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).

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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)

Hepatic (Within the Liver)

Post-Hepatic (After the Liver)

Geographic Variation

• Western World: Alcoholic and NAFLD cirrhosis predominate.
• East Asia: Hepatitis B cirrhosis.
• Africa/Middle East/South America: Schistosomiasis (pre-sinusoidal).

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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

1. Splanchnic vasodilation → underfilling of arterial circulation.
2. Activation of RAAS, ADH, sympathetic nervous system.
3. Renal vasoconstriction → reduced GFR.
4. Sodium and water retention → worsening ascites and oedema.
5. Severe underfilling → hepatorenal syndrome (functional renal failure).

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4. Clinical Presentation

Cardinal Manifestations

Variceal Bleeding Presentation

• 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).

Symptoms of Underlying Cirrhosis

• Fatigue, weakness.
• Weight loss (muscle wasting) or gain (ascites).
• Jaundice.
• Pruritus.
• Easy bruising/bleeding.
• Gynecomastia, spider naevi.

Red Flags - "The Don't Miss" Signs

1. Haematemesis/Melaena - Variceal bleed until proven otherwise in cirrhosis.
2. Altered consciousness - Encephalopathy; may be precipitant (SBP, bleed, drugs).
3. Rising creatinine - Hepatorenal syndrome.
4. Fever with ascites - SBP (urgent paracentesis needed).
5. Tense ascites with dyspnoea - Respiratory compromise requiring large volume paracentesis.

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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

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

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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)

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 measurement (LSM) correlates with HVPG.
• LSM less than 20 kPa + Platelets greater than 150 × 10⁹/L: Low probability of CSPH - can avoid screening endoscopy (Baveno VII criteria). [1]
• LSM 20-25 kPa: Suggests CSPH; consider NSBB even without varices if high-risk features.
• LSM greater than 25 kPa: High probability of varices; screening endoscopy recommended.
• Non-invasive alternative to HVPG for routine clinical practice. [12]

Spleen Stiffness Measurement

• Emerging modality; correlates with portal pressure and variceal risk.
• Not yet standard practice; research ongoing.

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 procedure: Catheter via jugular vein to hepatic vein.
• HVPG = Wedged hepatic venous pressure minus Free hepatic venous pressure.
• Normal: Less than 5 mmHg.
• Portal Hypertension: Greater than or equal to 5 mmHg.
• Clinically Significant Portal Hypertension (CSPH): Greater than or equal to 10 mmHg.
• High-risk varices/bleeding threshold: Greater than or equal to 12 mmHg. [10]

Clinical Utility

• Prognostic: HVPG greater than or equal to 10 mmHg predicts decompensation and mortality. [11]
• Treatment response: Greater than 20% reduction from baseline or to less than 12 mmHg = substantially reduced bleeding risk.
• Non-invasive alternatives: Liver stiffness measurement (LSM) by elastography correlates with HVPG; LSM greater than 20-25 kPa suggests CSPH. [12]
• Research tool: Used primarily in clinical trials; Baveno VII recommends non-invasive assessment in routine practice. [1]

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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

NSBB vs EVL

• NSBB: Addresses portal pressure globally; reduces ascites risk; lifelong therapy.
• EVL: Treats varices directly; no systemic effects; risk of post-banding ulcer bleeding (2-3%).
• Combination NOT recommended for primary prophylaxis (no added benefit, increased adverse events). [1]

NSBB Contraindications and Cautions

• Absolute: Severe bronchospasm/asthma; heart block (second/third degree); severe peripheral vascular disease.
• Relative: SBP with refractory ascites (controversial - may worsen outcomes); severe hypotension (SBP less than 90 mmHg); HR less than 50 bpm.
• Baveno VII Window Concept: Consider NSBB withdrawal in advanced decompensation (refractory ascites, HRS, severe sepsis) pending further evidence. [1,18]

Acute Variceal Bleeding (Emergency)

Variceal haemorrhage is a medical emergency with 15-20% 6-week mortality despite modern management. Immediate resuscitation, pharmacotherapy, endoscopic therapy, and prophylactic antibiotics form the cornerstone of treatment. [4,19]

Immediate Resuscitation

• ABC approach; secure airway if Grade 3-4 encephalopathy or massive haematemesis.
• Two large-bore IV cannulae (14-16G).
• Blood products: Target Hb 7-8 g/dL (restrictive strategy); avoid over-transfusion which increases portal pressure and re-bleeding. [19]
• Correct coagulopathy cautiously: Vitamin K 10mg IV; FFP controversial (may increase portal pressure); platelets if less than 50 × 10⁹/L and active bleeding.
• Volume resuscitation: Balanced crystalloids; aim MAP greater than 65 mmHg; avoid excessive fluids.

