Liver Cirrhosis & Portal Hypertension

Cirrhosis is the end-stage, diffuse, irreversible architectural distortion of the liver characterised by bridging fibrosis and regenerative nodules. Portal hypertension is its central haemodynamic consequence and drives nearly every lethal complication — varices, ascites, hepatic encephalopathy, SBP and the hepatorenal syndrome. This is one of the highest-yield areas in Medicine for NEET PG.

Definition & classification

Cirrhosis = bridging fibrosis + regenerative nodules replacing normal hepatic architecture, producing both hepatocellular dysfunction and portal hypertension. It is the histological common endpoint of chronic liver injury of any cause.

Morphological classification (largely of academic interest now):

Type	Nodule size	Classic causes
Micronodular	< 3 mm, uniform	Alcohol, haemochromatosis, biliary obstruction
Macronodular	> 3 mm, variable	Viral hepatitis (B, C), Wilson disease, α1-antitrypsin
Mixed	Both	Late evolution of any cirrhosis

Functionally, cirrhosis is divided into compensated (asymptomatic, may have varices but no decompensating event) and decompensated (ascites, variceal bleed, encephalopathy or jaundice). The transition from compensated to decompensated cirrhosis marks a sharp drop in median survival from >12 years to ~2 years.

High-yield: The single best non-invasive predictor of clinically significant portal hypertension is the Hepatic Venous Pressure Gradient (HVPG). Normal = 1–5 mmHg; >10 mmHg = clinically significant (varices form); >12 mmHg = risk of variceal bleeding; >20 mmHg during acute bleed predicts failure to control bleeding/early rebleed.

Etiology

Mnemonic for causes — "ABCDEFGHI": Alcohol, B & C hepatitis, Drugs (methotrexate, amiodarone, isoniazid), auto-immune (lupoid) hepatitis, Fatty liver (NAFLD/NASH), Galactosaemia/glycogen storage, Haemochromatosis, Inherited (Wilson, α1-antitrypsin), plus biliary causes (PBC, PSC) and venous outflow obstruction (Budd–Chiari, cardiac/"cardiac cirrhosis").

• Alcohol and chronic viral hepatitis (HCV, HBV) were historically the commonest worldwide; NASH/MAFLD is now the fastest-rising cause and the leading indication for transplant in many registries.
• Cryptogenic cirrhosis — large proportion now attributed to burnt-out NASH.
• Pointers: female + AMA-positive + pruritus + xanthelasma → primary biliary cholangitis (PBC); male + UC + beaded "string of beads" on MRCP → primary sclerosing cholangitis (PSC); young patient + Kayser–Fleischer rings + low ceruloplasmin → Wilson disease; diabetes + bronze skin + arthropathy + high ferritin/transferrin saturation → haemochromatosis.

Pathophysiology of portal hypertension

Portal hypertension = pathological increase in portal venous pressure (HVPG >5 mmHg). Mechanism = increased resistance + increased flow:

1. Increased intrahepatic resistance — mechanical (fibrosis, regenerative nodules) PLUS dynamic component (activated stellate cells, reduced intrahepatic nitric oxide, increased endothelin → sinusoidal vasoconstriction). The dynamic component is the rationale for drug therapy.
2. Splanchnic vasodilatation — excess NO in the splanchnic bed → increased portal inflow.
3. Hyperdynamic circulation — systemic vasodilatation → low SVR, high cardiac output, effective arterial underfilling → RAAS/ADH/sympathetic activation → sodium and water retention (the basis of ascites and HRS).

Classification by site of obstruction:

Site	Examples	HVPG	Notes
Pre-hepatic	Portal/splenic vein thrombosis	Normal	Liver function preserved
Pre-sinusoidal (intrahepatic)	Schistosomiasis, congenital hepatic fibrosis, early PBC	Normal/near-normal	Wedged pressure normal
Sinusoidal	Cirrhosis (commonest)	Raised	HVPG accurately reflects pressure
Post-sinusoidal	Veno-occlusive (SOS)	Raised
Post-hepatic	Budd–Chiari, constrictive pericarditis, IVC web	Raised (HVPG may be normal in Budd-Chiari)

High-yield: HVPG is the wedged hepatic venous pressure minus the free hepatic venous pressure. It is normal in pre-sinusoidal and pre-hepatic portal hypertension (e.g. schistosomiasis, portal vein thrombosis) because the obstruction is upstream of where the balloon wedges. This is a classic MCQ.

Clinical features

Hepatocellular failure signs: jaundice, spider naevi (SVC distribution), palmar erythema, gynaecomastia, testicular atrophy, loss of body hair, Dupuytren contracture, leuconychia (Terry nails), parotid enlargement, fetor hepaticus, asterixis (flapping tremor), bleeding tendency.

