The Liver and the The Liver and the Biliary TractBiliary Tract

DR MAHIPAL REDDYDR MAHIPAL REDDY

NIZAMABAD-INDIA.,NIZAMABAD-INDIA.,

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 necrosisCentrilobular, submassive, massive necrosis

FibrosisFibrosis Usually irreversibleUsually irreversible

CirrhosisCirrhosis

BileBile

Two major functionsTwo major functions Elimination of bilirubin, excess cholesterol, and Elimination of bilirubin, excess cholesterol, and

xenobiotics that are insufficiently water soluble to be xenobiotics that are insufficiently water soluble to be excreted in urineexcreted in urine

Emulsification of dietary fat in the gut by bile acids Emulsification of dietary fat in the gut by bile acids (cholic acid, chenodeoxycholic acid)(cholic acid, chenodeoxycholic acid)

Fig 16-1Fig 16-1 Unconjugated Unconjugated → Conjugated→ Conjugated Reabsorbed in terminal ileum (enterohepatic Reabsorbed in terminal ileum (enterohepatic

circulation)circulation)

JaundiceJaundice Excessive production of bilirubinExcessive production of bilirubin

Hemolytic anemias, ineffective erythropoiesisHemolytic anemias, ineffective erythropoiesis

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 but also Systemic retention of not only bilirubin but also other solutes eliminated in bile, particularly bile other solutes eliminated in bile, particularly bile salts and cholesterolsalts and cholesterol

Due to hepatocellular dysfunction or biliary Due to hepatocellular dysfunction or biliary obstructionobstruction

Accumulation of bile pigment within the hepatic Accumulation of bile pigment within the hepatic parenchyma – Kupffer cellsparenchyma – Kupffer cells

Bile ductular proliferationBile ductular proliferation Bile lakesBile lakes Portal tract fibrosisPortal tract fibrosis

Hepatic FailureHepatic Failure 80% to 90% of hepatic functional capacity must 80% to 90% of hepatic functional capacity must

to destroyedto destroyed Massive hepatic necrosisMassive hepatic necrosis

Fulminant viral hepatitisFulminant viral hepatitis Drugs and chemicals, e.g., acetaminophen, carbon Drugs and chemicals, e.g., acetaminophen, carbon

tetrachloride, mushroom poisoningtetrachloride, mushroom poisoning

Chronic liver diseaseChronic liver disease Hepatic dysfunction without overt necrosisHepatic dysfunction without overt necrosis

Acute fatty liver of pregnancyAcute fatty liver of pregnancy Tetracycline toxicityTetracycline toxicity Reye syndromeReye syndrome

Clinical FeaturesClinical Features

JaundiceJaundice HypoalbuminemiaHypoalbuminemia HyperammonemiaHyperammonemia Fetor hepaticusFetor hepaticus Palmar erythemaPalmar erythema Spider angiomasSpider angiomas HypogonadismHypogonadism GynecomastiaGynecomastia

ComplicationsComplications

Multiple organ failureMultiple organ failure CoagulopathyCoagulopathy Hepatic encephalopathyHepatic encephalopathy

Metabolic disorder of the CNS and NMSMetabolic disorder of the CNS and NMS Elevated blood ammonia level and deranged Elevated blood ammonia level and deranged

neurotransmissionneurotransmission 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 entire liverDisruption of the architecture of the entire liver EtiologiesEtiologies

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 portal veinOcclusive thrombosis, narrowing of the portal vein

IntrahepaticIntrahepatic CirrhosisCirrhosis Schistosomiasis, massive fatty change, diffuse Schistosomiasis, massive fatty change, diffuse

granulomatous diseases (sarcoidosis, miliary TB)granulomatous diseases (sarcoidosis, miliary TB)

PosthepaticPosthepatic Right-sided heart failure, constrictive pericarditis, Right-sided heart failure, constrictive pericarditis,

hepatic vein outflow obstructionhepatic vein outflow obstruction

Clinical SequelaeClinical Sequelae

AscitesAscites Portosystemic venous shuntsPortosystemic venous shunts

Esophageal varices 65% of casesEsophageal varices 65% of cases HemorrhoidsHemorrhoids Caput medusaeCaput medusae

SplenomegalySplenomegaly Hepatic encephalopathyHepatic encephalopathy

Drug Induced Liver DiseaseDrug Induced Liver Disease

Liver is the major drug metabolizing and Liver is the major drug metabolizing and detoxifying organ in the bodydetoxifying organ in the body

Direct toxicityDirect toxicity Hepatic conversion of a xenobiotic to an active Hepatic conversion of a xenobiotic to an active

toxintoxin Immune mechanismsImmune mechanisms Table 16-6Table 16-6

Alcoholic Liver DiseaseAlcoholic Liver Disease Hepatic steatosisHepatic steatosis

