354

Index

Note: page numbers in italics refer to figures; those inbold to tables. a 239, 239–240, 240 non-A non-G 31, 34–35, 35 ABCB4 gene 185, 347 pathophysiology 238–239 typical (non-fatal) 31–35 ABCB11 gene 185, 347 acute cholangitis adenofibroma, biliary 286 Abernethy malformation 160 mechanical bile duct adenomatosis, hepatocellular 268, abscesses, hepatic obstruction 85, 86 272, 283 amebic 113, 114 post-transplant biliary adenosine monophosphate- chronic granulomatous strictures 250, 250 dependent protein kinase 129 sepsis (bacteremia) 97 (AMPK) 53 fungal 109, 110, 110 tuberculosis 106 adenovirus 19, 48, 249 listeriosis 100 acute fatty liver of pregnancy adipokines 65 mechanical bile duct 344–346, 345 adiponectin 53, 65 obstruction 85, 86 acute graft failure (primary non- adipophilin 9, 50, 223 pyogenic 95–97 function) 236–237, 237, 238 ADPKD see autosomal dominant see also microabscesses acute hepatitis polycystic kidney disease acetaldehyde 52, 52 drug or toxin-induced 219–220, aflatoxins 218, 292 acetaminophen 215, 217, 219, 219 220, 221 AIRE (autoimmune regulatory acetyl co-enzyme A (CoA) 52, 52 viral see acute viral hepatitis protein) 132 acid β-glucosidase Wilson disease 178 Alagille syndrome 202–203 (glucocerebrosidase) 190 acute liver failure 16, 231 alanine aminotransferase (ALT) 21, acid–fast bacteria (AFB) 19, 105, see also fulminant hepatitis 22 106, 108 acute rejection albumin, serum 21, 23 acidophil bodies 33, 33 cellular see acute cellular rejection alcohol dehydrogenase (ADH) 52, 52 acid phosphatase 190–191 humoral (antibody- alcoholic cirrhosis 56, 62–63 acinar agglomerates 13 mediated) 237 abstained from drinking 62, 63, 222 acinar structures, hepatocellular acute viral hepatitis 31–37 active drinker 62, 62, 63, 63 carcinoma 296, 298 clinical presentation 24 clinical presentation 57 acinus, hepatic 12–13, 13 with confluent 35, hepatocellular carcinoma 57, 291 complex 13 COPYRIGHTED35–36, 36 MATERIALliver transplantation 231 simple 12–13, 13 cytomegalovirus infection 45, alcoholic fatty liver () 56 activin receptor-like kinase 1 45–46, 46 acute, with or without (ALK-1) 160 differential diagnosis 36–37, 141, cholestasis 57, 61, 61 acute alcoholic liver injury 57, 57, 181 grading 58 58–62 EBV infection 43–45, 44, 45 pathology 57, 57–58, 58, 224 acute cellular rejection 238–242 fulminant see fulminant hepatitis alcoholic fibrosis clinical presentation and general histology 31, 31–33, 32, 33 alcoholic hepatitis 59, 59 treatment 239 histology of specific viruses 31, cirrhosis 62, 62–63, 63 differential diagnosis 236, 237, 33–35, 34, 35 clinical manifestations 58, 59 241–242, 256 liver transplant recipients 241 55 grading 240–241, 241 neonatal 199 post-transplant recurrence 260, 260 Pathology of Liver , First Edition. Gary C. Kanel. © 2017 John Wiley & Sons, Ltd. Published 2017 by John Wiley & Sons, Ltd. Companion website: www.wiley.com/go/kanel/liverpathology

bindex 354 18 January 2017 1:39 AM Index 355

alcoholic foamy degeneration 57, aminotransferases 17–22, 21 anti-neutrophil cytoplasmic 61–62, 62 amiodarone 217, 218, 225, 226 antibodies (ANCA) alcoholic hepatitis 56, 58–61 ampulla of Vater 72 atypical 80, 133, 134 clinical presentation 56 amyloid A, serum see serum cytoplasmic (cANCA) 80 Mallory–Denk bodies 59, 59, 60, amyloid A perinuclear (pANCA) 80 60, 225 amyloid-associated (AA) anti-nuclear antibodies (ANA) 133, alcoholic liver disease (ALD) 50, protein 341 133, 134 51–63 amyloid light chain (AL) 337, 338 anti-smooth muscle antibody acute 57, 57, 58–62 staining techniques 340, 341 (SMA) 133, 133, 134 clinical presentation 56–57 amyloidosis 154, 337–341 anti-soluble liver/liver–pancreas differential diagnosis 68–70, 69, categories 337 antigen (SLA; SLA/LP) 182, 350 clinical presentation 337–338 antibody 133, 133, 134 epidemiology 51–52 differential diagnosis 341 apoptotic cells natural history 56 globular 339, 339–340 acute viral hepatitis 33, 33 pathology 57, 57–63 multiple myeloma 328, 337 Rocky Mountain spotted pathophysiology 53–56, 54 pathology 338–340 fever 103, 103 post-transplant recurrence primary 337, 340, 341 architecture, basic hepatic 4, 5, 16 259–260, 260 secondary 337, 340, 341 arginase 304 sinusoidal infiltrates 159 special staining patterns 340–341 ARPKD see autosomal recessive alcohol (ethanol) metabolism 52, 52 amyloid proteins 337, 338 polycystic kidney disease alkaline phosphatase 21, 22 anabolic steroids (including arsenic/arsenicals 218, 228, 292, alcoholic liver disease 57 oxymetholone) 217, 218 319 autoimmune hepatitis 135 hepatocellular adenoma 229, 266 arteriohepatic 202–203 drug-induced liver cell injury 216 malignant 229, 309 arterioportal fistulas 160 viral hepatitis 24 Anderson disease 188 asialoglycoprotein receptor Wilson disease 178 angiomatosis, diffuse 276, 277 (ASGPR) antibody 133 see also liver tests, routine angiomyolipoma 285, 285, 286 aspartate transaminase (AST) 17– Alpers disease 195 angioproliferative lesion see bacillary 22, 21 α1-antitrypsin (α1AT) 162 angioproliferative disease aspergillosis 108–109 allelic and structural angiosarcoma 318–320 aspirin 342–343 variants 162–163 differential diagnosis 277, AST see aspartate transaminase serum 21, 163 280–281, 320, 321 AST:ALT (aspartate stains 19, 20, 163–164, 164 pathology 319, 319–320, 320 transaminase:alanine α1-antitrypsin deficiency 162–166 toxin-induced 228, 318–319 aminotransferase) ratio 22, adult 165, 165 anthracotic (anthracite) 56, 57 clinical presentation 163 pigment 218, 229 asteroid bodies 127, 128 differential diagnosis 43, 165– antibody-mediated (humoral) atherosclerotic cardiovascular 166 rejection 237–238 disease 153 neonatal 164–165, 165 acute 237 ATP7B gene 177 pathogenesis 162–163 differential diagnosis 236, 238 ATP8B1 gene 185, 347 pathology 163–165 hyperacute 237–238, 238 , hepatocyte PiZZ phenotype 163, 164 anti-cyclic citrullinated peptide portal vein thrombosis 150 α-fetoprotein (AFP) (CCP) antibody 133 right-sided heart failure 147, 148 developing liver 2–3 anti-double-stranded DNA (dsDNA) sinusoidal obstruction 303, 305 antibody 133 syndrome 157 lectin binding (AFP-L3) 295 anti-F-actin antibody (AAA) 133, 134 autoimmune cholangitis 136, 136, serum 21, 295, 306, 316 anti-liver cytosol 1 (LC-1) 139 alpha-heavy chain disease antibody 133, 134 differential diagnosis 141 327–328, 328 anti-liver–kidney microsomal drug or toxin-induced 227 ALT see alanine aminotransferase (LKM) antibodies 133, laboratory tests 135 alternative medicines 215 133–134, 134 post-transplant recurrent amebiasis 112–114 anti-liver microsome (LM) autoimmune hepatitis 259 amino acid metabolism, disorders antibody 133 autoimmune diseases of 192–194 anti-mitochondrial antibodies autoimmune hepatitis aminolevulinic acid (ALA) (AMA) 133, 134 associations 135 synthetase 170 primary biliary cirrhosis 73–74, 75 non-cirrhotic portal fibrosis 151

bindex 355 18 January 2017 1:39 AM 356 Index

autoimmune hepatitis 131–141 bacteremia 95–97, 97 bile duct obstruction (BDO), acquired post-transplant 262, 263 bacterial 95–108, 96 mechanical 83–89 acute viral hepatitis vs. 36–37 differential diagnosis 121–122 causes and clinical course 84, classification 131, 132, 133 Gram-positive/Gram- 84–85 clinical presentation 134–135 negative 95–101, 96 differential diagnosis 91, 91–92, differential diagnosis 42, 141, 181 inflammatory pseudotumor 281 181, 242, 350 drug induced 132–133, 216, 222, post-transplant 245, 245 early-stage disease 85, 85, 86 223 Bacteroides 281 late-stage disease 88, 88, 89 with duct damage see ballooning, liver cell mid-stage disease 86–88, 87 autoimmune cholangitis acute viral hepatitis 33 pathology 85–89 epidemiology 131 alcoholic hepatitis 59, 59, 60 post-transplant 236, 249–250 histologic scoring systems 140–141 NAFLD 66–67, 67 secondary sclerosing pathogenesis 131–133 see also hydropic change of cholangitis 89–90 pathology 135–138 hepatocytes bile ducts post-transplant recurrence Banff scoring system acute cellular rejection 239, 240, 258–259, 259 acute rejection 240–241, 241 240 post-transplant recurrent chronic rejection 241, 244 development 2, 2 HCV 255, 262, 263 bare area 2 dimensions 72 primary biliary cirrhosis 75, 78 Bartonella henselae infection 158 drug or toxin-induced injury 218 133, 133–134, 134 angioproliferative lesion 100, ectasia see duct ectasia type 1 131, 132 101, 159 154, 154 type 2 131, 132 HIV infection 46 loss see ductopenia type 3 132 Batts–Ludwig scoring system, microanatomy 11–12 variants 138–140, 139 chronic viral hepatitis 43 post-transplant vascular autoimmune hepatitis–chronic B-cell , polyclonal, post- injury 251, 251 hepatitis C 42, 138, 139, 140 transplant 248 primary sclerosing autoimmune hepatitis–primary B-cell proliferation, monoclonal, cholangitis 80, 80–81, 81 biliary cirrhosis 75, 78, 138, post-transplant 248 trapped, inflammatory 139, 139, 140 BCG see bacille Calmette–Guérin pseudotumor 282, 282 autoimmune hepatitis–primary benign hepatic tumors 266–286, see also extrahepatic bile ducts; sclerosing cholangitis 267 intrahepatic bile ducts (autoimmune sclerosing benign intrahepatic cholestasis of bile ductular proliferation (duct cholangitis) 132, 135, 139 pregnancy 347 transformation; duct autoimmune hepatitis– benign recurrent intrahepatic ) 11 sarcoidosis 128, 139 cholestasis (BRIC) 185, acute viral hepatitis 32 autoimmune polyendocrinopathy– 186, 347 α1-antitrypsin deficiency 164, candidiasis–ectodermal benign tumor-like lesions 267 165 dystrophy (APECED) BerEP4 314 bacteremia 97 syndrome 131–132 Besnier–Boeck–Schaumann disease cystic fibrosis 167, 167 autosomal dominant polycystic see sarcoidosis extrahepatic biliary atresia 201, 201 kidney disease β-catenin-activated mutations facultative stem cells 14, 14 (ADPKD) 207, 212–214, 213 focal nodular hyperplasia 275 fulminant hepatitis 36, 36 autosomal recessive polycystic hepatocellular adenoma 267–268, mechanical bile duct kidney disease 268, 271, 272 obstruction 85, 85 (ARPKD) 207, 209–210, 211 hepatocellular carcinoma 293–294 post-transplant infantile 210, 211 β-catenin immunoperoxidase complications 245, 245 juvenile (congenital hepatic stain 305 primary sclerosing cholangitis 81 fibrosis) 210, 211, 212 bile bile ductules 11 neonatal 211, 211 copper excretion 177 atypical, focal nodular perinatal 211 intracellular 9, 226 hyperplasia 273, 274 bile acids, carcinogenicity 309 ectatic, cystic fibrosis 167, 167 b bile duct adenocarcinoma see bile impregnation bacillary angioproliferative cholangiocarcinoma mechanical bile duct disease 100, 101, 159 bile duct adenoma 284, 284–285, obstruction 88 bacille Calmette–Guérin 285 primary sclerosing (BCG) 107, 218 differential diagnosis 313–314 cholangitis 83, 84

