Cirrhosis
Summary
Cirrhosis is the end-stage of chronic liver disease characterised by diffuse hepatic fibrosis, replacement of normal liver architecture with regenerative nodules, and progressive hepatic dysfunction. Portal hypertension develops due to distorted intrahepatic vasculature, leading to complications including ascites, oesophageal varices, hepatic encephalopathy, and hypersplenism. Liver synthetic function declines, resulting in coagulopathy, hypoalbuminaemia, and jaundice. The condition can remain compensated for years or decompensate with life-threatening complications. The leading causes in developed countries are alcohol-related liver disease (ARLD), non-alcoholic fatty liver disease (NAFLD/MASLD), and viral hepatitis (HCV, HBV). Cirrhosis significantly increases the risk of hepatocellular carcinoma (HCC). Management involves treating the underlying cause, managing complications, and liver transplantation for advanced disease.
Key Facts
- Definition: End-stage chronic liver disease with fibrosis and regenerative nodules
- Causes: Alcohol (30-40%), NAFLD/MASLD (25-30%), Viral hepatitis (HBV, HCV), Autoimmune, PBC, Haemochromatosis
- Portal hypertension: Develops when hepatic venous pressure gradient (HVPG) >5 mmHg
- Compensated vs Decompensated: Key distinction; decompensation = ascites, variceal bleed, encephalopathy, jaundice
- Child-Pugh score: Grades A/B/C; surgical risk and prognosis
- MELD score: Model for End-stage Liver Disease; used for transplant prioritisation
- HCC surveillance: 6-monthly USS ± AFP for all cirrhotic patients
- Liver transplant: Only curative option for advanced cirrhosis
- Prognosis: Compensated cirrhosis ~10-year survival; decompensated ~2-year median survival
Clinical Pearls
"Decompensation Changes Everything": The transition from compensated to decompensated cirrhosis (ascites, encephalopathy, variceal bleed, jaundice) dramatically worsens prognosis. Median survival drops from >10 years to ~2 years.
"TIPS Is a Double-Edged Sword": Transjugular intrahepatic portosystemic shunt (TIPS) treats refractory ascites and variceal bleeding but can precipitate hepatic encephalopathy by shunting ammonia past the liver.
"Screen for HCC": All patients with cirrhosis should have 6-monthly ultrasound surveillance for hepatocellular carcinoma. Early detection enables curative treatment (ablation, resection, transplant).
"Rifaximin for Encephalopathy": Lactulose remains first-line, but rifaximin is an effective adjunct for recurrent hepatic encephalopathy and is now NICE-recommended.
"SBP: Tap Early, Treat Fast": Any patient with cirrhosis and ascites presenting with fever, abdominal pain, or deterioration should have a diagnostic ascitic tap. SBP is a medical emergency.
Why This Matters Clinically
Cirrhosis is common, often silent until decompensation, and is the 5th leading cause of death in middle-aged adults in the UK. Understanding the pathophysiology of portal hypertension, recognising decompensation, managing complications, and knowing when to refer for transplant assessment can be life-saving.[1,2]
Incidence & Prevalence
| Parameter | Data |
|---|---|
| Global prevalence | ~112 million with compensated; ~10 million with decompensated cirrhosis |
| UK prevalence | ~2-3% of population have chronic liver disease; ~5,000 deaths/year from cirrhosis |
| Trend | Rising due to NAFLD and alcohol |
| Age | Peak incidence 50-60 years |
Causes
| Cause | Proportion | Notes |
|---|---|---|
| Alcohol-related liver disease (ARLD) | 30-40% | Dose-dependent; >14 units/week for women, >21 for men |
