dr dinah parums. principal pathologist. liver and biliary tract pathology. teaching handout
DESCRIPTION
Dr Dinah Parums. Principal Pathologist. Liver and Biliary Tract Pathology. Teaching Handout.TRANSCRIPT
The Liver and the The Liver and the Biliary TractBiliary Tract
Dr Dinah ParumsDr Dinah Parums
Principal HistopathologistPrincipal Histopathologist
July 2007July 2007
Normal LiverNormal Liver Average liver weight is 1,400
to 1,800 gms Lower border can be felt under
the right costal margin on deep inspiration
The right lobe is six times the size of the left
Dual blood supply - 40% hepatic artery - the rest by the hepatic portal vein
Bile drains in to the right and left hepatic ducts, into the common hepatic duct which joins with the cystic duct from the gallbladder, to form the common bile duct draining in to the duodenum via the Ampulla of Vater
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Normal LiverNormal Liver Histology of the liver shows a solid
mass of parenchyma composed of hepatocytes and cells lining the sinusoids pierced by portal tracts and tributaries of the hepatic veins
The liver lobule has an architecture defined by the liver vasculature
HV - the hepatic vein is at the centre of the liver lobule (sometimes called the Central Vein)
P - the portal tract - contains the portal triad
hepatic arteriole, bile duct and portal vein
Blood flow is from P to HV Bile flow is from HV to P The distance between the HV and
the P is 0.5 mm
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
HV
P
Normal LiverNormal LiverThe Kupffer Cell and SinusoidsThe Kupffer Cell and Sinusoids
One type of cell lining the hepatic sinusoids, the Kupffer cell, is phagocytic and is a component of the mononuclear phagocyte system.
The Kupffer cell helps clear the blood of foreign substances and old erythrocytes.
The other major type of lining cell is a special endothelial cell containing numerous pores permitting free passage of plasma macromolecules between hepatocytes and blood. It is not phagocytic.
Finally, there are scattered lipocytes that store vitamin A and also are responsible for collagen synthesis in liver fibrosis.
Normal LiverNormal LiverBileBile
Bile, the exocrine product of the hepatocytes, is initially secreted into intercellular bile canaliculi and then passes into branches of the bile (hepatic) duct.
The bile canaliculi are tiny passageways between adjacent hepatocytes.
They are difficult to visualize with the light microscope unless they are selectively stained.
Apart from the connective tissue of the portal triads, the structural framework of hepatic lobules consists of reticular fibers which are arranged in small bundles located in the space between the endothelial cells lining the sinusoids and the hepatocytes. This space is called the space of Disse.
The space of Disse is too narrow to be seen with the light microscope
Hepatic InjuryHepatic Injury Inflammation = hepatitisInflammation = hepatitis
Portal tracts, lobulesPortal tracts, lobules DegenerationDegeneration
Damage from toxic or immunologic insultDamage from toxic or immunologic insult Accumulation of substances, e.g., steatosisAccumulation of substances, e.g., steatosis
Cell deathCell death Centrilobular, submassive, massive Centrilobular, submassive, massive
necrosisnecrosis FibrosisFibrosis
Usually irreversibleUsually irreversible CirrhosisCirrhosis
BileBile
Two major functionsTwo major functions Elimination of bilirubin, excess Elimination of bilirubin, excess
cholesterol, and xenobiotics that are cholesterol, and xenobiotics that are insufficiently water soluble to be insufficiently water soluble to be excreted in urineexcreted in urine
Emulsification of dietary fat in the gut Emulsification of dietary fat in the gut by bile acids (cholic acid, by bile acids (cholic acid, chenodeoxycholic acid)chenodeoxycholic acid)
Unconjugated Unconjugated → Conjugated→ Conjugated Reabsorbed in terminal ileum Reabsorbed in terminal ileum
(enterohepatic circulation)(enterohepatic circulation)
