Overview
Portal Hypertension
1. Clinical Overview
Summary
Portal hypertension is defined as a pathological elevation of the pressure gradient between the portal vein and the inferior vena cava (hepatic venous pressure gradient, HVPG) above 5 mmHg. Cirrhosis is the predominant cause in the developed world. The clinical consequences include gastro-oesophageal varices, ascites, splenomegaly, porto-systemic encephalopathy, and hepatorenal syndrome. Variceal haemorrhage is the most immediately life-threatening complication. [1,2]
Key Facts
- Definition: HVPG greater than 5 mmHg.
- Clinically Significant: HVPG greater than or equal to 10 mmHg (varices start forming).
- Bleeding Risk: HVPG greater than or equal to 12 mmHg (varices can bleed). [3]
- Prevalence: Present in greater than 90% of patients with cirrhosis.
- Variceal Bleeding: Occurs in 25-40% with varices; 15-20% mortality per episode.
- Treatment Revolution: NSBB and endoscopic therapy reduce bleeding and mortality.
Clinical Pearls
The HVPG Thresholds: Think of 5-10-12. Above 5 = portal hypertension exists. Above 10 = varices form, ascites develops. Above 12 = varices can bleed. Reduction to below 12 (or greater than 20% drop) = bleeding risk dramatically reduced.
Hepatic vs Pre-Hepatic PHT: In pre-hepatic causes (portal vein thrombosis), the liver function is preserved and prognosis is better. These patients may have massive splenomegaly but minimal ascites.
The Umbilical Vein: Recanalises in portal hypertension creating "caput medusae" - dilated veins radiating from umbilicus. The direction of flow is AWAY from the umbilicus.
Propranolol Dose: Target resting HR of 55-60 bpm OR 25% reduction from baseline. If HR doesn't drop, the drug isn't working (check compliance or consider carvedilol).
2. Epidemiology
Incidence and Demographics
- Cirrhosis Prevalence: Approximately 0.15% of the global population.
- Portal Hypertension in Cirrhosis: Greater than 90%.
- Oesophageal Varices: Present in 50% at diagnosis; 85% at 10 years.
- Variceal Bleeding: 25-40% of those with varices will bleed.
- Mortality Per Bleed: 15-20% at 6 weeks (improved from 50% in 1980s). [4]
Causes by Location
Pre-Hepatic (Before the Liver)
| Cause | Notes |
|---|---|
| Portal vein thrombosis | Most common pre-hepatic cause; prothrombotic states, cirrhosis, pancreatitis |
| Splenic vein thrombosis | "Left-sided PHT" → isolated gastric varices; commonly post-pancreatitis |
| Congenital portal vein atresia | Rare; cavernous transformation of portal vein |
| Extrinsic compression | Tumours, lymph nodes |
Hepatic (Within the Liver)
| Level | Cause | Notes |
|---|---|---|
| Pre-sinusoidal | Schistosomiasis (global #1), Primary biliary cholangitis, Sarcoidosis, Nodular regenerative hyperplasia | Preserved synthetic function initially |
| Sinusoidal | Cirrhosis (alcohol, viral, NAFLD) - most common in West | All liver functions affected |
| Post-sinusoidal | Sinusoidal obstruction syndrome (SOS/VOD), Severe alcoholic hepatitis | Often acute presentation |
Post-Hepatic (After the Liver)
| Cause | Notes |
|---|---|
| Budd-Chiari syndrome | Hepatic vein thrombosis; prothrombotic states, myeloproliferative |
| IVC obstruction | Webs (endemic in Asia), tumour thrombus |
| Right heart failure | Cardiac cirrhosis; constrictive pericarditis |
Geographic Variation
- Western World: Alcoholic and NAFLD cirrhosis predominate.
- East Asia: Hepatitis B cirrhosis.
- Africa/Middle East/South America: Schistosomiasis (pre-sinusoidal).
3. Pathophysiology
Step 1: Architectural Distortion (Structural Component)
- Cirrhosis: Nodule formation and fibrosis distort sinusoidal architecture.
- Increased Resistance: Blood flow through liver impeded (70% of portal hypertension).
- Capillarisation: Sinusoids lose fenestrations → increased resistance.
Step 2: Increased Vascular Tone (Dynamic Component)
- Endothelial Dysfunction: Reduced nitric oxide (NO) production within liver.
- Vasoconstrictor Excess: Increased endothelin-1, angiotensin II, norepinephrine.
- Stellate Cell Contraction: Activated hepatic stellate cells contract around sinusoids.
- Contribution: 30% of increased resistance is dynamic (and reversible with drugs).