bindex 356 18 January 2017 1:39 AM Index 357

bile infarcts biliary system 72, 72 Burkitt lymphoma 324–325 biliary tract disorders 92 embryonic development 2 bush tea 156 mechanical bile duct gross anatomy 4, 72 Byler disease (PFIC type 1) 184, obstruction 87, 87 microanatomy 11–12, 72 185, 186, 347 primary sclerosing cholangitis 82 biliary tract disorders 72–93 bile lakes 86–87, 87, 92 cystic fibrosis 166–167, 168 c bile plugs, cystic fibrosis 167, 167 developmental and congenital CA19-9 278, 310, 314, 315 biliary adenofibroma 286 cystic 204–207, 206 CA 125 314 biliary atresia 199–204 differential diagnosis 91, 91–92 canaliculi, bile see biliary canaliculi see also extrahepatic biliary HIV infection 46–47, 47, 93 canals of Hering 11 atresia; intrahepatic biliary parasites 84, 118–119, 119 candidiasis 109–110, 110 atresia bilirubin 21, 22 capsule of Glisson 10, 13–14 biliary canaliculi metabolism 72, 73 carbohydrate metabolism storage development 1, 2 see also hyperbilirubinemia diseases 184–189 dilated, hepatocellular Bismuth–Corlette staging carcinoembryonic antigen (CEA) carcinoma 296, 298 classification, monoclonal (mCEA) 303, 314, microanatomy 11, 11, 12 cholangiocarcinoma 311 315 biliary cirrhosis Blastocystis 121 polyclonal (pCEA) 271, 275, 303, α1-antitrypsin deficiency 164, blastomycosis 305, 314 165 Brazilian (South American) 112 serum, cholangiocarcinoma 310 biliary tract disorders 91 North American 109 carcinoid tumor 322, 332 extrahepatic biliary atresia 201, bone marrow transplant recipients cardiac cirrhosis 201 graft-versus-host disease 263– Budd–Chiari syndrome 146 mechanical bile duct 265, 264 right-sided heart failure 148, 148 obstruction 85, 88, 88, 89 sinusoidal obstruction sinusoidal obstruction multilobular, cystic fibrosis 167, syndrome 156, 264 syndrome 157 168 borreliosis (relapsing fever) 105 cardiovascular disease, paucity of duct syndrome 204, boutonneuse fever 103 atherosclerotic 153 204 BRAF-V600E gene mutation 329 Caroli disease 205, 206, 206, 209 primary biliary cirrhosis 75, branched chain 2-oxo-acid differential diagnosis 214 76–77, 77 dehydrogenase complex Caroli syndrome 206 primary sclerosing (BCOAD-E2) 74 , tuberculosis 106, cholangitis 82, 82 Brazilian blastomycosis 112 106 biliary cystadenoma see BRCA2 gene 293 catalase 52 cystadenoma, hepatobiliary bridging necrosis 35–36, 137 cat-scratch disease 100, 158 biliary cysts brood capsules 116 caudate lobe 3, 3 adult polycystic liver disease 213, brucellosis 99, 99 Budd–Chiari syndrome 145 213 Budd–Chiari syndrome (hepatic development 2 simple 208, 208 vein obstruction/ cavernous hemangioma 275–277, Todani’s classification 204–205, thrombosis) 143–146 277 205, 206 acute 145, 145–146, 146 differential diagnosis 277, 280, see also choledochal cysts chronic 145, 146, 146, 147 320 biliary fibrosis clinical presentation 145 giant 276 bridging, with focal interlobular differential diagnosis 148–149 sclerosed 276, 277 bile decrease 75, 76, 76 drug or toxin-induced 218, 228 CD1a immunoperoxidase stain 329, cystic fibrosis 167, 168 epidemiology 143–144 329 extrahepatic biliary atresia 201, etiology 144 CD4 T lymphocytes 201 metastatic liver tumors 331 acute cellular rejection 239 biliary micro-hamartomas see von pathogenesis 144–145 alcohol-induced liver injury 53–55 Meyenburg complexes post-transplant 252 granuloma formation 123 biliary strictures primary 143, 144 primary biliary cirrhosis 74 bile duct obstruction 84 secondary 143, 144 CD8 T lymphocytes post-transplant 236, 249–250, bull’s eye lesions 105, 110 acute cellular rejection 239 250 bupropion 217, 221 alcohol-induced liver primary sclerosing Burkholderia pseudomallei 100– injury 53–55 cholangitis 80, 80–81 101 primary biliary cirrhosis 74

bindex 357 18 January 2017 1:39 AM 358 Index

CD10 immunoperoxidase stain 304 immunohistochemistry 313, 314, acute 226, 226, 227 CD15 (LeuM1) immunoperoxidase 315 chronic 227, 227 stain 314, 324 inflammatory bowel disease 308, extrahepatic biliary atresia CD30 immunoperoxidase stain 324 342 201–202, 202 CD31 immunoperoxidase stain 276, in situ adenocarcinoma 312–313, harvesting (preservation) 280, 304, 321 313 injury 235, 235 CD34 immunoperoxidase stain intraductal infiltrating 312, 313 hereditary tyrosinemia 193, 193 cavernous hemangioma 276 intrahepatic 310, 311 mechanical bile duct epithelioid location-based classification 311 obstruction 85, 86, 88–89 hemangioendothelioma 321, mucinous type 311, 312 neonatal 200 321 mucoepidermoid type 311 primary biliary cirrhosis 78 focal nodular hyperplasia 275 pathology 310–313 primary sclerosing cholangitis 82 hepatocellular adenoma 271, 272 pathophysiology 309–310 simple 226, 226 hepatocellular carcinoma 297, poorly differentiated 310, 312, 313 Wilson disease 178, 179 304, 335 post-transplant recurrence 261 see also intrahepatic cholestasis infantile spindle type 311 cholestatic hepatitis hemangioendothelioma 280 cholangiohepatitis, recurrent drug or toxin-induced 226, 227 CD117 immunoperoxidase stain 332 pyogenic see recurrent fibrosing (FCH) 252, 253, CD154 135 pyogenic cholangiohepatitis 254–255, 255 CEA see carcinoembryonic antigen cholangioles 5, 11 cholestatic liver diseases central (hepatic) veins 5 see also bile ductular proliferation hereditary central (hepatic) venules see hepatic cholangiolitis hyperbilirubinemias 182, venules, terminal acute, drug-induced liver injury 226 182–183 central venulitis, acute cellular chronic viral hepatitis 38 post-transplant recurrence rejection 240 cholangitis 256–258, 257, 258 ceruloplasmin 177 acute see acute cholangitis see also biliary tract disorders serum 21, 179 autoimmune see autoimmune cholesterol ester storage disease 192 chancre, syphilitic 104 cholangitis chondroma 286, 287 chaparral 215 bacterial 89 chromogranin 332 Charcot–Leyden crystals 120 ischemia-induced 154, 154 chronic (ductopenic) graft Charcot triad 84 non-suppurative destructive see rejection 242–245 chicken wire fibrosis 59, 59 non-suppurative destructive clinical presentation 242–243 chlorpromazine 217, 218, 225, 227 cholangitis differential diagnosis 244–245 chlorpropamide 218, 220, 227 sclerosing see sclerosing grading 241, 244 cholangiocarcinoma 307–314 cholangitis pathology 243, 243–244, 244 adenosquamous type 311, 312 cholate stasis, primary biliary pathophysiology 242 clinical presentation 310 cirrhosis 78 chronic granulomatous disease combined hepatocellular choledochal cysts 204, 206–207 (CGD) of childhood 129 carcinoma see hepatocellular– malignancy risk 207, 308 chronic hepatitis cholangiocarcinoma, pathogenesis 205–206 carcinogenesis 294 combined pathology 207, 207 drug or toxin-induced 221–223, cystadenoma progressing to 278, Todani’s classification 205, 206 222, 223 279 choledochocele 205, 206 inflammatory bowel disease 342 differential diagnosis 305–306, choledocho-choledochostomy 249 viral see chronic viral hepatitis 313–314 choledochojejunostomy 249, 257 Wilson disease 178 epidemiology 307–308 choledocholithiasis 84 chronic liver disease etiologic factors 308, 308–309 cholelithiasis, sickle cell disease 196 indications for liver choledochal cysts 207, 308 cholestasis biopsy 15–16 drugs and toxins 228, 309 acute alcoholic fatty liver staging and grading 15–16 parasitic infestations 119, 309 with 61, 61 chronic myelogenous leukemia 326 primary sclerosing acute viral hepatitis 33, 33 chronic viral hepatitis 37–43 cholangitis 80, 308 alcoholic hepatitis 59, 60 clinical presentation 26 extrahepatic 310, 311, 312, 313 biliary tract disorders 92 differential diagnosis 36–37, fine needle aspiration cytology 313 chronic graft rejection 243, 244 42–43, 141 hilar 310, 311, 311–312, 312, chronic viral hepatitis 38 general histology 31, 37, 37–40, 313 drug or toxin-induced 216, 217 38, 39

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hepatocellular carcinoma hepatic artery hypoperfusion cords, hepatic 6, 6, 20 risk 290–291 154, 154 developing liver 1 histology of specific viruses 31, Lassa fever 48 hepatocellular adenoma 269, 40, 40–42, 41, 42 mucormycosis 112 269, 271 non-A non-G 42 post-transplant vascular hepatocellular carcinoma 271, scoring systems 43 injury 251, 251 295–296, 297 see also hepatitis B virus; hepatitis sickle cell disease 196 Councilman bodies 33, 33 C virus toxemia of pregnancy 346, 346 Cowdry type A inclusions 47, 47, 249 cirrhosis yellow fever 48, 48 Cowdry type B inclusions 47, 47, 249 alcoholic see alcoholic cirrhosis cocaine 216, 217, 218, 224 Coxiella burnetii 101 α1-antitrypsin deficiency 163, coccidioidomycosis 109, 110 coxsackie group B virus 49 164, 165, 165 collagen CREST syndrome 352–353 autoimmune hepatitis 134, 136, 137 amyloid vs. 341 Crigler–Najjar syndrome 182 biliary type see biliary cirrhosis fibers 6, 10 Crohn disease 341, 342, 342 Budd–Chiari syndrome 145, 146 sinusoidal obstruction Crotalaria fulva leaf tea 156 carcinogenesis 294 syndrome 157, 157 cryptococcosis 110–111, 111 cardiac see cardiac cirrhosis type I 10, 20 cryptosporidiosis, HIV-related 46 chronic granulomatous type III 10, 20 CTLA-4 (cytotoxic T-lymphocyte disease 129 type IV 10 antigen 4) 74 chronic viral hepatitis 39, 39–40, common bile duct 72 CYP2E1 52, 53, 65 43 primary sclerosing cholangitis 83 cystadenocarcinoma, biliary 278, coarsely nodular see computed tomography (CT) 279 macronodular cirrhosis cavernous hemangioma 276 cystadenoma, hepatobiliary 278, cryptogenic 68, 163 focal nodular hyperplasia 273 278–279 drug or toxin-induced liver hepatocellular adenoma 267 differential diagnosis 208–209, injury 221–222 hepatocellular carcinoma 295, 333 214, 278–279 finely nodular see micronodular confluent necrosis malignant transformation 278, cirrhosis acute viral hepatitis 35, 35–36 279 hereditary hemochromatosis autoimmune hepatitis 137, 138 with mesenchymal stroma 174–175, 175 dengue fever 48 (COMS; CMS) 214, 278, 279 hereditary tyrosinemia 193 drug or toxin-induced liver without mesenchymal histochemical stains 20 injury 220, 221 stroma 278 inflammatory bowel disease 342 heat stroke and cystic diseases 204–214 NAFLD 67, 68 hyperpyrexia 155, 155–156 cystic duct 72 portal vein thrombosis 150 hepatic artery cystic fibrosis 166–168 post-transplant HCV hypoperfusion 154, 154 differential diagnosis 43, 167–168 recurrence 253 Wilson disease 180, 180 pathology 167, 167, 168 regenerative nodules see congenital hepatic fibrosis 210, 211, secondary sclerosing regenerative nodules 212 cholangitis 89 sarcoidosis 128, 129 congestive hepatopathy see cystic fibrosis transmembrane venoportal 146 right-sided heart failure conductance regulator Wilson disease 178, 179 Congo Red stain 18, 340, 340 (CFTR) 166 clonorchiasis 118–119, 119 copper cystinosis 194 cholangiocarcinoma risk 119, 309 24 h urinary secretion 179 cysts, hepatic 204–209 recurrent pyogenic hepatic tissue quantitation 21 amebiasis 113 cholangiohepatitis 89, 119 increased hepatic differential diagnosis 159, CMV see cytomegalovirus biliary atresia 202, 204 208–209, 213–214, 278–279 primary biliary cirrhosis 79 hydatid 115–116, 116, 209, 279 acute graft failure 236, 237 primary sclerosing mesenchymal hamartoma 285–286 antibody-mediated graft cholangitis 83 peliosis hepatis 158, 158–159 rejection 237, 238 Wilson disease 178, 179, 180, simple non-parasitic 207–209, aspergillosis 109 181 208, 214 drug or toxin-induced liver induced hepatic neoplasms 228 toxoplasmosis 118, 118 injury 217, 218–219, 219 metabolism 176–177 see also biliary cysts; choledochal heat stroke and hyperpyrexia 155, serum 179 cysts; polycystic liver 155–156, 156 storage disorders 176–182 disease

