Portal Hypertension

Definition

Pathophysiology

1. Increased intrahepatic resistance — cirrhosis causes architectural distortion, collagen deposition in sinusoids (space of Disse), and contraction of hepatic stellate cells (HSCs), raising resistance to portal flow
2. Increased splanchnic blood flow — vasodilator mediators (primarily NO) cause splanchnic arterial vasodilation → hyperdynamic circulation → further increases portal inflow

• Splanchnic vasodilation → reduced effective arterial blood volume → activation of RAAS, sympathetic nervous system, and ADH → sodium and water retention
• Systemic inflammation via PAMPs (bacterial translocation) and DAMPs (liver injury) amplifies circulatory dysfunction

Pathophysiology of ascites and renal dysfunction in advanced cirrhosis — Sleisenger & Fordtran

Causes

Prehepatic

Intrahepatic (>95% of all cases)

• Schistosomiasis
• Congenital hepatic fibrosis
• Primary biliary cholangitis
• Nodular regenerative hyperplasia
• Idiopathic portal hypertension

• Cirrhosis (alcohol, viral hepatitis, NAFLD/NASH — most common in Western countries)
• Alcoholic hepatitis
• Infiltrative liver diseases
• Polycystic liver disease

• Hepatic sinusoidal obstruction syndrome (veno-occlusive disease)

Posthepatic

Cirrhosis is overwhelmingly the most common cause in North America; worldwide, schistosomiasis and portal vein thrombosis are frequent. Noncirrhotic causes account for ~10% of cases.

Clinical Features

Gastroesophageal Varices

• ~50% of cirrhotics have esophageal varices; ~5–15% develop new varices per year
• One-third of patients with varices will bleed
• Variceal hemorrhage mortality: 20–30% per episode (up to 68% in Child-Pugh C)
• Risk predictors: Child-Pugh class, MELD score, HVPG height, varix size/location, red wale signs, cherry red spots, hematocystic spots, tense ascites

Ascites

• Results from portal hypertension → splanchnic vasodilation → RAAS/SNS activation → sodium and water retention
• Diagnosed clinically and confirmed by serum-ascites albumin gradient (SAAG ≥ 1.1 g/dL = portal hypertensive cause)
• Complications: spontaneous bacterial peritonitis (SBP), dilutional hyponatremia, hepatorenal syndrome (HRS)

Hepatic Encephalopathy (HE)

• Due to gut-derived neurotoxins (ammonia, mercaptans, false neurotransmitters) bypassing the liver
• Precipitants: GI bleeding, infection, volume depletion, hyponatremia, constipation
• Clinical: confusion, personality change, asterixis ("liver flap")
• Grades I–IV

Splenomegaly & Hypersplenism

• Portal congestion → splenic enlargement → pancytopenia (thrombocytopenia most notable)
• Thrombocytopenia is often the first clue to portal hypertension

Other Complications

• Hepatorenal syndrome (HRS) — functional renal failure from severe circulatory dysfunction
• Hepatopulmonary syndrome — intrapulmonary vasodilation causing hypoxaemia
• Portopulmonary hypertension — pulmonary arterial hypertension associated with portal hypertension
• Portal hypertensive gastropathy — gastric mucosal changes from portal venous congestion
• Spontaneous bacterial peritonitis (SBP)
• Hepatic hydrothorax, dilutional hyponatremia, coagulopathy

Diagnosis

• Endoscopy: Gold standard for variceal identification and staging
• HVPG measurement: Interventional radiology; >12 mmHg = variceal bleeding risk
• Transient elastography (liver stiffness): Non-invasive; stiffness <20 kPa + no thrombocytopenia → low risk, surveillance not needed
• CT/MRI abdomen: Nodular liver, portosystemic collaterals, splenomegaly
• Liver biopsy: Gold standard for staging fibrosis but has sampling error; less frequently used

