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1 Index A Acute liver failure (ALF), viral hepatitis, 7 Adalimab, hepatitis B management in immunosuppression patients, 279 Alemtuzumab, hepatitis B management in immunosuppression patients, 280 ALF. See Acute liver failure Antisense RNA hepatitis D management, 350 hepatitis viruses, 267 APOBEC covalently closed circular DNA deamination, 38, 86 recruitment, 92 therapeutic targeting, woodchuck, 196 Apoptosis, HBx effects, AuAg. See Australian antigen Australian antigen (AuAg), discovery, 4 5, 14 B Bat hepatitis virus (BtHV), zoonotic infection, 47, 53 B-cell, hepatitis B virus immune response, 146 BtHV. See Bat hepatitis virus C Calcium flux, HBx effects, 119 cccdna. See Covalently closed circular DNA Cell cycle, HBx effects, 120 Chimpanzee model, hepatitis B virus infection blood test development, chronic infection, 211 historical perspective, immune response clearance mechanisms, innate immunity, 213 persistence mechanisms, 215, 218 prospects for study, 220 inoculum size and outcomes, 218 vaccine development, Cirrhosis hepatitis B association, hepatitis D management in decompensated cirrhosis patients, 348 Core proteins, hepatitis B virus capsid assembly, 92 93, 98 99, properties, 97 Covalently closed circular DNA (cccdna) animal model studies, 35 36, 38 deamination, 38, 86 eradication, 1, 9 formation, functions, 91 HBx interactions, host evasion, 142 mouse hepatitis B virus infection, 231 persistence, 9, 142 therapeutic targeting, 85 86, Cyclin-dependent kinases HBx effects, 120 hepatitis B virus assembly role, 93 D Dane particle, 97 DDB1, HBx interactions, , 267 Delta antigen. See Hepatitis D virus Delta hepatitis. See Hepatitis D virus DNA methyltransferase, upregulation by HBx, 117 Duck hepatitis B virus. See Hepatitis B virus C Endosomal sorting complex (ESCRT), hepatitis B virus particle transport and release, ESCRT. See Endosomal sorting complex Etanercept, hepatitis B management in immunosuppression patients, 279 F Fas, HBx effects, 119 G Glomerulonephritis, hepatitis B association, 22 Gorilla hepatitis B virus, phylogeny with other hepatitis viruses, 49 Ground squirrel hepatitis virus. See Hepatitis B virus Guillain Barré syndrome, hepatitis B association, 23 H HBIG. See Hepatitis B immunoglobulin HBV. See Hepatitis B virus 357

2 Index This is a free sample of content from The Hepatitis B and Delta Viruses. HBx. See Hepatitis B virus X HCC. See Hepatocellular carcinoma HCV. See Hepatitis C virus HDV. See Hepatitis D virus Hepatic decompensation, hepatitis B association, 19 Hepatitis B immunoglobulin (HBIG) liver transplant patient use, 281 passive immunization efficacy, Hepatitis B virus (HBV) animal models antiviral therapy, chimpanzee. See Chimpanzee model, hepatitis B virus infection duck hepatitis B virus, 29 31, 34 35, 37, ground squirrel hepatitis virus, 29, 31 hepatocellular carcinoma, 39, heron hepatitis B virus, 29 historical perspective, life cycle of virus, 35 molecular biology studies reverse transcription and priming, second-strand DNA synthesis, 34 mouse. See Mouse model, hepatitis B virus infection protein function elucidation, transient infection, woodchuck. See Woodchuck hepatitis virus woolly monkey hepatitis B virus, 29 capsid assembly allosteric regulation, 101 biochemistry, core protein determinants, 92 93, kinetics, nucleic acid synergy, overview, 92 capsid structure, cell entry multistep process, overview, prospects for study, sodium taurocholate cotransporting polypeptide role, 65, clinical manifestations of infection acute disease, chronic disease, extrahepatic manifestations, genotype influences on chronic disease course, HbeAg-negative disease, HbeAg-positive disease, 17 occult infection, 22 overview, 7 8 coinfection hepatitis C virus, 135 hepatitis D virus acute hepatitis D, chronic disease, helper-independent infection, hepatocellular carcinoma studies, overview, human immunodeficiency virus, 23, discovery, 27 envelopment and release envelope proteins, maturation signal, 93 subviral particles, 95 viral particle transport and release, epidemiology acute disease, 14 chronic disease, 14 genotype distributions, genotype influences, 134 global prevalence, 130, hepatocellular carcinoma, 136 high-prevalence populations, indigenous peoples, low-prevalence populations, 131 mortality, 132 overview, , genome intergenotypic recombination, 162 structure, 28 29, 77, 109, 160 geographic distribution of genotypes and subgenotypes, 46 history of study, host susceptibility studies, 70 immune response overview, immune response. See Immune response origins and evolution genomic fossils, genotype and subgenotype roles, human family tree, indigenous population implications for origins, mixed infections and recombination, most recent common ancestor, mutation rate, 50, 84 prospects for study, theories of origins bat origin, 53 coevolution, 53 cospeciation, 53 cross-species transmission, 53 New World origin, 52 outcomes by age, 242 prevention strategies, sequelae of chronic disease. See also Cirrhosis; Hepatocellular carcinoma cirrhosis, hepatic decompensation, 19 hepatocellular carcinoma, 19 20,

