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Glossary

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A

Acinus
One of the small saclike dilations composing a compound gland (plural, acini)

Active immune response
Resistance to an infectious agent acquired as the result of exposure to the agent or vaccination for the agent; also called acquired immune response

Acute
A short course; “acute” is part of the definition of several diseases and is, therefore, incorporated in their name (i.e., acute respiratory infection); in medicine, acute often refers to a condition lasting six months or less

Acute Exacerbation
Intermittent elevations of aminotransferase activity to more than 10 times upper limit of normal (ULN) and more than twice baseline value

Aesthenia
Abnormal loss of strength

Albumin
Most abundant plasma protein; primarily responsible for regulating movement of water between tissues and the
bloodstream

Allograft
Graft of tissue obtained from a donor genetically different from, though of the same species as, the recipient

Aminotransferase
An enzyme that catalyzes the transfer of an amino group from a donor molecule to a recipient molecule

Amplification
Technique used to enhance detection and quantification of HBV DNA in blood samples by increasing the number of target (i.e. DNA) molecules

Anhepatic Phase
Portion of the liver transplantation procedure in which the donor liver has been implanted into the recipient but has not yet been reperfused by the recipient's circulation

Apoptosis
Genetically determined destruction of cells from within; mechanism of eliminating superfluous and/or damaged cells; also referred to as programmed cell death

Arthralgia(s)
Non-inflammatory joint pain(s)

Ascites
Excess fluid in the space between the tissues lining the abdomen and abdominal organs

AUC (area under the curve)
The area under the plot of plasma concentration of drug (not logarithm of the concentration) against time after drug administration


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B

Baculovirus vectors
Baculovirus Expression Vector System (BEVS) is an enabling technology for the safe, abundant and rapid production of recombinant proteins

Basal core promoter (BCP) Mutation
Mutation in the section of viral DNA that controls the transcription of the precore and core proteins; results in reduced production of HBeAg

Bile
Fluid secreted by the liver, stored in the gallbladder, and released into the small intestine to aid digestion of fats

Bile canaliculi
Small inter-cellular channels that receive bile secreted by liver cells and transport it to the hepatic ducts

Bioavailability
A measure of the amount of drug that is actually absorbed from a given dose

Boxed Warning
A type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects

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C

Cmax
The peak serum concentration of a therapeutic drug

CD4
A glycoprotein on the surface of helper cells that serves as a receptor for HIV

Cerebral edema
Abnormal accumulation of fluid in brain tissue

CHB Phase 1
Immune Tolerance Phase

CHB Phase 2
Immune Clearance Phase

CHB Phase 3
Inactive Carrier Phase

CHB Phase 4
Reactivation Phase

Chemiluminescent
Emission of light due to a chemical reaction

Child-Pugh
Scoring system used to assess the prognosis of chronic liver disease using combined evaluation of bilirubin, serum, albumin, INR and presence of ascites or hepatic encephalopathy

Chimeric
Constructed by juxtaposition of fragments of unrelated genes or other DNA segments, which may themselves have been altered

Chronic
Long-lasting or recurrent; “chronic” can refer to a persistent and lasting medical condition

Chronic Hepatitis B (CHB)
Chronic necroinflammatory disease of the liver caused by persistent infection with HBV; can be subdivided into HBeAg-positive and HBeAg-negative chronic Hepatitis B

Clearance
A measurement of renal excretion ability

Coagulopathy
A defect in the body’s mechanism for blood clotting

Codon
Sequence of three bases in a strand of DNA (or mRNA) that is the genetic code for a specific amino acid

Collocate
To place together or in proper order; arrange side by side

Compensated cirrhosis
Condition where the liver is heavily scarred but can still perform many important bodily functions

Compensatory Mutations
Mutations that restore replication defects associated with primary drug resistance and may be associated with low-level reduced susceptibility

Complement
Group of proteins that stimulate immune system functions, such as phago-cytosis, inflam-mation and cell destruction

Complementary DNA (cDNA)
Single-stranded DNA that is complementary to mRNA (two bases always found across from each other are said to be complementary to each other

Confluent necrosis
Relatively large mass of dead cells

Continuous Ambulatory Peritoneal Dialysis (CAPD)
Method of peritoneal dialysis performed in ambulatory patients while they go about their normal activities

Covalent Conjugate
Describes molecules that are joined together via bonds between atoms from each molecule

Covalently closed circular
Circle of DNA in which both strands are closed or uninterrupted

C-reactive protein
Substance released in response to inflammation; high levels in the blood indicate presence of inflammation in the body

Cytidine
One of the four major ribonucleoside components of RNA

Cytotoxic
Of, relating to, or producing a toxic effect on cells


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D

De novo
Anew; often applied to particular biochemical pathways in which metabolites are newly biosynthesized