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cytokeratin DMT1 gene 172 primary sclerosing immunohistochemistry 19 DNA methylation, aberrant 293– cholangitis 80, 81 cholangiocarcinoma 314, 315 294 duct-like structures, hepatocellular focal nodular hyperplasia 273, donut (doughnut) lesions 102, 102 carcinoma 297 275, 275 drug or toxin-induced liver injury duct metaplasia see bile ductular hepatobiliary cystadenoma 278 (DILI) 215–229 proliferation hepatocellular carcinoma 303 autoimmune hepatitis 132–133, ductopenia (interlobular bile duct cytokeratins, Mallory–Denk 216, 222, 223 loss) bodies 55 cholestatic pattern 216, 226, α1-antitrypsin deficiency 164, cytokines 55, 65 226–227, 227 165 cytomegalovirus (CMV) diagnosis 217 autoimmune hepatitis 136, 136 hepatitis 45–46 differential diagnosis 37, 141, causes 93, 93 differential diagnosis 36 241 chronic graft rejection 242, 243, immunoperoxidase stain 19, granulomas 124, 224–225, 225 243 246, 246 hepatocellular injury see HIV-associated inclusions 45–46, 46 hepatocellular injury, drug cholangiopathy 93 post-transplant 245–247, 246, or toxin-induced Hodgkin disease 324 247 histologic variants 217–218 mechanical bile duct cytoplasm, hepatocyte 7, 7–9 HIV infection 46, 47 obstruction 88 cytoplasmic inclusions see idiosyncratic (hypersensitivity) paucity of duct syndrome 203, intracytoplasmic inclusions reaction 215–216 203 cytoskeleton, hepatocyte 7 inflammatory bowel disease 341 post-transplant recurrent primary intracytoplasmic inclusions 165, sclerosing cholangitis 258, d 229 258 daughter cysts 116 Mallory–Denk bodies 225–226, primary biliary cirrhosis 75, delta (δ) virus (HDV) 25, 27–28 226 76–77, 77 acute hepatitis 31, 34 mixed patterns 216 primary sclerosing antigen 19 neoplasms/related lesions 228 cholangitis 82, 82 chronic hepatitis 31, 41 angiosarcoma 228, 318–319 sarcoidosis 128, 129 epidemiology 30 cholangiocarcinoma 228, 309 ducts, bile see bile ducts HBV co-infection 30 hepatocellular adenoma 228, duct transformation see bile ductular serology 26, 30 228, 229, 266 proliferation superinfection 30 hepatocellular carcinoma 228, ductules, bile see bile ductules dengue fever 48 229, 292 ductus venosus 2 developmental and congenital non-cirrhotic portal fibrosis 152, dysplasia, liver cell cystic diseases of biliary 222 atypical hepatocellular system 204–207, 206 pathogenesis 216 adenoma 270, 270 developmental hepatobiliary peliosis hepatis 158 chronic viral hepatitis 38, 38 diseases 198–214 pigments 229 large cell 38, 301, 333, 334, 334 diabetes predictable dose dependent small cell 38, 333, 333–334 glycogenic hepatopathy 70 (intrinsic) 215 Wilson disease 178–180, 180 hepatocellular carcinoma risk factors 216 dysplastic cirrhotic nodules risk 291 steatosis and steatohepatitis 223– 332–336 NAFLD 64 224, 224 high-grade 333, 334–335, pyogenic abscesses 95–96 types 215–216 334–336 diabetic arteriopathy 154 vascular injury 227–228, 228 low-grade 334, 334, 334–335 dialysis-related amyloidosis 337 Dubin–Johnson syndrome 183, diclofenac 215, 217 184 e dietary factors, alcohol-induced ductal plates 210, 211 Ebola virus 37, 48 liver injury 53 duct ectasia EBV see Epstein–Barr virus diffuse angiomatosis 276, 277 ARPKD 210, 211, 212 E-cadherin gene 293 diffuse interstitial fibrosis 63, 204 Caroli disease 206 echinococcosis 115–116, 116, disseminated intravascular mechanical bile duct 117 coagulation (DIC) 346 obstruction 85, 85 differential diagnosis 209, 279 divalent metal transporter post-transplant biliary Echinococcus granulosus 115, 116 (DMT1) 171 strictures 250, 250 Echinococcus multilocularis 115, 116

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Echinococcus vogeli 115 eosinophils mass lesions 84 echovirus 49 drug or toxin-induced liver mechanical obstruction see eclampsia 346 injury 220 bile duct obstruction, edema echinococcosis 116, 117 mechanical mechanical bile duct mixed parasitic infestations 120– primary sclerosing cholangitis 80, obstruction 85, 85, 86, 88 121, 121 80–81, 83, 83 primary biliary cirrhosis 77 other parasitic infestations 121 segmental dilation 205 primary sclerosing primary biliary cirrhosis 77, 79 extrahepatic biliary atresia cholangitis 82, 82 toxocariasis 120, 121 (EBA) 199, 200–202 Edmundson grading system, epithelial membrane antigen differential diagnosis 202, 349 hepatocellular (EMA) 314 pathology 201, 201–202, 202 carcinoma 300–301 epithelioid granulomas 125, 125 eggs/ova candidiasis 110 f clonorchiasis 119, 119 coccidioidomycosis 109 factor VIII-associated antigen 276, schistosomiasis 117, 118 drug-induced liver injury 225 280, 304, 321 elastin 10 histoplasmosis 112 falciform ligament 3 embryology 1–3, 2 primary biliary cirrhosis 78, 78 familial hemophagocytic embryonal rhabdomyosarcoma 322, Q-fever 102 lymphohistiocytosis 323 tuberculosis 106, 106, 125 (FHL) 351 embryonal sarcoma 322 epithelioid hemangioendothelioma Fanconi–Bickel disease 188 embryonic stem cells 14 320–321, 321 Farber lipogranulomatosis 192 emperipolesis 34 EPM2 genes 184 Fasciola hepatica 120 endoglin (ENG) 160 Epstein–Barr encoded RNA Fas ligand (FasL) 239 Endolimax nana 121 (EBER) 19, 45, 45 fat droplets endoplasmic reticulum (ER) 7, 7 liver transplant recipients 248, hepatocytes 7, 9, 50 endoscopic retrograde 249 large see macrovesicular steatosis cholangiopancreatography non-Hodgkin lymphoma 325, small see microvesicular steatosis (ERCP), primary sclerosing 326 stellate cells 10 cholangitis 80, 80–81 Epstein–Barr nuclear-associated fat-storing cells see stellate cells endothelial cells antigen (EBNA) 248 fatty acid ethyl ester synthetase 52 cavernous hemangioma 276, 277 Epstein–Barr virus (EBV)-associated fatty acid oxidation disorders, infantile hemangioendothelioma lymphoproliferative disease/ mitochondrial 194–195 280, 280 lymphoma 325, 325, 326 fatty change see endothelialitis liver transplant recipients focal 285, 285 malignant, angiosarcoma 319, 247–249, 249 with inflammation 50–51 319–320, 320 Epstein–Barr virus (EBV) infection see also steatosis peliosis hepatis cysts 158, 159 acute hepatitis 43–45, 44, 45 fatty liver diseases 50–70 sinusoidal 6, 6, 9–10 differential diagnosis 36, 324 granulomas 124 sloughing and loss 157, 157, 158 hemophagocytic post-transplant endothelialitis lymphohistiocytosis 351 recurrence 259–260 acute cellular rejection 240, 240 liver transplant recipients 247– feathery degeneration, mechanical autoimmune hepatitis 137, 138 248 bile duct obstruction 87, 87 drug-induced liver injury 223 c-erbB2 gene 293, 310 Felty syndrome 352 EBV hepatitis 44, 45 erythema migrans 105 ferritin 172 NAFLD 67 erythrophagocytosis 351, 351, 352 serum 174, 174 post-transplant recurrent erythropoietic protoporphyria 170, ferrochetalase deficiency 170 autoimmune hepatitis 259 170–171, 171 ferrous sulfate 217, 219 endothelial massaging 13 Escherichia coli 96, 281 fibrin endotheliosarcoma, vasoablative estrogens 217, 292 amyloid vs. 341 see epithelioid see also oral contraceptives antibody-mediated graft hemangioendothelioma ethanol see alcohol rejection 237–238, 238 endotoxins, bacterial 79 extracellular matrix 10 bacteremia/pyogenic abscess 97 Entamoeba hartmanni 121 extrahepatic bile ducts sickle cell disease 196 Entamoeba histolytica 112–113 developmental and congenital sinusoidal obstruction Enterococcus 245 cystic diseases 204–207, 206 syndrome 157, 157 enteroviruses 49 liver flukes 119 toxemia of pregnancy 346, 346

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fibrin ring granulomas 102, 102, 125 focal nodular hyperplasia 274–275 fulminant hepatitis fibroblasts, palisading network, hepatoblastoma 318 differential diagnosis 37 toxocariasis 120, 120 hepatocellular adenoma 271 drug or toxin-induced 215 fibroconnective tissue 5–6 hepatocellular carcinoma 300, liver transplantation 231 fibrocystic liver diseases 207–214 302, 303 viral infections 24–26, 35, 35–36, malignancy risk 308 floxuridine 227 36 fibrocystin 210 fluorescence fumarylacetoacetate hydrolase fibrolamellar hepatocellular amyloid 341 (FAH) 192–193 carcinoma 306, 306–307, 307 protoporphyrin 170–171, 171 fungal infections 96, 108–112, 122 differential diagnosis 275, 307 uroporphyrin 169, 170 post-transplant 245 fibroma (solitary fibrous foam cells, subendothelial, chronic tumor) 282, 286, 287 graft rejection 243, 244 g fibronectin 10 foamy change 50 galactosemia 186–189 fibro-obliterative destructive donor livers 234 gallbladder 72 cholangitis drug or toxin-induced liver γ-glutamyl transferases (GGTP) 21 post-transplant recurrence 258, injury 223 gangliosidosis (GM1 and GM2) 192 258 see also microvesicular steatosis gap junctions 6 primary sclerosing foamy degeneration, alcoholic 57, gastrointestinal stromal tumor cholangitis 81, 81 61–62, 62 (GIST), metastatic 332 fibrosarcoma 322, 323 foamy granulomas 125 Gaucher cells 190 fibrosing cholestatic hepatitis (FCH) foamy histiocytes Gaucher disease 189–191 252, 253, 254–255, 255 chronic graft rejection 243, 244 pathology 190–191, 191 fibrosis, hepatic lepromatous leprosy 107, 107 sinusoidal infiltrates 159 alcohol-related see alcoholic Mycobacterium avium- gender differences fibrosis intracellulare 108, 108 alcoholic liver disease 51 α1-antitrypsin deficiency 163 primary biliary cirrhosis 78 drug-induced liver injury 216 Budd–Chiari syndrome 146, 146, sea blue, Niemann–Pick hepatocellular carcinoma 289 147 disease 192 gene micro-array analysis 19 congenital 210, 211, 212 foamy Kupffer cells, Niemann–Pick genetic disorders 162–196 cystic fibrosis 167 disease 191–192, 192 giant cell hepatitis α drug or toxin-induced liver focal biliary fibrosis, cystic 1-antitrypsin deficiency 164, injury 221–222 fibrosis 167, 168 165 NAFLD 66, 66, 67, 67, 68 focal fatty change 285, 285 neonatal 198–199, 199 paucity of duct syndrome 204, focal nodular hyperplasia giant hemangioma 276 204 (FNH) 273–275 Gilbert syndrome 183, 184 right-sided heart failure 148, 148 differential diagnosis 272, 272, global assessment, acute sinusoidal obstruction 275, 305, 307 rejection 240–241, 241 syndrome 157, 157 fine needle aspiration globulin, serum 21, 23, 135 total parenteral nutrition-induced cytology 274–275 glucocerebrosidase (acid liver injury 349, 349 immunohistochemistry 272, β-glucosidase) 190 Wilson disease 178 275, 275 glutamic oxaloacetic transaminase see also biliary fibrosis; interstitial non-classic variant 273 (SGOT) see aspartate fibrosis; periductal fibrosis; pathology 273–274, 274, 275 transaminase periportal fibrosis; portal telangiectatic see hepatocellular glutamic pyruvic transaminase fibrosis adenoma, inflammatory (SGPT) see alanine fibrous histiocytoma, Fontana–Masson stain 317 aminotransferase malignant 322 Forbes–Cori disease (glycogen glutamine synthetase (GS) fibrous septa storage disease type focal nodular hyperplasia 272, alcoholic cirrhosis 62, 63 III) 188, 189 275, 275 focal nodular hyperplasia foreign bodies, granulomas 124 hepatocellular adenoma 272 273–274, 274 c-FOS gene 293 hepatocellular carcinoma 304, NASH 68 Fouchet stain 18 335, 336 schistosomiasis 118 FPN1 gene 172 glycogen field fever 105 Francisella tularensis 99–100 developing liver 3 fine needle aspiration cytology free fatty acids (FFAs) 64–65 intracellular 7, 9 cholangiocarcinoma 313 fructose intolerance, hereditary 189 nuclear 9