| NAFLD/MASLD | 25-30% | Rising; associated with metabolic syndrome |
| Hepatitis C | 15-20% | Declining with DAA therapy |
| Hepatitis B | 5-10% | More common in endemic areas |
| Autoimmune hepatitis | 5% | Female predominance |
| Primary biliary cholangitis (PBC) | Variable | Anti-mitochondrial antibodies |
| Haemochromatosis | Variable | HFE mutation |
| Wilson's disease | Rare | Consider in young patients |
| Cryptogenic | 10-15% | Often "burnt-out" NASH |
Mechanism of Fibrosis
Step 1: Chronic Liver Injury
- Alcohol, viral infection, fat deposition, autoimmune attack → hepatocyte damage
- Repeated injury and inflammation
Step 2: Stellate Cell Activation
- Hepatic stellate cells (HSCs) activated by injury
- Transform from quiescent vitamin A-storing cells to myofibroblasts
- Produce extracellular matrix (ECM) — particularly collagen
Step 3: Fibrosis Deposition
- Excessive ECM accumulates in space of Disse
- Normal liver architecture disrupted
- Fibrous septa form between portal tracts and central veins
Step 4: Regenerative Nodules
- Surviving hepatocytes proliferate into nodules
- Lack normal lobular organisation
- Further distort architecture
Step 5: Cirrhosis End-Stage
- Diffuse fibrosis + regenerative nodules = cirrhosis
- Irreversible architectural distortion
- Leads to portal hypertension and synthetic failure
Portal Hypertension
| Consequence | Mechanism | Clinical Manifestation |
|---|---|---|
| Oesophageal varices | Portosystemic collaterals | Variceal haemorrhage |
| Ascites | Splanchnic vasodilation + RAAS activation + hypoalbuminaemia | Abdominal distension |
| Splenomegaly | Congestion | Hypersplenism (pancytopenia) |
| Caput medusae | Umbilical collaterals | Visible periumbilical veins |
| Rectal varices | Inferior mesenteric portosystemic shunt | Rectal bleeding |
| Hepatic encephalopathy | Bypassing of ammonia past liver | Confusion, asterixis |
Signs of Chronic Liver Disease
| Sign | Mechanism | Notes |
|---|---|---|
| Spider naevi | Oestrogen excess | >5 indicates significant disease |
| Palmar erythema | Oestrogen excess | Thenar/hypothenar erythema |
| Dupuytren's contracture | Fibrosis (alcohol) | Palmar fascia thickening |
| Gynaecomastia | Oestrogen/androgen imbalance | Male breast enlargement |
| Testicular atrophy | Hormonal disturbance | In males |
| Hepatomegaly | Early cirrhosis | Later: small, shrunken liver |
| Splenomegaly | Portal hypertension | May cause pancytopenia |
Signs of Decompensation
| Sign | Significance |
|---|---|
| Ascites | Abdominal distension; shifting dullness |
| Jaundice | Bilirubin elevated; scleral icterus |
| Hepatic encephalopathy | Confusion, asterixis, raised ammonia |
| Oedema | Peripheral pitting oedema (hypoalbuminaemia) |
| Bruising/bleeding | Coagulopathy (reduced clotting factors) |
| Fetor hepaticus | Sweet, musty breath odour |
Red Flags
[!CAUTION] Red Flags — Urgent Assessment:
- Haematemesis/melaena (variceal bleeding)
- New-onset confusion (hepatic encephalopathy)
- Fever + abdominal pain + ascites (spontaneous bacterial peritonitis)
- Rapid abdominal distension (new ascites, portal vein thrombosis, HCC)
- Rising creatinine (hepatorenal syndrome)
- New hepatic mass (hepatocellular carcinoma)
Systematic Approach
General Inspection:
- Jaundice (scleral, skin)
- Cachexia (muscle wasting)
- Mental state (encephalopathy)
- Fetor hepaticus
Hands:
- Clubbing
- Leuconychia (hypoalbuminaemia)
- Palmar erythema
- Dupuytren's contracture
- Asterixis (hepatic flap)