JaundiceJaundice Excessive production of bilirubinExcessive production of bilirubin
Hemolytic anemias, ineffective Hemolytic anemias, ineffective erythropoiesiserythropoiesis
Reduced hepatic uptakeReduced hepatic uptake Impaired conjugationImpaired conjugation
Physiologic jaundice of the newbornPhysiologic jaundice of the newborn Crigler-Najjar syndromes types I and IICrigler-Najjar syndromes types I and II Gilbert syndromeGilbert syndrome Viral or drug-induced hepatitis, cirrhosisViral or drug-induced hepatitis, cirrhosis
Decreased hepatocellular excretionDecreased hepatocellular excretion Dubin-Johnson syndrome, Rotor syndromeDubin-Johnson syndrome, Rotor syndrome
Impaired bile flowImpaired bile flow
CholestasisCholestasis Systemic retention of not only bilirubin Systemic retention of not only bilirubin
but also other solutes eliminated in but also other solutes eliminated in bile, particularly bile salts and bile, particularly bile salts and cholesterolcholesterol
Due to hepatocellular dysfunction or Due to hepatocellular dysfunction or biliary obstructionbiliary obstruction
Accumulation of bile pigment within Accumulation of bile pigment within the hepatic parenchyma – Kupffer cellsthe hepatic parenchyma – Kupffer cells
Bile ductular proliferationBile ductular proliferation Bile lakesBile lakes Portal tract fibrosisPortal tract fibrosis
Hepatic FailureHepatic Failure 80% to 90% of hepatic functional 80% to 90% of hepatic functional
capacity must to destroyedcapacity must to destroyed Massive hepatic necrosisMassive hepatic necrosis
Fulminant viral hepatitisFulminant viral hepatitis Drugs and chemicals, e.g., acetaminophen, Drugs and chemicals, e.g., acetaminophen,
carbon tetrachloride, mushroom poisoningcarbon tetrachloride, mushroom poisoning Chronic liver diseaseChronic liver disease Hepatic dysfunction without overt Hepatic dysfunction without overt
necrosisnecrosis Acute fatty liver of pregnancyAcute fatty liver of pregnancy Tetracycline toxicityTetracycline toxicity Reye syndromeReye syndrome
Clinical FeaturesClinical Features
JaundiceJaundice HypoalbuminaemiaHypoalbuminaemia HyperammonaemiaHyperammonaemia Fetor hepaticusFetor hepaticus Palmar erythaemaPalmar erythaema Spider angiomasSpider angiomas HypogonadismHypogonadism GynaecomastiaGynaecomastia
ComplicationsComplications Multiple organ failureMultiple organ failure CoagulopathyCoagulopathy Hepatic encephalopathyHepatic encephalopathy
Metabolic disorder of the CNS and Metabolic disorder of the CNS and NMSNMS
Elevated blood ammonia level and Elevated blood ammonia level and deranged neurotransmissionderanged neurotransmission
Rigidity, hyperreflexia, seizuresRigidity, hyperreflexia, seizures AsterixisAsterixis
Hepatorenal syndromeHepatorenal syndrome Idiopathic renal failureIdiopathic renal failure
CirrhosisCirrhosis Bridging fibrous septaBridging fibrous septa Parenchymal nodulesParenchymal nodules Disruption of the architecture of the Disruption of the architecture of the
entire liverentire liver AetiologiesAetiologies
Alcoholic liver disease 60% to 70%Alcoholic liver disease 60% to 70% Viral hepatitis 10%Viral hepatitis 10% Biliary diseases 5% to 10%Biliary diseases 5% to 10% Hereditary hemochromatosis 5%Hereditary hemochromatosis 5% Wilson disease rareWilson disease rare Cryptogenic cirrhosis 10% to 15%Cryptogenic cirrhosis 10% to 15%
Portal HypertensionPortal Hypertension PrehepaticPrehepatic
Occlusive thrombosis, narrowing of the Occlusive thrombosis, narrowing of the portal veinportal vein
IntrahepaticIntrahepatic CirrhosisCirrhosis Schistosomiasis, massive fatty change, Schistosomiasis, massive fatty change,
diffuse granulomatous diseases (sarcoidosis, diffuse granulomatous diseases (sarcoidosis, miliary TB)miliary TB)
PosthepaticPosthepatic Right-sided heart failure, constrictive Right-sided heart failure, constrictive
pericarditis, hepatic vein outflow obstructionpericarditis, hepatic vein outflow obstruction
Clinical SequelaeClinical Sequelae
AscitesAscites Portosystemic venous shuntsPortosystemic venous shunts