bindex 362 18 January 2017 1:39 AM Index 363

glycogenated nuclei tuberculosis 106, 106–107, 123, heat stroke 155, 155–156, 156 glycogenic hepatopathy 70, 70 125 HELLP (hemolysis, elevated liver NAFLD 66, 66 typhoid fever 98, 98 enzymes, low platelet) Wilson disease 178, 180 see also lipogranulomas syndrome 346–347 glycogenic hepatopathy 70, 70 granulomatous hepatitis 123–129 helminths 96, 112–121, 122 glycogen storage diseases idiopathic 123 hemangioendothelioma (GSD) 184, 187–188, 189 inflammatory bowel disease 342, epithelioid 320–321, 321 hepatocellular adenoma 266, 268 342 infantile see infantile glypican-3 (GPC3) granulomatous necrosis 126 hemangioendothelioma hepatocellular adenoma 271, 272 cytomegalovirus hepatitis 45, 46 malignant see angiosarcoma hepatocellular carcinoma 303, drug or toxin-induced 220 hemangioma, cavernous see 304, 335, 336 EBV hepatitis 44, 44 cavernous hemangioma Golgi apparatus 7 HCV infection 42 hematopoiesis, extramedullary 2, GPC1 gene 200 see also necrotizing granulomas 2, 327 graft-versus-host disease Grocott’s methenamine silver hematopoietic neoplasms 323–329 (GVHD) 263–265, 264 (GMS) stain 18, 108, 110 hematopoietic stem cells 15 Gram-negative bacteria 95–101, gross anatomy, normal 3–4 hematoxylin and eosin (H&E) 17, 18 96, 121 ground glass cells heme 72 Gram-positive bacteria 95–101, chronic hepatitis B 40, 40 biosynthesis 169 96, 121 differential diagnosis 341 dietary 171 Gram stain 18 hepatocellular carcinoma hemicirrhosis, primary sclerosing granulomas 123–126 296–297, 299 cholangitis 82 biliary tract disorders 92 post-transplant acquired hepatitis hemochromatosis, hereditary brucellosis 99, 99 B 262 (HH) 172–176, 176 candidiasis 110 post-transplant recurrent clinical presentation 172–173, 174 causes 123, 124 hepatitis B 254, 254 differential diagnosis 175–176 chronic granulomatous growth factors 294 genetics 172 disease 129 gummas, syphilitic 104–105 grading system 175 coccidioidomycosis 109, 110 hepatocellular carcinoma 175, cytomegalovirus hepatitis 45, 46, h 292, 299, 301, 302 247, 247 hairy cell leukemia 326, 327 pathology 173–175, 174, 175 differential diagnosis 129 Hall stain 18 hemolysis, elevated liver enzymes, drug or toxin-induced 218, halo low platelet (HELLP) 224–225, 225 α1-antitrypsin deficiency 163, syndrome 346–347 epithelioid see epithelioid 164 hemolytic anemia, Wilson granulomas histoplasmosis 111, 112 disease 178 histoplasmosis 111–112, 112 halothane 220 hemophagocytic lymphohistiocytosis HIV-associated liver diseases 46, HAMP gene 172 351, 352 47 Hand–Schuller–Christian disease acquired 351, 351 Hodgkin disease 324 see Langerhans cell inherited familial (FHL) 351 inflammatory 125, 125 histiocytosis hemorrhage leprosy 107, 107 harvesting injury, grafted Budd–Chiari syndrome 145, 145, Mycobacterium avium- livers 234–236, 235 147 intracellulare 108, 108 HAV see hepatitis A virus hepatocellular adenoma 268–269 NAFLD 67 HBV see hepatitis B virus sinusoidal obstruction necrotizing see necrotizing HBx gene 294 syndrome 157, 157 granulomas HCV see hepatitis C virus 3, 9, 172 non-caseating 127 HDV see delta (δ) virus hemophagocytic primary biliary cirrhosis 78, 78 heart failure lymphohistiocytosis 351 Q-fever 101–102, 102 congestive 146–147 hepatocellular carcinoma 301, sarcoidosis 127, 127–128, 128, 129 left-sided/hepatic ischemia 153, 302 schistosomiasis 117, 117 154, 155, 155 hereditary hemochromatosis 174, septate 127–128, 128 right-sided see right-sided heart 174–175, 175 subtypes 123–126 failure histochemistry 18, 20 syphilis 104 heat shock protein 70 (HSP70) 304, malaria 115 toxocariasis 120, 120 335, 336 sickle cell disease 196, 196

bindex 363 18 January 2017 1:39 AM 364 Index

hemosiderosis, β-thalassemia 176 hepatitis B e antigen (HBeAg) 27, differential diagnosis 255, 256 hemozoin 115, 115 29 pathology 253–255, 254, 255 hepar lobatum hepatitis B immune globulin triggering autoimmune acute viral hepatitis 36 (HBIG) 252 hepatitis 255, 262, 263 chronic granulomatous hepatitis B surface antigen serology 26, 30 disease 129 (HBsAg) hepatitis D virus (HDV) see delta cystic fibrosis 167 immunohistochemistry 19 virus syphilis 105 chronic HBV 40, 40–41, 41 hepatitis E virus (HEV) 25, 28 hepatic arterioles 5, 5 hepatocellular carcinoma 297, acute hepatitis 31, 34, 34 chronic graft rejection 243 299 chronic hepatitis 31 hepatic artery 3, 4, 143 post-transplant recurrent epidemiology 30 amyloid deposits 338, 339 HBV 254, 254 fulminant infection 24–26 disorders 153–156 serology 29 serology 26, 30 hypoperfusion 153, 153–155, hepatitis B virus (HBV) 25, 27 hepatitis G virus (GVH-C) 25, 28 156 acute hepatitis 31, 34 acute 34 microanatomy 12 with acute δ infection 34 chronic 42 post-transplant carriers 29 epidemiology 30 occlusion 250–251, 251 chronic infection 29 serology 26, 30–31 thrombosis 154, 154 clinical presentation 26 hepatobiliary cystadenoma see causes 154 hepatocellular carcinoma 290, cystadenoma, hepatobiliary post-transplant 154, 291, 294 hepatoblastoma 316–318, 317 250–251, 251 histology 31, 40, 40–41 epithelial 316, 317 vasculitis 153–155 phases 29 mixed epithelial– hepatic cords see cords, hepatic δ virus co-infection 30 mesenchymal 316, 317, hepatic cystadenoma see δ virus superinfection 30 317, 318 cystadenoma, hepatobiliary DNA (HBV-DNA), serum 29, hepatoblasts 1 hepatic diverticulum 1 252, 290 hepatocellular adenoma 266–273 hepatic ducts 3, 12, 72 epidemiology 28–29 atypical 270, 270, 271 hepatic encephalopathy 135, 232, 343 oncogenesis 294 β-catenin-activated 267–268, hepatic extinction 150 post-transplant acquisition 268, 271 hepatic fibrosis see fibrosis, hepatic (activation) 262, 262 clinical presentation 266–267 hepatic iron index (HII) 174, 175 post-transplant recurrence 252, differential diagnosis 271–273, hepatic lobes 3 253–255 272, 275, 304 hepatic sinusoids see sinusoids, differential diagnosis 255, 256 drug or toxin-induced 228, 228, hepatic pathology 253, 253–255, 254, 229, 266 hepatic veins 3, 4, 143 255 epidemiology 266 Budd–Chiari syndrome 146, 147 serology 26, 29 fine needle aspiration development 2 hepatitis B virus-encoded X antigen cytology 271 disorders 143–149 (HBX; HBxAg) 27, 294 HNF1α-inactivated 267, 268, outflow obstruction/thrombosis hepatitis C virus (HCV) 25, 27 268 see Budd–Chiari syndrome acute hepatitis 31, 34 immunohistochemistry 271, 272 patent, with outflow antigen (HCV Ag) staining 19, inflammatory (IHCA) 267, 268, impairment 148 42 270, 270, 274 hepatic venules, terminal chronic infection pathogenesis 267–268, 268 (central) 6, 6, 13 clinical presentation 26 pathology 268–271 acute cellular rejection 240 differential diagnosis 70 pelioid pattern 269 alcoholic liver disease 58, 59, 62 hepatocellular carcinoma 291 progression to carcinoma sinusoidal obstruction histology 31, 41, 41–42, 42 270–271, 271 syndrome 157, 157 liver transplantation 231 hepatocellular adenomatosis 268, hepatitis A virus (HAV) 25, 27 overlap syndrome 42, 138, 139, 272, 283 acute hepatitis 31, 34, 34 140 hepatocellular carcinoma 289–306 epidemiology 28 epidemiology 29–30 cirrhotomimetic growth serology 26, 28 oncogenesis 294 pattern 295 hepatitis B core antigen (HBcAg) post-transplant acquisition 262 clear cell 297, 300 serology 27 post-transplant recurrence clinical presentation 294–295 staining 19, 40, 41, 41, 254, 254 253–255 compact pattern 297

bindex 364 18 January 2017 1:39 AM Index 365

de novo post-transplant 261–262 acute necroinflammatory hephaestin 171 differential diagnosis 304–306, change 217, 219–220, 220, Hep Par 1 (hepatocyte paraffin 1) 307, 314, 318 221 antibody stain early, differential diagnosis chronic necroinflammatory cholangiocarcinoma 314 334–335, 334–336 change 217, 221–223, 222, focal nodular hyperplasia 275 epidemiology 289–290 223 hepatocellular adenoma 271 etiologic factors 290, 290–293 necrosis with no/minimal hepatocellular carcinoma 303, aflatoxins 292 necroinflammatory 304 alcoholic cirrhosis 57, 291 change 217, 218–219, 219 hereditary hemochromatosis autoimmune hepatitis 135 hepatocuprein 177 see hemochromatosis, chronic viral hepatitis 290–291 hepatocystin 212 hereditary drugs and toxins 228, 229, 292 hepatocyte nuclear factor 1α hereditary hemorrhagic HBV/HCV/HIV co- (HNF1α)-inactivated telangiectasia 160, 160 infections 291 hepatocellular hereditary hyperbilirubinemias 182, hereditary adenoma 267, 268, 268 182–183 hemochromatosis 175, 292 hepatocytes 6–9 herpes simplex virus (HSV) hereditary tyrosinemia 193, acute viral hepatitis 33 infection 47, 47, 249 292–293 atrophic see atrophy, hepatocyte herpesviruses NAFLD 291 ballooning see ballooning, liver immunohistochemistry 19 fibrolamellar 275, 306, 306–307, cell morphologic features 47, 47–48 307 canalicular membrane 6 post-transplant infections 249 fine needle aspiration chronic viral hepatitis 38, 38–39 herpes zoster 47–48 cytology 300, 302, 303 cytoplasm 7, 7–9 Hers disease 188 immunohistochemistry 302, development 2–3 HFE gene 172, 174, 176 303–304, 304, 305 dysplasia see dysplasia, liver cell high-density lipoprotein deficiency, in situ 299, 301 focal nodular hyperplasia familial 192 less differentiated 297, 299 273–274, 274 hilar bile ducts 12 liver transplantation 231 functional variations 8, 14 primary sclerosing macrotrabecular type 296, 297 ground glass appearance see cholangitis 83, 84 multinucleated giant cell 297, ground glass cells histiocytes 300 hydropic change see hydropic epithelioid 125, 125 pathology 295–300 change of hepatocytes fat-containing 126 pathophysiology 293, 293–294 ischemia see ischemic liver cell foamy see foamy histiocytes pelioid 297 injury inflammatory pseudotumor 281, poorly differentiated lateral (intercellular) 281 (anaplastic) 297, 299 membrane 6 sea blue 192 portal vein thrombosis 150, 302 necroinflammatory change see see also granulomas post-transplant recurrence 261 necroinflammatory change histiocytosis X see Langerhans cell precursor lesions 332–336, 333 necrosis see necrosis, liver cell histiocytosis sclerosing 297, 300 nucleus 6 histochemical stains 17, 18–19 screening high-risk patients 295, oncocytic (oxyphilic) 39, 180 histology 4–14 333 sinusoidal (basolateral) surface 6 histoplasmosis 111–112, 112 spindle cell 297 structural variations 8, 14 HIV see human immunodeficiency trabecular type 295–296, 296, 297 syncytial giant cell changes see virus tumor grading 300–301 syncytial giant cell changes HJV gene 172 well-differentiated 295–297, 296, of hepatocytes HLA associations 297, 298, 299 hepatolithiasis 90, 308–309 autoimmune hepatitis 131, 132 adenoma progression to 270– hepatoportal sclerosis 151, 222 primary biliary cirrhosis 74 271, 271 hepatotoxic agents 217–218 primary sclerosing differential diagnosis see also drug or toxin-induced cholangitis 79 271–272, 275 liver injury sarcoidosis 127 hepatocellular–cholangiocarcinoma, hepatotropic viruses 24–43, 25 Hodgkin disease 323–324, 324 combined 306, 315, epidemiology and serology 25, homocystinuria 194 315–316, 316 26, 28–31 human herpes virus-6 (HHV-6) 49, hepatocellular injury, drug or toxin- virology 27–28 249 induced 215–216 hepcidin 171–172 human herpes virus-7 (HHV-7) 249