Portal hypertension signs: splenomegaly (with hypersplenism → pancytopenia), caput medusae, ascites, dilated abdominal wall veins, oesophageal/gastric varices.

High-yield: Flow in caput medusae is away from the umbilicus (radiating outward), distinguishing it from IVC obstruction where flow is upward. A venous hum over the caput = Cruveilhier–Baumgarten murmur (recanalised umbilical vein).

Diagnosis & investigations

Investigation of choice for confirming cirrhosis (gold standard) = liver biopsy, but in practice diagnosis is made by combining clinical, biochemical, and imaging findings; biopsy is reserved for uncertain cases.

• Bloods: AST/ALT (AST:ALT >2 suggests alcohol), raised bilirubin, low albumin, prolonged PT/INR (best marker of synthetic function), thrombocytopenia (early, sensitive sign of portal HTN/hypersplenism), low sodium (marker of severity in advanced disease).
• Non-invasive fibrosis assessment (replacing biopsy): Transient elastography (FibroScan) measures liver stiffness; APRI and FIB-4 scores; serum markers.
• Imaging: USG — nodular surface, coarse echotexture, caudate lobe hypertrophy, splenomegaly, ascites, recanalised paraumbilical vein, reversed/hepatofugal portal flow on Doppler. Triphasic CT/MRI for HCC surveillance.
• Endoscopy (UGIE): screen ALL newly diagnosed cirrhotics for varices.
• HVPG: reference standard for severity of portal hypertension (research/specialised).

High-yield: Thrombocytopenia is often the earliest laboratory clue to portal hypertension (hypersplenic sequestration). A platelet count <150,000 with splenomegaly should prompt variceal screening.

Severity scoring

Child–Pugh (Turcotte) score — 5 parameters; remember "A BCDE" → Albumin, Bilirubin, Coagulation (INR/PT), D = ascites (Distension), Encephalopathy.

Parameter	1 point	2 points	3 points
Bilirubin (mg/dL)	<2	2–3	>3
Albumin (g/dL)	>3.5	2.8–3.5	<2.8
INR	<1.7	1.7–2.3	>2.3
Ascites	None	Mild/controlled	Moderate–severe/refractory
Encephalopathy	None	Grade 1–2	Grade 3–4

• Class A = 5–6 (well compensated, ~100% 1-yr survival)
• Class B = 7–9 (significant compromise)
• Class C = 10–15 (decompensated, ~45% 1-yr survival)

High-yield (PBC variant): For primary biliary cholangitis, the Child–Pugh bilirubin cut-offs are higher (1=<4, 2=4–10, 3=>10 mg/dL) because cholestasis raises bilirubin disproportionately.

MELD score (now MELD 3.0) — used to prioritise transplant allocation; based on bilirubin, INR, creatinine (and now sodium, albumin, sex). MELD-Na incorporates serum sodium. Range 6–40; higher = worse. MELD predicts 3-month mortality and decides organ allocation.

High-yield: Child–Pugh has subjective components (ascites, encephalopathy); MELD is fully objective (lab-based) and is used for transplant listing/organ allocation. MELD components = bilirubin, INR, creatinine (± Na). Mnemonic: "MELD = I Crush Beer" (INR, Creatinine, Bilirubin).

Management

General / disease-modifying

Treat the cause: abstinence in alcohol, antivirals for HBV/HCV (DAAs cure >95% HCV; viral suppression can regress fibrosis), weight loss for NASH, venesection for haemochromatosis, chelation/zinc for Wilson, ursodeoxycholic acid for PBC. Avoid hepatotoxins and sedatives; vaccinate against HAV/HBV; HCC surveillance with 6-monthly USG ± AFP.

Oesophageal varices

Primary prophylaxis (no prior bleed, medium/large varices): non-selective beta-blocker (NSBB) — propranolol/nadolol, or carvedilol (preferred, has added anti-α1 effect lowering intrahepatic resistance) OR endoscopic variceal band ligation (EVL). NSBBs work by β2-blockade → splanchnic vasoconstriction → reduced portal inflow; titrate to HR ~55–60/min.

Acute variceal bleed — stepwise approach:

Resuscitate (ABC, restrictive transfusion to Hb ~7–8 g/dL) → Vasoactive drug (terlipressin / octreotide / somatostatin, start before scope) → Prophylactic antibiotics (ceftriaxone — reduces infection, rebleed & mortality) → Urgent endoscopy within 12 h with band ligation (EVL) → if uncontrolled: balloon tamponade (Sengstaken–Blakemore) as bridge → rescue TIPS (transjugular intrahepatic portosystemic shunt).

