this blood contains oxygen and many nutrients brought to the liver from the intestines for processing

the blood mixes in the sinusoids, being then collected in the central vein, which drains into the hepatic vein and subsequently into the inferior vena cava

hexagonal structure with the portal system at the periphery and a central/terminal hepatic vein at the centre

portal triads consist of branches of the hepatic artery and of the portal vein, together with bile ducts

at the centre of the acinus there is the portal system and the central vein is at the apical part of the acinus

• zone 1: near the portal system, entrance of oxygenated blood from hepatic arteries
• zone 2: intermediate
• zone 3: around the central vein and poorly oxygenated compared to the other two zones

during an active inflammatory status, there is an infiltration of lymphocytes

when the lamina is intact, it limits the infilration of other cells

in the presence of more than one row of hepatocytes in the reticle, this may be due to regeneration, neoplastic transformation or cirrhotic events

high risk of hemorrhage due to the high vascularizatio of the liver (thus, rarely performed)

• positive lab tests (elevated ALT, AST) for liver damage
• presence of specific/generic suspicious signs and symptoms (e.g. jaundice, fever)
• confirmation of clinical diagnosis
• follow up of patients with known liver disease
• diagnosis of a "focal lesion" nature, i.e. a liver mass at imaging

• the liver should be subdivided into its different units
• the central vein must be a the centre, while in the periphery there must be the portal vein
• check the limiting lamina of hepatocytes
• there should be one single row of hepatocytes forming the parenchyma, which should be divided by the sinusoids
• the reticulum should be thin

check if they are well distributed or affected by inflammation, ductular proliferation or limiting lamina

sometimes it can be affected by fibroisis, limiting blood flow

chronic cholangitis, typical of primary biliary cirrhosis

through hepatocytes, typical of acute forms of hepatitis, lymphocytic

mostly biliary, vasculitic or
in alcoholic hepatitis

• pretty rare event
• generally coming from inanition or senility
• the stroma prevails everywhere with an increased consistency, in spite of hepatocytes which become progressively thinner
• at microscopy, the liver appears brown due to a profuse secretion of lipofuscin pigment into the cytoplasm of the hepatocytes
  --> "BROWN ATROPHY"

commonly seen in hepatitis, in particular NASH and HBV

hepatocytes show clear big lobules in their cytoplasm (macrovesicular) or microvesicles

quite common condition, caused by bad dietary habits, alcoholic hepatitis, NAFLD and NASH

eosinophilic amorphous material derived from the haptocytes cytoskeleton, accumulating in their cytoplasm

DD: hepatitis B/C, alcoholic/nonalcoholic fatty liver, HCC, PBC, chronic cholestasis, focal nodular hyperplasia, Wilson disease and copper toxicosis

signs of apoptotic death of single shrink, losing their normal size

accumulation of bile inside the cells with flocculant appearing cytoplasm (full of yellow round spots)

on the basis of the etiology, cholestasis may be intrahepatic or intravascular

hepatocyte nuclei appear completely empty, like rings

• hepatotropic viruses (A,B, C, delta, etc.)
• non-hepatotropic viruses (paramyxovirus, EBV, CMV, HSV)
• drugs
• alcohol-related, inducing acute hepatitis
• immunologic/inflammatory conditions
• metabolic or hereditary
• pregnancy-related
• ischemic and vascular diseases
• misclellaneous/mixed

• hepatocyte regeneration in a not-so-well organized form (mitotic cells, hepatocytic arrangement in two rows or pseudo-acini)
• collapse of reticular fibers due to fibrotic deposition, macrophage cells with PAS-d+ pigment
• bilirubinostasis - cholstasis

• the effect of drugs on the liver is dose-dependent
• it may be idiosynchratic
• etiology: mixed, mainly toxic or metabolic
• pathological findings: massive panacinar necrosis, apoptosis (cell debris and Kupffer hypertrophy), very scarce lymphocyte infiltrate, ductulogenesis, minimal hepatocyte regeration

in the advanced stage, the necrotic status is progressively worse and progressively substituted by fibrotic deposition with bridge formation (from central vein and portal triad) and evolution into cirrhosis

in severe chronic active hepatitis, the inflammatory infiltrate expands into the liver parenchyma, destroying it

• mild activity, formation of lymphatic follicles
• marked apoptosis (Councilman-eosinophilic bodies)
• steatosis
• presence of iron inside the hepatocytes