Step 3: Splanchnic Vasodilation
- Paradox: Intrahepatic vasoconstriction BUT splanchnic vasodilation.
- Mechanism: Gut bacteria → endotoxin → NO production → mesenteric vasodilation.
- Result: Increased portal venous inflow → worsens portal pressure.
- Clinical Consequence: High cardiac output, low systemic vascular resistance ("hyperdynamic circulation").
Step 4: Collateral Circulation Development
- Portal-Systemic Shunts: Blood bypasses liver via collaterals.
- Locations:
- Gastro-oesophageal junction → oesophageal varices.
- Retroperitoneal → splenorenal shunt.
- Umbilical vein → caput medusae.
- Rectal → haemorrhoids (less clinically significant).
- Consequence: Varices, encephalopathy (unfiltered toxins reach brain).
Step 5: Complications Cascade
PORTAL HYPERTENSION
↓
┌───────────────────┼───────────────────┐
↓ ↓ ↓
SPLANCHNIC COLLATERAL ASCITES
VASODILATION FORMATION
↓ ↓ ↓
Hyperdynamic Varices SBP risk
Circulation (GI bleed)
↓ ↓ ↓
Sodium/Water Encephalopathy HRS
Retention (shunted toxins)
The Hepatorenal Syndrome Cascade
- Splanchnic vasodilation → underfilling of arterial circulation.
- Activation of RAAS, ADH, sympathetic nervous system.
- Renal vasoconstriction → reduced GFR.
- Sodium and water retention → worsening ascites and oedema.
- Severe underfilling → hepatorenal syndrome (functional renal failure).
4. Clinical Presentation
Cardinal Manifestations
| Manifestation | Mechanism | Clinical Significance |
|---|---|---|
| Oesophageal varices | Porto-systemic collaterals | Risk of catastrophic haemorrhage |
| Gastric varices | Porto-systemic collaterals | Often larger, harder to treat |
| Ascites | Sinusoidal hypertension + sodium retention | Decompensated cirrhosis |
| Splenomegaly | Splenic vein congestion | Hypersplenism (pancytopenia) |
| Hepatic encephalopathy | Shunted ammonia, toxins | Confusion to coma |
| Caput medusae | Recanalised umbilical vein | Rare but classic sign |
Variceal Bleeding Presentation
Symptoms of Underlying Cirrhosis
Red Flags - "The Don't Miss" Signs
- Haematemesis/Melaena - Variceal bleed until proven otherwise in cirrhosis.
- Altered consciousness - Encephalopathy; may be precipitant (SBP, bleed, drugs).
- Rising creatinine - Hepatorenal syndrome.
- Fever with ascites - SBP (urgent paracentesis needed).
- Tense ascites with dyspnoea - Respiratory compromise requiring large volume paracentesis.
Haematemesis
Bright red blood or "coffee ground".
Melaena
Common.
Haematochezia
If massive bleed.
Haemodynamic Instability
Tachycardia, hypotension, shock.
Encephalopathy
Often precipitated by GI bleed (protein load + hypovolaemia).
5. Clinical Examination
General Inspection
- Jaundice, pallor (chronic anaemia or acute bleed).
- Muscle wasting (sarcopenia).
- Peripheral oedema.
- Asterixis (hepatic encephalopathy).
Stigmata of Chronic Liver Disease
| Sign | Description |
|---|---|
| Spider naevi | Central arteriole with radiating legs; blanch on pressure; SVC distribution |
| Palmar erythema | Mottled redness of thenar/hypothenar eminences |
| Dupuytren's contracture | Associated with alcohol |
| Leuconychia | White nails (hypoalbuminaemia) |
| Clubbing | May occur in cirrhosis |
| Gynaecomastia | Oestrogen excess |
| Testicular atrophy | Hypogonadism |
| Caput medusae | Dilated periumbilical veins |
| Fetor hepaticus | Sweet, musty breath |
Abdominal Examination
Splenomegaly
- Palpable in 30-50% with portal hypertension.
- May be massive in pre-hepatic causes.
- Indicates increased splenic congestion.
Ascites
- Shifting dullness (detects greater than 1500 mL).
- Fluid thrill (detects greater than 2000 mL).
- Ballottement of liver (floating liver sign).
Liver
- Size variable: large (early) or small/shrunken (advanced cirrhosis).
- Hard, irregular edge.
- Nodular surface (advanced).