bindex 365 18 January 2017 1:39 AM 366 Index

human immunodeficiency virus malignant tumors 261–262 bacteremia 96–97, 97 (HIV) Mycobacterium avium- biliary tract disorders 91 -associated cholangiopathy intracellulare 108, 108 chronic viral hepatitis 37, 37, 38, 46–47, 93 post-transplant 38 -associated liver diseases 46–47, lymphoproliferative clonorchiasis 119 47 disorder 247–248 drug-induced cholestatic liver HBV/HCV co-infection, tuberculosis 106, 107 injury 226, 227, 227 malignancy risk 291 see also liver transplantation drug-induced hepatocellular humoral rejection see antibody- immunoglobulin G4 (IgG4)- necrosis 219, 219 mediated rejection associated sclerosing EBV hepatitis 44, 44 hydatid cyst 115–116, 116 cholangitis 89, 90 echinococcosis 116, 117 differential diagnosis 209, 279 immunohistochemical stains 19 extrahepatic biliary atresia 201, hydatid sand 116, 116 immunologic-mediated disorders, 201 hydropic change of hepatocytes granulomas 124 fulminant hepatitis 35, 35 alcoholic liver disease 59, 59 immunoproliferative small intestinal heat stroke and chronic viral hepatitis 37, 38 disease (alpha-heavy chain hyperpyrexia 156, 156 drug or toxin-induced liver disease) 327–328, 328 inflammatory pseudotumor 281, injury 220, 221 inclusions see intracytoplasmic 281 harvesting (preservation) inclusions; nuclear mechanical bile duct injury 235, 235 inclusions obstruction 85, 85, 86, 86 nodular regenerative Indian childhood cirrhosis 181 NAFLD 66, 67, 67, 68 hyperplasia 283, 283 infantile hemangioendothelioma normal liver 6 Reye syndrome 343, 344 279–281 portal vein thrombosis 150, 150 see also ballooning, liver cell differential diagnosis 277, post-transplant recurrent 3-hydroxyl (long-chain) acyl- 280–281, 321 autoimmune hepatitis 259, CoA dehydrogenase pathology 279–280, 280 259 deficiency 195 type II variant 280 post-transplant recurrent viral hyperacute (humoral) infantile obstructive hepatitis 253, 253 rejection 237–238, 238 cholangiopathy 200 primary biliary cirrhosis 75–76, hyperbilirubinemia 21, 22 infarction, hepatic 154–155, 346 76, 77–78, 79 alcoholic liver disease 56 infection-associated (reactive) primary sclerosing extrahepatic biliary atresia 200 hemophagocytic syndrome, cholangitis 81–82, 83 hereditary 182, 182–183 acquired 351, 351 Rocky Mountain spotted malaria 114 infectious diseases fever 103, 103 sickle cell disease 196 causing granulomas 124 toxocariasis 120, 121 total parenteral nutrition 348 differential diagnosis 121, typhoid fever 98, 98, 99 viral hepatitis 24 121–122 see also granulomas; hypercoagulable states 144, 144, non-viral 95–121, 96 lymphocytes; 149 post-transplant 245 necroinflammatory change; hyperpyrexia 155, 155–156, 156 see also viral hepatitis neutrophils hyperthyroidism 353 infectious mononucleosis 43, 248 inflammatory granulomas 125, 125 hypofibrinogenemia, familial 165 inferior vena cava thrombosis, drug-induced liver injury 225 hypothyroidism 353 post-transplant 252 inflammatory pseudotumor hypoxia 153–155, 156 inflammatory bowel disease 341, (inflammatory Hy’s law 216 342, 342 myofibroblastic tumor) 281, autoimmune hepatitis 132, 135 281–282, 282 i cholangiocarcinoma 308, 342 insulin immune complexes, alcoholic liver primary sclerosing binding to its receptor 65 disease 55 cholangitis 79, 342 resistance 64, 65 immunocompromised patients inflammatory cells/infiltrates insulin-like growth factor-2 (IGF- Bartonella henselae acute cellular rejection 239, 239, 2) 294 infection 100, 101, 158 240, 240 interleukin-8 (IL-8) 53 candidiasis 110 acute viral hepatitis 32, 32–33 interlobar bile ducts 11 cytomegalovirus hepatitis 45–46 alcoholic hepatitis 61, 61 chronic graft rejection 243–244 EBV hepatitis 44 autoimmune hepatitis 135, primary sclerosing fungal infections 109, 111, 112 135–136, 136, 138 cholangitis 81, 83, 83

bindex 366 18 January 2017 1:39 AM Index 367

interlobular bile ducts 5, 5, 11 see also bile ductules; interlobar isoniazid 215, 217, 221, 227 acute cellular rejection 240, 240 bile ducts; interlobular bile Ito cells see stellate cells autoimmune hepatitis 136, 136 ducts biliary tract disorders 91 intrahepatic biliary atresia (paucity j chronic graft rejection 243, 243 of duct syndrome) 200, JAG1 gene 202–203 chronic viral hepatitis 37–38, 41, 202–204 jaundice 41 differential diagnosis 204 cholangiocarcinoma 310 extrahepatic biliary atresia 201, neonatal hepatitis 199 choledochal cysts 206–207 201, 202 non-syndromatic 203, 204 drug-induced liver cell focal nodular hyperplasia 273, pathology 203, 203–204, 204 injury 215–216 274 syndromatic 202–203 neonatal 200 graft-versus-host disease 264, intrahepatic cholestasis total parenteral nutrition 348 264 benign recurrent (BRIC) 185, see also hyperbilirubinemia loss of see ductopenia 186, 347 Jin Bu Huan 215, 217 mechanical bile duct of pregnancy, benign 347 obstruction 85, 85 progressive familial (PFIC) 184, k primary biliary cirrhosis 75, 75, 185, 186 Kaposi sarcoma 319, 320 76, 76–77 sickle cell crisis 196 Kasabach–Merritt syndrome 279 primary sclerosing total parenteral nutrition (TPN)- Kasai procedure 200–201 cholangitis 81, 81, 82–83 induced 348–349, 349 Kayser–Fleischer rings 178 intermediate filaments 7 intranuclear inclusions see nuclear Ki67 304, 333, 334 intermediate junctions 6 inclusions Klebsiella 96, 281 International Autoimmune Hepatitis intravenous drug users 39, 39, 229 Kupffer cell hyperplasia Group scoring system 140 iron acute viral hepatitis 32, 33 international normalized ratio disorders with increased chronic viral hepatitis 38 (INR) 21 hepatic 171–176, 176 drug or toxin-induced liver interstitial fibrosis hepatic tissue quantitation 21, injury 220 diffuse 63, 204 174 hemophagocytic hereditary tyrosinemia 193, 194 metabolism 171–172 lymphohistiocytosis 351, intracytoplasmic inclusions overload, causes 175–176, 176 352 alcoholic liver disease 57–58, 58 serum 174 malaria 115, 115 α1-antitrypsin deficiency 20, iron/iron-binding capacity 21 typhoid fever 99, 99 163–164, 164 ischemia, hepatic (shock liver) 153–155 Kupffer cell differential diagnosis 165, 341 causes 153 Gaucher disease 190–191, 191 drug or toxin-related 165, 218, pathology 153–155, 154 hemophagocytic 229, 229 post-transplant 238 lymphohistiocytosis 351, fibrolamellar hepatocellular ischemia-induced cholangitis 154, 352 carcinoma 307, 307 154 Niemann–Pick disease 191–192, hepatocellular carcinoma ischemic cholangiopathy 154, 154 192 296–297, 298, 299 ischemic liver cell injury typhoid fever 99, 99 Lafora disease 186, 189 Budd–Chiari syndrome 144, 145, Kupffer cells 6, 6, 9 porphyria cutanea tarda 169, 170 146 kwashiorkor 353 see also Mallory–Denk bodies hepatic artery intrahepatic bile ducts hypoperfusion 154, l anatomy 5, 11–12 154–155 laboratory tests 17–23, 21 cystic dilation see Caroli disease right-sided heart failure 147 see also liver tests, routine developmental and congenital ischemic necrosis lactic dehydrogenase (LDH) 21, cystic diseases 204–207, heat stroke and 153 206 hyperpyrexia 155, 155–156 Lafora bodies 186, 189 dilation see duct ectasia hepatic artery Lafora disease 165, 184–186, 189 liver flukes 119, 119 hypoperfusion 154, 154, laforin 184–186 mechanical obstruction of large 155 laminin 10 see bile duct obstruction, post-transplant vascular Langerhans cell histiocytosis mechanical injury 251, 251 328–329, 329 primary sclerosing Ishak scoring system, chronic viral secondary sclerosing cholangitis 80, 80–81, 83 hepatitis 43 cholangitis 89, 329, 330

