Steatosis, hepatitis, cholestasis, fibrosis and cirrhosis
Mnemonic
“Transaminases mean hepatocytes, alkaline phosphatase means ducts”:
- Hepatitic - ALT and AST dominant
- Cholestatic - ALP and gamma GT dominant
- Mixed
Transaminases above 1000 narrow the differential to three: ischaemic hepatitis (“shock liver”), paracetamol overdose, and acute viral hepatitis.
“AST to ALT above 2 means alcohol”, since alcohol impairs the pyridoxine dependent ALT more; ALT above AST suggests non-alcoholic fatty liver or viral hepatitis.
“Isolated ALP: check the gamma GT.” If gamma GT is normal, the source is bone (Paget’s, metastases, osteomalacia, growth), placenta or intestine.
True liver function is albumin, prothrombin time and bilirubin, not the enzymes, which measure damage rather than function. In acute liver failure a falling ALT with a rising INR and bilirubin indicates loss of hepatocyte mass, not recovery.
Expansion
| Pattern | Appearance | Typical causes |
|---|---|---|
| Steatosis | Fat vacuoles | Alcohol, obesity, diabetes, pregnancy, drugs |
| Steatohepatitis | Fat plus inflammation, Mallory bodies, ballooning | Alcohol, non-alcoholic fatty liver disease |
| Acute hepatitis | Lobular inflammation, apoptotic bodies | Viral, drug |
| Chronic hepatitis | Portal inflammation with interface hepatitis | Hepatitis B and C, autoimmune |
| Cholestasis | Bile plugs | Obstruction, drugs, sepsis |
| Centrilobular (zone 3) necrosis | Paracetamol, ischaemia, congestion | |
| Cirrhosis | Diffuse fibrosis with regenerative nodules | End stage of any chronic injury |
Zonal anatomy explains the distribution: zone 1 is periportal and best oxygenated, so it is hit first by ingested toxins and viral hepatitis; zone 3 is centrilobular and least oxygenated, so it is hit first by ischaemia and by drugs requiring cytochrome P450 activation such as paracetamol.
Congestive hepatopathy in right heart failure produces the nutmeg liver, with alternating congested centrilobular and pale periportal areas.
Cirrhosis is classified as micronodular (alcohol, haemochromatosis) or macronodular (viral, Wilson disease), though the distinction has limited practical value once established.