3 Index species specificity, surface antigen discovery, 5 genotype and variant clinical significance, prognostic value, seroclearance, structure, vaccine development, 5 6, 28 surface protein domains in infection, tissue tropism, 71 transmission, 14 15, , 242 treatment cure definitions, early intervention rationale, failure management, resistance, genotype effects on antiviral therapy interferon therapy, nucleoside/nucleotide analogs, overview, goals and treatment end points, 254 HBeAg-negative patients duration of therapy, on-treatment factors in treatment response prediction, 258 outcomes, pretreatment factors in treatment response prediction, 258 HBeAg-positive patients on-treatment factors in treatment response prediction, outcomes, 256 pretreatment factors in treatment response prediction, 257 hepatitis C virus coinfection patients, human immunodeficiency virus coinfection patients, immunosuppression patients anti-cd20 therapy effects, 280 anti-cd52 therapy effects, 280 anti-tnf-a therapy effects, 279 exacerbation of chronic disease, immunosuppressants in reactivation, 279 prevention and management of reactivation, indications, liver transplant patients, novel drug target identification, pregnant patients efficacy of antiviral drugs, infant transmission prevention, pregnancy effects on virus course, 276 safety of antiviral drugs, 277 therapeutic targets, variant effects on antiviral therapy, 171 vaccination. See Vaccination virion structure, Hepatitis B virus X (HBx) animal model studies of function, apoptosis effects, calcium signaling effects, 119 cancer studies, 121 cell cycle effects, 120 covalently closed circular DNA interactions, DDB1 interactions, , 267 enhancer and promoter interactions, functional diversity, hepatocellular carcinoma role, 121, 166, 186 innate immunity, 143 overview, prospects for study, 123 replication role, structure, Hepatitis C virus (HCV) discovery, 7 epidemiology, 2 hepatitis B virus coinfection management, overview, 135 management, 1 milestones in research and treatment, 2 3 Hepatitis D virus (HDV) assembly, cell entry multistep process, overview, prospects for study, sodium taurocholate cotransporting polypeptide role, 65, clinical manifestations, 8 delta antigen forms, 317, diagnosis, 306 discovery, 6 7, 305 epidemiology prevalence, studies 1980s 1990s, Europe, ) genome circular conformation and uniqueness, genotypes, 317 types of RNA, hepatitis B virus coinfection acute hepatitis D, chronic disease, helper-independent infection, hepatocellular carcinoma studies, overview,