Pharmacological Therapy (Start Immediately - DO NOT Wait for Endoscopy)

• Terlipressin: 2mg IV bolus, then 1-2mg IV every 4-6 hours (up to 5 days).
  • Splanchnic vasoconstrictor; reduces portal pressure by 20-30%.
  • Superior to octreotide/somatostatin for mortality reduction.
  • Contraindications: severe IHD, peripheral vascular disease, pregnancy. [19]
• Octreotide (alternative): 50 mcg IV bolus, then 50 mcg/hr infusion (if terlipressin unavailable).
• PPI: IV omeprazole 80mg bolus then 8mg/hr infusion or pantoprazole 80mg BD (reduces ulcer bleeding).
• Antibiotics: MANDATORY - Ceftriaxone 1g IV daily for 7 days (or norfloxacin 400mg BD PO if not severely ill).
  • Reduces bacterial infections, re-bleeding, and mortality by 30-40%. [6]
  • Prophylaxis against SBP in this high-risk period. [20]

Endoscopic Therapy (Within 12 Hours When Haemodynamically Stable)

• Oesophageal Varices: Endoscopic Variceal Ligation (EVL) is first-line.
  • Achieves haemostasis in 85-90%.
  • Sclerotherapy (ethanolamine/polidocanol) if banding technically difficult.
• Gastric Varices (GOV2, IGV1): Cyanoacrylate (tissue glue) injection.
  • Superior to banding for gastric varices.
  • Risk: systemic embolization (rare, 1-2%). [1,19]

Rescue Therapy (Uncontrolled Bleeding Despite Above)

1. Balloon Tamponade: Sengstaken-Blakemore or Minnesota tube.
   • Temporary measure (maximum 24 hours); bridge to definitive therapy.
   • Risk: oesophageal perforation, aspiration.
   • Must have endotracheal tube in situ before insertion.
2. TIPS (Transjugular Intrahepatic Portosystemic Shunt): See TIPS section below.
   • Consider early (within 72 hours) in high-risk patients.
3. Surgery: Rarely performed now (oesophageal transection, porto-systemic shunt surgery); reserved for TIPS failure or contraindication.

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 at endoscopy). [7]

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Overview TIPS creates a low-resistance channel within the liver connecting the portal vein to a hepatic vein, effectively reducing portal pressure. Performed by interventional radiology under fluoroscopy and ultrasound guidance. [21]

Indications

1. Acute Variceal Bleeding:
   • Early TIPS (within 72 hours): High-risk patients (Child-Pugh C less than 14, or Child B with active bleeding at endoscopy). Reduces mortality from 30% to 12%. [7]
   • Rescue TIPS: Uncontrolled bleeding despite pharmacological + endoscopic therapy.
2. Recurrent Variceal Bleeding: Despite optimal secondary prophylaxis (NSBB + EVL).
3. Refractory Ascites: Non-responsive to maximum diuretics; requires frequent large-volume paracentesis. [21]
4. Hepatic Hydrothorax: Refractory to medical management.
5. Budd-Chiari Syndrome: As a bridge to transplant.
6. Hepatorenal Syndrome Type 2: Selected cases.

Contraindications

• Absolute: Right heart failure; severe pulmonary hypertension; polycystic liver disease; uncontrolled sepsis; hepatic encephalopathy grade 3-4.
• Relative: Child-Pugh greater than 13 (consider transplant instead); MELD greater than 18-20 (high mortality); hepatocellular carcinoma (central/extensive); portal vein thrombosis (technical difficulty). [21]

Procedure

• Jugular venous access → hepatic vein cannulation → transhepatic puncture of portal vein → dilation of tract → stent deployment (usually covered stent to reduce stenosis).
• Procedure time: 1-2 hours.
• Post-procedure: Monitor for complications; repeat Doppler ultrasound at 24 hours, 6 months, then annually.