Oesophageal varices 65% of casesOesophageal varices 65% of cases HemorrhoidsHemorrhoids Caput medusaeCaput medusae
SplenomegalySplenomegaly Hepatic encephalopathyHepatic encephalopathy
Drug Induced Liver Drug Induced Liver DiseaseDisease
Liver is the major drug metabolizing Liver is the major drug metabolizing and detoxifying organ in the bodyand detoxifying organ in the body
Direct toxicityDirect toxicity Hepatic conversion of a xenobiotic to Hepatic conversion of a xenobiotic to
an active toxinan active toxin Immune mechanismsImmune mechanisms
Alcoholic Liver DiseaseAlcoholic Liver Disease Hepatic steatosisHepatic steatosis
Micro and Micro and macrovesicularmacrovesicular
Initially centrilobularInitially centrilobular Alcoholic hepatitisAlcoholic hepatitis
Hepatocyte swelling Hepatocyte swelling and necrosisand necrosis
Mallory bodiesMallory bodies Neutrophilic reactionNeutrophilic reaction FibrosisFibrosis
Alcoholic cirrhosisAlcoholic cirrhosis MicronodularMicronodular IrreversibleIrreversible
PathogenesisPathogenesis Shunting of normal substrates away Shunting of normal substrates away
from catabolism toward lipid from catabolism toward lipid biosynthesisbiosynthesis
Induction of cytochrome P-450Induction of cytochrome P-450 Free radicals generated by microsomal Free radicals generated by microsomal
ethanol oxidizing systemethanol oxidizing system Alcohol directly affects microtubular Alcohol directly affects microtubular
and mitochondrial functionand mitochondrial function Acetaldehyde induces lipid peroxidationAcetaldehyde induces lipid peroxidation Neutrophil infiltrationNeutrophil infiltration Immunologic attack of hepatocytesImmunologic attack of hepatocytes
Causes of DeathCauses of Death
Hepatic failureHepatic failure Massive GI hemorrhageMassive GI hemorrhage InfectionInfection Hepatorenal syndromeHepatorenal syndrome Hepatocellular carcinomaHepatocellular carcinoma
Nonalcoholic Fatty LiverNonalcoholic Fatty Liver
Elevated serum aminotransferase Elevated serum aminotransferase levelslevels
Low risk for development of hepatic Low risk for development of hepatic fibrosis or cirrhosisfibrosis or cirrhosis
Associated with obesity, type 2 DM, Associated with obesity, type 2 DM, hyperlipidemiahyperlipidemia
Need to exclude other causesNeed to exclude other causes
HemochromatosisHemochromatosis
Primary or hereditaryPrimary or hereditary HLA-linked autosomal recessive diseaseHLA-linked autosomal recessive disease
SecondarySecondary Transfusion dependentTransfusion dependent Chronic liver diseaseChronic liver disease
PathogenesisPathogenesis Total body iron pool 2 to 6 gmTotal body iron pool 2 to 6 gm Primary defect in regulation of Primary defect in regulation of
intestinal absorption of dietary iron, intestinal absorption of dietary iron, leading to a net iron accumulation of leading to a net iron accumulation of 0.5 to 1.0 g/yr0.5 to 1.0 g/yr
HFE gene on 6pHFE gene on 6p Interacts with transferrin receptor of Interacts with transferrin receptor of
intestinal enterocyte and modulates intestinal enterocyte and modulates interaction with transferrin-iron complexesinteraction with transferrin-iron complexes
C282Y – disulfide bridge disruptedC282Y – disulfide bridge disrupted H63DH63D Lipid peroxidation, collagen formation, Lipid peroxidation, collagen formation,
DNA interactionsDNA interactions
MorphologyMorphology Deposition of hemosiderin in the liver, Deposition of hemosiderin in the liver,
pancreas, myocardium, pituitary, adrenal, pancreas, myocardium, pituitary, adrenal, thyroid and parathyroid glands, joints, and skinthyroid and parathyroid glands, joints, and skin
Cirrhosis, micronodularCirrhosis, micronodular Pancreatic interstitial fibrosis and parenchymal Pancreatic interstitial fibrosis and parenchymal
atrophy atrophy → DM→ DM
Clinical FeaturesClinical Features M:F = 5-7:1M:F = 5-7:1 Symptoms usually appear in the fifth to Symptoms usually appear in the fifth to
sixth decades of life.sixth decades of life. Classic triad: cirrhosis with Classic triad: cirrhosis with
