The document discusses various patterns of hepatic injury and diseases of the liver. It describes the functions of the liver and different types of necrosis, inflammation, and fibrosis that can occur from injury. Specific conditions discussed include alcoholic liver disease, cirrhosis, portal hypertension, jaundice, and several hereditary conditions involving hyperbilirubinemia.

1. Diseases of the Liver Fe A. Bartolome, M.D. FPASMAP Department of Pathology

6. Macrovesicular steatosis Iron stain using the Prussian Blue Reaction (x400). Hemosiderin granules stain as dark blue, coarse granules.

8. Necrosis (left lower) is around the centrilobular area. The periportal area is viable.

9. Ischemia of centrilobular area resulting in coagulative necrosis of hepatic cords. (Preservation of cellular contour with disappearance of nucleus) Some viable hepatocytes with nucleus are seen in the upper middle and upper right areas.

10. Bridging confluent lytic necrosis in severe chronic viral hepatitis B. Inflamed portal tract ‘bridged’ through area of necrosis with centrilobular area (lower left). The upper right part corresponds to an area of extensive lytic necrosis.

12. Interface hepatitis

32. Bridging fibrous septae Nodules

36. Histological features of alcoholic hepatitis. (A) Low- power view demonstrating the cardinal features of steatosis, fibrosis, inflammation, and hepatocellular injury.

37. Histological features of alcoholic hepatitis. (B) (Black arrows) Mallory bodies are irregular eosinophilic cytoplasmic structures with a rope-like appearance. (Open arrow) Ballooning degeneration of hepatocytes.

38. Histological features of alcoholic hepatitis. (c) (Open arrow) Pericellular fibrosis, also termed 'chicken-wire' fibrosis surrounds individual degenerate hepatocytes; (Black arrow) Perivenular fibrosis extends from the central vein.

39. Histological features of alcoholic hepatitis. (d) The unit lesion (also termed satellitosis) comprises a degenerating hepatocyte with (arrow) a surrounding cuff of neutrophils. Marked steatosis is also evident.

47. Gynecomastia due to alcoholic cirrhosis A 32 year old male patient with normal secondary sex characteristics, no testicular mass, no hystory of drug ingestion, no other endocrine abnormalities and a normal neurological examination. Nevertheless, he had a history of more than 15 years of large amounts of alcohol intake and a liver biopsy confirm alcoholic cirrhosis (Laennec's Cirrhosis).

55. Photograph shows a caput medusae accentuated by a large amount of ascites in a patient being prepared for liver transplantation. An extensive plexus of veins is seen emanating from the umbilical region and radiating across the anterior abdominal wall.

63. Differential Diagnosis of Hereditary Jaundice with Normal Liver Chemistries & No Signs or Symptoms of Liver Disease Unconjugated Hyperbilirubinemia Crigler-Najjar Syndrome Gilbert’s Type I Type II Incidence Inheritance mode Serum bilirubin usual total (mg/dL) Defect Age at onset of jaundice <7% of pop’n Very rare Uncommon AD AR AD <3; < 6 >20 <20 Mostly B1; inc. All indirect All indirect with fasting Hepatic UDP-glucuronyl transferase activity Decreased Absent Marked dec. Adolescence Infancy Childhood, adolescence

64. Differential Diagnosis of Hereditary Jaundice with Normal Liver Chemistries & No Signs or Symptoms of Liver Disease Unconjugated Hyperbilirubinemia Crigler-Najjar Syndrome Gilbert’s Type I Type II Usual clinical features Liver biopsy Treatment Appear in early Jaundice, Asymptomatic adulthood; kernicterus in jaundice, often 1 st re- infants, kernicterus cognized w/ young adults rare fasting Normal Normal Normal Not needed Liver transplant Phenobarbital

65. Differential Diagnosis of Hereditary Jaundice with Normal Liver Chemistries & No Signs or Symptoms of Liver Disease Conjugated Hyperbilirubinemia Dubin-Johnson Rotor’s Syndrome Incidence Inheritance mode Serum bilirubin usual total (mg/dL) Defect Urine total coproporphyrin Age at onset of jaundice Usual clinical features Oral cholecystogram Liver biopsy Treatment Uncommon AR 2-7; < 25 Direct ~ 60% Impaired biliary excretion Normal Childhood, adolescence Asymptomatic jaundice in young adults GB not visualized Charac. pigment Not needed Rare AR 2-7; < 20 Direct ~ 60% Impaired biliary excretion Increased Adolescence, early adulthood Asymptomatic jaundice Normal No pigment None

66. Comparison of Jaundice (Cholestatic & Hepatocelllular) *Serum bilirubin > 10 mg/dL is rarely seen with CBD stone and usually indicates carcinoma. Hepatocellular Cholestasis Infiltration Disease example Acute viral hep. CBD stone Metastatic tumor Serum bilirubin (mg/dL) 4 – 8 6 – 20* Usually <4, often normal AST, ALT (U/mL) Markedly inc., often 500-1,000 May be sl. Inc., < 200 May be slightly inc., < 100 Serum ALP 1-2x normal 3-5x normal 2-4x normal PT Inc. in severe disease Inc. in chronic cases Normal Response to parenteral vit. K No Yes