Outcomes

• Bleeding control: 90-95% effective for acute variceal bleeding.
• Ascites control: 60-80% respond; may discontinue or reduce diuretics.
• Survival: Improved in acute variceal bleeding (early TIPS); neutral or improved in refractory ascites. [21]

Complications

TIPS vs Liver Transplant

• TIPS is a bridge to transplant, not a definitive therapy.
• Does NOT improve long-term survival in advanced cirrhosis (Child C).
• Transplant evaluation should proceed in parallel. [1,21]

Ascites Management

Ascites is the most common complication of cirrhosis, occurring in 50% within 10 years. It signifies decompensation with 50% 2-year mortality without transplant. [22]

Diagnosis

• Clinical: Shifting dullness (greater than 1500 mL); fluid thrill (greater than 2000 mL).
• Ultrasound: Confirms and quantifies.
• Diagnostic Paracentesis (ALWAYS in new-onset ascites or admitted patients):
  • SAAG (Serum-Ascites Albumin Gradient) = Serum albumin minus Ascitic fluid albumin.
  • SAAG greater than or equal to 11 g/L = Portal hypertension (97% specificity).
  • SAAG less than 11 g/L = Non-portal hypertension causes (malignancy, TB, pancreatitis).
  • Ascitic protein less than 25 g/L = cirrhotic ascites (low protein = high SBP risk).
  • Cell count: Neutrophils greater than 250/mm³ = SBP (treat immediately). [20,22]

Classification

• Grade 1: Mild; detectable only on ultrasound.
• Grade 2: Moderate; clinically detectable; responsive to diuretics.
• Grade 3: Large/tense; requires large-volume paracentesis.
• Refractory: Non-responsive to maximum diuretics OR diuretic-intolerant OR recurs rapidly.

Management - Stepwise Approach

Step 1: Sodium Restriction + Diuretics (First-Line)

• Sodium restriction: Less than 2g (88 mmol) per day - critical but difficult to achieve.
• Fluid restriction: Only if hyponatraemia (Na less than 125 mmol/L); limit to 1-1.5 L/day.
• Diuretics:
  • Spironolactone 100mg OD (aldosterone antagonist) + Furosemide 40mg OD.
  • Maintain ratio 100:40 (spironolactone:furosemide) - maximizes natriuresis, minimizes hypokalaemia.
  • Titrate every 3-5 days to maximum: Spironolactone 400mg + Furosemide 160mg.
  • Target weight loss: 0.5 kg/day (no peripheral oedema) or 1 kg/day (with oedema). [22]
• Monitor: Weight daily; U\u0026Es twice weekly; avoid over-diuresis (precipitates AKI, encephalopathy).

Step 2: Large-Volume Paracentesis (LVP)

• Indications: Tense ascites (respiratory compromise); refractory ascites; diagnostic.
• Technique: Drain fluid completely (safer than partial drainage); USS-guided if difficult.
• Albumin replacement: 8g IV albumin per litre drained if greater than 5 litres removed (prevents post-paracentesis circulatory dysfunction). [22]
• Safety: Can safely drain 10-15 litres in single session; risk of bleeding low even with coagulopathy/thrombocytopenia.

Step 3: Refractory Ascites

• Definition: Non-responsive to maximum diuretics (spironolactone 400mg + furosemide 160mg + sodium restriction) OR diuretic-intolerant (AKI, hyponatraemia, encephalopathy).
• Options:
  1. Serial LVP + albumin: Every 2-4 weeks as needed; safe long-term.
  2. TIPS: Improves ascites control in 60-80%; consider if frequent LVP needed (greater than 3 per month) and suitable candidate. [21]
  3. Liver transplant evaluation: Mandatory - median survival 6 months without transplant.
  4. Alfapump (automated LVP system): Emerging; not widely available.

Step 4: Complications Management

• Spontaneous Bacterial Peritonitis (SBP): See SBP section below.
• Hepatic Hydrothorax: Usually right-sided; manage as ascites; AVOID chest drain (rapid re-accumulation, protein loss, infection risk); TIPS if refractory.
• Umbilical Hernia: Common; repair ONLY if strangulation risk (thin skin, ulceration); elective repair after transplant preferred. [22]

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).

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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

Spontaneous Bacterial Peritonitis (SBP)

SBP is bacterial infection of ascitic fluid without an intra-abdominal source. It carries 20-30% in-hospital mortality and 70% 1-year mortality without transplant. [20]

Pathophysiology

• Bacterial translocation from gut (usually Gram-negative: E. coli, Klebsiella) due to increased intestinal permeability and impaired immune function in cirrhosis.
• Low ascitic protein (less than 15 g/L) = deficient opsonins = high SBP risk.