Encephalopathy Assessment
West Haven Criteria
| Grade | Features |
|---|---|
| Minimal | Abnormal psychometric tests only |
| 1 | Lack of awareness, shortened attention, sleep disturbance |
| 2 | Lethargy, disorientation, asterixis |
| 3 | Somnolent but rousable, confusion, gross asterixis |
| 4 | Coma (unresponsive to painful stimuli) |
6. Investigations
Laboratory Tests
Liver Function Tests
- Bilirubin, ALT, AST, ALP, GGT.
- Albumin (synthetic function).
- PT/INR (synthetic function).
Full Blood Count
- Pancytopenia (hypersplenism).
- Anaemia (chronic disease, GI blood loss).
- Macrocytosis (alcohol, folate deficiency).
Renal Function
- Creatinine often misleadingly low (muscle wasting).
- Monitor for hepatorenal syndrome.
Coagulation
- PT/INR prolonged (reduced clotting factors).
- Note: INR doesn't predict bleeding risk well in cirrhosis.
Ascitic Fluid Analysis (Diagnostic Paracentesis)
| Parameter | Significance |
|---|---|
| SAAG (Serum-Ascites Albumin Gradient) | Greater than or equal to 11 g/L = portal hypertension |
| Total protein | Less than 25 g/L = cirrhotic ascites |
| Neutrophils | Greater than 250/mm³ = SBP |
| Culture | Identify organism (inoculate blood culture bottles) |
| Cytology | If malignancy suspected |
Imaging
Ultrasound with Doppler
- First-line investigation.
- Portal vein diameter greater than 13mm (suggests PHT).
- Flow direction (hepatopetal vs hepatofugal).
- Splenomegaly.
- Ascites.
- Hepatic vein patency (Budd-Chiari).
CT/MRI
- Cirrhotic liver morphology.
- Porto-systemic collaterals visualisation.
- HCC screening (arterial phase enhancement).
- Portal/hepatic vein thrombosis.
Transient Elastography (FibroScan)
- Liver stiffness greater than 20 kPa associated with clinically significant portal hypertension.
- Non-invasive alternative to HVPG.
Endoscopy
Oesophagogastroduodenoscopy (OGD)
- Gold standard for variceal assessment.
- Grading: Small/Medium/Large.
- Red signs (cherry red spots, red wale marks) = high bleeding risk.
- Gastric varices (GOV1, GOV2, IGV1).
HVPG Measurement (Gold Standard)
Hepatic Venous Pressure Gradient
- Invasive: Catheter via jugular vein to hepatic vein.
- HVPG = Wedged hepatic venous pressure - Free hepatic venous pressure.
- Used in clinical trials; less in routine practice.
- Guides treatment response (greater than 20% reduction = good response).
7. Management
Management Algorithm
CONFIRMED PORTAL HYPERTENSION
↓
ASSESS FOR VARICES
(OGD)
↓
┌───────────────┼───────────────┐
↓ ↓ ↓
NO VARICES SMALL VARICES MEDIUM/LARGE
↓ ↓ VARICES
Repeat OGD Consider NSBB ↓
in 2-3 years (if high-risk) ┌─────┴─────┐
(or 1yr if ↓ ↓
cirrhosis NSBB EVL
progresses) or
(Carvedilol)
PRIMARY PROPHYLAXIS
(Before first bleed)
Primary Prophylaxis (Preventing First Bleed)
Indications
- Medium to large varices.
- Small varices with red signs or Child C cirrhosis.
Options
| Treatment | Mechanism | Notes |
|---|---|---|
| Non-selective beta-blocker (NSBB) | Decrease cardiac output + splanchnic vasoconstriction | Propranolol 40-80mg BD or Nadolol; target HR 55-60 |
| Carvedilol | NSBB + alpha-blockade (additional afterload reduction) | 6.25-12.5mg daily; may be superior to propranolol |
| Endoscopic Variceal Ligation (EVL) | Mechanical obliteration | If NSBB contraindicated or intolerant |
NSBB Contraindications
- SBP with refractory ascites.
- Severe hypotension (SBP less than 90 mmHg).
- HR less than 50.
- Severe asthma.
- Peripheral vascular disease.
Acute Variceal Bleeding (Emergency)
Immediate Resuscitation
- ABC approach.
- Two large-bore IV cannulae.
- Blood products: Target Hb 7-8 g/dL (avoid over-transfusion → increases portal pressure).
- Correct coagulopathy cautiously (vitamin K; FFP controversial).
- Airway protection if encephalopathic.
Pharmacological
- Terlipressin: 2mg IV bolus then 1-2mg every 4-6 hours (up to 5 days).
- Alternative: Octreotide (or somatostatin in some countries).
- PPI: IV omeprazole/pantoprazole high dose.