Decompensated cirrhosis
Condition where the liver is extensively scarred and unable to function properly

Degeneration
Abnormal and excessive accumulation of water or other substances within hepatocytes

Denature
Breaking bonds between base pairs in a DNA molecule to produce a single strand of nucleotides

Deoxy-guanosine triphosphate
Deoxyribose molecule with the purine guanine attached to the 1'-carbon and a chain of three oxygenated phosphorus atoms attached to the 5'-carbon; a high energy molecule that serves as a precursor for the assembly of DNA

Dialysis
Filtration method using a membrane to separate waste products from the blood of individuals with severe kidney
impairment

Dideoxy
Attached to 2-deoxyribose, the sugar molecule modifying bases in DNA

Diester
An organic compound that contains two ester groups

Direct Sequencing
Analysis of the HBV polymerase gene is used for the detection of resistance-conferring mutations in population-based sequencing

DNA Polymerase
Enzyme that catalyzes the formation of DNA using a strand of DNA as a template

DNA virus
Virus containing its genetic material in the form of DNA

DNA-RNA Hybrid
Double-stranded molecule consisting of complementary strands of RNA and DNA

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E

Elimination Half-life
The time it takes for a substance to lose half of its pharmacologic activity

Endemic
An infection constantly present and maintained in a population without the need for external inputs

Endocytosis
Process by which extracellular particles, such as viruses, enter a cell via progressive invagination and eventual pinching off of a region of the cell membrane, forming a membrane-bound vesicle within the cytoplasm

Endoplasmic reticulum (ER)
Complex series of membrane-enclosed channels within the cytoplasm of a cell; provides a site for protein synthesis and serves as a path to transport materials from one part of the cell to another

Eosin
Fluorescent dye used in staining tissue preparations for histologic examination

Esophageal varices
Twisted, dilated esophageal veins generally found in the lower end of the esophagus; results from increased pressure within the portal circulation; highly suscept-ible to rupture and massive bleeding


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F

Fatty acid
Building block of fat molecules

Flare
See definition for acute exacerbation

Focal (spotty) lytic necrosis
Single or small clusters of swollen cells with nuclear changes consistent with cell death

Fractionation
To separate (a chemical compound) into components, as by distillation or crystallization

Fulminant
Occurring suddenly, rapidly, and with great severity or intensity


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G

Gallbladder
Pear-shaped sac attached to the under surface of the liver by the cystic duct; stores bile

Genome
All of the genetic material in a particular organism

Genotype
Genetic information carried by an organism's genes, whether or not the genes are actively expressed as proteins

Globulin
Type of plasma protein; serves several functions including transport of substances in blood

Glycogen
Principal carbohydrate storage material in the body

Golgi apparatus
Series of membranous sacs usually located near the nucleus and connected to the ER; serves as the packaging and shipping plant of the cell

Guanosine
One of the major four ribonucleoside components of RNA

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H

HAART
When several such drugs, typically three or four, are taken in combination, the approach is known as highly active antiretroviral therapy, or HAART

HBeAb/Anti-HBe
The Hepatitis B “e” antibody

HBeAg
The Hepatitis B “e” Antigen; the “e” antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating

HBeAg Clearance
Loss of HBeAg in a person who was previously HBeAg-positive

HBeAg Reversion
Reappearance of HBeAg in a person who was previously HBeAg-negative and anti-HBe-positive

HBeAg Seroconversion
Loss of HBeAg and detection of anti-HBe in a person who was previously HBeAg-positive and anti-HBeAg-negative; associated with a decrease in serum HBV DNA to <105 copies/mL

HBIg
Hepatitis B immune globulin; Protein fraction isolated from the plasma of individuals with high levels of immunity to HBV; can be injected into nonimmune individuals to transfer that immunity

HBsAb/Anti-HBs
The Hepatitis B surface antibody

HBsAg
The surface antigen of the Hepatitis B virus; indicates current HBV infection.

HBsAg Clearance
Loss of HBsAg in a person who was previously HBsAg-positive

HBsAg Seroconversion
Loss of HBsAg and detection of anti-HBs in a person who was previously HBsAg-positive and anti-HBsAg-negative

Hemoglobin
Iron-containing protein within red blood cells that transports O2 and CO2

Hepadnaviridae
Hepatotropic (having an affinity for hepatocytes) DNA viruses; family of related viruses found in some mammals (woodchucks, ground squirrels, and tree squirrels), birds (Peking ducks), and primates (including apes and man)

Hepatectomy
A surgical procedure performed to remove a portion of the liver

Hepatic encephalopathy
Disorder of brain function caused by accumulation of toxic sub-ances as a result of liver failure; characterized
by impaired consciousness, memory loss, tremor, seizures and coma