Diagnosis

• High Index of Suspicion: Any deterioration in cirrhotic patient with ascites.
• Symptoms: Fever (50-70%); abdominal pain (50%); altered mental status; worsening ascites; OFTEN SUBTLE OR ABSENT.
• Diagnostic Paracentesis (MANDATORY):
  • Ascitic neutrophils greater than 250 cells/mm³ = SBP (treat immediately; do NOT wait for culture).
  • Culture: Inoculate blood culture bottles at bedside (30mL into aerobic + anaerobic bottles) - increases yield to 80%.
  • Positive culture in 40-60% only.
• Variants:
  • Culture-negative SBP: Neutrophils greater than 250 but culture negative (treat as SBP).
  • Bacterascites: Positive culture but neutrophils less than 250 (repeat tap; treat if symptomatic or high-risk).
  • Secondary peritonitis: Neutrophils greater than 250 + multiple organisms + ascitic protein greater than 10 g/L (think perforation). [20]

Treatment

• Antibiotics:
  • First-line: Ceftriaxone 2g IV daily for 5-7 days (superior to older quinolones; high quinolone resistance).
  • Alternatives: Piperacillin-tazobactam 4.5g TDS (if nosocomial); meropenem (if ESBL risk).
  • Avoid nephrotoxic agents (aminoglycosides).
• Albumin: 1.5 g/kg IV on day 1, then 1 g/kg on day 3 - reduces mortality and hepatorenal syndrome by 50%. [20]
• Repeat Paracentesis: 48 hours post-antibiotics if not improving (neutrophils should decrease by greater than 25%).

Secondary Prophylaxis (After First SBP Episode)

• Lifelong antibiotic prophylaxis: Norfloxacin 400mg OD PO (or ciprofloxacin 750mg weekly).
• Transplant evaluation: Mandatory (SBP is a decompensation event).
• Recurrence without prophylaxis: 70% at 1 year. [20]

Primary Prophylaxis (Before First SBP)

• Indicated if:
  1. Ascitic protein less than 15 g/L + advanced cirrhosis (Child greater than 9, bilirubin greater than 50).
  2. Prior variceal bleed (high risk during bleed episode).
  3. Hepatorenal syndrome.
• Agent: Norfloxacin 400mg OD or ciprofloxacin 750mg weekly.

Hepatorenal Syndrome (HRS)

HRS is functional renal failure in advanced cirrhosis without intrinsic kidney disease. It reflects extreme underfilling of arterial circulation due to severe splanchnic vasodilation and is associated with very poor prognosis without transplant. [23]

Pathophysiology

• Portal hypertension → splanchnic vasodilation → effective arterial hypovolaemia.
• Activation of RAAS, SNS, ADH → renal vasoconstriction.
• Severe cortical vasoconstriction → reduced GFR → functional renal failure.
• Kidneys are structurally normal (can function if transplanted).

Diagnostic Criteria (Revised ICA-AKI Criteria)

• Cirrhosis with ascites.
• AKI: Increase in creatinine greater than or equal to 0.3 mg/dL (26.5 μmol/L) within 48 hours OR greater than or equal to 50% from baseline.
• No response to diuretic withdrawal + 2 days IV albumin (1 g/kg/day).
• No shock, nephrotoxic drugs, or parenchymal kidney disease (urine protein less than 500 mg/day; no haematuria; normal renal ultrasound). [23]

Classification

• HRS-AKI (formerly Type 1): Rapidly progressive; creatinine doubling to greater than 2.5 mg/dL (220 μmol/L) within 2 weeks. Often precipitated by SBP, GI bleed, or LVP without albumin. Median survival 2 weeks without treatment.
• HRS-CKD (formerly Type 2): Gradual decline; associated with refractory ascites. Median survival 6 months. [23]

Treatment Step 1: Identify and Treat Precipitant

• Stop diuretics, NSAIDs, ACE-I, nephrotoxins.
• Treat SBP if present.
• Volume expansion: Albumin 1 g/kg IV (max 100g) for 2 days.

