Hepatitis

• Hepatitis is the inflammation of liver. Etiology: 1. Infectious hepatitis:

• Viral hepatitis: o Hepatotrophic viruses: HAV, HBV, HCV…. o Non hepatotrophic viruses: CMV, EBV,

• Bacteria: Mycobacterium. • Protozoa: hydatid cyst, E. histolytica,

schistosomiasis. 2. Autoimmune hepatitis. 3. Toxic exposure (alcohol and drugs). 4. Metabolic diseases:

Wilson’s disease, hemochromatosis.

Clinical Features and Outcomes of Viral Hepatitis: 1. Acute Asymptomatic Acute Infection with Recovery

• It is usually incidentally identified because of mild elevation of serum transaminases or presence of antiviral antibodies.

2. Acute viral hepatitis a. Caused by all hepatitis viruses. b. Four phases.

• Incubation period • Symptomatic pre-icteric phase: Nonspecific, constitutional symptoms • Symptomatic icteric phase: conjugated hyperbilirubinemia. • Convalescence (recovery phase).

3. Fulminant hepatitis: • Progression of hepatic insufficiency from onset of symptoms to hepatic encephalopathy within 2-3 weeks, is called

fulminant hepatic failure a. Massive hepatic necrosis. b. Regenerative hyperplasia.

• Acute liver failure.

4. Carrier state: • Caused by HBV and HDV, HCV. • Defective immunity is the major determinant in development of chronic hepatitis.

5. Chronic hepatitis: with or without progression to liver cirrhosis. • Defined as presence of clinical , biochemical, or serological evidence of continuing or relapsing hepatic disease for

more than 6 months, with histologically evidence inflammation and necrosis.

6. Liver cirrhosis Investigations • Biochemical: Raised serum bilirubin and aminotransferase levels. • Serology: Hepatitis viral genome in the liver and serum followed by antibodies to viral antigens. • Microscopy: Varying degrees of necrosis of hepatocyte and inflammation.

Acute Hepatitis

Pathology Gross: Enlarged, reddened liver; greenish if cholestatic. Microscopy: • Portal tract: mixed inflammatory cells with excess lymphocytes • Interphase hepatitis: inflammation spill over to adjacent parenchyma • Parenchyma:

o Degeneration: hydropic swelling, fatty change (steatosis), cholestaisis o Apoptosis

• Hepatocyte necrosis: o Single cells necrosis. o Bridging necrosis: p-p, p-c, c-c. o Pan acinar necrosis. o Hepatocyte's proliferation. o Lobular disorganization.

Specific findings as ground glass hepatocytes (HBV). Steatosis and lymphoid follicles within the portal tract (HCV). Acute Hepatitis: Dense portal and lobular lymphoplasmacytic infiltrate, and degenerated hepatocytes.

Ground glass hepatocytes, feature of hepatitis B infection.

Chronic Hepatitis

Changes shared with acute hepatitis • Hepatocyte injury, apoptosis. • Hepatocyte's regeneration. • Portal tract inflammation • interphase hepatitis. • Bridging inflammation and necrosis.

Fibrous collagen deposition in portal tracts.

Later bridging fibrosis (p-p, c-c, p-c).

At last—end stage cirrhosis. Specific findings as • Ground glass hepatocytes (HBV). • Steatosis and lymphoid follicles within the portal tract

(HCV). • Mallory bodies (alcoholic hepatitis). • Dysplasia.

Dense portal lymphocytic aggregate/lymphoid follicle with germinal center in chronic hepatitis C.

Chronic hepatitis C with dispersed steatosis.

Viral hepatitis C which is at a high stage with extensive fibrosis and progression to macronodular cirrhosis, as evidenced by the large regenerative nodule at the center right.

Grading of chronic hepatitis: Measuring necroinflammatory activity.