Micro and macrovesicularMicro and macrovesicular Initially centrilobularInitially centrilobular

Alcoholic hepatitisAlcoholic hepatitis Hepatocyte swelling and Hepatocyte swelling and

necrosisnecrosis Mallory bodiesMallory bodies Neutrophilic reactionNeutrophilic reaction FibrosisFibrosis

Alcoholic cirrhosisAlcoholic cirrhosis MicronodularMicronodular IrreversibleIrreversible

PathogenesisPathogenesis

Shunting of normal substrates away from Shunting of normal substrates away from catabolism toward lipid biosynthesiscatabolism toward lipid biosynthesis

Induction of cytochrome P-450Induction of cytochrome P-450 Free radicals generated by microsomal ethanol Free radicals generated by microsomal ethanol

oxidizing systemoxidizing system Alcohol directly affects microtubular and Alcohol directly affects microtubular and

mitochondrial functionmitochondrial 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 levelsElevated serum aminotransferase levels Low risk for development of hepatic fibrosis or Low risk for development of hepatic fibrosis or

cirrhosiscirrhosis 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 intestinal Primary defect in regulation of intestinal

absorption of dietary iron, leading to a net iron absorption of dietary iron, leading to a net iron accumulation of 0.5 to 1.0 g/yraccumulation of 0.5 to 1.0 g/yr

HFE gene on 6pHFE gene on 6p Interacts with transferrin receptor of intestinal Interacts with transferrin receptor of intestinal

enterocyte and modulates interaction with enterocyte and modulates interaction with transferrin-iron complexestransferrin-iron complexes

C282Y – disulfide bridge disruptedC282Y – disulfide bridge disrupted H63DH63D Lipid peroxidation, collagen formation, DNA Lipid peroxidation, collagen formation, DNA

interactionsinteractions

MorphologyMorphology Deposition of hemosiderin in the liver, pancreas, Deposition of hemosiderin in the liver, pancreas,

myocardium, pituitary, adrenal, thyroid and parathyroid myocardium, pituitary, adrenal, thyroid and parathyroid glands, joints, and skinglands, joints, and skin

Cirrhosis, micronodularCirrhosis, micronodular Pancreatic interstitial fibrosis and parenchymal atrophy Pancreatic interstitial fibrosis and parenchymal atrophy

→ DM→ DM

Clinical FeaturesClinical Features M:F = 5-7:1M:F = 5-7:1 Symptoms usually appear in the fifth to sixth Symptoms usually appear in the fifth to sixth

decades of life.decades of life. Classic triad: cirrhosis with hepatomegaly, skin Classic triad: cirrhosis with hepatomegaly, skin

pigmentation, DM (late in course)pigmentation, DM (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 copper Autosomal recessive disorder of copper

metabolismmetabolism ATP7B on chr 13 ATP-dependent metal ion ATP7B on chr 13 ATP-dependent metal ion

transporter on the Golgi of hepatocytestransporter on the Golgi of hepatocytes 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, joints, and Affects brain, cornea, kidneys, bones, joints, and

parathyroid glandsparathyroid glands Dx: Dx: ↓ serum ceruloplasmin, ↑ hepatic copper ↓ serum ceruloplasmin, ↑ hepatic copper

content, ↑ urinary coppercontent, ↑ urinary copper

MorphologyMorphology Liver – fatty change, acute Liver – fatty change, acute

hepatitis, chronic hepatitis, hepatitis, chronic hepatitis, cirrhosiscirrhosis Rhodanine stain for copperRhodanine stain for copper Orcein stain for copper-Orcein stain for copper-

associated proteinassociated protein

Brain – Basal ganglia Brain – Basal ganglia (putamen) shows atrophy (putamen) shows atrophy and cavitationand cavitation

Eye – Kayser-Fleischer Eye – Kayser-Fleischer ringsrings

Aka hepatolenticular Aka hepatolenticular degenerationdegeneration

Clinical FeaturesClinical Features

Manifestations rare before 6 yoManifestations rare before 6 yo Acute or chronic liver disease – most commonAcute or chronic liver disease – most common Neuropsychiatric manifestationsNeuropsychiatric manifestations Copper chelation therapy with D-penicillamineCopper chelation therapy with D-penicillamine Liver transplantationLiver transplantation

αα11-Antitrypsin Deficiency-Antitrypsin Deficiency

Autosomal recessive disorderAutosomal recessive disorder AAT is a protease inhibitor, particularly AAT is a protease inhibitor, particularly

neutrophil elastase released at sites of neutrophil elastase released at sites of inflammationinflammation

AAT gene on chr 14AAT gene on chr 14 M allele normal, Z allele abnormal M allele normal, Z allele abnormal → misfolding of → misfolding of

the nascent polypeptide in the hepatocyte ER, the nascent polypeptide in the hepatocyte ER, accumulation, degradationaccumulation, degradation

