Liver disease - chronic
Description
- Cirrhosis = histological diagnosis: bands of fibrous tissue linking portal and central areas, destroying normal architecture
- Regenerative nodules + fibrosis -> inc intrahepatic resistance -> portal hypertension
- Two axes determine everything downstream
- Compensated vs decompensated
- Portal pressure (HVPG)
- Compensated advanced chronic liver disease (cACLD) is the modern framing
- Continuum, not a binary; can regress if the driver is removed
- Decompensation = ascites, variceal bleed, or overt encephalopathy (+/- jaundice, coagulopathy)
- Median survival drops from >12 years to ~2 years
Epidemiology
- Rising in Australia - driven by MASLD and alcohol
- Alcohol + MASLD now exceed viral hepatitis as causes of transplant listing
- ~6th leading cause of death in working-age adults globally
- Aboriginal and Torres Strait Islander peoples: higher rates, earlier onset
Aetiopathogenesis
Causes of cirrhosis
- Common - alcohol-related, MASLD/MASH, chronic hepatitis C
- Less common - chronic hepatitis B, autoimmune hepatitis, PBC
- Rare - PSC, haemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, drugs (methotrexate, amiodarone, methyldopa)
- Two causes coexisting is common and multiplies risk - alcohol + MASLD, HCV + alcohol
Portal hypertension - classified by site
- Cirrhosis is the commonest cause by far. Otherwise:
| Site | Causes |
|---|---|
| Pre-hepatic / pre-sinusoidal | Portal vein thrombosis (myeloproliferative, PNH), tumour/lymphoma compression, schistosomiasis, congenital hepatic fibrosis |
| Sinusoidal | Cirrhosis, sarcoid, lymphoma/leukaemic infiltration |
| Post-sinusoidal / post-hepatic | Budd-Chiari (MPN, OCP, pregnancy, PNH), sinusoidal obstruction syndrome, constrictive pericarditis, severe TR, RHF |
- Also inc portal inflow - splenomegaly, AVM
- Splenomegaly + varices + preserved LFTs = think pre-sinusoidal, not cirrhosis
Diagnosis
Signs - and what each points to
| Sign | Points to |
|---|---|
| Dupuytren, parotid enlargement, facial telangiectasia, cerebellar signs, peripheral neuropathy | Alcohol |
| Tattoos, track marks | Viral hepatitis |
| Xanthelasma + jaundice + scratch marks | PBC |
| Slate-grey pigmentation, arthropathy, diabetes | Haemochromatosis |
| Kayser-Fleischer rings, movement disorder | Wilson |
- Hands: leuconychia, clubbing, palmar erythema, bruising, asterixis
- Face/chest: scleral icterus, fetor hepaticus, spider naevi (SVC distribution, >5 abnormal), gynaecomastia, loss of body hair
- Abdomen: hepatosplenomegaly, ascites, caput medusae, Cruveilhier-Baumgarten venous hum, testicular atrophy
- Gynaecomastia may be the drug, not the disease - spironolactone, digoxin, cimetidine
- Liver may be small and impalpable - absent hepatomegaly does not exclude cirrhosis
Portal hypertension
- Splenomegaly, collaterals (varices, caput medusae), ascites, venous hum
- HVPG = wedged minus free hepatic venous pressure
- Normal 3-5 mmHg
- >10 mmHg = clinically significant portal hypertension (CSPH) - varices, decompensation
- >12 mmHg - variceal bleeding risk
- Sinusoidal pressure only - normal in pre-sinusoidal causes such as PVT
- Non-invasive CSPH (Baveno VII)
- Liver stiffness >=25 kPa = CSPH
- Liver stiffness <15 kPa + platelets >150 = rules out cACLD
Ascites - SAAG does the work
| SAAG >=11 g/L (portal HTN) | SAAG <11 g/L |
|---|---|
| Cirrhosis, alcoholic hepatitis | Peritoneal carcinomatosis |
| Budd-Chiari, sinusoidal obstruction | Peritoneal TB |
| Cardiac (CCF, constrictive pericarditis) | Pancreatic ascites |
| Fulminant hepatic failure | Nephrotic syndrome |
- Diagnostic tap on every new or newly worsening ascites
- PMN >250/microL = SBP, treat before culture returns