• signs of viral infection associated with features of alcoholic disease or autoimmune disease
• increased inflammatory component and possibly marked steatosis

if these structures are compromised, the grade of inflammation is higher

among the different forms, the portal-central vein fibrosis is the worst one

• blood from superior mesenteric and portal veins
• it contains a denser network of biliary canaliculi and accounts for more hepatic bacterial infections
• favored by immunosuppressive conditions
• to be recognized and treated, otherwise fatal

the structure is surrounded by pink amorphous chitinous material

• STEATOSIS: also seen at US and PET; macrivesicular up to rupture of membranes, formation of lipogranuloma
• HEPATITIS: Mallory bodies, hepatocyte necrosis and neutrophilic granulocytes

clinical manifestations are frequently associated with obesity, DMII

lipid-induced hepatocyte sub-lethal and lethal stress

on the basis of steatosis/ballooning and lobular inflammation

the cirrhotic status can eventually evolve into HCC

normal iron-driven erythropoiesis, with toxic accumulation of iron in parenchymal cells of the liver (cirrhosis), heart (cardiomyopathy) and endocrine glands (hypogonadism, DM, arthropathy and skin pigmentation)

hemosiderin is first deposited in the periportal area

hepatocytes affected die and are progressively substituted by fibrotic material, eventually leading to cirrhosis development

• AR genetic disease
• accumulation of toxic levels of copper in various organs, i.e. liver, brain, eyes, kidneys
• there are also forms of intoxicarion from copper due to excessive exposition, leading to transitory neurological symptoms

• AAT protein is synthesized by the liver, then secreted into the serum
• it inhibits neutrophil proteases
• the mutant Z gene of AAT causes the synthesis of a mutant protein, which is retained intracellularly, rather than efficiently secreted, causing liver injury and triggering a cascade of chronic hepatocellular apoptosis, regeneration and end-organ damage (followed by cirrhosis and HCC)
• the lungs may develop panacinar emphysema
• at H&E, PINK INCLUSIONS (retained mutant proteins)
  --> globular PAD-d+ inclusions
• IHC: specific anti-AAT antibodies

• viral hepatitis
• alcohol (ethanol metabolites-related damage; alcohol's effect on bile acid uptake and secretion)
• NASHD
• NASH
• drug-induced liver injury
• ischemic hepatitis
• genetic hepatic disease (Wilson's disease, hemochromatosis)
• primary or metastatic liver cancer

• bilirubinostasis and biliary thrombi
• portal edema
• portal ductular proliferation with granulocyte infiltrate
• hepatocyte degeneration in the vicinity of biliruin deposits
• bridging fibrous septae with evolution into cirrhosis

consistent amount of granulocytes, causing inflammation and damage of hepatic parenchyma

difficult to diagnose as it may mimic different entities, e.g. HCC

• intrahepatic ducts (intralobular bile ducts)
• F>M
• etiology: AI, AMA, ANA
• histology: early portal inflammatory stage, demonstrating granulomatous features; inflammatory infiltrate of lymphocytes and plasma cells; large roundish portal systems with complete disruption of the bile ducts
• therapy: UDCA + anticholestatic and antifibrotic effects
• prognosis: variable

• intrahepatic and/or extrahepatic ducts
• F<M
• etiology: idiopathic (HLA?, IBD?)
• histology: predominant fibrosis at different parts of the biliary tract, periductal concentric "onion skin" fibrosis and stricturing
• therapy: no effective therapy other than LT
• prognosis: possible evolution into different hepatobiliary cancers

• fibrous bands that disrupt the hepatic parenchyma
• fibsoris-sequestration-regeneration (micro-macronodular)
• defects of microcirculation with venous shunts and arterial hypoperfusion, increased vascular resistance

• sinusoidal remodelling (ECM deposition from proliferating activated stellate cells, resulting in capillarisation of hepatic sinusoids)
• formation of intrahepatic shunts (due to angiogenesis and loss of parenchymal cells) and consequent arterial hypoperfusion
• hepatic endothelial dysfunction with hepatocyte damage

ascites may be complicated by spontaneous bacterial peritonitis (due to bacterial translocation from enteric origin)

the increased secretion of aldosterone causes an increased Na+ and H2O reabsorption at
the level of the distal tubules

caused by the formation of obstructing intratubular bile acid casts at the level of the kidneys

bile at the level of the kidneys is able to exert a direct acid toxic effect on tubular cells

intra-abdominal hypertension

neurological/psychiatric abnormalities, ranging from subclinical alterations to coma

this leads to the increase in the levels of inflammatory cytokines, causing BBB damage

consequence:
pulmonary hypertension and loss of alveolar type II cells
(HYPOXEMIA)