hepatomegaly, skin pigmentation, DM hepatomegaly, skin pigmentation, DM (late in course)(late in course)
Cardiac dysfunction, e.g., arrhythmias, Cardiac dysfunction, e.g., arrhythmias, cardiomyopathycardiomyopathy
Atypical arthritisAtypical arthritis HypogonadismHypogonadism Tx: phlebotomy, iron chelatorsTx: phlebotomy, iron chelators
Wilson DiseaseWilson Disease Autosomal recessive disorder of Autosomal recessive disorder of
copper metabolismcopper metabolism ATP7B on chr 13 ATP-dependent ATP7B on chr 13 ATP-dependent
metal ion transporter on the Golgi of metal ion transporter on the Golgi of hepatocyteshepatocytes
Failure to excrete copper into bileFailure to excrete copper into bile Copper causes progressive liver injuryCopper causes progressive liver injury Affects brain, cornea, kidneys, bones, Affects brain, cornea, kidneys, bones,
joints, and parathyroid glandsjoints, and parathyroid glands Dx: Dx: ↓ serum caeruloplasmin, ↑ hepatic ↓ serum caeruloplasmin, ↑ hepatic
copper content, ↑ urinary coppercopper content, ↑ urinary copper
MorphologyMorphology Liver – fatty change, Liver – fatty change,
acute hepatitis, acute hepatitis, chronic hepatitis, chronic hepatitis, cirrhosiscirrhosis Rhodanine stain for Rhodanine stain for
coppercopper Orcein stain for copper-Orcein stain for copper-
associated proteinassociated protein Brain – Basal ganglia Brain – Basal ganglia
(putamen) shows (putamen) shows atrophy and cavitationatrophy and cavitation
Eye – Kayser-Fleischer Eye – Kayser-Fleischer ringsrings
Aka hepatolenticular Aka hepatolenticular degenerationdegeneration
Clinical FeaturesClinical Features
Manifestations rare before 6 yrsManifestations rare before 6 yrs Acute or chronic liver disease – most Acute or chronic liver disease – most
commoncommon Neuropsychiatric manifestationsNeuropsychiatric manifestations Copper chelation therapy with D-Copper chelation therapy with D-
penicillaminepenicillamine Liver transplantationLiver transplantation
αα11-Antitrypsin Deficiency-Antitrypsin Deficiency
Autosomal recessive disorderAutosomal recessive disorder AAT is a protease inhibitor, AAT is a protease inhibitor,
particularly neutrophil elastase particularly neutrophil elastase released at sites of inflammationreleased at sites of inflammation
AAT gene on chr 14AAT gene on chr 14 M allele normal, Z allele abnormal M allele normal, Z allele abnormal → →
misfolding of the nascent polypeptide in misfolding of the nascent polypeptide in the hepatocyte ER, accumulation, the hepatocyte ER, accumulation, degradationdegradation
Leads to pulmonary emphysema due Leads to pulmonary emphysema due to tissue destructive enzymesto tissue destructive enzymes
MorphologyMorphology Round to oval Round to oval
cytoplasmic cytoplasmic inclusions of retained inclusions of retained AATAAT Periodic acid-Schiff Periodic acid-Schiff
(PAS) positive(PAS) positive Marked cholestasis Marked cholestasis
with hepatocyte with hepatocyte necrosis in newbornsnecrosis in newborns
Childhood cirrhosisChildhood cirrhosis Chronic hepatitis or Chronic hepatitis or
cirrhosis later in lifecirrhosis later in life Tx: liver Tx: liver
transplantationtransplantation
Neonatal HepatitisNeonatal Hepatitis
Not a specific entityNot a specific entity Not necessarily inflammatoryNot necessarily inflammatory
Extrahepatic biliary atresia (20%), Extrahepatic biliary atresia (20%), toxic, metabolic diseases, AAT toxic, metabolic diseases, AAT deficiency (1.5%), idiopathic (50% to deficiency (1.5%), idiopathic (50% to 60%)60%)
Neonatal cholestasis (prolonged Neonatal cholestasis (prolonged conjugated hyperbilirubinemia)conjugated hyperbilirubinemia)
Present with jaundice, dark urine, Present with jaundice, dark urine, light or acholic stools, hepatomegalylight or acholic stools, hepatomegaly
Marked Marked bilirubin stasis bilirubin stasis in hepatocytes, in hepatocytes, canaliculi, and canaliculi, and Kupffer cells in Kupffer cells in neonate with neonate with extrahepatic extrahepatic bile duct bile duct atresia.atresia.