Staging of hepatitis: Extent of fibrosis

Cirrhosis

• Cirrhosis refers to the diffuse transformation of the liver into regenerative parenchymal nodules surrounded by fibrous bands. o It is among the top 10 causes of death in the Western world. o It is the end-stage of chronic liver disease. o The main worldwide causes are:

1. Alcohol abuse 2. Viral hepatitis

o Other causes include: a. Biliary disease b. iron overload c. Others (autoimmune and drug)

Cirrhosis is defined by three characteristics: 1. Fibrosis in the form of delicate bands or broad scars/septae (Bridging fibrous septa). 2. Nodules containing regenerating hepatocytes encircled by fibrosis, with diameters varying from very small (<3 mm,

micronodules) to large (several centimeters, macronodules). 3. Disruption of the architecture of the entire liver.

Clinical Features • May be clinically silent. • When symptomatic they lead to nonspecific clinical manifestations: anorexia, weight loss, weakness and in advanced

disease, frank debilitation. • Jaundice. • Hepatic failure may develop. Macroscopic picture • Reduced in size. • Firm in consistency, fibrosis. • Thick capsule and nodular surface. Microscopy: Complete replacement of the normal parenchyma by rounded regeneration nodules, separated by grayish white fibrous septa. • According to size

o Micronodular cirrhosis: 1-3 mm in diameter. o Macronodular cirrhosis: >3 mm in diameter. o Mixed.

Gross Feature: Macronodular cirrhosis.

Gross Feature: Micronodular cirrhosis

Microscopy: Regenerative nodules of hepatocytes are surrounded by fibrous connective tissue that bridges between portal tracts. Within this collagenous tissue are scattered lymphocytes as well as a proliferation of bile ducts.

Alcoholic Liver Disease

Alcoholic Hepatitis: Three features: 1. Steatosis (fatty change). 2. Hepatitis (steatohepatitis). 3. Fibrosis. Hepatitis (steatohepatitis) characterized by the following: 1. Hepatocyte swelling and necrosis. 2. Mallory Bodies. 3. Neutrophil Infiltration.

Hemochromatosis

• Familial defect in control of iron metabolism (primary), or secondary due to iron overload (repeated blood transfusion, Ineffective erythropoiesis (as in β-thalassemia) and Increased iron intake).

Effect: • Massive accumulation of hemosiderin in hepatic cells, pancreas, and other organs. • Triad of cirrhosis, Diabetes (Bronze Diabetes), and skin pigmentation.

Wilson’s Disease

• AR. • Defect in copper metabolism. • Accumulation of copper in liver, kidney, brain

(extrapyramidal symptoms), cornea (Kayser-Fleisher ring).

α1-Antitrypsin (AAT) Deficiency

• Autosomal recessive disorder. • Marked by abnormally low serum levels of

this protease inhibitor. • Newborns: cholestasis. • In older children, adolescents, and adults:

chronic hepatitis, cirrhosis or pulmonary disease.

• Hepatocellular carcinoma develop.

Primary Biliary Cirrhosis

• Middle age female • Etiology, autoimmune disease, elevated

levels of autoantibodies as antimitochondrial antiobdy and bilirubin.

• Destructive disorder of the intrahepatic biliary tree.

• Grossly: greenish color • Microscopy: • Bile ductules destruction and bile stasis in

lobules, infiltration of portal tracts by chronic inflammatory cells, necrosis of the neighboring cells epithelioid granulomas, fibrosis.

Secondary Biliary Cirrhosis

• Prolonged obstruction of the extrahepatic biliary tree results in profound alteration of the liver itself.

• The most common cause of obstruction extrahepatic cholelithiasis (gallstones), followed by malignancies of the biliary tree or head of the pancreas and strictures resulting from previous surgical procedures.

Morphology: • Secondary inflammation resulting from

biliary obstruction initiates periportal fibrosis, which eventually leads to hepatic scarring and nodule formation, generating secondary biliary cirrhosis.

Complications of Liver

Cirrhosis

1. Hepatic failure a. Coagulopathy b. Hypoalbuminemia c. Hepatic

encephalopathy

2. Portal hypertension: a. Variceal bleeding b. Splenomegaly c. Hemorrhoids d. Periumbilical

venous collaterals (caput medusa)

3. Ascites 4. Hepatorenal syndrome 5. Hyperestrinism in males 6. Hepatocellular carcinoma 7. Spontaneous bacterial

peritonitis 8. Jaundice and cholestasis