What are the causes and management of portal hypertension?

Portal Hypertension: Causes and Management

Causes of Portal Hypertension

Portal hypertension develops from increased resistance to portal blood flow combined with increased portal venous inflow, with cirrhosis being the most common cause. 1

Primary Mechanism

Portal hypertension is defined as a pathological increase in portal pressure with hepatic venous pressure gradient (HVPG) >5 mmHg, following the hydraulic principle where Pressure = Resistance × Flow. 2, 3

Anatomic Classification of Causes

Intrahepatic causes (most common):

• Cirrhosis from any chronic liver disease is the predominant cause, accounting for the majority of cases 1
  • Alcoholic liver disease 4
  • Viral hepatitis (hepatitis B and C) 4
  • Non-alcoholic fatty liver disease 4
  • Autoimmune hepatitis 4
  • Primary biliary cirrhosis (can develop portal hypertension early, even before established cirrhosis) 1
  • Genetic/metabolic diseases 4
• Idiopathic non-cirrhotic portal hypertension (INCPH) - diagnosed only after excluding other causes 3

Prehepatic causes:

• Extrahepatic portal vein obstruction/thrombosis 1, 3
• Congenital hepatic fibrosis 1
• Splenic vein thrombosis 5

Posthepatic causes:

• Acute hepatic vein thrombosis (Budd-Chiari syndrome) - usually associated with ascites 1
• Right-sided heart failure 5

Pathophysiologic Mechanisms in Cirrhosis

The increased intrahepatic resistance has two components 3:

1. Structural component (70%): Architectural distortion from fibrous tissue deposition, regenerative nodules, vascular distortion, and microthrombi 1, 3

2. Functional component (30%): Active intrahepatic vasoconstriction due to decreased endogenous nitric oxide production and endothelial dysfunction 1, 3

Despite collateral formation, portal hypertension persists due to: 1

• Increased portal venous inflow from splanchnic arteriolar vasodilation
• Insufficient portal decompression through collaterals (which have higher resistance than normal liver)

---

Management of Portal Hypertension

Diagnostic Approach

HVPG measurement is the gold standard for diagnosis and quantification: 2, 3

• Normal: 1-5 mmHg
• Portal hypertension: >5 mmHg
• Clinically significant portal hypertension (CSPH): ≥10 mmHg
• High mortality risk: ≥16 mmHg 3

Non-invasive assessment alternatives: 2, 3

• Transient elastography: 90-96% sensitivity, 48-50% specificity at 15 kPa cutoff
• APRI score: 56% sensitivity, 68% specificity
• Doppler ultrasound as first-line for extrahepatic portal vein obstruction 3, 6

When ascites is present, perform diagnostic paracentesis with: 1, 2

• Ascitic fluid albumin/protein measurement
• Neutrophil count and culture
• Amylase level
• Cytology if malignancy suspected 1

Stage-Based Management Algorithm

Stage 1: Mild Portal Hypertension (HVPG >5 but <10 mmHg) 3

• Focus on treating underlying liver disease
• Non-selective beta-blockers (NSBBs) are ineffective at this stage 2

Stage 2: CSPH Without Varices (HVPG ≥10 mmHg) 3

• NSBBs including carvedilol can be considered to prevent clinical decompensation 2
• HVPG reduction of ≥10% after therapy decreases risk of first variceal hemorrhage 2, 3

Stage 3: CSPH With Varices

Primary prophylaxis (preventing first bleed):

• Non-selective beta-blockers (propranolol, nadolol, or carvedilol) are first-line 7, 8, 9
• Endoscopic variceal ligation for large varices or when beta-blockers contraindicated 1

Acute variceal bleeding:

• Combination of vasoactive agents (terlipressin, octreotide, or somatostatin) plus endoscopic therapy improves hemostasis and reduces mortality 2, 10
• Terlipressin increases mean arterial pressure and reduces portal hypertension by decreasing portal blood flow 10
• Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis 1

Secondary prophylaxis (preventing rebleeding):

• Combination of NSBBs plus endoscopic variceal ligation 1, 8
• Consider TIPS if refractory to medical/endoscopic therapy 2

Stage 4: Refractory Ascites 1, 2

• Defined as ascites unresponsive to spironolactone 400 mg/day plus furosemide 160 mg/day for ≥1 week with sodium restriction <90 mmol/day 1
• TIPS is recommended by the American College of Radiology 2
• Large-volume paracentesis with albumin replacement
• Liver transplantation should be considered for all patients with decompensated cirrhosis 2, 3

Emerging and Adjunctive Therapies

Statins (used alone or with NSBBs) have shown improved portal pressure and mortality in cirrhotic patients, though larger randomized trials are needed 9, 4

Antibiotics reduce portal hypertension by blunting inflammatory stimuli 4

Critical Prognostic Factors

Predictors of variceal bleeding: 2, 6

• Previous gastrointestinal bleeding
• Size of esophageal varices
• Presence of red wale marks (longitudinal dilated venules on variceal surface) 1

Predictors of mortality: 2, 6

• Age
• Presence of ascites
• Extension to superior mesenteric vein
• Severity of underlying liver disease (Child-Pugh score)

Common Pitfalls to Avoid

• Do not assume alcoholic patients have alcoholic liver disease - always investigate other causes 1
• Do not use NSBBs in mild portal hypertension (HVPG <10 mmHg) - they are ineffective and may cause harm 2
• Do not delay liver transplantation evaluation once decompensation occurs, as 5-year survival drops from 80% to 50% with ascites development 2, 3
• Screen for prothrombotic conditions in patients with extrahepatic portal vein obstruction (myeloproliferative disease, antiphospholipid syndrome) 3