Management

1. Primary Prophylaxis (Prevention of first bleed)

• Non-selective beta-blockers (NSBBs): Propranolol, nadolol — target heart rate 55–60 bpm; systolic BP >90 mmHg
• Carvedilol — now the preferred NSBB; additional anti-α-adrenergic vasodilating action lowers portal pressure more effectively; may prevent decompensation and improve survival
• Endoscopic Variceal Ligation (EVL) — equivalent efficacy to NSBBs for bleeding prevention; used if NSBBs not tolerated
• NSBBs are generally preferred as first-line (additional benefits beyond bleeding)

2. Active Variceal Hemorrhage

3. Secondary Prophylaxis (Prevention of rebleed)

• Combination of NSBB + EVL is standard
• TIPS for those who fail medical/endoscopic therapy

4. Ascites Management

• Sodium restriction (88 mmol/day)
• Diuretics: Spironolactone ± furosemide
• Large-volume paracentesis + albumin (8 g/L ascites removed) for tense/refractory ascites
• TIPS for refractory ascites unresponsive to diuretics
• Liver transplantation — definitive

5. Hepatic Encephalopathy

• Identify and treat precipitants
• Lactulose (first-line) — reduces intestinal ammonia production
• Rifaximin — poorly absorbed antibiotic; reduces gut bacteria; preferred for recurrence prevention
• Avoid protein restriction; maintain nutrition

6. Definitive Treatment

• Liver transplantation — gold standard for intrahepatic portal hypertension; cures both liver dysfunction and all complications of portal hypertension

TIPS / TIPSS (Transjugular Intrahepatic Portosystemic Shunt)

Principle

Technique

1. Access the right internal jugular vein → advance catheter into a hepatic venous branch under fluoroscopy
2. Pass a needle (Colapinto) through the hepatic vein → portal vein through the liver parenchyma
3. Dilate the tract
4. Deploy a covered stent (e.g., Viatorr e-PTFE stent) across the tract
5. Target: HVPG < 12 mmHg post-procedure

Indications

Contraindications

• Absolute: Congestive heart failure, severe pulmonary hypertension (moderate-severe), uncontrolled hepatic encephalopathy, unrelieved biliary obstruction, severe coagulopathy
• Relative: Tricuspid regurgitation, portal vein thrombosis (relative, specialist decision)

Post-procedure Monitoring

• Doppler ultrasound to monitor shunt patency (stent stenosis/thrombosis is the main long-term issue)
• Covered stents (PTFE) significantly reduce stenosis rates vs. bare metal stents

Complications

Outcomes

• Success in controlling hemorrhage: >90%
• TIPS has largely replaced surgical shunt procedures in current practice
• Surgical shunts remain useful when TIPS is not feasible, or in extrahepatic portal hypertension with intact liver function

Summary: Management Algorithm

Portal Hypertension
│
├── Varices present?
│   ├── Primary prophylaxis: NSBBs (carvedilol preferred) or EVL
│   └── Active bleeding:
│       ├── Vasoactive drugs + EVL + antibiotics
│       ├── Refractory → TIPS (>90% success)
│       └── Bridge: Sengstaken-Blakemore tube (<24 h)
│
├── Ascites: Diuretics → paracentesis → TIPS → transplant
├── Encephalopathy: Lactulose + rifaximin + treat precipitants
└── Definitive: Liver transplantation

• Harrison's Principles of Internal Medicine, 22E — Portal Hypertension chapter
• Current Surgical Therapy, 14E — Portal Hypertension: Role of Shunting Procedures
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease — Pathophysiology of ascites
• Miller's Anesthesia, 10E — TIPS procedural details

• TIPS for ectopic variceal bleeding (systematic review, 2024) — PMID 38935315
• TIPS in hepatocellular carcinoma — meta-analysis, 2024 — PMID 39126599
• Cardiovascular risk and cardiac decompensation post-TIPS — systematic review, 2025 — PMID 40741106