Reye SyndromeReye Syndrome Rare disease characterized by fatty Rare disease characterized by fatty
change in the liver and change in the liver and encephalopathyencephalopathy
Children < 4 yoChildren < 4 yo 3 to 5 days after a viral illness3 to 5 days after a viral illness
Associated with salicylate (aspirin) useAssociated with salicylate (aspirin) use Present with vomiting, irritability or Present with vomiting, irritability or
lethargy, hepatomegalylethargy, hepatomegaly 25% progress to coma25% progress to coma Death due to progressive neurologic Death due to progressive neurologic
deterioration or liver failuredeterioration or liver failure Tx: symptomatic, supportiveTx: symptomatic, supportive
MorphologyMorphology
Liver – microvesicular steatosisLiver – microvesicular steatosis EM – mitochondrial enlargement with EM – mitochondrial enlargement with
disruption of cristaedisruption of cristae Brain – cerebral oedemaBrain – cerebral oedema
Astrocytes swollen, mitochondrial Astrocytes swollen, mitochondrial changeschanges
Skeletal muscles, kidneys, and heart Skeletal muscles, kidneys, and heart may have microvesicular steatosis.may have microvesicular steatosis.
Obstructive Obstructive Biliary Tract Biliary Tract
DiseaseDisease
Secondary Biliary Secondary Biliary CirrhosisCirrhosis
Most common cause is extrahepatic Most common cause is extrahepatic cholelithiasischolelithiasis
Biliary atresia, malignancies of the Biliary atresia, malignancies of the biliary tree and head of the biliary tree and head of the pancreas, and stricturespancreas, and strictures
CholestasisCholestasis Bile duct proliferation with Bile duct proliferation with
surrounding neutrophilssurrounding neutrophils Periportal fibrosisPeriportal fibrosis
Primary Biliary CirrhosisPrimary Biliary Cirrhosis
Middle-aged womenMiddle-aged women M:F = 1:10M:F = 1:10 Possibly autoimmunePossibly autoimmune
Autoantibodies to mitochondrial pyruvate Autoantibodies to mitochondrial pyruvate dehydrogenase 90%dehydrogenase 90%
Insidious onset, usually presenting Insidious onset, usually presenting with prurituswith pruritus
Hyperbilirubinemia, jaundice, Hyperbilirubinemia, jaundice, cirrhosis latecirrhosis late
↑ ↑ alkaline phosphatase, cholesterolalkaline phosphatase, cholesterol
NonsuppurativeNonsuppurative, granulomatous , granulomatous destruction of destruction of medium-sized medium-sized intrahepatic bile intrahepatic bile ducts = florid ducts = florid duct lesionduct lesion
Primary Sclerosing Primary Sclerosing CholangitisCholangitis
Inflammation, obliterative onion-skin Inflammation, obliterative onion-skin fibrosis, and segmental dilatation of the fibrosis, and segmental dilatation of the obstructed intrahepatic and obstructed intrahepatic and extrahepatic bile ductsextrahepatic bile ducts
String of beads on ERCPString of beads on ERCP 70% associated with inflammatory bowel 70% associated with inflammatory bowel
disease, particularly ulcerative colitisdisease, particularly ulcerative colitis M:F = 2:1, third through fifth decadesM:F = 2:1, third through fifth decades Progressive fatigue, pruritus, jaundiceProgressive fatigue, pruritus, jaundice Chronic courseChronic course Increased risk for cholangiocarcinomaIncreased risk for cholangiocarcinoma
Circulatory Circulatory DisordersDisorders
Hepatic Artery InflowHepatic Artery Inflow
Liver has dual blood supply.Liver has dual blood supply. Thrombosis of hepatic artery in Thrombosis of hepatic artery in
transplanted liver transplanted liver → loss of organ→ loss of organ
Portal Vein ObstructionPortal Vein Obstruction ExtrahepaticExtrahepatic