High-yield: Prophylactic antibiotics (IV ceftriaxone) are MANDATORY in any cirrhotic with GI bleed — they independently improve survival. Restrictive transfusion (target Hb 7 g/dL) is associated with better outcomes than liberal transfusion (which raises portal pressure and rebleed risk).

High-yield: Gastric varices (esp. fundal/isolated) → treatment of choice is endoscopic cyanoacrylate (glue) injection, not band ligation. EVL is for oesophageal varices.

Secondary prophylaxis (after a bleed): NSBB + EVL combined is standard; TIPS if recurrent despite this. Pre-emptive (early) TIPS within 72 h benefits high-risk patients (Child C <14, or Child B with active bleeding).

Ascites

Stepwise: **salt restriction (<2 g/day Na) + spironolactone ± furosemide (ratio 100:40 mg)** → large-volume paracentesis with albumin (8 g/L of fluid removed if >5 L tapped) → TIPS for refractory ascites → transplant. Avoid NSAIDs and ACE inhibitors.

High-yield — SAAG: Serum-Ascites Albumin Gradient = serum albumin − ascitic albumin. SAAG ≥ 1.1 g/dL = portal hypertension (cirrhosis, cardiac, Budd–Chiari — "high gradient"); SAAG < 1.1 g/dL = non-portal causes (TB peritonitis, malignancy, pancreatic, nephrotic). High gradient = high portal pressure.

Spontaneous bacterial peritonitis (SBP)

Infection of ascitic fluid without a surgical source.

• Diagnosis: ascitic fluid PMN (neutrophil) count ≥ 250 cells/mm³ (regardless of culture). Most common organism = E. coli (Gram-negative enterics); culture often negative.
• Treatment: IV third-generation cephalosporin (cefotaxime/ceftriaxone) × 5 days.
• IV albumin (1.5 g/kg day 1, 1 g/kg day 3) reduces hepatorenal syndrome and mortality, especially if bilirubin >4 or creatinine >1.
• Prophylaxis (norfloxacin/ciprofloxacin) indicated for: prior SBP, ascitic protein <1.5 g/dL with renal/hepatic impairment, or during GI bleed.

High-yield: PMN ≥250/mm³ defines SBP. If polymicrobial, very high PMN, high LDH, low glucose, multiple organisms → suspect secondary (surgical) peritonitis → image and consider surgery. CTP (culture-negative neutrocytic ascites, PMN ≥250 but culture −ve) and bacterascites (culture +ve, PMN <250) are variants.

Hepatic encephalopathy (HE)

Neuropsychiatric syndrome from gut-derived neurotoxins (chiefly ammonia) bypassing the liver.

West Haven grading: Grade 0 (minimal) → 1 (mild confusion, altered sleep) → 2 (lethargy, asterixis, disorientation) → 3 (somnolent but rousable, gross disorientation) → 4 (coma).

Precipitants — mnemonic "HEPATICS": Haemorrhage (GI bleed), Electrolyte imbalance (hypokalaemia, alkalosis), Protein load, infection, TIPS/shunts, Azotaemia, Constipation, Sedatives. Treat the precipitant.

Management: Lactulose (first-line; titrate to 2–3 soft stools/day, acidifies colon trapping NH4+) → add rifaximin (non-absorbed antibiotic, reduces recurrence) → L-ornithine-L-aspartate / treat precipitant. Protein restriction is NO LONGER routinely advised.

High-yield: Lactulose is DOC for hepatic encephalopathy. Rifaximin is added for recurrent/refractory HE. Asterixis is characteristic but not specific (also in uraemia, CO2 retention).

Hepatorenal syndrome (HRS)

Functional renal failure (kidneys histologically normal) from extreme splanchnic vasodilatation → renal vasoconstriction, in a patient with advanced cirrhosis + ascites. Diagnosis of exclusion (no shock, no nephrotoxins, no structural renal disease, no response to volume expansion with albumin).

Feature	HRS-AKI (Type 1)	HRS-NAKI (Type 2)
Onset	Rapid (<2 weeks), often after SBP	Insidious
Creatinine	Doubling to >2.5 quickly	Moderate, steady
Association	Acute precipitant	Refractory ascites
Prognosis	Very poor (weeks)	Better (months)

Treatment: Terlipressin (splanchnic vasoconstrictor) + IV albumin is first-line; noradrenaline is an alternative. Definitive treatment = liver transplantation. TIPS and renal replacement are bridges.

High-yield: HRS treatment of choice = terlipressin + albumin; cure = liver transplant. Urinary sodium is characteristically very low (<10 mmol/L) with normal urine sediment.