Arms:
- Bruising
- Scratch marks (pruritus)
- Spider naevi
Face/Chest:
- Spider naevi (>5 significant)
- Gynaecomastia
- Loss of axillary hair
Abdomen:
- Hepatomegaly (early) or small liver (late)
- Splenomegaly
- Ascites (shifting dullness, fluid thrill)
- Caput medusae
- Testicular atrophy (males)
Legs:
- Peripheral oedema
Asterixis (Hepatic Flap)
| Step | Technique |
|---|---|
| 1 | Ask patient to extend wrists with arms outstretched |
| 2 | Hold position for 30 seconds |
| 3 | Positive = flapping tremor (sudden loss of position sense) |
| 4 | Indicates hepatic encephalopathy |
First-Line Investigations
| Investigation | Finding | Notes |
|---|---|---|
| LFTs | Raised bilirubin; low albumin; variable transaminases | AST:ALT >2 suggests alcohol |
| Coagulation (INR) | Prolonged | Synthetic dysfunction |
| FBC | Pancytopenia (hypersplenism); macrocytosis (alcohol) | |
| U&E | May be normal; monitor for hepatorenal syndrome | |
| Ammonia | Raised | Encephalopathy |
| AFP | Raised if HCC | Used in surveillance |
Aetiological Investigations
| Investigation | Purpose |
|---|---|
| Hepatitis serology (HBV, HCV) | Viral causes |
| Autoimmune markers (ANA, SMA, anti-LKM) | Autoimmune hepatitis |
| Immunoglobulins | IgG raised in AIH; IgM in PBC |
| AMA | Primary biliary cholangitis |
| Iron studies, ferritin, HFE gene | Haemochromatosis |
| Caeruloplasmin | Wilson's disease |
| Alpha-1 antitrypsin | A1AT deficiency |
Imaging
| Modality | Role |
|---|---|
| USS Liver | Cirrhotic nodular liver, ascites, splenomegaly, HCC surveillance |
| Fibroscan | Non-invasive fibrosis assessment (kPa) |
| CT/MRI Liver | HCC characterisation, portal vein patency |
| OGD | Variceal screening; all cirrhotics should have OGD |
Scoring Systems
Child-Pugh Score:
| Parameter | 1 Point | 2 Points | 3 Points |
|---|---|---|---|
| Bilirubin (µmol/L) | <34 | 34-50 | >50 |
| Albumin (g/L) | >35 | 28-35 | <28 |
| INR | <1.7 | 1.7-2.3 | >2.3 |
| Ascites | None | Mild | Moderate-severe |
| Encephalopathy | None | Grade I-II | Grade III-IV |
| Grade | Points | 1-Year Survival |
|---|---|---|
| A | 5-6 | 100% |
| B | 7-9 | 80% |
| C | 10-15 | 45% |
MELD Score:
- Uses: Bilirubin, INR, Creatinine, (± Sodium)
- Online calculator; used for transplant listing priority
- Higher MELD = more urgent for transplant
Management Algorithm
CIRRHOSIS MANAGEMENT
↓
┌─────────────────────────────────────────────────────────────────┐
│ TREAT UNDERLYING CAUSE │
├─────────────────────────────────────────────────────────────────┤
│ ➤ Alcohol: Abstinence essential; support services │
│ ➤ HCV: Direct-acting antivirals (DAA) — curative │
│ ➤ HBV: Antivirals (entecavir, tenofovir) — suppress │
│ ➤ NAFLD/MASLD: Weight loss, control metabolic syndrome │
│ ➤ Autoimmune hepatitis: Steroids + azathioprine │
│ ➤ PBC: Ursodeoxycholic acid │
│ ➤ Haemochromatosis: Venesection │
│ ➤ Wilson's: Chelation (penicillamine) │
└─────────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────────┐
│ HCC SURVEILLANCE │
├─────────────────────────────────────────────────────────────────┤
│ ➤ USS Liver ± AFP every 6 months │
│ ➤ If suspicious lesion → CT/MRI (contrast) for characterisation│
│ ➤ HCC diagnosis often made on imaging (arterial enhancement) │
│ ➤ Treatment: Ablation, TACE, resection, transplant │
└─────────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────────┐
│ VARICEAL SURVEILLANCE & PROPHYLAXIS │
├─────────────────────────────────────────────────────────────────┤
│ ➤ OGD at diagnosis of cirrhosis │