Peritoneal sepsis leads to phlebitisPeritoneal sepsis leads to phlebitis Lymphatic metastases to hilar lymph nodesLymphatic metastases to hilar lymph nodes Pancreatitis leads to splenic vein thrombosisPancreatitis leads to splenic vein thrombosis Postsurgical thrombosesPostsurgical thromboses Banti syndrome umbilical vein catheterizationBanti syndrome umbilical vein catheterization
Intrahepatic thrombus does not cause an Intrahepatic thrombus does not cause an ischemic infarction but results in an area ischemic infarction but results in an area of red-blue discoloration (infarct of Zahn).of red-blue discoloration (infarct of Zahn). Invasive carcinomaInvasive carcinoma Hepatoportal sclerosisHepatoportal sclerosis
Impaired Blood Flow Impaired Blood Flow Through the LiverThrough the Liver
CirrhosisCirrhosis Sickle cell diseaseSickle cell disease DIC – disseminated intravascular DIC – disseminated intravascular
coagulation - potentially fatal subcapsular coagulation - potentially fatal subcapsular haematoma in pts with eclampsiahaematoma in pts with eclampsia
Right-sided heart failure Right-sided heart failure → congestion of → congestion of centrilobular sinusoidscentrilobular sinusoids
Left-sided heart failure → hypoperfusion Left-sided heart failure → hypoperfusion and hypoxia → centrilobular necrosisand hypoxia → centrilobular necrosis
Peliosis hepatis – primary sinusoidal Peliosis hepatis – primary sinusoidal dilation associated with anabolic steroids, dilation associated with anabolic steroids, danazol, and oral contraceptivesdanazol, and oral contraceptives
Hepatic Vein ThrombosisHepatic Vein Thrombosis
Aka Budd-Chiari syndromeAka Budd-Chiari syndrome Hepatomegaly, weight gain, ascites, Hepatomegaly, weight gain, ascites,
abdominal painabdominal pain Polycythaemia vera or other Polycythaemia vera or other
myeloprolifera-tive disorders, pregnancy, myeloprolifera-tive disorders, pregnancy, the postpartum state, oral contraceptive the postpartum state, oral contraceptive use, PNH, intra-abdominal cancers, esp. use, PNH, intra-abdominal cancers, esp. HCCHCC
Massive intrahepatic abscess or parasitic Massive intrahepatic abscess or parasitic cystcyst
Centrilobular congestion and necrosisCentrilobular congestion and necrosis
Veno-Occlusive DiseaseVeno-Occlusive Disease
Shortly after bone marrow Shortly after bone marrow transplantationtransplantation
25% incidence25% incidence Subendothelial swelling and Subendothelial swelling and
reticulated collagenreticulated collagen Due to toxic endothelial injury Due to toxic endothelial injury
secondary to chemotherapy and secondary to chemotherapy and radiation therapyradiation therapy
Hepatic NeoplasmsHepatic Neoplasms
Metastatic carcinomas – most Metastatic carcinomas – most commoncommon ColonColon LungLung BreastBreast
Benign tumorsBenign tumors Primary liver carcinomaPrimary liver carcinoma
Hepatocellular carcinomaHepatocellular carcinoma CholangiocarcinomasCholangiocarcinomas Hepatoblastoma – childrenHepatoblastoma – children Angiosarcoma – associated with vinyl Angiosarcoma – associated with vinyl
chloride, arsenic, or Thorotrast exposurechloride, arsenic, or Thorotrast exposure
Benign TumorsBenign Tumors
Cavernous hemangioma – most Cavernous hemangioma – most commoncommon Well-circumscribed, subcapsular, < 2 Well-circumscribed, subcapsular, < 2
cmcm Focal nodular hyperplasiaFocal nodular hyperplasia
Young to middle aged adultsYoung to middle aged adults Poorly encapsulatedPoorly encapsulated Central fibrous scarCentral fibrous scar Response to local vascular injuryResponse to local vascular injury
Focal Nodular Focal Nodular HyperplasiaHyperplasia