TIPS

TIPS creates a low-resistance channel between portal and hepatic veins, decompressing the portal system. Indications: refractory variceal bleeding, refractory ascites, refractory hepatic hydrothorax, Budd–Chiari, HRS bridging. Main complications: worsening/new hepatic encephalopathy (~30%, because gut blood bypasses liver) and shunt stenosis. Contraindications: severe HE, heart failure, severe pulmonary hypertension, polycystic liver, sepsis.

High-yield: The commonest adverse effect of TIPS is new or worsened hepatic encephalopathy. TIPS lowers portal pressure but at the cost of diverting ammonia-laden blood past the liver.

Complications (summary)

Variceal bleeding · ascites · SBP · hepatic encephalopathy · hepatorenal & hepatopulmonary syndrome · hepatocellular carcinoma (cirrhosis is the dominant risk factor; surveillance 6-monthly USG ± AFP) · portal vein thrombosis · coagulopathy · malnutrition/sarcopenia · cirrhotic cardiomyopathy. Hepatopulmonary syndrome = triad of liver disease + hypoxaemia + intrapulmonary vascular dilatation (platypnoea, orthodeoxia, positive contrast echo "bubble study"); contrast portopulmonary hypertension (true pulmonary arterial hypertension).

Key differentials

• Ascites work-up by SAAG distinguishes portal (≥1.1) from peritoneal/malignant (<1.1) causes.
• Non-cirrhotic portal hypertension: schistosomiasis (pre-sinusoidal, commonest non-cirrhotic cause worldwide), non-cirrhotic portal fibrosis / idiopathic portal hypertension (massive splenomegaly, preserved liver function, normal HVPG), portal vein thrombosis, Budd–Chiari.
• Causes of isolated splenomegaly with portal HTN but normal liver: extrahepatic portal vein obstruction (commonest cause of variceal bleed in children), NCPF.
• Hepatic vs pre-renal vs ATN azotaemia in the decompensated cirrhotic (urinary Na, response to albumin challenge).

Recently asked / exam angle

• SAAG ≥1.1 = portal hypertension; the value and its interpretation are repeatedly tested image/clinical-vignette style.
• SBP diagnostic cut-off = PMN ≥250/mm³; commonest organism E. coli; DOC cefotaxime; albumin reduces HRS.
• HVPG cut-offs: >10 (clinically significant), >12 (bleed risk) — and that HVPG is normal in pre-sinusoidal portal HTN (schistosomiasis).
• MELD components vs Child–Pugh components — "which is objective / used for transplant allocation" (MELD).
• DOC questions: variceal bleed → terlipressin/octreotide + EVL + ceftriaxone; HE → lactulose then rifaximin; HRS → terlipressin + albumin; gastric varices → cyanoacrylate glue.
• Commonest complication of TIPS = hepatic encephalopathy.
• Carvedilol preferred NSBB for primary prophylaxis; restrictive transfusion (Hb 7) in variceal bleed.
• Direction of flow in caput medusae (away from umbilicus); Cruveilhier–Baumgarten murmur.

Rapid revision

1. Cirrhosis = bridging fibrosis + regenerative nodules; compensated vs decompensated decides prognosis.
2. HVPG >10 mmHg = clinically significant portal hypertension; >12 = variceal bleed risk; normal in pre-sinusoidal/pre-hepatic causes.
3. SAAG ≥1.1 g/dL = portal hypertension; <1.1 = malignancy/TB/nephrotic.
4. SBP: ascitic PMN ≥250/mm³, commonest organism E. coli, DOC cefotaxime, give albumin to prevent HRS.
5. Child–Pugh = Albumin, Bilirubin, Coagulation(INR), Distension(ascites), Encephalopathy; MELD (objective: bilirubin/INR/creatinine ± Na) for transplant allocation.
6. Acute variceal bleed: terlipressin/octreotide + ceftriaxone + EVL; balloon tamponade then rescue TIPS if uncontrolled; restrictive transfusion to Hb 7.
7. Gastric varices → cyanoacrylate glue, not band ligation.
8. Hepatic encephalopathy DOC = lactulose; add rifaximin for recurrence; don't restrict protein.
9. HRS = functional renal failure; Rx = terlipressin + albumin; cure = liver transplant; urine Na very low.
10. Commonest complication of TIPS = hepatic encephalopathy.
11. Thrombocytopenia = earliest lab marker of portal hypertension (hypersplenism).
12. Cirrhosis is the major risk factor for HCC → 6-monthly USG ± AFP surveillance; hepatopulmonary syndrome = liver disease + hypoxaemia + intrapulmonary shunts (positive bubble echo).