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Aetiology	Extrahepatic cholestasis - due to large duct obstruction of bile flow at any point in the biliary tree distal to the bile canaliculi Intrahepatic cholestasis - failure of bile secretion - mechanisms include inhibition of basolateral Na+/K+-ATPase, decreased fluidity of sinusoidal plasma membrane, disruption of microfilaments responsible for canalicular tone, damage to tight junctions - inflammatory change in ductular cells
Presentation	History Symptoms of acute liver disease: - malaise, anorexia, fever Symptoms of chronic liver disease: - may be asymptomatic/nonspecific - right hypochondrial pain due to liver distension - abdominal distension with ascites - ankle oedema - GI haemorrhage -> haematemesis and melaena - pruritus - gynaecomastia, loss of libido and amenorrhoea - portosystemic encephalopathy (PSE) -> confusion and drowsiness, foetor hepaticus, flap Examination Signs of acute liver disease - jaundice - hepatomegaly - pale stools and dark urine in cholestatic phase - in severe acute liver disease, there may be spider naevi and liver palms Signs of chronic liver disease - skin - spider naevi in SVC distribution, palmar erythema, (clubbing), Dupuytren's contracture in alcoholic cirrhosis, xanthomas in palmar creases/above eyes in primary biliary cirrhosis - abdomen - initial hepatomegaly, followed by small, cirrhotic liver; splenomegaly with portal hypertension - endocrine system - gynaecomastia and testicular atrophy in males - decompensated cirrhosis - jaundice, ascites ± peripheral oedema, evidence of PSE, caput medusae - a palpable gallbladder may indicate CA head of pancreas - generalised lymphadenopathy suggests lymphoma Differential diagnosis - country of origin - e.g. prevalence of HBV - duration of illness - prolonged course suggests malignancy, brief course suggests viral hepatitis - recent outbreak in community? - suggests HAV - recent consumption of shellfish? -suggests HAV - IVDU? - increased risk of HBV/HCV - Male homosexual/Female prostitution? - increased risk of HBV - Blood transfusion/blood products?- increased risk of HBV/HCV - Alcohol/Drugs/Recent anaesthetics (e.g. halothane)? - Travel? - Family Hx of e.g. Gilbert's disease - Recent surgery on biliary tract/for carcinoma - Environment - e.g. agricultural workers at risk of leptospirosis - Fevers/rigors - suggest cholangitis or liver abscess
Investigations	Viral markers - HAV, HBV, HCV USS - exclude extrahepatic obstruction - demonstrates size of bile ducts, level of obstruction - demonstrates cause of obstruction in virtually all patients with tumours, 75% of those with gallstones FNA/Needle biopsy - allows pathological diagnosis of mass lesion Liver biochemistry - acute hepatitis - high AST and ALT, small rise in ALP initially - extrahepatic obstruction - high ALP, small rise in AST/ALT - chronic liver disease - PTT prolonged, albumin low Haemotological tests - cholangitis - raised WCC - viral hepatitis - leucopenia - infectious mononucleosis - abnormal mononuclear cells - monospot test Other blood tests - CMV antibodies - primary biliary cirrhosis - anti-mitochondrial Ab - HCC - a-fetoprotein
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Hepatobiliary medicine

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