Key Facts

Cirrhosis is the common end-point of progressive liver disease from various causes. It represents irreversible architectural distortion of the liver, though with cause removal and treatment, compensated patients can remain stable for years.

Epidemiology

Liver disease is the 3rd commonest cause of premature death in the UK. Cirrhosis prevalence is ~100-150 per 100,000. Liver disease mortality has increased >400% since 1970 (contrasting with cardiovascular and cancer mortality declines). Alcohol and NAFLD are the main drivers.

Aetiology

• Alcohol: ~40% (most common single cause in UK)
• NAFLD/MASLD: ~30% (rapidly increasing)
• Hepatitis C: ~10% (declining with DAA treatment)
• Other: hepatitis B, autoimmune hepatitis, PBC, PSC, haemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, cryptogenic (~5%)

Pathophysiology

Chronic liver injury → hepatic stellate cell activation → excessive collagen deposition → disruption of normal hepatic architecture with formation of regenerative nodules surrounded by fibrous septa. This causes:

1. Increased intrahepatic resistance → portal hypertension (HVPG >5 mmHg; clinically significant >10 mmHg)
2. Loss of functional hepatocytes → synthetic failure (hypoalbuminaemia, coagulopathy), impaired metabolism (jaundice, encephalopathy)
3. Splanchnic vasodilation → effective hypovolaemia → RAAS/ADH activation → sodium/water retention → ascites
4. Immune dysfunction → susceptibility to infection (SBP, pneumonia, UTI)

Compensated Cirrhosis

• May be asymptomatic for years
• Fatigue, anorexia, weight loss
• Hepatomegaly (early) → shrunken liver (late)
• Splenomegaly

Stigmata of Chronic Liver Disease

• Spider naevi (>5 is significant), palmar erythema
• Gynaecomastia, testicular atrophy (oestrogen excess)
• Dupuytren's contracture (alcohol-related)
• Parotid enlargement (alcohol-related)
• Leukonychia, Terry's nails
• Muscle wasting, easy bruising

Decompensated Cirrhosis

• Ascites (most common decompensation event)
• Variceal bleeding (haematemesis/melaena)
• Hepatic encephalopathy (confusion, asterixis)
• Jaundice

Red Flags

• New-onset ascites (decompensation, exclude SBP and malignancy)
• Variceal haemorrhage (emergency)
• Confusion/drowsiness (encephalopathy — exclude other causes, especially infection)
• Rapidly worsening jaundice (acute-on-chronic liver failure)
• New hepatic mass (HCC)

Bedside

• Examination: stigmata of CLD, ascites (shifting dullness, fluid thrill), hepatomegaly/splenomegaly

Bloods

• LFTs: ALT/AST may be normal or mildly raised; ALP/GGT raised in cholestatic causes; raised bilirubin (conjugated)
• Albumin: low (synthetic failure)
• INR/PT: raised (reduced clotting factor synthesis)
• FBC: thrombocytopaenia (splenic sequestration), anaemia, leucopaenia
• U&Es: renal function (hepatorenal syndrome)
• Sodium: often low (dilutional hyponatraemia)
• AFP: HCC screening (>200 ng/mL strongly suggestive)
• Aetiology screen: hepatitis B/C serology, autoantibodies (ANA, SMA, AMA, anti-LKM), immunoglobulins, iron studies, caeruloplasmin, alpha-1 antitrypsin, coeliac serology

Imaging

• USS abdomen: liver morphology (nodular surface, coarse echo-texture), splenomegaly, ascites, portal vein patency, HCC screening
• Transient elastography (FibroScan): liver stiffness >12.5 kPa = cirrhosis
• CT/MRI abdomen: HCC characterisation (arterial enhancement + portal venous washout = diagnostic), portal vein assessment

Special Tests

• Upper GI endoscopy: variceal screening at diagnosis of cirrhosis
• Ascitic tap: if new ascites — cell count (SBP: neutrophils >250/mm³), albumin (SAAG calculation), culture, cytology
• HVPG measurement: gold standard for portal hypertension (specialist centres)
• Liver biopsy: if aetiology unclear or non-invasive tests discordant; not always required if clinical/imaging diagnosis clear
• Child-Pugh score: bilirubin, albumin, INR, ascites, encephalopathy → A (5-6), B (7-9), C (10-15)
• MELD score: bilirubin, INR, creatinine → predicts 3-month mortality; used for transplant listing priority

Non-pharmacological

• Treat underlying cause: alcohol abstinence, antiviral therapy, immunosuppression, iron depletion
• Nutritional support: high-protein diet (1.2-1.5 g/kg/day — protein restriction is outdated), small frequent meals, late-evening snack, salt restriction (<5 g/day for ascites)
• HCC surveillance: USS ± AFP every 6 months
• Variceal screening: OGD at diagnosis; repeat at intervals based on findings
• Vaccination: hepatitis A/B (if not immune), influenza, pneumococcal, COVID-19
• Avoid hepatotoxic drugs and NSAIDs (renal risk)

Pharmacological

• Ascites: spironolactone 100 mg OD (increase to max 400 mg) ± furosemide 40 mg OD (increase to max 160 mg) in 100:40 ratio; target weight loss 0.5 kg/day (1 kg/day if peripheral oedema)
• SBP prophylaxis: ciprofloxacin 500 mg OD or norfloxacin 400 mg OD (if prior SBP, ascitic protein <15 g/L with renal/liver dysfunction)
• Variceal prophylaxis: propranolol 40 mg BD or carvedilol 6.25-12.5 mg OD; or variceal band ligation
• Hepatic encephalopathy: lactulose 15-30 mL BD-TDS (target 2-3 soft stools/day); rifaximin 550 mg BD (secondary prophylaxis after first episode — NICE TA613)
• Hepatorenal syndrome: terlipressin 1-2 mg IV QDS + albumin 20-40 g/day
• Bone protection: calcium/vitamin D; DEXA screening

Surgical/Interventional

• Large volume paracentesis: for tense ascites (>5L with albumin replacement — 8 g per litre drained)
• TIPSS: for refractory ascites or recurrent variceal bleeding
• Liver transplantation: definitive treatment for decompensated cirrhosis; MELD score guides listing; contraindicated by active alcohol/substance use, advanced HCC beyond criteria, uncontrolled sepsis

Referral Criteria

• All cirrhosis to hepatology for specialist management
• Transplant assessment: decompensated disease, MELD ≥15, HCC meeting Milan criteria
• Palliative care: if not transplant candidate with decompensated disease

Compensated cirrhosis: median survival >12 years. Rate of decompensation: ~5-7% per year. Decompensated cirrhosis: median survival 2-4 years without transplant. Child-Pugh A: 1-year survival ~100%; B: ~80%; C: ~45%. MELD score predicts 3-month mortality. Liver transplant: 5-year survival ~75%. Leading causes of death: variceal bleeding, liver failure, HCC, infection/sepsis.

Child-Pugh Score

Cirrhosis Complications Summary