Liver Pathology 4:Liver Pathology 4:••Biliary diseasesBiliary diseases

gygy••Biliary diseasesBiliary diseases••Vascular diseasesVascular diseasesVascular diseasesVascular diseases••ParasitesParasites••TumorsTumors••Liver transplantationLiver transplantation

Causes of Large Bile Duct Obstruction

Extrahepatic Biliary Atresia (EHBA)Biliary Atresia (EHBA)

•Reovirus 3•RotavirusI•Immune targeting?

Loop of smallintestine

KasaiH tiHepaticPortoenterostomy

EHBARx Liver TransplantationRx

Primary Sclerosing Cholangitis (PSC)

ERCP: endoscopic retrogradecholangiopancreatography

, fewer Crohn’s

Primary Biliary CirrhosisPrimary Biliary Cirrhosis(PBC)

Guys’ Hospital ReportLondon, 1851

Addison & GullAddison & Gull

Mrs. Elizabeth Peacock

PBC: Primary biliary cirrhosis----Chronic nonsuppurative destructive cholangitis

•middle-aged women+ AMA (anti-mitochondrial

PDC-E2MolecularMimicry?

antibodies); M2 subtype• Alkaline Phosphatase• IgM

Gram –bacteriaIgM

•AMA directed against innermitochondrial membranePDC E2 ( t d h d HLAPDC-E2 (pyruvate dehydrogenasecomplex-E2)

bile duct

HLAII

•Assoc. with other autoimmunedis: e.g. RA, sicca, celiac, scleroderma

T

g , , ,

florid bileduct lesion

AMAT TT

Vascular Disease &the Liver

•Veins•Sinusoids•Arteries

•Liver is often involved in heart disease or other outflow problems(“hepatic venous( poutflow obstruction”)

Budd-Chiari Syndrome(H ti tfl(Hepatic venous outflowobstruction)

•oral contraceptives( S C•coagulopathy (prot. S, C,

factor V Leiden def.,anti cardiolipin Ab’santi-cardiolipin Ab s

•tumor invasion of hep. V’sor IVC: renal cell CA + HCC

ascites•small vein disease: VOD

Peliosis hepatis: blood lakes of the liver-HIV, C17-alkylated steroids (OC’s,HIV, C17 alkylated steroids (OC s,

anabolic steroids; systemic inflamm.

Infarct: Arterial disease (PAN, ligation,h R i t ll ti )chemoRx installation)

Portal vein: Zahn infarct

P.V.P.V.

Pylephlebitis:Pylephlebitis:Pylephlebitis:-perforated ulcer, ruptured appendix etc

Pylephlebitis:-perforated ulcer, ruptured appendix etc-ruptured appendix, etc.-ruptured appendix, etc.

Schistosomiasis: Pre-sinusoidal,,intrahepaticportal hypertensionportal hypertension

(Symmers’ “clay pipestem fibrosis”)

pancreas

LIVER-CELL ADENOMA-oral contraceptivesp-hepatocyte nuclear factor 1α (HNF-1α)

mutations-benign hepatocytes, bld vessels, NO b.d.’s

FOCAL NODULAR HYPERPLASIA (FNH)malformation: central scar with artery-malformation: central scar with artery,outgrowth of cirrhosis-like mass

HCCHCC

•75% of pts have cirrhosis75% of pts have cirrhosis•75% are serum AFP +Ri k Ci h i d t HBV•Risks: Cirrhosis due to HBV,

HCV, alcohol, hemochromatosis•Invades veins: portal vein/hepatic vein/IVC to lungsvein/IVC- to lungs

Hepatocellular carcinoma (HCC)

FIBROLAMELLAR Ca: young, no risks-better prognosis with resection/txbetter prognosis with resection/tx

NNocirrhosis

CholangiocarcinomaCholangiocarcinoma(bile duct Ca)

Cholangiocarcinomai t d ithassociated with:

•Liver flukes:-Clonorchis sinensis

-Opisthorcis viverrini

•PSC•Gallstone disease,hepatolithiasis

Liver Transplantation

•Cirrhosis-HBV, HCVHBV, HCV

• PBC• PSC• Extrahepatic biliary

atresiaA / A• AFLD/NAFLD

•Metabolic disorders

Acute Rejection

HLA II endothelium

TBD

Portal tractT

Liver Transplantation PathologyLiver Transplantation Pathology

inflammation

1. Acute rejection: triad2. Preservation injury

bile duct damageendotheliitisj y

(ischemia/reperfusion)3. CMV hepatitis3. CMV hepatitis

4 Recurrent original disease6 mos.

4. Recurrent original disease5. De novo autoimmune hepatitis6 Ch i j ti6. Chronic rejection

DameSheila Sherlock

The Royal FreeHospitalpLondon, U.K.

“Diseases of the Liver & Biliary System”

Peter J. Scheuer Hans Popper

Peter J. Scheuer, M.D.

Royal Free HospitalProf. of Histopathology

“Liver Biopsy Interpretation”“Liver Biopsy Interpretation”-1st Edition: 1968-7th Edition: 20057 Edition: 2005