Step 2: Vasoconstrictor + Albumin (First-Line)

• Terlipressin 1mg IV every 4-6 hours (or continuous infusion 2-12 mg/24h) + Albumin 20-40g/day.
  • Increase terlipressin to 2mg every 4-6 hours if creatinine not decreasing after 3 days.
  • Continue until creatinine less than 1.5 mg/dL or max 14 days.
  • Reversal rate: 40-50% with terlipressin + albumin (vs 10% placebo). [23]
• Alternatives (if terlipressin unavailable): Noradrenaline 0.5-3 mg/h IV (requires ICU) + albumin; or midodrine + octreotide + albumin (less effective).

Step 3: TIPS

• Consider in HRS-AKI if responding to medical therapy (bridge to transplant).
• Not suitable if Child greater than 13 or severe encephalopathy.

Step 4: Renal Replacement Therapy

• Bridge to transplant only.
• Does NOT improve survival without transplant.

Step 5: Liver Transplant

• Only definitive therapy.
• Simultaneous liver-kidney transplant if HRS duration greater than 4 weeks or other kidney injury markers.

Hepatic Encephalopathy Management

Overview

• Neuropsychiatric syndrome in cirrhosis due to porto-systemic shunting and liver failure.
• Ammonia and other toxins (mercaptans, false neurotransmitters) bypass hepatic detoxification.
• Prevalence: 30-40% of cirrhotic patients; 50% with TIPS.

Classification

• Covert (Minimal + Grade 1): Subtle cognitive impairment; abnormal psychometric tests; affects driving, quality of life.
• Overt (Grade 2-4): Clinically apparent; West Haven criteria (see Clinical Examination section).

Precipitants (Always Identify and Treat)

• Infection: SBP, UTI, pneumonia (most common).
• GI bleed: Protein load from blood.
• Constipation: Increased ammonia production.
• Dehydration: Over-diuresis, diarrhoea.
• Drugs: Benzodiazepines, opiates.
• Electrolyte disturbance: Hypokalaemia, hyponatraemia.
• Hepatocellular carcinoma.
• TIPS insertion.

Management

1. Identify and treat precipitant: Cultures, imaging, stop offending drugs.
2. Lactulose: 15-30mL BD-TDS (titrate to 2-3 soft stools/day); reduces ammonia-producing bacteria and acidifies colon (traps ammonia).
3. Rifaximin: 550mg BD (non-absorbable antibiotic); reduces recurrence when added to lactulose; expensive.
4. Dietary protein: Do NOT restrict - maintain 1.2-1.5 g/kg/day (restriction worsens muscle wasting and outcomes).
5. Branched-chain amino acids: May help in refractory cases.
6. TIPS reduction/occlusion: If encephalopathy refractory and related to TIPS.
7. Transplant evaluation: Recurrent/persistent encephalopathy indicates decompensation.

Prevention

• Lactulose maintenance in patients with prior episodes.
• Rifaximin added for recurrent encephalopathy (reduces recurrence from 46% to 22%).

Hypersplenism

• Thrombocytopenia most common (platelets 50-100 × 10⁹/L).
• Leucopenia (WCC 2-4 × 10⁹/L).
• Rarely clinically significant anaemia from splenic sequestration.
• Treatment: Usually none required; transfuse platelets only if invasive procedure + active bleeding.
• Splenectomy NOT recommended (high peri-operative mortality in cirrhosis).

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13. Viva and Exam Preparation

Opening Statement for Viva

"Portal hypertension is defined as elevation of the hepatic venous pressure gradient above 5 mmHg, most commonly caused by cirrhosis in the Western world. It becomes clinically significant at 10 mmHg when varices develop, and bleeding risk becomes substantial at 12 mmHg. The major complications include variceal haemorrhage, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, and hepatorenal syndrome. Management focuses on primary and secondary prophylaxis of variceal bleeding, control of ascites, and ultimately liver transplantation for decompensated cirrhosis."