│ ➤ Primary prophylaxis (if medium/large varices): │
│ • Non-selective beta-blocker (propranolol, carvedilol) OR │
│ • Endoscopic variceal band ligation (EVL) │
│ ➤ Repeat OGD: │
│ • Every 2 years if compensated, no varices │
│ • Annually if decompensated or small varices │
└─────────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────────┐
│ MANAGE DECOMPENSATION │
├─────────────────────────────────────────────────────────────────┤
│ ASCITES: │
│ ➤ Salt restriction (<2g sodium/day) │
│ ➤ Spironolactone (100-400 mg OD) ± Furosemide (40-160 mg OD) │
│ ➤ Therapeutic paracentesis if tense (give albumin 6-8g/L) │
│ ➤ Refractory: Consider TIPS │
│ │
│ HEPATIC ENCEPHALOPATHY: │
│ ➤ Identify and treat precipitant (infection, GI bleed, drugs) │
│ ➤ Lactulose 15-30 mL BD-TDS (aim 2-3 soft stools/day) │
│ ➤ Rifaximin 550 mg BD (adjunct for recurrent HE) │
│ │
│ VARICEAL BLEED: │
│ ➤ Resuscitate (restrictive transfusion; PCC if needed) │
│ ➤ Terlipressin IV + Antibiotics (ceftriaxone) │
│ ➤ Urgent OGD for band ligation (within 12 hours) │
│ ➤ Sengstaken-Blakemore if uncontrolled; TIPS if recurrent │
│ │
│ SBP (PMN >250/mm³ in ascitic fluid): │
│ ➤ IV antibiotics (ceftriaxone or piperacillin-tazobactam) │
│ ➤ Albumin infusion (1.5 g/kg day 1, 1 g/kg day 3) │
│ ➤ Secondary prophylaxis: Ciprofloxacin or norfloxacin │
└─────────────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────────────┐
│ LIVER TRANSPLANT │
├─────────────────────────────────────────────────────────────────┤
│ ➤ Only curative option for advanced cirrhosis │
│ ➤ Refer when MELD ≥15 or decompensation │
│ ➤ Contraindications: Active alcohol/drug use, extrahepatic │
│ malignancy, severe cardiopulmonary disease │
│ ➤ Post-transplant: Lifelong immunosuppression │
└─────────────────────────────────────────────────────────────────┘
Major Complications
| Complication | Incidence | Management |
|---|---|---|
| Ascites | 50% at 10 years | Diuretics; paracentesis; TIPS |
| Oesophageal varices | 50-60% of cirrhotics | Primary prophylaxis (beta-blocker or EVL); band ligation for bleed |
| Hepatic encephalopathy | 30-45% | Lactulose; rifaximin; treat precipitant |
| SBP | ~20% of ascitic cirrhotics | Antibiotics; albumin; secondary prophylaxis |
| Hepatorenal syndrome | 10-20% | Terlipressin + albumin; transplant |
| Hepatocellular carcinoma | 1-5%/year | Surveillance; ablation; resection; transplant |
Hepatorenal Syndrome
| Type | Features | Prognosis |
|---|---|---|
| Type 1 | Rapidly progressive renal failure; creatinine doubles in <2 weeks | Poor; weeks survival without treatment |
| Type 2 | Gradual renal impairment; often with refractory ascites | Months survival |
Survival
| Status | Median Survival |
|---|---|
| Compensated cirrhosis | >10-12 years |
| Decompensated cirrhosis | 2-3 years |
| Child-Pugh A | 100% 1-year survival |
| Child-Pugh C | 45% 1-year survival |
| Post-transplant | 80-90% 5-year survival |
Prognostic Factors
| Good Prognosis | Poor Prognosis |
|---|---|
| Compensated | Decompensated |
| Cause removed (abstinence, viral cure) | Ongoing alcohol, active virus |
| Child-Pugh A | Child-Pugh C |
| Low MELD | High MELD |
| No HCC | HCC present |
Key Guidelines
| Guideline | Organisation | Year | Key Points |
|---|---|---|---|
| Cirrhosis Management | EASL | 2018 | Comprehensive cirrhosis management |
| NICE Cirrhosis | NICE | NG50, 2016 | Assessment and management in UK |
| HCC Management | AASLD | 2018 | Surveillance, staging, treatment |
Landmark Studies
Carvedilol vs Propranolol for Varices (Banares et al.)