- Also: albumin (for SAAG), protein, cytology, culture in blood-culture bottles at bedside
- Oedema out of proportion to ascites + inc JVP = right heart failure, not liver
Staging
- Child-Pugh - encephalopathy, ascites, bilirubin, albumin, INR
- MELD/MELD 3.0 - bilirubin, INR, creatinine, sodium (+ albumin, sex) - drives transplant allocation
Workup of new cirrhosis
- Hepatitis B and C serology, autoantibodies + immunoglobulins (ANA, ASMA, AMA), iron studies, caeruloplasmin if <40 yrs, alpha-1 antitrypsin
- Alcohol history, metabolic profile
- US with Dopplers (portal vein patency), elastography
- Biopsy now rarely needed - reserve for diagnostic uncertainty
Management
1. Remove the driver - the only thing that reverses fibrosis
- Alcohol abstinence - improvement possible even in decompensated disease
- Antivirals for HBV; DAAs for HCV
- Weight loss/metabolic control (and MASH-directed therapy) in MASLD
- Prednisolone + azathioprine for autoimmune hepatitis
- Venesection or chelation for haemochromatosis; UDCA for PBC; trientine/zinc for Wilson
2. Prevent first decompensation
- Carvedilol if CSPH - now to prevent decompensation, not only variceal bleeding
- Superseded the old "screen endoscopically, band the varices" default
- Gastroscopy for varices if elastography/platelets do not exclude them
- Baveno: can skip endoscopy if liver stiffness <20 kPa AND platelets >150
- Vaccinate: HAV, HBV, influenza, COVID, pneumococcal
- Avoid NSAIDs, aminoglycosides, and unnecessary sedation
- Nutrition: high-protein, late evening snack. Protein restriction is obsolete and harmful
- Salt restriction ~<2 g Na/day once ascitic
3. Surveillance
- 6-monthly liver ultrasound +/- AFP for HCC in all cirrhosis
- Varices - interval by stage and stiffness
- Bone density; osteoporosis common in cholestatic disease
4. Decompensation - treat the specific complication
See chronic liver disease complications. In brief:
- Ascites - spironolactone +/- frusemide; large-volume paracentesis with albumin 6-8 g/L ascites removed if >5 L
- SBP - IV ceftriaxone + albumin 1.5 g/kg day 1, 1 g/kg day 3 (dec HRS, dec mortality)
- HRS-AKI - terlipressin + albumin 1 g/kg/day
- Encephalopathy - lactulose, then rifaximin add-on; find the precipitant
- Variceal bleed - terlipressin + antibiotic prophylaxis + endoscopic banding <12 h
5. Transplant
- Refer early - do not wait for MELD to climb
- Triggers: first decompensation, MELD >=15, refractory ascites, HCC within criteria, HPS/PPH
Associations
- Type 2 diabetes - both cause and consequence (hepatogenous diabetes)
- Osteoporosis - especially cholestatic disease
- Hypogonadism, feminisation
- Coagulopathy - rebalanced haemostasis, NOT auto-anticoagulated; PVT and VTE still occur
- Sarcopenia and frailty - independent predictors of mortality
- Cirrhotic cardiomyopathy
- Hepatopulmonary syndrome (platypnoea-orthodeoxia) and portopulmonary hypertension
- Relative adrenal insufficiency in critical illness
Natural history & complications
Survival by Child-Pugh class
| Class | 1 yr | 2 yr |
|---|---|---|
| A | ~100% | ~85% |
| B | ~81% | ~57% |
| C | ~45% | ~35% |
- Compensated: median survival >12 years
- After first decompensation: ~2 years - the inflection point that should trigger transplant referral
Signs of decompensation
- Jaundice, ascites, encephalopathy/asterixis, coagulopathy, variceal bleeding
Complications
- Variceal haemorrhage
- Ascites -> refractory ascites -> SBP -> hepatorenal syndrome
- Hepatic encephalopathy
- HCC - ~2-4%/yr in cirrhosis
- Portal vein thrombosis
- Malnutrition, sarcopenia
- Acute-on-chronic liver failure - organ failure on a background of cirrhosis, high short-term mortality, reversible if the precipitant is treated
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