• hepatic vein at the center
• portal tracts at the periphery.

• consists of 3 functional zones, with the in-flowing blood in the portal tract at the center (zone 1), and the out-flowing blood in the hepatic venule at the periphery (zone 3).

• alcohol-related injury in 60-70% of cases
• viral hepatitis is second most common (10% of cases)
• biliary tract diseases (5-10%)
• metabolic diseases

1. severe fibrosis increases vascular resistance in liver
2. results in shunting of blood away from hepatocytes
3. increase of collagen along the capillaries (in Disse’s space between endothelium and hepatocyte)
4. disrupts the access of hepatocytes to circulation
5. interferes with their many important functions

• parenchymal nodules of isolated regenerative hepatocytes replace normal lobular architecture

• fibrous bands encircle the regenerative nodules

extrahepatic

• venous collaterals - varices (dilated esophageal and possibly                gastric veins); hemorrhoids; umbilical vein (“caput medusae”)

• splenomegaly - thrombocytopenia results from entrapment of platelets

• ascites, usually a transudate, resulting from combination of portal hypertension, sodium and water

  retention, and hypoalbuminemia

• physical signs and “stigmata” of chronic liver disease

  • jaundice

  • spider telangiectasia

  • gynecomastia

  • testicular atrophy

  • bruising (coagulopathy)

  • edema

• viral hepatitis
• autoimmune hepatitis
• alcohol or drug-related damage
• metabolic disease
• chronic bile duct obstruction

• hepatic vein thrombosis
• increased outflow resistance (cor pulmonale, for example)

• gross- "nutmeg liver” - centrilobular sinusoidal congestion, and hepatocyte necrosis
• histo- progressive centrilobular fibrosis, which can lead to cirrhosis (cor pulmonale can lead to “cardiac cirrhosis”)   

• histopathology- centrilobular congestion and fibrosis similar to that seen in passive congestion
• gross- hepatic vein occlusion with intraluminal thrombus

• rapid development of
  • liver necrosis
  • fibrosis/ cirrhosis
• average survival < 2 yrs without surgery to create a vascular shunt and/ or liver transplant   

• simple cysts
• choledochal cysts

• Entameoba histolytica
• Echinococcus

• lined by cuboidal epithelium
• contains serous fluid
• multiple cysts associated with polycystic diseases

• Viral hepatitis - Hepatitis B (+/- delta virus)Hepatitis C
• Autoimmune hepatitis 
• Drug-related hepatitis

• both a direct cytotoxic effect of the etiologic agent, such as a virus, and the host immune response to the inciting agent
• The balance of these two pathogenic mechanisms differs with   specific etiologies of the chronic hepatitis
• Chronic  hepatitis caused by virus is a combination of cytopathic effect and immune response to the virus
• autoimmune disease hepatitis is largely mediated through host immune response, autoantibodies
• drug induced hepatitis largely mediated through allergic HS rxn

• active disease with progressive scarring is more likely to proceed to cirrhosis and its complications

• activity of disease - as determined on biopsy by degree of inflammation and extent of hepatocyte necrosis (erosion of the limiting plate and loss of hepatocytes or apoptosis)
• stage of disease - as determined on biopsy by extent of fibrosis or cirrhosis

• fungal infections
• parasitic infection (Schistosomiasis)
• foreign body type most often in response to lipid (lipoid granuloma)

• alcohol induced
• obesity
• diabetes

• appearance strongly associated with progression to chronic hepatitis and cirrhosis (Laennec's cirrhosis)

• associated with a genetic mutation on chromosome 6 (C282Y)

• iron presumably stimulates free-radical/cytokine-mediated injury.
• Iron also deposits in skin, pancreas, heart, and joints.