Liver Cell AdenomaLiver Cell Adenoma Women of Women of
childbearing age who childbearing age who have used oral have used oral contraceptivescontraceptives
Often subcapsularOften subcapsular Sheets and cords of Sheets and cords of
hepatocyteshepatocytes Portal tracts are Portal tracts are
absentabsent Prominent vessels Prominent vessels
throughoutthroughout Risk for rupture, esp Risk for rupture, esp
during pregnancyduring pregnancy
Hepatocellular Hepatocellular CarcinomaCarcinoma
Annual incidenceAnnual incidence Americas, Northern Europe, Australia 3-7 Americas, Northern Europe, Australia 3-7
cases/100,000cases/100,000 Southern Europe 20 cases/100,000Southern Europe 20 cases/100,000 Southeast China, Taiwan 150 Southeast China, Taiwan 150
cases/100,000cases/100,000 HBV carrier since infancy = 200 fold riskHBV carrier since infancy = 200 fold risk
Cirrhosis in 85% to 90% vs 50%Cirrhosis in 85% to 90% vs 50% M:F = 3:1 vs 8:1M:F = 3:1 vs 8:1 Sixth to seventh decades vs third to Sixth to seventh decades vs third to
fifthfifth
PathogenesisPathogenesis Infection with HBVInfection with HBV
Genomic instability with integrated HBV Genomic instability with integrated HBV DNADNA
Integration pattern is clonalIntegration pattern is clonal HBV X-protein disrupts cell cycle controlHBV X-protein disrupts cell cycle control Certain HBV proteins inactivate p53Certain HBV proteins inactivate p53
Chronic liver disease, esp HCV and EtohChronic liver disease, esp HCV and Etoh Cirrhosis plays an important role.Cirrhosis plays an important role.
Hepatocarcinogens in food (aflatoxins Hepatocarcinogens in food (aflatoxins from the fungus from the fungus Aspergillus flavusAspergillus flavus))
Repeated cycles of cell death and Repeated cycles of cell death and regeneration, i.e., chronic hepatitis, regeneration, i.e., chronic hepatitis, with possible mutationswith possible mutations
MorphologyMorphology Unifocal, multifocal, or infiltrativeUnifocal, multifocal, or infiltrative Strong propensity for vascular invasionStrong propensity for vascular invasion
Portal vein or IVC involvementPortal vein or IVC involvement Well-differentiated – intracellular bileWell-differentiated – intracellular bile Scant stroma Scant stroma → soft→ soft Metastasizes to LN, lung, bone, adrenalMetastasizes to LN, lung, bone, adrenal Fibrolamellar carcinomaFibrolamellar carcinoma
20-40 yo, M=F20-40 yo, M=F No assoc. with cirrhosis or other risk No assoc. with cirrhosis or other risk
factorsfactors Tumor cells separated by dense collagenTumor cells separated by dense collagen Better prognosisBetter prognosis
HCCHCC
Clinical FeaturesClinical Features Rapid increase in liver sizeRapid increase in liver size Sudden worsening of ascitesSudden worsening of ascites Appearance of bloody ascites, fever, painAppearance of bloody ascites, fever, pain ↑ ↑ serum AFP, esp if > 1000 ng/mlserum AFP, esp if > 1000 ng/ml Median survival 7 monthsMedian survival 7 months Death due to GI or esophageal variceal Death due to GI or esophageal variceal
bleeding or liver failure with hepatic bleeding or liver failure with hepatic comacoma
Surgical resection for smaller tumorsSurgical resection for smaller tumors Recurrence rate 60% at 5 yrsRecurrence rate 60% at 5 yrs
Liver transplantationLiver transplantation
Disorders of the Disorders of the GallbladderGallbladder
CholelithiasisCholelithiasis Very commonVery common Cholesterol stones Cholesterol stones
Bile is supersaturated with cholesterolBile is supersaturated with cholesterol Gallbladder stasisGallbladder stasis F>MF>M ObesityObesity Advancing ageAdvancing age
