Hepatobiliary Tutorial

Normal Liver - Functions

• Synthesis– Proteins: albumin, clotting factors– Bile– Cholesterol & lipoproteins

• Storage and secretion– Glucose– Fat-soluble vitamins (vitamins A, D, E and K)– Folate, vitamin B12 , copper, iron.

• Excretion– Ammonia, bilirubin, steroid hormones, many drugs,

alcohol, toxins

Normal liver: 1200 – 1600g

Acute liver injury

• Causes– Viruses– Alcohol– Toxins– Ischaemia

• Presentation– Fatigue, malaise, anorexia, jaundice

Viruses

• Hepatotrophic viruses– HAV– HBV +/- HDV– HCV– HEV– All cause viral hepatitis

• Other viruses– EBV– CMV– HSV– Affect liver as part of generalized infection– Immunocompetent and immunocompromised hosts

Areas of hepatic necrosis

Specific Features

• Portal tract lymphocytes• Piecemeal necrosis• Lobular lymphocytes• Focal hepatocyte necrosis in lobule

– Councilman bodies and ballooning degeneration

• HAV – plasma cell infiltrate• HBV – ground glass cells (HBsAg)• HCV – lymphoid aggregates, bile duct damage

Consequences

• Resolution• Fulminant acute hepatitis

– HAV, HBV, HDV, HEV in pregnancy

• Progression to chronic hepatitis– HBV +/- HDV, HCV

• Progression to cirrhosis– HBV +/- HDV, HCV

• Hepatocellular carcinoma– HBV, HCV

Alcohol

• Consequences– Steatosis– Alcoholic hepatitis– Progression to chronic hepatitis– Progression to cirrhosis– Hepatocellular carcinoma

Toxins• Examples• Types of liver damage

– Steatosis • ethanol, salicylates, methotrexate

– Centrilobular necrosis• Paracetamol, CCl4, halothane

– Diffuse necrosis• Halothane, isoniazid, paracetamol, -methyldopa

– Hepatitis -methyldopa, isoniazid, phenytoin

– Fibrosis• Ethanol, methotrexate, amiodarone

– Granulomas – sulphonamides, -methyldopa– Cholestasis – chlorpromazine, anabolic steroids, OCP– Vascular disorders – VOD (chemo), Budd Chiari (OCP/oestrogen)– Tumours – adenoma (OCP)

Toxins• Examples• Types of liver damage

– Steatosis • ethanol, salicylates, methotrexate

– Centrilobular necrosis• Paracetamol, CCl4, halothane

– Diffuse necrosis• Halothane, isoniazid, paracetamol, -methyldopa

– Hepatitis -methyldopa, isoniazid, phenytoin

– Fibrosis• Ethanol, methotrexate, amiodarone

– Granulomas – sulphonamides, -methyldopa– Cholestasis – chlorpromazine, anabolic steroids, OCP– Vascular disorders – VOD (chemo), Budd Chiari (OCP/oestrogen)– Tumours – adenoma (OCP)

Hepatic necrosis due to paracetamol overdose

• Consequences– Massive hepatic necrosis– Progression to chronic hepatitis– Progression to cirrhosis

Ischaemia

• Causes of ischaemia– Obstruction to inflow

• Hepatic arteries– Surgical trauma, arteritis

• Portal veins– Thrombosis due to pancreatitis/sepsis

– Outflow obstruction• Hepatic vein / IVC thrombosis (Budd-Chiari)• Destruction of central veins (Veno-occlusive disease)• Congestive heart failure

– Systemic hypoperfusion

Hepatic infarcts

Nutmeg liver

Centrilobular congestion

Centrilobular necrosis

Chronic liver injury

• Causes– Viruses– Alcohol– Toxins– Ischaemia – Autoimmune disease– Metabolic disease

Autoimmune disease

• Autoimmune hepatitis• Primary Biliary Cirrhosis• Primary Sclerosing Cholangitis

• Autoimmune hepatitis– AI destruction of hepatocytes– Portal tract inflammation– Lobular inflammation– Piecemeal and lobular necrosis– Middle aged women– Associated with other AI diseases– Antinuclear, anti-smooth muscle, antimitochondrial antibodies– Anti liver and kidney microsomal antibodies

Autoimmune disease

• PBC– AI destruction of intrahepatic bile ducts– Portal tract inflammation, granulomas, fibrosis– Absent/damaged bile ducts– Middle aged women, pruritus, cholestasis– Associated with other AI diseases– antimitochondrial antibodies

• PSC– Segmental fibrotic obliteration of bile ducts– PT inflammation, concentric bile duct fibrosis– Replacement of bile duct with fibrous scar– Middle aged men, cholestasis– Associated with UC in 70%

Metabolic disease

• Haemochromatosis

• Alpha1antitrypsin deficiency

• Wilson’s disease

Haemochromatosis

Haemochromatosis

Haemochromatosis

• Affected organs– Liver, with cirrhosis – Heart, with cardiomyopathy – Pancreas, with diabetes mellitus – Skin, with pigmentation – Joints, with polyarthropathy – Gonads, with hypogonadotrophic

hypogonadism

Diagnosis

• serum iron • % saturation • Serum ferritin • estimation of hepatic iron content

• DDx in liver– haemosiderosis - alcoholic liver disease– lipofuscin

Alpha 1 antitrypsin deficiency

Normal Liver - Functions

• Synthesis– Proteins: albumin, clotting factors– Bile– Cholesterol & lipoproteins

• Storage and secretion– Glucose– Fat-soluble vitamins (vitamins A, D, E and K)– Folate, vitamin B12 , copper, iron.

• Excretion– Ammonia, bilirubin, steroid hormones, many drugs,

alcohol, toxins

Chronic liver injury

• Presentation– Fatigue, malaise, anorexia– Synthesis

• Hypoalbuminaemia• Coagulopathy

– Storage and secretion• Hypoglycaemia• Vitamin deficiency• Anaemia

– Excretion• Hyperammonaemia – hepatic encephalopathy, fetor• Jaundice• Hyperoestrogenism

• Causes of Chronic Hepatitis

• Causes of Cirrhosis

• Definition

• Classification of cirrhosis– Aetiology– Size of nodules

Micronodular – Alcohol/Biliary/HaemoChromatosis

Macronodular – Viruses/Wilson’s/Alpha1AT

1. Diffuse Nodularity, 2. Fibrotic bands, 3. Regenerative nodules

Consequences

Differential diagnosis of HCC

Adenoma

Differential diagnosis of HCC

Cholangiocarcinoma

Differential diagnosis of HCC

Metastases