High-Yield Exam Topics

1. HVPG Thresholds (Memorize These)

• 5 mmHg: Portal hypertension defined.
• 10 mmHg: Clinically significant portal hypertension (CSPH) - varices form, ascites develops.
• 12 mmHg: High-risk threshold - varices can bleed.
• 20% reduction in HVPG: Target for NSBB therapy - significantly reduces bleeding risk. [1,10]

2. Baveno VII Criteria (2022)

• Ruling out varices: LSM less than 20 kPa + platelets greater than 150 × 10⁹/L = can avoid screening endoscopy.
• CSPH screening: LSM 20-25 kPa suggests CSPH; consider NSBB if high-risk features even without varices.
• Carvedilol preference: Baveno VII suggests carvedilol may be preferred over propranolol for HVPG reduction. [1]

3. Early TIPS Criteria

• High-risk acute variceal bleed: Child-Pugh C (score less than 14) OR Child B with active bleeding at index endoscopy.
• Timing: Within 72 hours (ideally within 24 hours).
• Outcome: Reduces treatment failure from 50% to 12%; mortality from 30% to 12%. [7]

4. SBP Management - The Critical Steps

1. Diagnostic paracentesis (ascitic neutrophils greater than 250/mm³).
2. Ceftriaxone 2g IV daily (start immediately - do NOT wait for culture).
3. Albumin 1.5 g/kg day 1, then 1 g/kg day 3 (reduces HRS and mortality).
4. Secondary prophylaxis: Norfloxacin 400mg OD lifelong.
5. Transplant evaluation. [20]

5. Child-Pugh Quick Recall

• 5 parameters: Bilirubin, Albumin, INR, Ascites, Encephalopathy (mnemonic: "BAEAE").
• Class A (5-6): 100% 1-year survival.
• Class B (7-9): 80% 1-year survival; 30% peri-operative mortality.
• Class C (10-15): 45% 1-year survival; avoid surgery. [13,14]

Common Viva Questions with Model Answers

Q1: A 55-year-old with known cirrhosis presents with haematemesis. Describe your immediate management.

Model Answer: "This is likely variceal bleeding until proven otherwise in a cirrhotic patient. My immediate approach follows an ABCDE algorithm:

A-B: Assess airway - if Grade 3-4 encephalopathy or massive haematemesis, I would secure the airway with endotracheal intubation before endoscopy to prevent aspiration.

C: Two large-bore IV cannulae; bloods including FBC, coagulation, G\u0026S, renal and liver function. Resuscitate with crystalloid initially, then blood products targeting Hb 7-8 g/dL - restrictive transfusion strategy to avoid increasing portal pressure.

Pharmacological therapy - START IMMEDIATELY:

• Terlipressin 2mg IV bolus, then 1-2mg every 4-6 hours.
• Ceftriaxone 1g IV (prophylactic antibiotics reduce mortality by 30-40%).
• PPI infusion.

Endoscopy: Arrange urgent OGD within 12 hours when haemodynamically stable. If oesophageal varices confirmed, endoscopic band ligation is first-line.

Assess severity: Child-Pugh score - if Child C or Child B with active bleeding, consider early TIPS within 72 hours per Baveno VII guidelines."

Q2: What are the indications for TIPS?

Model Answer: "TIPS has several evidence-based indications:

Variceal bleeding:

1. Early TIPS for high-risk acute bleed (Child C less than 14 or Child B with active bleeding) - shown to reduce mortality.
2. Rescue TIPS for uncontrolled bleeding despite medical and endoscopic therapy.
3. Recurrent bleeding despite optimal secondary prophylaxis.

Refractory ascites: Non-responsive to maximum diuretics or requiring frequent large-volume paracentesis (typically more than 3 per month).

Other indications: Hepatic hydrothorax, Budd-Chiari syndrome, selected cases of hepatorenal syndrome type 2.

Key contraindications include right heart failure, severe pulmonary hypertension, and advanced liver failure (Child greater than 13). The main complication is hepatic encephalopathy in 30-40% of patients." [7,21]

Q3: How do you manage refractory ascites?

Model Answer: "Refractory ascites is defined as ascites that doesn't respond to maximum diuretic therapy - spironolactone 400mg plus furosemide 160mg with sodium restriction - or recurs rapidly after paracentesis, or the patient is diuretic-intolerant.

Management options:

1. Serial large-volume paracentesis: Safest option; drain completely with albumin replacement (8g per litre if greater than 5L removed). Can be repeated every 2-4 weeks as needed.

2. TIPS: Consider if requiring frequent paracentesis (greater than 3 per month) and suitable candidate. TIPS improves ascites control in 60-80% but carries risk of encephalopathy. Contraindicated if Child-Pugh greater than 13 or pre-existing severe encephalopathy.

3. Liver transplantation: This is a decompensation event - median survival 6 months without transplant. Mandatory to list for transplant evaluation.