Leads to pulmonary emphysema due to tissue Leads to pulmonary emphysema due to tissue destructive enzymesdestructive enzymes

MorphologyMorphology Round to oval Round to oval

cytoplasmic inclusions of cytoplasmic inclusions of retained AATretained AAT Periodic acid-Schiff (PAS) Periodic acid-Schiff (PAS)

positivepositive

Marked cholestasis with Marked cholestasis with hepatocyte necrosis in hepatocyte necrosis in newbornsnewborns

Childhood cirrhosisChildhood cirrhosis Chronic hepatitis or Chronic hepatitis or

cirrhosis later in lifecirrhosis later in life Tx: liver transplantationTx: liver transplantation

Neonatal HepatitisNeonatal Hepatitis

Not a specific entityNot a specific entity Not necessarily inflammatoryNot necessarily inflammatory

Extrahepatic biliary atresia (20%), toxic, metabolic Extrahepatic biliary atresia (20%), toxic, metabolic diseases, AAT deficiency (1.5%), idiopathic (50% to diseases, AAT deficiency (1.5%), idiopathic (50% to 60%)60%)

Neonatal cholestasis (prolonged conjugated Neonatal cholestasis (prolonged conjugated hyperbilirubinemia)hyperbilirubinemia)

Present with jaundice, dark urine, light or acholic Present with jaundice, dark urine, light or acholic stools, hepatomegalystools, hepatomegaly

Marked bilirubin Marked bilirubin stasis in stasis in hepatocytes, hepatocytes, canaliculi, and canaliculi, and Kupffer cells in Kupffer cells in neonate with neonate with extrahepatic bile extrahepatic bile duct atresia.duct atresia.

Reye SyndromeReye Syndrome Rare disease characterized by fatty change in the Rare disease characterized by fatty change in the

liver and encephalopathyliver and encephalopathy 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 lethargy, Present with vomiting, irritability or lethargy, hepatomegalyhepatomegaly

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 disruption of EM – mitochondrial enlargement with disruption of

cristaecristae

Brain – cerebral edemaBrain – cerebral edema Astrocytes swollen, mitochondrial changesAstrocytes swollen, mitochondrial changes

Skeletal muscles, kidneys, and heart may have Skeletal muscles, kidneys, and heart may have microvesicular steatosis.microvesicular steatosis.

Obstructive Biliary Obstructive Biliary Tract DiseaseTract Disease

Secondary Biliary CirrhosisSecondary Biliary Cirrhosis

Most common cause is extrahepatic Most common cause is extrahepatic cholelithiasischolelithiasis

Biliary atresia, malignancies of the biliary tree Biliary atresia, malignancies of the biliary tree and head of the pancreas, and stricturesand head of the pancreas, and strictures

CholestasisCholestasis Bile duct proliferation with surrounding Bile duct proliferation with surrounding

neutrophilsneutrophils 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 with pruritusInsidious onset, usually presenting with pruritus Hyperbilirubinemia, jaundice, cirrhosis lateHyperbilirubinemia, jaundice, cirrhosis late ↑ ↑ alkaline phosphatase, cholesterolalkaline phosphatase, cholesterol

Nonsuppurative, Nonsuppurative, granulomatous granulomatous destruction of destruction of medium-sized medium-sized intrahepatic bile intrahepatic bile ducts = florid duct ducts = florid duct lesionlesion

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

Inflammation, obliterative onion-skin fibrosis, Inflammation, obliterative onion-skin fibrosis, and segmental dilatation of the obstructed and segmental dilatation of the obstructed intrahepatic and extrahepatic bile ductsintrahepatic and extrahepatic 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 DisordersCirculatory Disorders

Hepatic Artery InflowHepatic Artery Inflow

Liver has dual blood supply.Liver has dual blood supply. Thrombosis of hepatic artery in transplanted Thrombosis of hepatic artery in transplanted

liver 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 of red-ischemic infarction but results in an area of red-blue discoloration (infarct of Zahn).blue discoloration (infarct of Zahn). Invasive carcinomaInvasive carcinoma Hepatoportal sclerosisHepatoportal sclerosis

Impaired Blood Flow Through the Impaired Blood Flow Through the LiverLiver

CirrhosisCirrhosis Sickle cell diseaseSickle cell disease DIC – potentially fatal subcapsular hematoma in pts DIC – potentially fatal subcapsular hematoma in pts

with eclampsiawith eclampsia Right-sided heart failure Right-sided heart failure → congestion of centrilobular → congestion of centrilobular

sinusoidssinusoids Left-sided heart failure → hypoperfusion and hypoxia Left-sided heart failure → hypoperfusion and hypoxia