bindex 367 18 January 2017 1:39 AM 368 Index

Langerhans cells 329, 329 cholangiocarcinoma 310 lobules, hepatic 6, 12–13 large cell dysplasia 38, 301, 333, cystic fibrosis 167 long-chain (3-hydroxyl) acyl- 334, 334 fatty liver diseases 50 CoA dehydrogenase Lassa fever 48 heat stroke and hyperpyrexia 155 deficiency 195, 345 latent membrane proteins hepatic ischemia 153 Lugol’s iodine 338 (LMP) 248 indications for liver biopsy 15, 16 Lyme disease 105 left anterior segments 3, 3 liver graft recipients 235, 239, 243 lymph, hepatic 13 left posterior segments 3, 3 NAFLD 65 lymphangioma 286, 287 leiomyoma 282 primary biliary cirrhosis 74 lymphatics 4, 13–14 leiomyosarcoma 322, 323 right-sided heart failure 147 lymphocytes Leishmania infections viral hepatitis 24, 26 acute viral hepatitis 32, 32 (leishmaniasis) 120, 159 see also alkaline phosphatase; alcoholic hepatitis 61, 61 leprosy 107, 107 aminotransferases; bilirubin alcohol-induced liver injury leptin 65 liver transplantation 231–265 53–55 leptospirosis 105 acute graft failure (primary non- autoimmune hepatitis 135, 135, Letterer–Siwe disease see function) 236–237, 237 136, 136, 138 Langerhans cell histiocytosis biopsy indications 16 chronic graft rejection 243, 243 leukemia 326–327, 327 complications 245–252 chronic viral hepatitis 37, 37 acute 326 contraindications 233 cytomegalovirus hepatitis 45, 45, blood flow impairment 159, 159 disease recurrence 252, 252–260 247, 247 chronic 326, 326 differential diagnosis 242, drug-induced cholestatic liver secondary changes 327 244–245 injury 227, 227 Lewis disease 187 donor liver evaluation 233–234 drug-induced hepatocellular light chain disease 341 graft rejection see rejection, liver injury 220, 220, 221 light chains, amyloid see amyloid allograft EBV hepatitis 44, 44 light chain harvesting (preservation) focal nodular hyperplasia 273, 274 lipid droplets see fat droplets injury 234–236, 235 graft-versus-host disease 264, 264 lipochrome 9 indications 231–232, 232 heat stroke and drug-induced liver injury 229 latent and acquired (de novo) liver hyperpyrexia 156, 156 hepatocellular carcinoma 296 disease 262–263 leprosy 107, 107 intracellular bile vs. 226 living donor 232 liver-associated (pit cells) 10 Wilson disease 178 malignancies after 261–262 lymphoma 324–325, 325 lipogranulomas 126, 126 mechanical bile duct NAFLD 67, 68 alcoholic liver disease 57, 58 obstruction 84, 249–250 paucity of duct syndrome 203, NAFLD 67 non-specific reactive changes 203 lipoma 286, 287 after 262–263, 350–351 portal tracts 6 listeriosis 100 numbers of transplants 231, 231 post-transplant lithocholic acid 348 patient selection 232 lymphoproliferative liver, normal 1–23 secondary sclerosing disease 248, 248–249, 249 liver biopsy 15–23 cholangitis 89 primary biliary cirrhosis 75–76, indications 15, 15–16 sequence of events 234, 234 76 organizational approach to vascular complications 154, primary sclerosing evaluation 16–17 250–252, 251 cholangitis 81, 81 routine and special stains 17, lobes, hepatic 3 typhoid fever 98, 98 18–19, 20 atrophy, portal vein see also plasma cells; sinusoidal routine laboratory tests 17–23, 21 thrombosis 150 lymphocytosis; T special laboratory tests 21, 23 development 1, 2 lymphocytes liver cell adenoma see hepatocellular lobular inflammation lymphocytic cholangitis 136 adenoma acute viral hepatitis 32, 32–33, lymphocytic interface activity, liver cells see hepatocytes 34 apparent, acute viral liver fatty acid binding protein alcoholic hepatitis 59, 60, 60 hepatitis 77–78 (LFABP) 272 chronic viral hepatitis 38, 38 lymphocytic phlebitis, alcoholic liver liver flukes 118–119, 119 drug or toxin-induced 219–220, disease 58 liver tests, routine (liver panel) 220, 221 lymphoid aggregates 17–23, 21 NASH 67, 67 chronic HCV 41, 41 alcoholic liver disease 56–57 neonatal hepatitis 199, 199 primary biliary cirrhosis 76, 77

bindex 368 18 January 2017 1:39 AM Index 369

lymphoma 323–326 malignant hepatic tumors 289, mesoderm 1–2 Hodgkin 323–324, 324 289–336 metabolic hepatic disorders liver transplant recipients 248 hematopoietic neoplasms 323–329 162–196 non-Hodgkin 324–326, 325, 326 metastatic 330, 330–332 metabolic syndrome 64, 260 lysosomal storage disorders 191–192 post-transplant 261–262 metals, granulomas 124 lysosomes 7–9 primary 289–321 metastatic adenocarcinoma 331 enlarged, Wilson disease 180 rare primary 321, 322, 323 differential diagnosis 305–306, primary 9 vascular 318–321 313, 314 secondary 7, 9 malignant mixed tumor 322, 323 metastatic liver tumors 330–332, lytic necrosis, alcoholic hepatitis 61 malin 184–186 331, 332 Mallory–Denk bodies 55–56 primary sites of origin 330, m alcoholic cirrhosis 62, 63 330–331 macronodular (coarsely nodular) alcoholic hepatitis 59, 59, 60, unknown primary site 331–332 cirrhosis 40 60, 225 METAVIR scoring system 43 alcoholic liver disease 62, 63 associated disorders 55, 55 methotrexate 217, 218, 222, 222 Wilson disease 178 atypical hepatocellular microabscesses macrophages 123 adenoma 270, 271 bacteremia 97, 97 see also foamy histiocytes; biliary tract disorders 92 Bartonella henselae infection 100 histiocytes drug or toxin-induced liver cytomegalovirus infection 46, macroregenerative cirrhotic injury 218, 225–226, 226 246, 247 nodules 40, 332–336 hepatocellular carcinoma 296, 298 mechanical bile duct differential diagnosis 305, mechanical bile duct obstruction 85, 86 334–335, 334–336 obstruction 87, 87–88 nocardiasis 100 dysplastic see dysplastic cirrhotic NAFLD 67, 67 see also abscesses nodules primary biliary cirrhosis 78, 78 microanatomy, hepatic 4–14, 5 without cellular atypia 333, 333, primary sclerosing microbodies (peroxisomes) 7, 9 334–335 cholangitis 82, 83 microfilaments 7 macrovesicular steatosis 50 Wilson disease 178 micronodular (finely nodular) acute fatty liver of marasmus 353 cirrhosis 39–40 pregnancy 345, 345–346 Marburg virus 37, 48 alcoholic liver disease 62, 62 alcoholic liver disease 57, 57, 61, Marseilles fever 103 mechanical bile duct 61–62, 224 massive hepatic necrosis 35–36, 220 obstruction 88, 88, 89 associated disorders 51 Masson trichrome stain 18, 20 primary biliary cirrhosis 77 chronic HCV 42, 42 alcoholic liver disease 57, 58, 59, right-sided heart failure 148, 148 donor livers 233 59, 63 Wilson disease 178, 179 drug or toxin-induced liver amyloidosis 341 microsomal ethanol oxidizing injury 218, 223–224, 224 viral hepatitis 36, 39 system (MEOS) 52, 52 focal fatty change 285, 285 mastocytosis, systemic 326, 327 microtubules 7 hepatocellular carcinoma 296, 298 Mediterranean lymphoma microvesicular steatosis 9, 50 NAFLD 66, 66 (alpha-heavy chain acute fatty liver of post-transplant recurrent alcoholic disease) 327–328, 328 pregnancy 345, 345 liver disease 260, 260 Mediterranean spotted fever 103 alcoholic foamy post-transplant recurrent medium-chain acyl CoA degeneration 61–62, 62 HCV 254, 255 dehydrogenase (MCAD) alcoholic liver disease 57 magnetic resonance cholangiogram deficiency 194, 195 associated disorders 51 (MRC), primary sclerosing 57–58, 58, 165 differential diagnosis 344 cholangitis 80–81 melanoma, metastatic donor livers 233–234 magnetic resonance imaging (MRI) malignant 331 drug or toxin-induced liver cavernous hemangioma 276 MELD (Model for End-Stage Liver injury 218, 223, 224 hepatocellular adenoma 267 Disease) score 232 medium-chain acyl CoA hepatocellular carcinoma 295, melioidosis 100–101 dehydrogenase 333 mesenchymal hamartoma 285–286, deficiency 194, 195 major histocompatibility complex 286 post-transplant recurrent viral (MHC) 238–239 mesenchymal stroma, cystadenoma hepatitis 255, 255 malaria 114, 114–115, 115 with (COMS; CMS) 214, Reye syndrome 343, 343, 344 malignant fibrous histiocytoma 322 278, 279 viral hepatitis 34, 41, 42, 42

bindex 369 18 January 2017 1:39 AM 370 Index

microvilli 11, 11, 12 acute viral hepatitis 32, 32–33 nerve supply, liver 4, 14 midzone (zone 2) 13, 13 autoimmune hepatitis 136–137, neutrophils Milan criteria, hepatocellular 137 alcoholic hepatitis 59, 60, 60, carcinoma 231, 261 chronic drug-induced 217, 61, 61 minocycline 132–133, 215, 217, 221–223, 222, 223 alcohol-induced liver injury 222, 223 chronic viral hepatitis 38, 38, 53 mitochondria 7, 7 42, 42 autoimmune hepatitis 135 enlarged (megamitochondria) EBV hepatitis 44, 44 bacteremia 96–97, 97 57–58, 58, 165 fulminant hepatitis 35, 35–36 chronic cholestatic drug-induced mitochondrial antibodies see anti- neonatal hepatitis 199 liver injury 227 mitochondrial antibodies primary biliary cirrhosis 78 mechanical bile duct mitochondrial cytopathies 194 Rocky Mountain spotted obstruction 85, 86 mitochondrial fatty acid oxidation fever 103, 103 NAFLD 67, 67 disorders 194–195 secondary syphilis 104, 104 post-transplant biliary MOC31 314 typhoid fever 98, 99 strictures 250, 250 Model for End-Stage Liver Disease Wilson disease 178, 179, 180, 180 primary biliary cirrhosis 77 (MELD) score 232 necrosis, liver cell Niemann–Pick disease 191–192, molecular techniques 19 acute viral hepatitis 32–33, 35, 192 moniliasis (candidiasis) 109, 110 35–36 nitric oxide synthase, inducible monoclonal B-cell proliferation, amebiasis 113, 113 (iNOS) 309, 343 post-transplant 248 bridging 35–36, 137 nitrofurantoin 133, 217, 222 monoclonal carcinoembryonic dengue fever 48 nocardiasis 100 antigen (mCEA) 303, 314, drug or toxin-induced liver nodular regenerative hyperplasia 315 injury 218–219, 219 (NRH) 282–284, 283 mono spot test 43–44 fulminant hepatitis 35, 35–36 differential diagnosis 272, mucicarmine stain 111, 111, 331 hepatic artery 283–284 mucolipidoses 192 hypoperfusion 154, 154, Felty syndrome 352 mucopolysaccharidoses 192 155 nodule-within-nodule mucormycosis 112 massive (panacinar) 35–36, 220 formation 333, 335 mucoviscidosis see cystic fibrosis submassive 35, 35, 220 non-alcoholic fatty liver 66, 66 multilobular necrosis 35–36 see also coagulative necrosis; non-alcoholic fatty liver disease muralium multiplex 1 confluent necrosis; ischemic (NAFLD) 50, 63–68 muralium simplex 1 necrosis clinical presentation 65–66 c-MYC gene 293, 294 necrotizing granulomas 125–126 de novo post-transplant 262 Mycobacterium 96, 105–108, 121 brucellosis 99 differential diagnosis 68–70, 69 Mycobacterium-avium complex toxocariasis 120, 120 epidemiology 63–64 (MAC) 108 see also granulomatous necrosis hepatocellular carcinoma 291, Mycobacterium avium- neocholangioles 36 294 intracellulare 108, 108 neonatal giant cell hepatitis pathology 66–68 Mycobacterium gordonae 74 198–199, 199 pathophysiology 64–65 Mycobacterium leprae 107 neonatal hepatitis 198, 198–199, post-transplant recurrence 260, Mycobacterium tuberculosis 105–106 199 261 myeloma, multiple 327–328, 328, differential diagnosis 199, scoring systems 68 337 349–350 non-alcoholic steatohepatitis myeloproliferative disorders 144, neonates (NASH) 326–327, 327 α1-antitrypsin deficiency 163, differential diagnosis 69, 69, 182, myoclonus epilepsy 165, 184–186 164–165, 165 350 biliary atresia 199–204 epidemiology 64 n cavernous hemangioma 276 pathology 66, 66–68, 67, 68 NAFLD see non-alcoholic fatty liver cystic fibrosis 166, 167 pathophysiology 65 disease hereditary hemochromatosis pediatric 68 NASH see non-alcoholic 174 post-transplant recurrence 260, steatohepatitis total parenteral nutrition-induced 261 necroinflammatory change liver injury 347–348, 349 non-A non-G hepatitis acute drug-induced 217, neoplasms, hepatic see tumors, acute 31, 34–35, 35 219–220, 220, 221 hepatic chronic 42

