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 B 12, 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

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 B 12, 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