The presence of refractory ascites indicates a very poor prognosis and transplant should be the definitive goal." [21,22]

Q4: Explain the pathophysiology of portal hypertension.

Model Answer: "Portal hypertension results from two components - structural and dynamic:

Structural (70%): In cirrhosis, nodular regeneration and fibrosis distort the hepatic architecture, increasing resistance to blood flow. Sinusoids undergo capillarisation, losing their normal fenestrations.

Dynamic (30%): Hepatic stellate cells contract around sinusoids, and there's endothelial dysfunction with reduced nitric oxide production in the liver, leading to increased intrahepatic vascular tone. This component is reversible with drugs like beta-blockers.

Paradoxically, while there's intrahepatic vasoconstriction, portal hypertension also causes splanchnic vasodilation through bacterial translocation and increased nitric oxide production in the mesenteric circulation. This creates a hyperdynamic circulation with high cardiac output and low systemic vascular resistance, further increasing portal inflow.

Consequences: The increased pressure leads to porto-systemic collateral formation (varices), ascites formation through sinusoidal hypertension, and a cascade involving RAAS activation, sodium retention, and ultimately hepatorenal syndrome in severe cases."

Common Exam Pitfalls to Avoid

❌ Mistake 1: Waiting for endoscopy before starting terlipressin. ✅ Correct: Start pharmacological therapy (terlipressin + antibiotics) IMMEDIATELY on suspicion of variceal bleed.

❌ Mistake 2: Aggressively transfusing to Hb greater than 10 g/dL in variceal bleeding. ✅ Correct: Target Hb 7-8 g/dL - over-transfusion increases portal pressure and re-bleeding risk.

❌ Mistake 3: Treating elevated INR in cirrhosis with FFP before procedures. ✅ Correct: INR in cirrhosis reflects reduced clotting factors but also reduced anticoagulants (balanced haemostasis). FFP may increase portal pressure. Use only if active bleeding.

❌ Mistake 4: Forgetting albumin in SBP treatment. ✅ Correct: Albumin (1.5 g/kg day 1, 1 g/kg day 3) reduces HRS and mortality by 50% - essential, not optional.

❌ Mistake 5: Combining NSBB + EVL for primary prophylaxis. ✅ Correct: Combination NOT recommended for primary prophylaxis (no benefit, more adverse events). Use either/or. Combination IS used for secondary prophylaxis.

❌ Mistake 6: Continuing beta-blockers in severe decompensation (refractory ascites + SBP). ✅ Correct: Baveno VII "window concept"

• consider withdrawal in advanced decompensation; may worsen outcomes.

Key Citations to Quote in Viva

1. Baveno VII (2022): "The consensus guidelines recommend carvedilol may be preferred over propranolol for portal hypertension, and early TIPS within 72 hours for high-risk variceal bleeding." [1]

2. Garcia-Pagan NEJM (2010): "Early TIPS reduced treatment failure from 50% to 12% and improved survival in high-risk patients with acute variceal bleeding." [7]

3. Bernard meta-analysis (1999): "Prophylactic antibiotics in variceal bleeding reduced bacterial infections, re-bleeding, and mortality." [6]

4. CONFIRM trial (2021): "Terlipressin plus albumin achieved HRS reversal in 32% vs 17% placebo, improving short-term renal function." [23]

Mnemonics

HVPG Thresholds (5-10-12 Rule):

• 5: Portal hypertension exists.
• 10: Varices form ("TEN-sion makes veins").
• 12: Bleeding risk ("TWELve = bleeds").

Child-Pugh (BAEAE):

• Bilirubin
• Albumin
• Encephalopathy
• Ascites
• Extra = INR (doesn't fit, but remember as "extra clotting test")

SBP Treatment (CAAN):

• Ceftriaxone 2g IV
• Albumin 1.5 then 1 g/kg
• Ascitic tap (repeat if not improving)
• Norfloxacin prophylaxis lifelong

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9. Prognosis and Outcomes

Child-Pugh Classification

Used to assess the severity of cirrhosis and predict mortality. The Child-Pugh score has been a cornerstone of prognostication since the 1970s, though MELD score is increasingly preferred for transplant listing. [13,14]

Interpretation

Clinical Application

• Child A: Compensated cirrhosis; good surgical candidates.
• Child B: Intermediate risk; individualized decision-making.
• Child C: Decompensated; transplant evaluation priority; avoid elective surgery. [14]

Limitations

• Subjective components (ascites, encephalopathy grading).
• Does not account for renal function (critical in cirrhosis).
• MELD score (bilirubin, INR, creatinine) preferred for transplant prioritization but Child-Pugh remains useful for general prognostication and clinical decision-making. [13]

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%.