- Antibiotics: Ceftriaxone 1g IV daily for 7 days (reduces infection, re-bleeding, mortality). [6]
Endoscopic Therapy
- Urgent OGD within 12 hours (when haemodynamically stable).
- Oesophageal Varices: Band ligation (EVL) is first choice.
- Gastric Varices (GOV2, IGV1): Cyanoacrylate (tissue glue) injection.
Rescue Therapy (Failure to Control)
- Balloon Tamponade: Sengstaken-Blakemore tube (bridge to definitive therapy; max 24 hours).
- TIPS: Transjugular Intrahepatic Portosystemic Shunt - very effective but increases encephalopathy risk.
- Surgery: Rarely used now (oesophageal transection, portosystemic shunt).
Secondary Prophylaxis (After First Bleed)
Combination Therapy
- NSBB + EVL is standard of care.
- Repeat EVL every 2-4 weeks until varices obliterated.
- Continue NSBB lifelong (or until transplant).
Consider TIPS
- If re-bleeding despite optimal medical + endoscopic therapy.
- Early TIPS (within 72 hours) for high-risk patients (Child C or Child B with active bleeding). [7]
Ascites Management
- Sodium restriction (less than 2g/day).
- Diuretics: Spironolactone 100-400mg + Furosemide 40-160mg (ratio 100:40).
- Large volume paracentesis with albumin replacement (8g per litre removed).
- TIPS for refractory ascites.
- Transplant evaluation.
Hepatic Encephalopathy Management
- Identify and treat precipitant (infection, GI bleed, constipation, drugs).
- Lactulose: 15-30mL BD-TDS (target 2-3 soft stools/day).
- Rifaximin: 550mg BD (reduces recurrence).
- Dietary protein: Do NOT restrict (maintain 1.2-1.5 g/kg/day).
8. Complications
Variceal Haemorrhage
- Mortality 15-20% per episode.
- Recurrence 60% at 1-2 years without prophylaxis.
- Risk factors: Variceal size, red signs, Child class.
Ascites Complications
| Complication | Features | Management |
|---|---|---|
| SBP | Fever, abdominal pain, worsening encephalopathy; ascitic WCC greater than 250 | IV ceftriaxone + albumin day 1 and 3 |
| Refractory Ascites | Does not respond to diuretics, or diuretic intolerance | TIPS, repeated paracentesis, transplant |
| Hepatic Hydrothorax | Transudative pleural effusion (usually right-sided) | Diuretics, TIPS; avoid chest drain |
Hepatorenal Syndrome
Type 1 (AKI-HRS)
- Rapidly progressive renal failure.
- Doubling of creatinine to greater than 2.5 mg/dL within 2 weeks.
- Often precipitated by SBP.
- Treatment: Terlipressin + Albumin; transplant is definitive.
Type 2 (CKD-HRS)
- More gradual decline.
- Associated with refractory ascites.
- Median survival 6 months.
Hepatic Encephalopathy
- Covert (minimal) or overt (West Haven 1-4).
- Usually reversible with treatment.
- Precipitants: Infection, GI bleed, constipation, sedatives, hypokalaemia.
Hypersplenism
- Thrombocytopenia most common (platelets 50-100).
- Leucopenia.
- Rarely clinically significant anaemia from splenic sequestration.
9. Prognosis and Outcomes
Child-Pugh Classification
| Parameter | 1 Point | 2 Points | 3 Points |
|---|---|---|---|
| Bilirubin (μmol/L) | Less than 34 | 34-50 | Greater than 50 |
| Albumin (g/L) | Greater than 35 | 28-35 | Less than 28 |
| INR | Less than 1.7 | 1.7-2.3 | Greater than 2.3 |
| Ascites | None | Mild/controlled | Moderate-severe |
| Encephalopathy | None | Grade 1-2 | Grade 3-4 |
Interpretation
| Class | Points | 1-Year Survival | 2-Year Survival |
|---|---|---|---|
| A | 5-6 | 100% | 85% |
| B | 7-9 | 80% | 60% |
| C | 10-15 | 45% | 35% |
MELD Score
- Used for transplant listing prioritisation.
- Formula: Based on bilirubin, INR, creatinine (+ sodium in MELD-Na).
- Higher score = Higher mortality = Higher transplant priority.
Prognosis After Variceal Bleed
- In-hospital mortality: 10-15%.
- 6-week mortality: 15-20%.
- 1-year mortality: 30-50%.
- Re-bleeding without prophylaxis: 60% at 1-2 years.
- With NSBB + EVL: Re-bleeding approximately 20-30%.
Liver Transplantation
- Only definitive cure for portal hypertension from cirrhosis.