4 Index This is a free sample of content from The Hepatitis B and Delta Viruses. Hepatitis D virus (HDV) (Continued) host susceptibility studies, 70 origins and evolution, 46, pathogenesis, posttranscriptional RNA editing, replication, 319, 322 ribozymes, severity of disease, factors affecting, 333 species specificity, surface protein domains in infection, tissue tropism, 71 transmission, treatment acute disease, chronic disease, decompensated cirrhosis patients, 348 interferon combination therapy with nucleoside analogs, novel therapies antisense RNA, 350 hepatocyte entry inhibitors, immunotherapy, 350 overview, 348 prenylation inhibitors, 350 nucleoside analogs, overview, prospects, 350 thymic humoral factor-g2, 348 thymosin-a1, 348 virion structure, Hepatitis E virus (HEV), discovery, 7 Hepatocellular carcinoma (HCC) animal models, hepatitis B association, DNA integration studies, epidemiology, 136 genomic alterations and oncogenic pathways, genotypes in risk, HBx role, 121, 166, 186 variants in risk, hepatitis D virus studies, immunization in prevention, 247 incidence, 290 mortality, 179 overview, risk factors, staging BCLC staging, CLIP score, 291 Okuda system, 291 overview, selection of staging system, 292 TNM staging, 291 treatment advanced disease chemotherapy, 293 immunotherapy, novel therapies, 295 oncolytic virus therapy, standard frontline therapy, early disease adjuvant therapy after hepatectomy, liver transplantation, 298 locoregional ablative therapy, surgical resection, 297 transarterial embolization with chemotherapy, Hepadnaviridae comparison of family members, phylogenetic tree, 48 Heron hepatitis B virus. See Hepatitis B virus HEV. See Hepatitis E virus Hippocrates, hepatitis studies, 3 Historical perspective, viral hepatitis Australian antigen discovery, 4 5 early characterization, 3 4 screening tools, 5 vaccination and treatment, 5 6 HIV. See Human immunodeficiency virus Human immunodeficiency virus (HIV), hepatitis B virus coinfection management, overview, 23, I Immune response chimpanzee hepatitis B virus infection clearance mechanisms, innate immunity, 213 persistence mechanisms, 215, 218 prospects for study, 220 hepatitis B virus adaptive immunity B-cells, 146 regulatory T cells, 148 T-cells, Th17 cells, 148 Th22 cells, 148 antigen immunomodulation, innate immunity, mouse hepatitis B virus infection acute hepatitis, chronic hepatitis, natural killer cells, natural killer T cells, overview, replication control, therapies, vaccination,

5 Index hepatitis D virus, 334 woodchuck hepatitis virus cloning and characterization of components in woodchuck, T-cell response, 196 Immunization. See Vaccination Immunosuppression patients with hepatitis B anti-cd20 therapy effects, 280 anti-cd52 therapy effects, 280 anti-tnf-a therapy effects, 279 exacerbation of chronic disease, immunosuppressants in reactivation, 279 prevention and management of reactivation, Infliximab, hepatitis B management in immunosuppression patients, 279 Interferon chimpanzee hepatitis B virus infection immune response, 215, 220 hepatitis B virus genotype effect on therapy, immune response, treatment outcomes, hepatitis C virus management, 1 hepatitis D management acute disease, chronic disease, combination therapy with nucleoside analogs, history of hepatitis management, 6 hepatitis D virus, 324 hepatocellular carcinoma role, 39 L Lamivudine, liver transplant patient use, Liver cancer. See Hepatocellular carcinoma Liver transplantation hepatitis B management in recipients, hepatocellular carcinoma treatment, 298 Lonafarnib, hepatitis D management, 350 M Minus-strand, synthesis, 79 Mouse model, hepatitis B virus infection acute hepatitis, chronic hepatitis, historical perspective and types, N Natural killer (NK) cell, hepatitis B virus immune response, Natural killer T (NKT) cell, hepatitis B virus immune response, NF-kB. See Nuclear factor-kb Nivolumab, hepatocellular carcinoma management, 293 NK cell. See Natural killer cell NKT cell. See Natural killer T cell NTCP. See Sodium taurocholate cotransporting polypeptide Nuclear factor-kb (NF-kB), HBx effects, O Ofatumumab, hepatitis B management in immunosuppression patients, 280 P PAN. See Polyarteritis nodosa PD-1, therapeutic targeting in hepatocellular carcinoma, 293 Pembrolizumab, hepatocellular carcinoma management, 293 Pexa-Vec, hepatocellular carcinoma management, pgrna. See Pregenomic RNA Pidilizumab, hepatocellular carcinoma management, 293 PKA. See Protein kinase A PKC. See Protein kinase C Plus-strand. See Second-strand DNA synthesis Polyarteritis nodosa (PAN), hepatitis B association, 22 PreCore, animal model studies of function, Pregenomic RNA ( pgrna) digestion, 91 1RNA requirement in packaging and protein priming, 82 packaging, Pregnancy, hepatitis B efficacy of antiviral drugs, infant transmission prevention, pregnancy effects on virus course, 276 safety of antiviral drugs, 277 Pre-S, hepatocellular carcinoma mutations, 167, 181 Protein kinase A (PKA), hepatitis B virus assembly role, 93 Protein kinase C (PKC), hepatitis B virus assembly role, 93 R Replication complex, assembly, Reverse transcription animal studies model, overview, 31 priming, RNA requirement in packaging and protein priming,