→ centrilobular necrosis→ centrilobular necrosis Peliosis hepatis – primary sinusoidal dilation associated Peliosis hepatis – primary sinusoidal dilation associated

with anabolic steroids, danazol, and oral contraceptiveswith anabolic steroids, danazol, and oral contraceptives

Hepatic Vein ThrombosisHepatic Vein Thrombosis

Aka Budd-Chiari syndromeAka Budd-Chiari syndrome Hepatomegaly, weight gain, ascites, abdominal Hepatomegaly, weight gain, ascites, abdominal

painpain Polycythemia vera or other myeloprolifera-tive Polycythemia vera or other myeloprolifera-tive

disorders, pregnancy, the postpartum state, oral disorders, pregnancy, the postpartum state, oral contraceptive use, PNH, intra-abdominal contraceptive use, PNH, intra-abdominal cancers, esp. HCCcancers, esp. HCC

Massive intrahepatic abscess or parasitic cystMassive intrahepatic abscess or parasitic cyst Centrilobular congestion and necrosisCentrilobular congestion and necrosis

Veno-Occlusive DiseaseVeno-Occlusive Disease

Shortly after bone marrow transplantationShortly after bone marrow transplantation 25% incidence25% incidence Subendothelial swelling and reticulated collagenSubendothelial swelling and reticulated collagen Due to toxic endothelial injury secondary to Due to toxic endothelial injury secondary to

chemotherapy and radiation therapychemotherapy and radiation therapy

Hepatic NeoplasmsHepatic Neoplasms

Metastatic carcinomas – most commonMetastatic carcinomas – most common ColonColon LungLung BreastBreast

Benign tumorsBenign tumors Primary liver carcinomaPrimary liver carcinoma

Hepatocellular carcinomaHepatocellular carcinoma CholangiocarcinomasCholangiocarcinomas Hepatoblastoma – childrenHepatoblastoma – children Angiosarcoma – associated with vinyl chloride, Angiosarcoma – associated with vinyl chloride,

arsenic, or Thorotrast exposurearsenic, or Thorotrast exposure

Benign TumorsBenign Tumors

Cavernous hemangioma – most commonCavernous hemangioma – most common Well-circumscribed, subcapsular, < 2 cmWell-circumscribed, subcapsular, < 2 cm

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 HyperplasiaFocal Nodular Hyperplasia

Liver Cell AdenomaLiver Cell Adenoma

Women of childbearing Women of childbearing age who have used oral age who have used oral contraceptivescontraceptives

Often subcapsularOften subcapsular Sheets and cords of Sheets and cords of

hepatocyteshepatocytes Portal tracts are absentPortal tracts are absent Prominent vessels Prominent vessels

throughoutthroughout Risk for rupture, esp Risk for rupture, esp

during pregnancyduring pregnancy

Hepatocellular CarcinomaHepatocellular Carcinoma

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 cases/100,000Southeast China, Taiwan 150 cases/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 fifthSixth to seventh decades vs third to fifth

PathogenesisPathogenesis

Infection with HBVInfection with HBV Genomic instability with integrated HBV DNAGenomic instability with integrated HBV DNA 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 from the Hepatocarcinogens in food (aflatoxins from the fungus fungus Aspergillus flavusAspergillus flavus))

Repeated cycles of cell death and regeneration, Repeated cycles of cell death and regeneration, i.e., chronic hepatitis, with possible mutationsi.e., chronic hepatitis, with 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 factorsNo assoc. with cirrhosis or other risk factors 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 bleeding Death due to GI or esophageal variceal bleeding

or liver failure with hepatic comaor liver failure with hepatic coma 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 saltsPigment stones – calcium bilirubinate salts 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 intrahepatic stone Asia – primary ductal and intrahepatic stone

formationformation 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., gram negative Bacterial infection from gut, i.e., gram negative

aerobesaerobes Fever, chills, abdominal pain, jaundiceFever, chills, abdominal pain, jaundice

Latin America and Near East: Fasciola hepatica, Latin America and Near East: Fasciola hepatica, schistosomiasisschistosomiasis

Far East: Clonorchis sinensis, Opisthorchis Far East: Clonorchis sinensis, Opisthorchis viverriniviverrini

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 caused by Complete obstruction of bile flow caused by

destruction or absence of all or part of the destruction or absence of all or part of the extrahepatic bile ductsextrahepatic bile ducts

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 incidentalDiscovered at late stage, usually incidental 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), PSC, Opisthorchis sinensis (liver fluke), PSC,

inflammatory bowel diseaseinflammatory bowel disease Tumors usually small at dx yet not resectableTumors usually small at dx yet not resectable Klatskin tumor – arises at bifurcationKlatskin tumor – arises at bifurcation AdenocarcinomaAdenocarcinoma Mean survival 6 to 18 monthsMean survival 6 to 18 months

Questions?Questions?