- Carvedilol reduces portal pressure more effectively
- Increasingly used for primary prophylaxis
STOPAH Trial (2015)
- Severe alcoholic hepatitis: Prednisolone reduces 28-day mortality
- Pentoxifylline does not improve outcomes
- PMID: 25836888
What is Cirrhosis?
Cirrhosis is severe scarring of the liver caused by long-term liver damage. Over time, healthy liver tissue is replaced by scar tissue, which prevents the liver from working properly.
What causes it?
Common causes include:
- Alcohol — drinking too much over many years
- Fatty liver disease — often related to being overweight
- Viral hepatitis — Hepatitis B and C infections
What are the symptoms?
Early cirrhosis often has no symptoms. As it progresses:
- Tiredness
- Feeling sick, loss of appetite
- Swollen tummy (fluid — ascites)
- Yellow skin and eyes (jaundice)
- Confusion (hepatic encephalopathy)
- Vomiting blood (from varices)
How is it treated?
- Stop the cause — stop alcohol, treat hepatitis
- Medications — to control fluid, confusion, and prevent bleeding
- Regular checks — ultrasound scans for liver cancer
- Liver transplant — for advanced disease (the only cure)
Guidelines
-
EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460. PMID: 29653741
-
NICE. Cirrhosis in over 16s: assessment and management (NG50). 2016. nice.org.uk/guidance/ng50
Key Studies
- Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015;372(17):1619-1628. PMID: 25901427
High-Yield Exam Topics
| Topic | Key Points |
|---|---|
| Signs of CLD | Spider naevi, palmar erythema, gynaecomastia, caput medusae, splenomegaly |
| Decompensation | Ascites, encephalopathy, variceal bleed, jaundice |
| Child-Pugh | Bilirubin, Albumin, INR, Ascites, Encephalopathy (grades A/B/C) |
| MELD | Bilirubin, INR, Creatinine (transplant listing) |
| HCC surveillance | USS ± AFP every 6 months |
| Variceal prophylaxis | Beta-blocker or EVL for medium/large varices |
Sample Viva Questions
Q1: A patient with known cirrhosis presents with confusion. How do you manage?
Model Answer: This is likely hepatic encephalopathy. Initial assessment: ABCDE, check blood glucose. Identify and treat precipitant (GI bleed, sepsis, constipation, electrolyte disturbance, drugs like sedatives). Investigations: FBC, U&E, LFTs, ammonia, blood cultures, CXR, ascitic tap if ascites. Treatment: Lactulose 15-30 mL BD-TDS aiming for 2-3 soft stools/day. If recurrent, add rifaximin 550 mg BD. If infection suspected, empirical antibiotics. Correct electrolytes. If severe, may need ICU.
Q2: What are the causes of acute decompensation in cirrhosis?
Model Answer: The common precipitants include: Infection (SBP, UTI, chest infection), GI bleeding (variceal or peptic), Constipation (increased ammonia absorption), Electrolyte imbalance (hypokalaemia, hyponatraemia), Drugs (sedatives, NSAIDs, opioids), Dehydration (overdiuresis), Portal vein thrombosis, HCC development, and Non-compliance with medications (lactulose, diuretics).
Q3: How do you manage a patient with tense ascites?
Model Answer: Therapeutic paracentesis is the first-line treatment for tense ascites. I would insert an ascitic drain and drain the fluid. For large-volume paracentesis (>5L), administer human albumin solution 6-8g per litre of ascites removed to prevent post-paracentesis circulatory dysfunction. Ongoing management: Salt restriction (<2g sodium/day), diuretics (spironolactone ± furosemide), monitor weight, U&E. If refractory (≥2 large-volume paracenteses/month despite maximal diuretics), consider TIPS. Always send ascitic fluid for cell count and culture (exclude SBP).
Common Exam Errors
| Error | Correct Approach |
|---|---|
| Forgetting to check for SBP | Any ascitic patient with fever/pain/deterioration needs diagnostic tap |
| Not offering variceal surveillance | All cirrhotics need OGD to screen for varices |
| Missing HCC screening | 6-monthly USS ± AFP for all cirrhotics |
| Not mentioning transplant | Liver transplant is the only cure for advanced cirrhosis |
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.