6 Index This is a free sample of content from The Hepatitis B and Delta Viruses. Reverse transcription (Continued) genome variability role, 84 host factors in replication, reverse transcriptase human and duck hepatitis B virus comparison, structure and function, therapeutic targeting, Ribavirin hepatitis C management, 1 hepatitis D management, Ribonuclease H, pregenomic RNA digestion, 91 Rituximab, hepatitis B management in immunosuppression patients, 280 RNA interference. See Antisense RNA S Second-strand DNA synthesis animal studies, 34 priming, 80 Small interfering RNA. See Antisense RNA Sodium taurocholate cotransporting polypeptide (NTCP) hepatitis B/D cell entry role, 65, therapeutic targeting, , , 349 SRPK, hepatitis B virus assembly role, 93 T TACE. See Transarterial embolization with chemotherapy T-cell chimpanzee hepatitis B virus infection immune response, 215, hepatitis B virus immune response CD4 and CD8 T-cells, regulatory T cells, 148 Th17 cells, 148 Th22 cells, 148 hepatitis D virus response, 334 mouse hepatitis B virus response, therapeutic targeting, 268 woodchuck hepatitis virus immune response, 196 vaccines, 197 Telomelysin, hepatocellular carcinoma management, 295 Telomerase reverse transcriptase (TERT), hepatocellular carcinoma mutations, TERT. See Telomerase reverse transcriptase TGF-b. See Transforming growth factor-b Thymic humoral factor-g2, hepatitis D management, 348 Thymosin-a1, hepatitis D management, 348 TLRs. See Toll-like receptors TNF-a. See Tumor necrosis factor-a Toll-like receptors (TLRs) therapeutic targeting hepatitis B, 268 hepatitis D, 350 woodchucks, 194 Transarterial embolization with chemotherapy (TACE), hepatocellular carcinoma management, Transforming growth factor-b (TGF-b), hepatitis B virus immune response, Tumor necrosis factor-a (TNF-a), HBx effects, 119 V Vaccination hepatitis B virus barriers compliance, infant protection duration, resources, 247 vaccine failure, 249 chimpanzee hepatitis B virus infection immune response, combination of passive and active immunization, development, 243 global view, immune response, passive immunization with HBIG, prevention efficacy active immunization, hepatocellular carcinoma, 247 passive immunization with recombinant vaccine, 245 universal immunization, surface antigen, 5 6, 28 universal mass immunization program, 245 woodchuck hepatitis virus combination therapy studies, 199 recombinant viral vector immunization, T-cell vaccines, 197 W WHO. See World Health Organization WHV. See Woodchuck hepatitis virus Woodchuck hepatitis virus (WHV) hepatocellular carcinoma studies, history of study, 29 30, 191 immune response cloning and characterization of components in woodchuck,

7 Index T-cell response, 196 persistence, 85 replication studies, 34 species specificity, 192 therapy studies combination therapy studies, 199 overview, prospects for study, recombinant viral vector immunization, T-cell vaccines, 197 X role, 37 Woolly monkey hepatitis B virus. See Hepatitis B virus World Health Organization (WHO), Global Hepatitis Programme, X X. See Hepatitis B virus X 363

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