- Indicated for decompensated cirrhosis (MELD typically greater than or equal to 15).
- 1-year survival post-transplant: 85-90%.
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| AASLD/EASL Baveno VII | International | Carvedilol considered first-line; early TIPS in high-risk bleed |
| NICE NG50 | UK | Band ligation or NSBB for medium/large varices |
| ACG Guidelines | USA | EBL + NSBB for secondary prophylaxis |
Landmark Trials
1. Carvedilol vs Propranolol (2017) [5]
- Trial: Meta-analysis and multiple RCTs.
- Result: Carvedilol superior for reducing HVPG and preventing bleeding.
- Impact: Carvedilol increasingly used as first-line NSBB.
- PMID: Systematic reviews PMID: 28501847.
2. Early TIPS (Garcia-Pagan, 2010) [7]
- Question: Early TIPS (within 72h) vs standard care for high-risk bleeds?
- N: 63 patients Child B with active bleeding or Child C.
- Result: TIPS significantly reduced treatment failure (12% vs 50%) and mortality.
- Impact: Early TIPS now recommended for high-risk patients.
- PMID: 20558883.
3. Antibiotic Prophylaxis in Variceal Bleed (Bernard, 1999) [6]
- Question: Do antibiotics improve outcomes in variceal bleed?
- N: Meta-analysis.
- Result: Antibiotics reduced infections, re-bleeding, and mortality.
- Impact: Antibiotics now mandatory in acute variceal bleed.
- PMID: 10520692.
4. NSBB Discontinuation in Refractory Ascites (Serste, 2010) [9]
- Question: Are NSBB harmful in patients with refractory ascites?
- N: Observational study raising concerns.
- Result: Conflicting data; individualised assessment needed.
- Impact: Cautious NSBB use in advanced decompensation.
- PMID: 20665667.
11. Patient and Layperson Explanation
What is Portal Hypertension?
Portal hypertension is high blood pressure in the vein that carries blood from your intestines to your liver (the portal vein). It usually happens because of liver scarring (cirrhosis), which makes it harder for blood to flow through the liver.
Why Does It Matter?
When blood can't flow easily through the liver, it finds other routes. This creates swollen blood vessels (varices) in places like the gullet (oesophagus) and stomach. These can burst and cause serious bleeding.
What Are the Signs?
- Vomiting blood or passing black, tarry stools (bleeding from varices).
- Swollen belly (fluid called ascites).
- Confusion or drowsiness (toxins not filtered by liver).
- Yellow skin (jaundice).
- Easy bruising or bleeding.
How is it Diagnosed?
- Blood tests: To check liver function.
- Ultrasound: To look at the liver and blood flow.
- Endoscopy (camera test): To check for varices in the gullet.
How is it Treated?
Medications
- Beta-blockers (like propranolol or carvedilol) to reduce pressure and bleeding risk.
- Water tablets (diuretics) for fluid in the belly.
- Lactulose for confusion.
Procedures
- Banding: Rubber bands placed on varices during endoscopy.
- TIPS: A tube placed in the liver to redirect blood flow.
- Liver transplant: The only cure for advanced cases.
What Can You Do?
- Avoid alcohol completely.
- Take all prescribed medications.
- Follow a low-salt diet.
- Attend all appointments and screening tests.
- Seek urgent help if vomiting blood or becoming confused.
When to Seek Emergency Help
- Vomiting blood or blood in stools.
- Sudden confusion or difficulty staying awake.
- Fever with a swollen belly.
- Breathing difficulty.
12. References
Primary Sources
- Bosch J, Garcia-Pagan JC. Complications of cirrhosis. I. Portal hypertension. J Hepatol. 2000;32:141-156. PMID: 10728801.
- Tsochatzis EA, et al. Liver cirrhosis. Lancet. 2014;383:1749-1761. PMID: 24480518.
- Groszmann RJ, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005;353:2254-2261. PMID: 16306522.
- D'Amico G, et al. Upper digestive bleeding in cirrhosis. J Hepatol. 2014;60:1317-1318. PMID: 24486332.
- Sinagra E, et al. Carvedilol versus propranolol for primary prophylaxis of variceal bleeding. Eur J Gastroenterol Hepatol. 2017;29:245-252. PMID: 28501847.
- Bernard B, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. Hepatology. 1999;29:1655-1661. PMID: 10347104.
- Garcia-Pagan JC, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010;362:2370-2379. PMID: 20558883.
- de Franchis R, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76:959-974. PMID: 35120736.
- Serste T, et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010;52:1017-1022. PMID: 20665667.
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