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non-caseating granulomas 127 oncocytic hepatocytes 39, 180 parasympathetic nerve fibers 4, non-cirrhotic portal fibrosis 151, oncogenes 293–294, 310 14 151–153, 152 opisthorchiasis 118–119, 309 parenchyma, hepatic 6–10, 17 causes 152, 152–153 opportunistic infections, HIV- parenteral nutrition see total drug and toxin-induced related 46, 47 parenteral nutrition injury 152, 222 oral contraceptives partial nodular transformation non-Hodgkin lymphoma 324–326, cholestatic injury 217, 226 (PNT) 272–273, 284 325 hepatocellular adenoma 228, parvovirus B19 49 EBV-positive 325, 325, 326 228, 266 paucity of duct syndrome see liver transplant recipients 248 hepatocellular carcinoma 292 intrahepatic biliary atresia primary hepatic vascular injury 228 PBC see primary biliary cirrhosis involvement 325–326 orcein (Shikata) stain 19, 40, 79, peliosis hepatis 158, 158–159 non-specific reactive hepatitis 350, 83, 180 differential diagnosis 159, 277 350–351 Osler–Weber–Rendu drug or toxin-induced 218, 228 inflammatory bowel disease342 syndrome 160, 160 peribiliary cysts 209, 209 liver transplant recipients ova see eggs/ova peribiliary gland hamartoma see bile 262–263, 350–351 oval cells (facultative stem cells) 14, duct adenoma non-suppurative destructive 14, 15 peribiliary plexus 12 cholangitis (duct injury) overlap syndromes 138–140, 139 pericellular fibrosis acute cellular rejection 239 chronic hepatitis C 42, 138, 139, alcoholic hepatitis 59, 59 drug or toxin-induced 227, 227 140 Budd–Chiari syndrome 146 primary biliary cirrhosis 75, primary biliary cirrhosis see NAFLD 66 75–76, 76 autoimmune hepatitis– pericholangitis, acute 85, 85 sarcoidosis 128, 129 primary biliary cirrhosis periductal fibrosis normal liver 1–23 primary sclerosing drug or toxin-induced liver NOTCH2 gene 202–203 cholangitis 132, 135, 139 injury 227 NPC1 gene 191 sarcoidosis 128, 139 mechanical bile duct nuclear anisocytosis, liver cell see oxidative stress 53, 65, 144 obstruction 88, 89 dysplasia, liver cell 2-oxo-acid dehydrogenase primary sclerosing nuclear inclusions complexes 74 cholangitis 81, 81, 83, adenovirus infections 48, 249 oxymetholone 218, 229, 309 83 cytomegalovirus infection 46, 46, oxyphilic hepatocytes 39, 180 periductular fibrosis, mechanical 246, 246 bile duct obstruction herpes simplex virus p 86 infection 47, 47, 249 p16 gene/p16 protein 293, 334, perigranulomatous fibrosis, 5’-nucleotidase (5’NT) 21 334 sarcoidosis 128, 128 nucleus, liver cell 7 P53 gene/p53 protein 292, 293, perilipin 9, 50, 223 nutrient factors, alcohol-induced 294 perineural invasion, liver injury 53 pale bodies cholangiocarcinoma 312, fibrolamellar hepatocellular 312 o carcinoma 275, 307, 307 periodic acid–Schiff (PAS) 18, obesity globular amyloid vs. 341 50 hepatocellular carcinoma panacinar necrosis 35–36, 220 amyloidosis 340–341 risk 291 pancreatic carcinoma, fungi 108, 110, 110 liver graft survival and 260 metastatic 313, 330, 331 periodic acid–Schiff after diastase NAFLD 63, 64 pancreatic disease, cystic digestion (DiPAS) 18, 20, post-transplant 262 fibrosis 166 165 obliterative cholangiopathy 200 panlobular necrosis 154, 155, 156 α1-antitrypsin deficiency 163, obliterative vasculopathy, chronic paracoccidioidomycosis 112 164, 164–165 graft rejection 243–244, paraneoplastic disorders 294–295 Whipple disease 100 244 parasites 96, 112–121, 122 periportal (sinusoidal) fibrosis Ohio Valley disease 111 biliary system 84, 118–119, 119 alcoholic liver disease 55, 58, 59, Oil Red O stain 19, 50 cholangiocarcinoma risk 119, 61, 62 acute fatty liver of 309 biliary atresia 201, 204 pregnancy 345, 345 secondary sclerosing biliary tract disorders 86, 91 Reye syndrome 344, 344 cholangitis 89 NAFLD 67

bindex 371 18 January 2017 1:39 AM 372 Index

periportal interface inflammatory phosphotungstic acid hematoxylin polyvinyl chloride 218, 222, 228, activity (PTAH) 19 292, 319 apparent, acute viral hepatitis 32 hepatoblastoma 317 Pompe disease 187 autoimmune hepatitis 135, 136, Q fever 102, 102 porphyria cutanea tarda 168–169, 259, 259 toxemia of pregnancy 346 170 biliary tract disorders 77–78, phycomycosis 112 porphyrias 168–171, 169 81–82, 91 pica 120 portal fibrosis chronic viral hepatitis 37, 37 pigments, drug or toxin- alcoholic liver disease 55 drug or toxin-induced liver related 218, 229, 229 ARPKD 210, 212 injury 221, 222, 223 pipestem lesion, schistosomiasis 117 with atypical ductular erythropoietic pit cells 10 reaction 75, 76, 76 protoporphyria 171, 171 PKD1 gene 212 autoimmune hepatitis 136 NAFLD 67 PKD2 gene 212 chronic viral hepatitis 39, 39–40, periportal plexus 12 PKHD1 gene 210 43 periportal zone (zone 1) 8, 13, 13 plasma cell dyscrasias 327–328 drug or toxin-induced 221–222, acute viral hepatitis 34 plasma cells 222, 223 α1-antitrypsin deficiency autoimmune hepatitis 135, 135, erythropoietic 163–164, 164 136, 137, 138 protoporphyria 171 perisinusoidal cells see stellate cells post-transplant extrahepatic biliary atresia 201, 201 perivenular fibrosis lymphoproliferative hereditary hemochromatosis 174 alcoholic liver disease 58, 59, disease 248, 248 mechanical bile duct 59, 62 post-transplant recurrent obstruction 86, 88, 91 Budd–Chiari syndrome 146 autoimmune hepatitis 259, NAFLD 67 NAFLD 66, 66, 67 259 non-cirrhotic see non-cirrhotic right-sided heart failure 148 primary biliary cirrhosis 75–76, portal fibrosis perivenular zone (zone 3) 8, 13, 13 76, 77 primary biliary cirrhosis 75, 76, acute viral hepatitis 33 secondary sclerosing 76, 91 alcoholic liver disease 55, 57 cholangitis 90 primary sclerosing Budd–Chiari syndrome 145, Plasmodium falciparum 114, 114, cholangitis 82, 82, 91 145–146, 146 115 sarcoidosis 128 chronic graft rejection 243, 244 Plasmodium knowlesi 114 schistosomiasis 117, 118 drug or toxin-induced liver Plasmodium vivax 114 portal hypertension injury 219, 219 polyarteritis nodosa 154 Budd–Chiari syndrome 145 ethanol metabolism 52 polyclonal B-cell hyperplasia 248 cystic fibrosis 167 hepatic artery hypoperfusion 153 polyclonal carcinoembryonic drug or toxin-induced liver mechanical bile duct antigen (pCEA) 271, 275, injury 221–222 obstruction 85, 86 303, 305, 314 non-cirrhotic see non-cirrhotic right-sided heart failure 147, 148 polycystic kidney disease portal fibrosis total parenteral nutrition-induced autosomal dominant portal vein thrombosis 150 liver injury 348–349 (ADPKD) 207, 212–214, 213 pre-sinusoidal Perl’s iron stain 18, 20, 174, 174, 175 autosomal recessive arterioportal fistulas 160 peroxisome proliferator-activated (ARPKD) 207, 209–210, nodular regenerative receptor-α (PPAR-α) 53 211, 211, hyperplasia 282 peroxisomes (microbodies) 7, 9 212 partial nodular phenacetin 218, 229 polycystic liver disease (PCLD) 207, transformation 272–273 phenobarbital 229 209–214 sarcoidosis 127 phenytoin 217, 218, 220 adult 212–214, 213 schistosomiasis 117 pheochromocytoma 322 differential diagnosis 213–214 vascular shunts 160 phlebitis, Budd–Chiari von Meyenburg complexes 209, portal–systemic shunts 160 syndrome 146 213, 213 portal tracts phlebosclerosis polycystin 212 acute viral hepatitis 32, 32 alcoholic liver disease 58, 62 polycythemia vera 144, 327 autoimmune hepatitis 135, right-sided heart failure 148 polymerase chain reaction 135–136, 136 phospholipidosis, drug- (PCR) 19 chronic HCV 41–42 induced 218, 224 polymyalgia rheumatica 353 evaluation 16–17 phosphorus 217, 219 polyunsaturated fatty acids (PUFA) 53 fulminant hepatitis 36, 36

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hematopoiesis 2, 2 histologic staging 75, 75–77, r intravenous drug users 39, 39 76, 77 RB (pRB) gene 293 microanatomy 5, 5–6 overlap syndrome see reactive hepatitis, non-specific neonatal hepatitis 199 autoimmune hepatitis– see non-specific reactive non-cirrhotic portal fibrosis 151, primary biliary cirrhosis hepatitis 151–152 pathology 75–79, 78 reactive inflammatory changes 282 Schistosoma ova 117, 118 pathophysiology 73–74 rectal adenocarcinoma, portal vein 3, 4, 143 post-transplant recurrence metastatic 331 development 2 256–257, 257 recurrent pyogenic disorders 149–153 primary non-function, liver cholangiohepatitis microanatomy 12 graft 236–237, 237, 238 cholangiocarcinoma risk 308–309 non-cirrhotic portal fibrosis 151, primary sclerosing cholangitis clonorchiasis 119 151 (PSC) 79–83 secondary sclerosing stenosis, post-transplant 251 cholangiocarcinoma risk 80, cholangitis 89, 90, 91 thrombosis 149–150 308 red blood cells differential diagnosis 149, 150 clinical presentation 80–81 degradation, iron turnover 171, 172 hepatocellular carcinoma 150, differential diagnosis 42, 91, extravasation 156 302 91–92, 141, 181 malaria parasites 115, 115 pathology 150, 150 epidemiology and natural sickle cell disease 196, 196 post-transplant 251 history 79 red blood cell – trabecular lesion portal venous radicals inflammatory bowel disease 79, Budd–Chiari syndrome 145–146, increased 342 146 non-cirrhotic portal overlap syndrome 132, 135, 139 left-sided heart failure 155, 155 fibrosis 151, 151 pathology 81–83, 81–84 redox potential 52, 53 primary biliary cirrhosis 79 pathophysiology 79–80 Reed–Sternberg cells 324, 324 primary sclerosing post-transplant recurrence 257– regenerative nodules cholangitis 82 258, 258 alcoholic cirrhosis 62, 62, 63 schistosomiasis 117 small cell variant 83 chronic viral hepatitis 39, 39–40 portal venules 5, 5, 12 small duct 81 differential diagnosis 283–284 acute cellular rejection 240, 240 procainamide 218, 229, 229 dysplastic see dysplastic cirrhotic non-cirrhotic portal fibrosis 151, progenitor cells 14–15 nodules 151–152 progressive familial intrahepatic fulminant hepatitis 36 pylephlebitis, bacteremia 97 cholestasis (PFIC) 184 large see macroregenerative thrombosis 150, 150 type 1 184, 185, 186, 347 cirrhotic nodules portoenterostomy, Kasai 200–201 type 2 184, 185 mechanical bile duct post-transplant lymphoproliferative type 3 184, 185 obstruction 88, 88 disorder (PTLD) 247–249, proliferating cell nuclear antigen NAFLD 67, 68 248, 249, 261 (PCNA) index 333, pre-neoplastic potential 332–336 potato-like nodules see hepar lobatum 333–334 primary biliary cirrhosis 76, 77 pre-eclampsia (toxemia of protoporphyrin 170, 170–171, 171 primary sclerosing pregnancy) 346, 346 protoscolices 116, 116 cholangitis 82, 82 pregnancy 344–347 protozoa 96, 112–121 see also cirrhosis; nodular acute fatty liver of 344–346, 345 Prussian blue stain 18, 174 regenerative hyperplasia; benign intrahepatic cholestasis PSC see primary sclerosing partial nodular of 347 cholangitis transformation HELLP syndrome 346–347 pseudoglands, hepatocellular rejection, liver allograft 237–245 toxemia of 346, 346 carcinoma 296, 298 acute cellular see acute cellular preservation injury, grafted pylephlebitis 97, 150, 150 rejection livers 234–236, 235 pyogenic abscesses, hepatic 95–97 antibody-mediated primary biliary cirrhosis (PBC) pyrrolizidine alkaloids 156, 218 (humoral) 237–238, 238 73–79 pyruvate dehydrogenase multi- chronic ductopenic 241, clinical presentation and enzyme complex, E2 242–245, 243, 244 course 74–75 component (PDC-E2) 74, 75 grading 241 differential diagnosis 42, 91, q hyperacute 237–238, 238 91–92, 141, 181 rejection activity index (RAI) epidemiology 73 Q-fever 101–102, 102 240–241, 241

