病毒性肝炎 Rukun He MD Depart of Pathology Guangxi Med University

Viral hepatitis is an infection of liver caused by a group of viruses having a particular affinity for the liver. Hepatitis A Virus Hepatitis B Virus Hepatitis C Virus Hepatitis D Virus Hepatitis E Virus Hepatitis G Virus

The main characteristics of hepatitis A are : most seen in children,conferring life long immunity Fecal- oral spread relatively short incubation period sporadic or epidemic directly cytopathic ( ? ) no carrier state ; no cirrhosis;no cancer mild illness, full recovery usual.

The sequence of serologic markers in acute hepatitis A infection

The main characteristics of hepatitis B are : spread by blood- contaminated instruments, blood products and venereal relatively long incubation period liver damage by antiviral immune reaction carrier state, chronic hepatitis, liver cirrhosis & cancer possibility exists relatively serious infection

The sequence of serologic markers in acute hepatitis B infection

The potential outcomes of Hepatitis B infection in adults

Ballooning change Basic morphological changes of hepatitis Spotty Necrosis ( focal necrosis )

Spotty necrosis Apoptosis

Piecemeal Necrosis : liver cells at the interface between parenchymal cells and fibrous tissue are destroyed,with lymphocytes or plasma cell infiltrate Limiting plate

Bridging Necrosis ( connecting portal areas to portal areas, central veins to central veins, or portal areas to central regions of adjacent lobules. Limiting plate

Cholestasis : The bile plugs in canaliculi and brown pigmentation of hepatocytes, seen in icteric hepatitis.

Fatty changes major see in HCV infection

Lymphocytes and plasma cells infiltrate major in the portal tracts

There are proliferation reaction, including : Hepatocytes regeneration Epithelium of bile duct regeneration Kupffer cells proliferation Fibrocytes to form fibrosis

Hepatocytes proliferate after damaging Hepatocytes nodular regenerate after damaging with collapse of the sinusoidal collagen reticulin

Carrier state : A carrier is an individual without manifest symptoms who harbors virus and therefore can transmit it to the others. Whose HBsAg is positive and the liver is essentially normal, but have ground-glass hepatocytes

ground- glass hepatocytes A fine granular, eosinophilic cytoplasm Anti-HBsAg reaction is positive

Smooth endoplasmic reticulum is hyperplasia; The arrow shows the HBsAg in high resolution EM

Acute hepatitis Spotty necrosis Inflamma- tory cell in the portal tract Ballooning hepatocytes 1, striking feature is ballooning hepatocytes; 2, the necrotic changes are slight; 3, most of the patients will recover within 6 months. ( anicteric or icteric )

Chronic hepatitis ( caused by viruses B, C and D ): Inflammation of the liver shown symptomatic, biochemical, serological or histological evidence lasts at least 6 months without evidence of resolution. It may come from acute hepatitis or insidious

Chronic hepatitis : 1, Inflammatory cell infiltration and expansion of portal areas with or without slightly proliferation of fibrosis; 2, Spotty necrosis in the limiting plate of lobules ( piecemeal necrosis ) 3, keep the features of acute hepatitis within lobules. 4, the lobular architectures are intect ( mild cases)

Chronic hepatitis : 1, prominent inflammatory changes in portal area with moderate piecemeal necrosis 2, severe intra-lobular inflammation,with a few bridging necrosis 3, fibrous septa could be seen but the architectures in most lobules remain intact. ( moderate cases)

Chronic hepatitis : ( severe cases) 1, severe inflammation in portal areas with severe piecemeal necrosis 2, bridging necrosis involveing most of the lobules 3, large amount of fibrous septa formed and lobular architectures destroyed, looks like early liver cirrhosis.

Fibrous septa formation in the severe chronic hepatitis accompanied nodular proliferation of hepatocytes

Massive hepatic necrosis or Fulminant hepatitis denotes clinic hepatic insufficiency that progresses from onset of symptoms to hepatic encephalopathy within 2 to 3 weeks. Acute submassive necrosis or Subacute severe hepatitis denotes hepatocytes and bile ductal epithelium regenerate and fibrous tissue proliferates in the patient survival for more than 3 months.

The histological correlation of fulminant hepatitis is massive hepatic necrosis. Viral hepatitis accounts for 50% to 65% Drugs & chemical are responsible for 25% to 30%

Fulminant hepatitis or massive hepatic necrosis Massive hepatic necrosis without regeneration of hepatocytes and little inflammatory reaction. The entire liver may be involved

The liver weight is about 600 to 900 g, and become transformed into a red or yellow organ covered by a wrinkled capsule.

Hepatocytes and bile ductal epithelium regenerate and fibrous tissue proliferates in the patient survival for more than several weeks. Submassive hepatic necrosis

Regeneration of hepatocytes are disorder, yielding nodular masses of liver cells. It may led to macronodular cirrhosis of liver finally.

Mechanism of Hepatocytes Necrosis : Immuno- reaction injury HBsAg HBsAb Lysis of hepatocytes

Although the pathogenesis of the liver cell damage resulting from HAV & HBV infection is different, the morphology of the liver in a typical case is very similar. The principal features are : Cytoplasmic swelling of liver cells or lytic necrosis. Apoptosis of individual liver cells Infiltration of portal tracts by inflammatory cells & make it expansion Hyperplasia of Kupffer cells Accumulation of bile in the liver cells in the cholestatic hepatitis

HBsAg HBeAg HBcAg Anti-HBs Anti-HBe Anti-HBc HBV-DNA DNA-polymerase HBsAg+HBsAg+ HBeAg+HBeAb ＋ HBcAb+HBcAb ＋

Clinical manifestation of hepatitis: Anorexia, nausea, fatigue and abdominal pain Hepatomegaly, jundice Hepatic functional change ( AST or ALT ) Check for the viral antibodies in the serum Needle biopsy of the liver may find out something changes

酒精性肝病 Alcoholic Liver disease 绿螘新醅酒， 红泥小火炉。 晚来天欲雪， 能饮一杯无 ?

Hepatic steatosis ( Fatty liver )

Alcoholic hepatitis : Hepatocyte swelling & necrosis Mallory bodies Neutrophilic reaction fibrosis

Mallory bodies are tangled skeins of cytokeratin intermediate filaments and other proteins, visible as eosinophilic cytoplasmic inclusions in hepatocytes

1, the ratio of reduced nicotinamide-adenine dinucleotide and NAD change 2,free radicles are generated during oxidation of ethanol 3,alcohol directly affects microtubular & mitochondrial function 4, elevated level of interleukin 8, which is a chemo- attractant of neutrophils AlcoholAcetaldehydeAcetate CO 2 & H 2 O

Alcoholic cirrhosis ( micronodular cirrhosis )