Hepatocellular carcinoma (HCC)
Type of liver cancer

Heterogenous
Composed of parts having dissimilar characteristics or properties

Histology
The science concerned with the minute structure of tissues and organs in relation to their function; also called microanatomy

HLA Class I Molecule
Protein that identifies a cell as "self" and is found on virtually all cells in the body; also called major histocompatibility complex (MHC) class I protein

HLA Class I-restricted CD8+ Lymphocyte
Mature cytotoxic T lymphocyte that will bind only with cells presenting antigens in conjunction with HLA class I molecules

HLA Class II Molecule
Protein that identifies a cell as "self" and is found on antigen-presenting cells such as macrophages; also called major histocompatibility complex (MHC) class II protein

HLA Class II-Restricted CD4 Lymphocyte
Mature helper T lymphocyte that will bind only with cells presenting antigens in conjunction with HLA class II molecules

Horizontal transmission
Transmission via direct or indirect contact between members of the same species that are not in a parent-child relationship

Hypophosphatemia
An electrolyte disturbance in which there is an abnormally low level of phosphate in the blood


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I

Icteric
Relating to or affected with jaundice (yellowish discoloration of the whites of the eyes, skin, and mucous membranes caused by deposition of bile salts in these tissues)

Immune Clearance
Low levels of viral replication, but increasing liver injury

Immunoglobulin M (IgG)
Most abundant class of circulating antibodies produced in response to the presence of a foreign substance (e.g., virus); able to leave the bloodstream and enter tissues to fight infection

Immunoglobulin M (IgM)
First class of circulating antibodies produced in response to the presence of a foreign substance (e.g., virus)

Immunosuppressant Agent
Pharmacologic agent that can suppress or prevent the immune response; used to prevent rejection of a transplanted organ and to treat autoimmune diseases

Inhibition Constant (Ki)
Measurement of the simple comparison of progress curves in the presence and in the absence of inhibitor

Interleukin-6 (IL-6)
Substance produced by many cell types, including white blood cells and endothelial cells that line the blood vessels; mediates several immune system reactions

Interventional Radiologist
Board certified radiologist who has completed a fellowship in percutaneous interventions using guided imaging


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J

Jaundice
Also known as “icterus,” jaundice is yellowish discoloration of the skin, whites of the eyes and mucous membranes caused by increased levels of bilirubin in the blood

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K


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L

Lactic Acidemia
Elevated lactic acid levels in the blood in conjunction with a normal arterial pH

Lipoprotein
Any complex or compound containing both lipid and protein; chemical linking of lipids to proteins facilitates transport of lipids throughout the body

L-Nucleoside
Mirror image of a naturally occurring nucleoside in which the sugar component is in an unnatural L-configuration

Lysis
Disintegration or dissolution of a cell or structure

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M

Macrophage
Type of white blood cell (WBC) that has left the circulation and settled and matured in a tissue

Mitosis
Type of cell division in which each daughter cell contains the same number of chromosomes as the parent cell

Moiety
Any equal part; also any part or portion, as a portion of a molecule

Monocyte
White blood cell that engulfs foreign antigens and cell debris; one of the first lines of defense in the inflammatory process

MSM
Men who have sex with men


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N

Naïve
Patients who have not taken a drug; in the case of nucleoside naïve patients, they have never had nucleoside analog drugs

Nanometer
One billionth of a meter

Natural history
Progression of the disease over time

Nucleoside analog
Molecule with close structural similarities to naturally occurring nucleosides that competes for binding with the active site of DNA polymerase to inhibit the viral enzyme reverse transcriptase; often used in the treatment of HIV and HBV infection

Nucleotide
Structural component of DNA and RNA; consists of a base plus a molecule of sugar and one of phosphoric acid

Nucleotide analog
Compounds that look like the nucleotides in DNA; they are used as antiviral compounds because the nucleic acids assembled with these analogs fall apart, preventing the viral genome from being copied


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O

Oncogenic
Malignant transformation leading to the formation of a cancer or tumor

Open Reading Frame (ORF)
DNA sequence that is potentially able to encode for a production of a protein


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P

Parenchyma
Functional tissue of an organ, as distinct from structures such as the framework or fibrous outer layer(s) that holds the organ together

Pathology
The branch of medicine dealing with the essential nature of disease, especially changes in body tissues and organs that cause or are caused by disease

PCR Assay
A highly sensitive test that can detect small amounts of DNA or RNA in blood or tissue samples using an amplification technique that multiplies the existing DNA/RNA so that it can more easily be detected

Pegylated
Molecule with added polyethylene glycol (PEG)