• partial or complete
• found in cirrhotic pts with concomitant HCC
• increase in pressure in the portal vein with possible rupture of esophageal varices and ascites

cirrhosis, chronic acute hepatitis, alcoholic hepatitis, fatty liver

schistosomiasis, primary biliary cirrhosis, sarcoidosis, myeloproliferative diseases, nodular regenerative hyperplasia

hepatic arteriovenous fistula, conditions associated with massive splenomegaly

at the level of hepatic sinusoids and terminal venules

sinusoidal endothelial injury, due to HSCT, CT, abdominal RT and pyrrolizidine alkaloids

induced by hepatic venous thrombosis, inducing hypoxic damage to the hepatocytes (along with possible IVC webs), due to compression of hepatic veins or IVC by tumor, cyst or abscess

• sinusoidal dilation and perivascular fibrosis
• centrilobular liver cell necrosis (from the central vein, then extending to peripheral areas)
• deposition and spread of connective tissue (with fibrotic processes substituting the parenchyma)
• bridging one central vein to the other
• cirrhosis

liver appears heavy and very consistent (hard) at the US

in cases of acute decrease in cardiac output, there may be a form of acute cardiogenic ischemic hepatitis

similar in appearance to solitary cysts, but multiple, hereditary and often associated with PCKD

• AR
• typical of adolescents and young adults with portal hypertension
• proliferation of fibrous tissue and small ducts with enlargement of portal spaces

• AR
• segmental dilation of the biliary branches with dense bile and stones
• sometimes portal hypertension

• second most frequent benign liver nodule (after hemangioma)
• a current hypothesis is that the primary lesion is an outflow obstruction and the resulting congestive injury leads to parenchymal collapse and fibrosis, arteriovenous shunting and loss of portal veins and ducts

central stellate fibrous scar with radiating extensions that partially surround nodules

fibrous septa searate hepatocellular nodules of different size, resempling cirrhosis

populations at risk:

• women taking oral contraceptives (duration of usage, reversible)
• men using anabolic steroids

• proliferation of the bile ducts at the level of the portal tracts
• lesions can be single or multiple
• grayish in complexion
• micro: bile ducts proliferating in more or less dense connective tissue
• DD: adenocarcinoma

• most frequent tumor of the liver
• affecting both sexes at all ages
• often diagnosed at the core biopsy
• the cavernous form is the one most frequently observed
• angiomas can be single or multiple
• high risk of rupture and bleeding

frequently arising from cirrhotic liver, but it can also appear in non-cirrhotic hepatic conditions

• HBV/HCV infection
• cirrhosis
• carcinogens
• genetic conditions (hemochromatosis and alpha1 antitrypsin deficiency)

sometimes, it may look similar to normal liver parenchyma affected by minor non-neoplastic alterations, such as infections

single mass (>10 cm) or multiple masses (multifocal), lardaceous, irregular margins, greenish-yellow

• G1 (well differentiated): of trabecular type with little atypia
• G2 (intermediate differentiated): of pseudoglandular type with greater atypia
• G3 (poorly differentiated) or G4 (undifferentiated): with various extensions of pleomorphic, spindle or giant cells

AFP, canalicular CEA, CK8-18 (CK19 neg), glipican 3, hepar 1

• distinguished by age (20-40y)
• lack of typical risk factors of HCC
• well-differentiated form with marked deposition of fibrous tissue

cachexia, ruptured esophageal varices liver failure

number of nodes, tumor diameter, vascular invasion, affeced lobes

• 10% of the primitive liver tumors
• one of the main tumors to be related with CUP syndrome
• diffuse metastases
• etiology: use of Thorotrast, intrahepatic biliary parasites, HBV, smoking, alcohol, biliary tree anomalies
• macro: withish, usually single, no bile content, sometimes copious mucus
• micro: mucinous regions are indicative, well glandular differentiation, richness in fibrous stroma
• very aggressive, bad prognosis
• lymphatic and henatogenous spread
• DD: ACC with metastases in liver and primary cholangiocarcinoma

rare, childhood age (90% <5aa), rapidly growing abdominal mass, increased AFP, rare HCG production, at microscopy there are embryonic features

rare, associated with the use of thorotrast, PVC monomer or arsenic

• most frequent tumors in the liver
• origin can be via hepatic artery or portal vein
• mostly multiple
• good chances of remission after surgical treatment (recommended only in the presence of single lesions)

• association with lithiasis or infections
• macro: mostly in the collar, infiltrating or exophytic appearance with different histotypes
• micro: histotype prevalent adenocarcinoma (papillary, mucinous, clear cells), but also squamous, adenosquamous or carcinoid
  

• rare, affecting mostly elderly males, pretty aggressive
• causes: lithiasis, sclerosing cholangitis or infections
• macro: stenosing lesion, small (early jaundice)
• micro: histotype adenocarcinoma, often desmoplastic