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10. Evidence and Guidelines

Key Guidelines

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.

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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.

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12. References

Primary Sources

1. de Franchis R, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76:959-974. PMID: 35120736. doi:10.1016/j.jhep.2021.12.022
2. Tsochatzis EA, et al. Liver cirrhosis. Lancet. 2014;383:1749-1761. PMID: 24480518. doi:10.1016/S0140-6736(14)60121-5
3. Groszmann RJ, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005;353:2254-2261. PMID: 16306522. doi:10.1056/NEJMoa044456
4. D'Amico G, et al. Upper digestive bleeding in cirrhosis. J Hepatol. 2014;60:1317-1318. PMID: 24486332. doi:10.1016/j.jhep.2014.01.020
5. Reiberger T, et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhosis: A meta-analysis. Hepatology. 2015;62:1354A. PMID: Not fully indexed.
6. 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. doi:10.1002/hep.510290608
7. 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. doi:10.1056/NEJMoa0910102
8. Not used (removed duplicate).
9. 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. doi:10.1002/hep.23775
10. Bosch J, Garcia-Pagan JC. Complications of cirrhosis. I. Portal hypertension. J Hepatol. 2000;32:141-156. PMID: 10728801. doi:10.1016/S0168-8278(00)80422-5
11. Paternostro R, et al. Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD. J Hepatol. 2024;81:755-763. PMID: 38823501. doi:10.1016/j.jhep.2024.05.021
12. Jachs M, et al. Prognostic performance of non-invasive tests for portal hypertension is comparable to that of hepatic venous pressure gradient. J Hepatol. 2024;80:673-682. PMID: 38218352. doi:10.1016/j.jhep.2024.01.008
13. Cholongitas E, et al. Systematic review: The model for end-stage liver disease--should it replace Child-Pugh's classification for assessing prognosis in cirrhosis? Aliment Pharmacol Ther. 2005;22:1079-1089. PMID: 16305721. doi:10.1111/j.1365-2036.2005.02691.x
14. Kok B, et al. Child-Pugh Classification: Time to Abandon? Semin Liver Dis. 2019;39:96-103. PMID: 30634187. doi:10.1055/s-0038-1676805
15. Villanueva C, et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2019;393:1597-1608. PMID: 30910320. doi:10.1016/S0140-6736(18)31875-0
16. Zacharias AP, et al. Carvedilol versus traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices. Cochrane Database Syst Rev. 2018;10:CD011510. PMID: 30372514. doi:10.1002/14651858.CD011510.pub2
17. Turco L, et al. Carvedilol as the new non-selective beta-blocker of choice in patients with cirrhosis and portal hypertension. Liver Int. 2023;43:1165-1177. PMID: 36897563. doi:10.1111/liv.15557
18. Mendizabal M, et al. Evolving portal hypertension through Baveno VII recommendations. Ann Hepatol. 2024;29:101159. PMID: 37984701. doi:10.1016/j.aohep.2023.101159
19. Stanley AJ, et al. Management of acute upper gastrointestinal bleeding. BMJ. 2019;364:l536. PMID: 30910853. doi:10.1136/bmj.l536
20. Biggins SW, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74:1014-1048. PMID: 33942342. doi:10.1002/hep.31884
21. Vizzutti F, et al. Transjugular intrahepatic portosystemic shunt (TIPS): current indications and strategies to improve the outcomes. Intern Emerg Med. 2020;15:37-48. PMID: 31919780. doi:10.1007/s11739-019-02252-8
22. Aithal GP, et al. Guidelines on the management of ascites in cirrhosis. Gut. 2021;70:9-29. PMID: 33067334. doi:10.1136/gutjnl-2020-321790
23. Wong F, et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 2021;384:818-828. PMID: 33657294. doi:10.1056/NEJMoa2008290

Additional Reading

• Gralnek IM, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022;54:1094-1120. PMID: 36174643.
• Boike JR, et al. North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension. Clin Gastroenterol Hepatol. 2022;20:1636-1662. PMID: 34274511.

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.