg, and high mortality risk is ≥16 mmHg 3, 4, 2
• In PSC, HVPG often underestimates the full degree of portal hypertension because gastroesophageal varices may be present with HVPG values <10 mmHg, unlike in alcohol-related or viral hepatitis where this does not occur 1

Management Principles

Management of portal hypertension complications should follow established guidelines regardless of etiology, though the anatomic classification influences diagnostic approach. 1

• Non-selective beta-blockers (propranolol, nadolol, carvedilol) are the pharmacologic mainstay, acting through β-1 blockade (decreased cardiac output) and β-2 blockade (splanchnic vasoconstriction) 1
• Endoscopic variceal ligation is recommended for high-risk varices when beta-blockers are contraindicated or not tolerated 1
• TIPS is indicated for refractory variceal bleeding or refractory ascites 3, 4
• Liver transplantation should be considered for all patients with decompensated cirrhosis 3, 4, 2