Phagocytosis
Process by which cells ingest, digest, and destroy bacteria, bits of dead tissue, or other solid substances, such as other
cells

Phospholipid
Fat molecule that contains phosphates; important constituent of cell membranes

Phosphorylated
The metabolic process of introducing a phosphate group into an organic molecule

Plasmid
Stable replicating and functioning segment of genetic information separate from and not essential to the host cell's chromosome; can be used to produce large amounts of gene product (e.g., mammalian protein) in cells in which it does not normally occur

Polyclonal
Producing a number of different cell types

Polyethylene glycol (PEG)
One of a class of viscous-to-waxy water-soluble polymers created from the condensation of ethylene glycol and water; used in pharmaceuticals

Pregenomic RNA
RNA that ultimately serves as the template for synthesis of viral DNA; also called PG mRNA

Prodrome
Symptoms and signs indicating onset of disease or infection

Prodrug
Inactive form of a drug that is converted to the active form by metabolism in the patient's body

Pruritus
Severe itching, often of undamaged skin


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Q


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R

Recombinant
Refers to genetic material produced by joining DNA from different sources (e.g., strains or organisms) or the progeny from such genetic material

Recurrent Viremia
Reappearance of virus in the bloodstream after a period of remission

Resolved Hepatitis B
Previous HBV infection without further virologic, biochemical or histologic evidence of active virus infection or disease

Retrovirus
Any of several viruses whose genetic specification is encoded in RNA rather than DNA and that are able to reverse the normal flow of genetic information from DNA to RNA by transcribing RNA into DNA

Reverse Hybridization
A line probe technology for the detection of LAM-resistant HBV mutants

Reverse Transcriptase (RT)
Enzyme that creates DNA from RNA

Ribavarin
Synthetic nucleoside antiviral agent that is used in combination with PEG-IFN to treat Hepatitis C infection

RNA Probe
RNA sequence used to detect the presence of a complementary sequence of DNA


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S

Self-limited
Denoting a disease that tends to cease after a definite period of time

Sensitivity
Probability that a test result is positive when the disease is present, "true positive rate" = sensitivity (%)

Septum
Thin membrane dividing two masses of soft tissue (plural: septa)

Sequelae
A pathological condition resulting from a disease

Serotype
A group of closely related microorganisms distinguished by a characteristic set of antigens

Signal Amplification
Technique used to enhance the ability of a test to detect and quantify HBV DNA in blood samples by augmenting the signal obtained from each molecule

Sinusoid
Vascular tunnel through hepatic tissue; site of nutrient, oxygen, and waste exchange between blood and hepatocytes

Specificity
Probability that a test result is negative when disease is not present; "true negative rate" = specificity (%)

Stop Mutation
Mutation in one base of DNA that creates a signal for termination of protein synthesis

Stupor
State of altered mental status in which a person is arousable only with vigorous or unpleasant stimulation

Subcloning
A restriction fragment of an original DNA that has been cloned; may be further digested with another restriction enzyme and the smaller fragments cloned

Subunit viral vaccine
Vaccine that protects against a virus as a whole by raising immunity to one particular component of the virus


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T

Taxonomy
Classification of organisms in an ordered system that indicates natural relationships

Thiacytidine
Cytidine with a sulfur atom substituted for one of the carbon atoms

Thymidine
One of the four major ribonucleoside components of DNA

Transfection
Infection of a cell with purified viral nucleic acid, resulting in subsequent replication of the virus in the cell

Triglycerides
Lipid (fat) composed of glycerol and fatty acids

Tumor necrosis factor (TNF)
Substance released primarily by white blood cells that helps regulate the immune response


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U

Upstream Region
Region of DNA that precedes the transcription start site for a particular gene

Urea
Waste product formed during the breakdown of proteins and/or ammonia

Urticaria
A skin condition characterized by the formation of itchy red or whitish raised patches, commonly referred to as "hives"


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V

Vertical transmission
Another way to describe maternal-neonatal transmission; the transmission of an infection or other disease from mother to child (i.e. from one generation to another) immediately before or after birth during the perinatal period

Viral capsid
Protective layer of protein molecules that surrounds the nucleic acid of a virus

Viral Load
Amount of virus present in the blood

Viremia
The presence of viruses in the bloodstream

Virion
Structurally complete and infectious virus particle


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W


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X

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Y

YMDD Mutation
Specific mutation occurring in the tyrosine-methionine-aspartate-aspartate (abbreviated YMDD) portion of the HBV polymerase gene associated with the active site of the DNA polymerase



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Z

Zones of acinus
The zones of the hepatic acinus correspond to the folling areas of the liver:
Zone 1 corresponds to the peripheral zone of the lobule, Zone 2 corresponds to the midzonal region, and Zone 3 corresponds to the centrilobular region.

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