• increase or iron in the circulation
• with secondary uptake in liver macrophages(Kupffer cells) and excess spill-over to hepatocytes

• AR defect at chromosome 13 that affects copper transport ATPase

• accumulation of copper in hepatocytes is toxic
• leads to necrosis, chronic inflammation, and progressive fibrosis
• this leads to cirrosis
• copper also deposits in brain and cornea

• diffuse deposition of copper in hepatocytes
• histopath of chronic hepatitis
  • portal lymphocytic infiltrate
  • reosion of limiting plate
  • bridges of fibrosis progressing to cirrhosis

• but could see secondary accumulation of copper in biliary obstruction

• auto-codominat recessive (PiZZ associated with liver disease)
• inherited deficiency in alpha antitrypisn

• accumulation of protease inhibitor in hepatocellular SER
• becomes toxic
• causes panacinar emphysema as well

• detect via periodic acid schiff stain (PAS-D)
• PAS-D positive globules appear in periportal hepatocytes

• drug related
• chronic active hepatitis
• cirrhosis
• result of severe liver injury, liver dysfunction, and/or severly distorted liver architecture

• bile droplets in hepatocytes and canaliculi only, without bile in bile ducts

• granulomatous non suppurative portal inflammation
• destruction of septal and medium sized intrahepatic bile ducts
• progressive loss of intrahepatic bile ducts and fibrosis

• female predominance
• associated with other autoimmune disease

• portal tract chronic inflammation
• interface hepatitis with characteristics granulomatous inflammation damaging bile duct epithelial cells
• progressivfe scar (cirrhosis)

• progressive loss (decrease in number) of bile ducts and ductular proliferation

• young males

• progressive sclerosis and obliteration of biliary tree (both extrahepatic and intrahepatic)
• associated peri-ductal inflammatory infiltrate and cholestasis
• punctuated by episodic cholangitis

• periductal fibrosis occludin the duct lumen (onion skinning)
• variable periductal chronic inflammation (mainly lymphocytes)
• progressive cirrhosis
• ductopenia

• obstruction via gallstone
• fibrosis/stricture of bile duct due to injury or inflammation affecgint extrahepatic bile ducts

• can lead to ascending life threating infection called ascending cholangitis
• tx- urgent drainage

• bile stasis in canaliculi anbd bile ducts
• similar features to primary schlerosing cholangints

• risk factors
  • oral contraceptives
  • anabolic steroids.
  • young women of child-bearing age.

• discrete mass(es)
• variably encapsulated
• made up of normal-appearing hepatocytes
• may contain bile
• but no normal triads or central veins

• tumors are highly vascular and can rupture under pressure, such as pregnancy

• well-demarcated mass, poorly encapsulated
• dense central scar with radiating fibrous arms
• normal hepatocytes and sinusoids, but without normal lobular architecture

• well-defined, nonencapsulated nodules, often small (<5mm); single or multiple
• consists of numerous endothelial-lined vascular channels
• a cavernous hemangioma is a variant in which the vascular nodule becomes a larger mass within the liver; a fibrous stroma appears between vascular channels.

• well-defined white nodules
• cluster of irregular bile ducts in a stromal nodule

• HCC occurs as a complication of cirrhosis, especially:
  • chronic viral hepatitis B and C,
  • alcoholic liver disease
  • hemochromatosis
  • aflatoxin (from Aspergillus flavus in stored nuts)

• single mass
  • metastatic tumor is more commonly multifocal
• variably-differentiated hepatocytes arranged in clusters or trabeculae
• formation of canaliculi and/ or accumulation of bile is pathognomonic

• very poor prognosis (generally < 1 yr survival)
• metastases usually present at the time of diagnosis
• intravascular invasion into the portal vein is particularly common

• clinical significance- so may present in association with symptoms and signs of biliary obstruction.

• PSC
• infection
• common sequelae of liver fluke(Clonorchis) infection.

• arising from bile ducts, appearing first as an intraductal or single intrahepatic mass
• duct-like epithelial cells forming glands
• cells produce mucin (like GI adenocarcinomas, but in contrast to HCC which is mucin-negative)

• hemorrhagic nodules, often multiple
• infiltrating tumor composed of numerous vascular channels lined by malignant endothelial cells.