67. Liver Function Tests: Normal Values & Changes Tests Normal Values Hepatocellular Jaundice Uncomplicated Obstructive Jaundice Bilirubin Direct Indirect 0.1-0.3 mg/dL 0.2-0.7 mg/dL Increased Increased Increased Increased Urine bilirubin None Increased Increased Serum albumin/ total protein Alb, 3.5-5.5 g/dL Tot, 6.5-8.4 g/dL Albumin decreased Unchanged Alk phos 30-115 IU/L Increased (+) Increased (++++) Prothrombin time INR of 1.0-1.4; 10% inc. after vit K in 24 hrs No response to parenteral vit. K; prolonged Prolonged but responds to parenteral vit. K ALT, AST ALT: 5-35 IU/L AST: 5-40 IU/L Inc. in hepato- cellular damage, viral hepatitis Minimally increased

72. “ Onion-skinning” around bile duct

74. Skin xanthomas

85. Hepatitis B: Common Serologic Patterns HBsAg HBsAb HBeAg HBeAb HBcAb (TOTAL) HBcAb-IgM Interpretation + -- -- -- -- -- Late incubation or early acute HBV + -- + -- -- -- Early acute HBV; highly infectious + -- + -- + + Acute HBV -- -- -- -- + + Serologic window -- -- -- + + + Convalescence + -- + + + -- Chronic infection (chronic carrier) -- + -- -- -- -- Old previous HBV with recovery and immunity OR vaccination OR passive transfer of antibody

86. Hepatitis B: Serologic Tests of Candidate for HBV Vaccine Test HBsAg HBsAb HBcAb Interpretation Follow-up + -- -- Acute HBV infection Repeat serology for resolution or chronicity -- -- + Acute HBV or carrier Previous HBV infection; vaccinate -- + + Immune; previous HBV infection or vaccination None + -- + Previous HBV infection; may not be immune Vaccinate -- -- -- Not immune Vaccinate

92. Hepatitis D

93. Comparison of Types of HDV Infections Coinfection Superinfection HBV infection Acute Chronic HDV infection Acute Acute to chronic Chronicity rate < 5% > 75% Serology HBsAg HBcAb-IgM Anti-HDV-total Anti-HDV-IgM HDAg + + Negative or low Transient + Transient + Usu. persistent Negative + Transient Usu. persistent Liver HDAg Transient + Usu. persistent

99. Also known as acidophilic bodies, apoptotic bodies, or Councilman bodies (arrows), these intensely eosinophilic dead hepatocytes are engulfed by Kupffer cells and digested.

129. Amebic liver abscess Amebic liver abscess with perforation of abscess through abdominal wall

130. Pyogenic liver abscess

135. Congested liver of HELLP syndrome

137. Acute fatty liver of pregnancy: lobular parenchyma characterized by microvesicular steatosis and a small number of lymphocytes. (H&E)

140. Focal Nodular Hyperplasia: Subcapsular solid mass with central scar, composed of the normal components of liver lobule

141. Central portion of nodular hyperplasia showing the interphase between the fibrous scar and the hepatocytic nodules.

143. Nodular Regenerative Hyperplasia: non-cirrhotic non-neoplastic nodular transformation of the liver parenchyma.

145. Cavernous Hemangioma Normal liver Hemangioma

147. The hepatic adenoma is composed of cells that closely resemble normal hepatocytes with disorganized hepatocyte cords and does not contain a normal lobular architecture. At the upper right is a well-circumscribed neoplasm that is arising in liver. This is an hepatic adenoma. Normal liver Adenoma

149. Hepatoblastoma Hepatoblastoma found to be invading the inferior vena cava at the time of surgical exploration.

152. Angiosarcoma: Section of liver, showing multiple hemorrhagic tumor deposits.

154. Intrahepatic cholangiocarcinomas are classified as either peripheral or hilar. The hilar variety are located in the hepatic hilum region and appear as discrete masses.

155. Peripheral cholangiocarcinoma is the most common and develops in the interlobular ducts of the liver, where the interlobular bile duct branches within the portal triads. They may be a single or multiple masses.

173. Patterns of Liver Chemistry Test Abnormalities Pattern Bilirubin Alkaline phosphatase Amino- transferase Albumin Prothrombin time Hemolysis Inc. (usu. B1) Normal Normal Normal Normal Acute hepatocellular +/- inc. (B1 and B2) Normal or < 3x normal Usu. >400 (ALT>AST) Normal Normal Chronic hepatocellular +/- inc. (B1 and B2) Normal or < 3x normal Usu. <300 U/L May be dec. Often prolonged; doesn’t correct with vit. K Cholestasis Usually inc. (B1 and B2) > 4x normal Usually < 300 U/L Usually normal Normal; corrects with vit. K if prolonged Infiltrative Usually normal > 4x normal; inc. GGT < 300 U/L Usually normal Normal