Pigment stones – calcium bilirubinate Pigment stones – calcium bilirubinate saltssalts Asian more than WesternAsian more than Western Chronic hemolytic syndromesChronic hemolytic syndromes
Clinical FeaturesClinical Features AsymptomaticAsymptomatic Biliary colicBiliary colic CholecystitisCholecystitis Gallstone ileusGallstone ileus
CholecystitisCholecystitis
Acute calculousAcute calculous Obstruction of GB neck or cystic ductObstruction of GB neck or cystic duct RUQ pain radiating to right shoulderRUQ pain radiating to right shoulder Fever, nausea, leukocytosisFever, nausea, leukocytosis Potential surgical emergencyPotential surgical emergency
Acute acalculous – seriously ill ptsAcute acalculous – seriously ill pts ChronicChronic
Recurrent attacks of painRecurrent attacks of pain Nausea and vomitingNausea and vomiting Associated with fatty mealsAssociated with fatty meals
CholedocholithiasisCholedocholithiasis
Stones within the biliary treeStones within the biliary tree West – from gallbladderWest – from gallbladder Asia – primary ductal and Asia – primary ductal and
intrahepatic stone formationintrahepatic stone formation Symptoms due to:Symptoms due to:
Biliary obstructionBiliary obstruction PancreatitisPancreatitis CholangitisCholangitis Hepatic abscessHepatic abscess
CholangitisCholangitis Acute inflammation of bile ductsAcute inflammation of bile ducts Due to biliary obstruction, usually Due to biliary obstruction, usually
choledocholithiasischoledocholithiasis Bacterial infection from gut, i.e., Bacterial infection from gut, i.e.,
gram negative aerobesgram negative aerobes Fever, chills, abdominal pain, jaundiceFever, chills, abdominal pain, jaundice
Latin America and Near East: Latin America and Near East: Fasciola hepatica, schistosomiasisFasciola hepatica, schistosomiasis
Far East: Clonorchis sinensis, Far East: Clonorchis sinensis, Opisthorchis viverriniOpisthorchis viverrini
AIDS: cryptosporidiosisAIDS: cryptosporidiosis
Biliary AtresiaBiliary Atresia 1/3 of cases of neonatal cholestasis1/3 of cases of neonatal cholestasis 1 in 10,000 live births1 in 10,000 live births Complete obstruction of bile flow Complete obstruction of bile flow
caused by destruction or absence of caused by destruction or absence of all or part of the extrahepatic bile all or part of the extrahepatic bile ductsducts
Acquired inflammatory disorderAcquired inflammatory disorder Normal stools to acholic stoolsNormal stools to acholic stools Bile ductular proliferation on liver bxBile ductular proliferation on liver bx Cirrhosis by 3 to 6 months of age.Cirrhosis by 3 to 6 months of age. Require liver transplantationRequire liver transplantation
Gallbladder CarcinomaGallbladder Carcinoma
Seventh decadeSeventh decade F>MF>M Discovered at late stage, usually Discovered at late stage, usually
incidentalincidental Exophytic and infiltrating typesExophytic and infiltrating types AdenocarcinomaAdenocarcinoma Local extension into liver, cystic duct, Local extension into liver, cystic duct,
portahepatic LNsportahepatic LNs Mean 5 yr survival 1%Mean 5 yr survival 1%
CholangiocarcinomaCholangiocarcinoma
Older ptsOlder pts M>FM>F Painless jaundice, N/V, weight lossPainless jaundice, N/V, weight loss Opisthorchis sinensis (liver fluke), Opisthorchis sinensis (liver fluke),
PSC, inflammatory bowel diseasePSC, inflammatory bowel disease Tumors usually small at dx yet not Tumors usually small at dx yet not
resectableresectable Klatskin tumor – arises at bifurcationKlatskin tumor – arises at bifurcation AdenocarcinomaAdenocarcinoma Mean survival 6 to 18 monthsMean survival 6 to 18 months
Questions?Questions?