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relapsing fever (borreliosis) 105 salmonellosis 97–99, 98, 99 serum amyloid A (SAA; AA) 272, residual bodies 9 sarcoidosis 123, 126–129 337, 338 retention cysts, peribiliary 209, 209 clinical presentation 126–127 staining techniques 340, 341 reticulin fibers, fulminant differential diagnosis 42, 129 serum amyloid P 341 hepatitis 36 epidemiology 126 serum ascites albumin gradient reticulin stain 18, 20 overlap syndrome 128, 139 (SAAG) 145, 147 hepatocellular adenoma 269, 271 pathogenesis 127 shock liver see ischemia, hepatic hepatocellular carcinoma pathology 127, 127–128, 128, 129 sickle cell anemia 195–196, 196 295–296, 296, 297, 301 sarcomas, hepatic signet-ring cells, macroregenerative nodules 335 differential diagnosis 282, 318, cholangiocarcinoma 311 nodular regenerative 320 Simplified Criteria for the hyperplasia 283, 284 rare primary 322, 323 Diagnosis of Autoimmune reversed lobulation see also angiosarcoma; Kaposi Hepatitis 140–141 Budd–Chiari syndrome 146 sarcoma sinusoidal lymphocytosis right-sided heart failure 148, 148 satellitosis 60, 60, 225 cytomegalovirus infection 45, 45 Reye syndrome 342–344, 343, 344 Schaumann bodies 127, 128 drug or toxin-induced liver rhabdomyosarcoma, Scheuer scoring system, chronic injury 220 embryonal 322, 323 viral hepatitis 43 Epstein–Barr virus hepatitis 44, 44 rheumatoid arthritis 351–352 Schistosoma hematobium 117 hepatitis C virus 34, 42 rhodanine stain 19, 79, 180, 181 Schistosoma japonicum 117 typhoid fever 98, 99 Richner–Hanhart syndrome 193 Schistosoma mansoni 117 sinusoidal obstruction syndrome Rickettsia 96, 101–103, 122 schistosomiasis 116–118, 117, 118 (veno-occlusive disease; Rickettsia conorii 103 scleroderma 352–353 VOD) 156–158 Rickettsia rickettsii 102 sclerosed hemangioma 276, 277 acute phase 157, 157 right anterolateral segments 3, 3 sclerosing cholangitis bone marrow transplant right posterolateral segments 3, 3 autoimmune 132, 139 recipients 264 right-sided heart failure (congestive IgG4-associated 89, 90 chronic phase 157, 157 hepatopathy) 146–149 primary see primary sclerosing differential diagnosis 69–70, 158 clinical presentation 146–147 cholangitis drug-induced liver injury 218, differential diagnosis 69–70, secondary (acquired) see 228 148–149 secondary sclerosing sinusoids, hepatic 143 pathogenesis 147 cholangitis amyloid deposits 338, 339, 339 pathology 147–148, 148 sclerosing hyaline necrosis see Budd–Chiari syndrome 145, ring forms, Plasmodium alcoholic hepatitis 145–146, 146 falciparum 115 sea blue histiocytes 192 development 1, 2 ring granulomas 102, 102 secondary sclerosing cholangitis disorders 156–159 Rocky Mountain spotted fever 102– (SSC) 89, 89–90 hematopoiesis 2, 2 103, 103 Langerhans cell histiocytosis 329, infiltrates with blood flow rosette formation 330 impairment 152, 159, 159 chronic viral hepatitis 38 parasitic infestations 116, 119 lining cells 9–10 total parenteral nutrition (TPN)- pathology 90, 91 microanatomy 6, 6 induced liver injury 349, segmental bile ducts 12 oral contraceptive-associated 349 segmental involvement, primary dilation 228 Rotor syndrome 183 sclerosing cholangitis 82 right-sided heart failure 147 rubeanic acid stain 19, 79, 180, 181 segments, functional anatomical Sirius Red stain 18, 340 rubella 48 hepatic 3, 3 small cell dysplasia 38, 333, 333–334 rubeola 48–49 Senecio alkaloids 156, 228 smooth muscle actin (SMA) 278, RUCAM (Roussel Uclaf Causality SEN virus (SEN-V) 35 282, 285, 286 Assessment Method) sepsis (bacteremia) 95–97, 97 SMPD1 gene 191 score 217 post-transplant 245, 245 smudge cells 48, 249 septal bile ducts 11 space-occupying lesions, s septum transversum 1 evaluation 16 Salmonella bongori 97–98 serine protease inhibitors space of Disse 5, 13 Salmonella enterica 98 (SERPINs) 162 spherules, coccidioidomycosis 109, Salmonella enterica serovar Typhi serological markers, hepatotropic 110 (S. typhi) 98 viruses 26 sphingomyelin 191–192, 192

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spirochetes 96, 103–105, 122 Sudan B stain 19, 344, 345 thrush (candidiasis) 109–110, 110 squamous cell carcinoma, primary sulfasalazine 218, 224, 225 tick-borne diseases 99, 102, 103, 105 hepatic 322 sunflower cataracts 178 tight junctions 6 stains, histochemical 17, 18–19 superoxides 53 T lymphocytes Staphylococcus 96, 245 surgical hepatitis 235 autoreactive 131, 132 steatohepatitis 50–51 sweat test 167 immunoperoxidase stains 248 drug or toxin-induced 223–224, sympathetic nerve fibers 4, 14 liver allograft rejection 238–239 224 syncytial giant cell changes of primary sclerosing cholangitis 79 non-alcoholic see non-alcoholic hepatocytes see also CD4 T lymphocytes; CD8 steatohepatitis acute viral hepatitis 33 T lymphocytes steatosis (fatty change) 50–51 autoimmune hepatitis 137, 137 Todani’s classification, biliary acute fatty liver of extrahepatic biliary atresia cysts 204–205, 205, 206 pregnancy 345, 345–346 201–202, 202 total parenteral nutrition (TPN)- alcoholic see alcoholic fatty liver neonatal cytomegalovirus induced liver injury 217, chronic hepatitis C 42, 42 infection 45 347–350, 349 diffuse 50 neonatal hepatitis 199, 199 toxemia of pregnancy 346, 346 donor livers 233–234 non-A non-G hepatitis 35, 35 toxin-induced liver injury see drug drug or toxin-induced 218, Wilson disease 180 or toxin-induced liver injury 223–224, 224 syphilis 103–105 Toxocara canis 120 focal fatty change 285, 285 congenital 104, 104 Toxocara cati 120 hepatocellular carcinoma 296, secondary 104, 104 toxocariasis 119–120, 120 298 systemic circulation, disorders 153– toxoplasmosis 118, 118 large droplet see macrovesicular 156 transaminases 17–22, 21 steatosis systemic lupus erythematosus transferrin, serum 174 NASH 67–68, 68 (SLE) 352 transferrin receptor 1 (TfR1) 171, 172 non-alcoholic 66, 66 transferrin receptor 2 (TfR2) 172 patchy 50 t transferrin saturation, serum 174 porphyria cutanea tarda 169, 170 Tangier disease 192 transfusion-transmitted virus Reye syndrome 343, 343, 344 T-cell lymphoma, post- (TTV) 35 small droplet see microvesicular transplant 248 transplantation see liver steatosis T cells see T lymphocytes transplantation total parenteral nutrition-induced telomerase reverse transcriptase, Treponema pallidum 103–104 liver injury 348, 349, 349 human (hTERT) 309–310 trichrome stain 18, 20 Wilson disease 178, 179, 180 telomere shortening 293 Tropheryma whippelii 100 zonal 50 teratoma 286, 287 trophozoites, amebic 113, 113–114 stellate cells (perisinusoidal, fat- TfR2 gene 172 tropical splenomegaly storing, Ito cells) 6, 10 Th1 T lymphocytes 123 syndrome 115 alcohol-induced liver injury 55 Th2 T lymphocytes 123 TTV (transfusion-transmitted drug-induced liver injury 223, 224 Th17 T cells 132 virus) 35 stem cells 14–15 β-thalassemia 175, 176, 176 tuberculoma 106 embryonic 14 Thioflavin T stain 341 tuberculosis 105–107, 106 facultative (oval cells) 14, 14, 15 thorotrast (thorium dioxide) 218, 228 granulomas 106, 106–107, 123, hematopoietic 15 angiosarcoma 318–319 125 sterol regulator element binding cholangiocarcinoma 309 tubular structures, protein 1 (SREBP-1) 53 hepatocellular carcinoma 292 cholangiocarcinoma 310, stones, intrahepatic pigment deposits 229, 229 311 (hepatolithiasis) 90, thrombosis tularemia 99–100 308–309 cavernous hemangioma 276 tumor-like lesions, benign 267 storage diseases 184–192 infantile tumor necrosis factor-α (TNF-α) 65 Streptococcus 96 hemangioendothelioma 280 tumors, hepatic stroma, hepatic 10 inflammatory pseudotumor 282 benign 266–286, 267 sublobular veins 5, 13 post-transplant 250–252, 251 drug or toxin-induced 218, 228, alcoholic cirrhosis 62 see also Budd–Chiari syndrome; 228, 229, 292 Budd–Chiari syndrome 146, 147 hepatic artery, thrombosis; granulomas 124 submassive necrosis 35, 35, 220 portal vein, thrombosis; malignant 289, 289–336 see also confluent necrosis tumor thrombi tumor-suppressor genes (TSGs) 293

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tumor thrombi cavernous hemangioma 276, 277 visceral larva migrans 119–120, hepatocellular carcinoma 300, infantile hemangioendothelioma 120, 121 302 280, 280 vitamin A (retinoyl palmitate) metastatic tumors 331 vascular tumors induced steatosis 218, 224 typhoid fever 97, 98 benign 275–277, 279–281 intracellular 10 typhoid nodule 98, 98 malignant 318–321 von Gierke disease 187 tyrosinemia, hereditary 192–193, vasculitis von Meyenburg complexes 209, 210 193, 194 drug or toxin-induced 218, 228 adult polycystic liver disease 209, hepatocellular carcinoma 193, hepatic arteries 153, 154 213, 213 292–293, 299, 302 Rocky Mountain spotted fever 103 w u secondary syphilis 104 Waldenström ubiquitin immunoperoxidase vasoablative endotheliosarcoma macroglobulinemia 327–328 stain 19, 55, 60 see epithelioid Warthin–Starry reaction 19, 100, ulcerative colitis 341, 342 hemangioendothelioma 101 autoimmune hepatitis 132 veno-occlusive changes Weber–Christian disease 353 cholangiocarcinoma 308 alcoholic liver disease 58 weight, adult liver 3 primary sclerosing cholangitis 79 drug or toxin-induced liver Weil disease 105 umbilical veins 2, 3 injury 218, 227–228, 228 Whipple disease 100 University of Wisconsin (UW) vs. sinusoidal obstruction Williams–Beuren syndrome 202– solution 234–235 syndrome 157 203 uroporphyrinogen decarboxylase veno-occlusive disease see sinusoidal Wilson disease 177–182 deficiency 168 obstruction syndrome acute hepatitis 178 uroporphyrinogen inclusions 169, venoportal cirrhosis 146 chronic hepatitis 178 170 Victoria blue stain 19, 40, 180 clinical presentation 177–178 vimentin 278, 282 differential diagnosis 37, 42, 70, v vinyl chloride see polyvinyl chloride 180–182, 181–182 valley fever 109 viral hemorrhagic fever 48 fulminant liver disease 178 valproic acid 218, 344 viral hepatitis 24–49 genetics 177 van Gieson stain 18, 36 acute see acute viral hepatitis laboratory tests 178, 179 vanishing bile duct syndrome 93, chronic see chronic viral hepatitis pathology 178–180, 179, 180, 181 239, 324 epidemiology and serology 25, Wolman disease 192 see also ductopenia 26, 28–31 variceal bleeding 145, 232 fulminant 24–26, 35–36 y vascular disorders 143–160 hepatotropic viruses 24–43 yellow fever 37, 48, 48 vascular endothelial growth factor other viruses 47–49 yolk sac tumors 322 (VEGF) 294 pathology 31–43 vascular injury pathophysiologic processes z chronic graft rejection 242, 26–27 Ziehl–Neelson acid–fast stain 243–244, 244 post-transplant infections (AFB) 19, 106 drug or toxin-induced 218, 245–249 Zimmerman, Hyman J. 216 227–228, 228 post-transplant recurrence zone 1 see periportal zone post-transplant 250–252, 251 252–255, 253, 254, 255, zone 2 (midzone) 13, 13 vascular network, hepatic 2, 12–14 256 zone 3 see perivenular zone vascular shunts 160, 160 systemic viruses 43–47 zones of Rappaport, hepatic 13, 13 vascular spaces virology 27–28 zygomycosis 112

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