Chronic Hepatitis Tutorial Materials

Chronic hepatitis – histologic features • • • • • Portal tract inflammation Interface hepatitis – inflammatory cells infiltrating and damaging hepatocytes along edges of portal tracts Portal fibrosis, bridging fibrosis (portal-portal, portal-central), cirrhosis Lobular parenchymal changes o Focal (spotty) inflammation o Focal hepatocyte dropout or apoptotic bodies o Confluent necrosis in very active cases All changes variable in degree from case to case and over time Grading and staging • Grading: degree of inflammatory activity • Stage: degree of fibrosis and remodelling • Numerical scoring systems – Scheuer, METAVIR, Ishak-Knodell • Fibroscan Fatty liver disease: steatosis • Steatosis: fat accumulates as globules of triglyceride in hepatocytes due to imbalance between synthesis and secretion of lipids • Usually reversible • Types: o Macrovesicular: common o Microvesicular: rare as pure pattern → often drug or toxin related o Mixed: relatively common • Macrovesicular: o Macroscopic (if severe) ▪ Large liver (from 4 to 6 kg) ▪ Soft yellow and greasy o Microscopic ▪ Single/few cytoplasmic large clear globules) compress/displace liver cell nucleus to one side ▪ Distribution of fat within liver lobule is related to cause and severity of disease o Common causes ▪ Alcoholic fatty liver disease ▪ Non-alcoholic fatty liver disease (NAFLD) → metabolic syndrome, T2DM, obesity ▪ Drugs e.g. Methotrexate ▪ Hepatitis C virus infection ▪ Wilsons disease o Distribution ▪ Zone 3 NAFLD, alcohol ▪ Random hepatitis C Fatty liver disease: steatohepatitis • Steatosis + damage to hepatocytes + inflammation • Alcoholic steatohepatitis: damage to cytoskeleton of hepatocytes by acetaldehyde from oxidation of ethanol • Non-alcoholic steatohepatitis (NASH): subgroup of NAFLD → metabolic syndrome • Histology o Steatosis: early = predominantly zone 3 → later = diffuse o Lobular focal (spotty) inflammation, apoptosis and cell drop out o Ballooning degeneration of hepatocytes ▪ Can also have Mallory-Denk bodies (Mallory body, Mallory hyaline) o Neutrophils are particularly present in alcoholic steatohepatitis o Sometimes portal inflammation and ductular reaction o Fibrosis ▪ Perisinusoidal (pericellular) → zone 3 ▪ Portal tract/periportaL ▪ Bridging from portal tracts to central veins ▪ Cirrhosis Cholestatic liver disease Causes • Any interruption to the flow of bile constituents into the intestine • Intrahepatic o Transport from hepatocyte into bile canaliculus o Damage canals of Herring/bile ductules/small bile ducts • Extrahepatic: obstruction of larger bile ducts at liver hilum or beyond (hepatic ducts / common bile duct) • • • Intrahepatic o Canaliculi: congenital metabolic effects (bile salt transporter defects), drug sensitivity, steroids – anabolic, some oral contraceptives, complication of pregnancy o Bile ductules – drug reaction o Intra hepatic bile ducts – autoimmunity – primary biliary cirrhosis Extrahepatic o Gallstones o Tumours o Chronic inflammatory strictures, ischaemia, trauma o Congenital biliary atresia Both e.g. primary sclerosing cholangitis Clinical presentation • Jaundice: ‘obstructive’ type o Bile present in urine o Reduced or absent in faeces • Not much evidence of fever or of hepatocyte injury • May be features of causal condition e.g. gall stones • ‘Cholestatic’ pattern of LFT abnormality: GGT, serum alkaline phosphatase, bilirubin • Radiology: ERCP/MRCP important Histologic patterns • Variable • Changes evolve over time – acute or chronic • Pattern depends on the level of the biliary system which is primarily affected • Fibrosis may be present and progresses over time, eventually cirrhosis – fibrosis may progress rapidly (months) or slowly (years) Acute cholestasis • Bile stasis canalicular & hepatocellular (zone 3) • Large duct obstruction → abnormal portal tracts: o Oematous and expanded o Ductular reaction with neutrophils with/without lymphocytes and plasma cells o Small bile ducts not injured • Acute cholestasis with portal inflammation and small bile duct injury e.g. drug reactions • Pure canalicular or hepatocellular cholestasis → canalicular bile plugs, normal portal tracts o Drugs, sepsis, pregnancy induced, familial Chronic/late cholestatic/biliary diseases • Bile stasis is more wide spread through parenchyma (all zones) • Features of ‘cholate stasis’ develop (bile salt injury) o Periportal hepatocyte swelling (feathery change, pseudoxanthomatous change) o Copper associated protein and copper accumulation o Mallory-Denk bodies • Interface inflammation and ductular reaction • Portal and periportal septal fibrosis (portal tract to portal tract) • Maybe inflammation and damage in small • intrahepatic ducts in some conditions