Liver Diseases: Pathological processes of the LIVER.Liver Diseases, Alcoholic: Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Fatty Liver: Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another.Liver Neoplasms: Tumors or cancer of the LIVER.End Stage Liver Disease: Final stage of a liver disease when the liver failure is irreversible and LIVER TRANSPLANTATION is needed.Liver Function Tests: Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions.Hepatitis: INFLAMMATION of the LIVER.Liver Cirrhosis, Alcoholic: FIBROSIS of the hepatic parenchyma due to chronic excess ALCOHOL DRINKING.Liver Regeneration: Repair or renewal of hepatic tissue.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Drug-Induced Liver Injury: A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.Hepatitis, Alcoholic: INFLAMMATION of the LIVER due to ALCOHOL ABUSE. It is characterized by NECROSIS of HEPATOCYTES, infiltration by NEUTROPHILS, and deposit of MALLORY BODIES. Depending on its severity, the inflammatory lesion may be reversible or progress to LIVER CIRRHOSIS.Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 220.127.116.11.Liver Failure: Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)Hepatitis, Chronic: INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.Mitochondria, Liver: Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Liver Failure, Acute: A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.Liver Cirrhosis, Biliary: FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.Liver Circulation: The circulation of BLOOD through the LIVER.Fatty Liver, Alcoholic: Lipid infiltration of the hepatic parenchymal cells that is due to ALCOHOL ABUSE. The fatty changes in the alcoholic fatty liver may be reversible, depending on the amounts of TRIGLYCERIDES accumulated.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Hepatitis C, Chronic: INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Liver Extracts: Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia.Hepatitis, Autoimmune: A chronic self-perpetuating hepatocellular INFLAMMATION of unknown cause, usually with HYPERGAMMAGLOBULINEMIA and serum AUTOANTIBODIES.Hepatitis, Viral, Human: INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D).Liver Neoplasms, Experimental: Experimentally induced tumors of the LIVER.Hepatectomy: Excision of all or part of the liver. (Dorland, 28th ed)Liver Cirrhosis, Experimental: Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.Hepatitis C: INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.Hepatic Encephalopathy: A syndrome characterized by central nervous system dysfunction in association with LIVER FAILURE, including portal-systemic shunts. Clinical features include lethargy and CONFUSION (frequently progressing to COMA); ASTERIXIS; NYSTAGMUS, PATHOLOGIC; brisk oculovestibular reflexes; decorticate and decerebrate posturing; MUSCLE SPASTICITY; and bilateral extensor plantar reflexes (see REFLEX, BABINSKI). ELECTROENCEPHALOGRAPHY may demonstrate triphasic waves. (From Adams et al., Principles of Neurology, 6th ed, pp1117-20; Plum & Posner, Diagnosis of Stupor and Coma, 3rd ed, p222-5)Hepatitis B: INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.Bilirubin: A bile pigment that is a degradation product of HEME.Cholestasis, Intrahepatic: Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).Aspartate Aminotransferases: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 18.104.22.168.Liver Abscess: Solitary or multiple collections of PUS within the liver as a result of infection by bacteria, protozoa, or other agents.Bile Ducts: The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.alpha 1-Antitrypsin Deficiency: Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.Hepacivirus: A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.Liver, Artificial: Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.Cholangitis, Sclerosing: Chronic inflammatory disease of the BILIARY TRACT. It is characterized by fibrosis and hardening of the intrahepatic and extrahepatic biliary ductal systems leading to bile duct strictures, CHOLESTASIS, and eventual BILIARY CIRRHOSIS.Kupffer Cells: Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells.Hypertension, Portal: Abnormal increase of resistance to blood flow within the hepatic PORTAL SYSTEM, frequently seen in LIVER CIRRHOSIS and conditions with obstruction of the PORTAL VEIN.gamma-Glutamyltransferase: An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Ascites: Accumulation or retention of free fluid within the peritoneal cavity.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Waiting Lists: Prospective patient listings for appointments or treatments.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Carbon Tetrachloride: A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)Hepatitis B, Chronic: INFLAMMATION of the LIVER in humans caused by HEPATITIS B VIRUS lasting six months or more. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Hepatic Stellate Cells: Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.Drug-Induced Liver Injury, Chronic: Liver disease lasting six months or more, caused by an adverse drug effect. The adverse effect may result from a direct toxic effect of a drug or metabolite, or an idiosyncratic response to a drug or metabolite.Hepatomegaly: Enlargement of the liver.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Hepatopulmonary Syndrome: A syndrome characterized by the clinical triad of advanced chronic liver disease, pulmonary vascular dilatations, and reduced arterial oxygenation (HYPOXEMIA) in the absence of intrinsic cardiopulmonary disease. This syndrome is common in the patients with LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL).Hepatitis B virus: The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum.Hepatic Veins: Veins which drain the liver.Hepatic Insufficiency: Conditions in which the LIVER functions fall below the normal ranges. Severe hepatic insufficiency may cause LIVER FAILURE or DEATH. Treatment may include LIVER TRANSPLANTATION.Hepatitis, Animal: INFLAMMATION of the LIVER in non-human animals.Cysts: Any fluid-filled closed cavity or sac that is lined by an EPITHELIUM. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues.Tissue and Organ Procurement: The administrative procedures involved with acquiring TISSUES or organs for TRANSPLANTATION through various programs, systems, or organizations. These procedures include obtaining consent from TISSUE DONORS and arranging for transportation of donated tissues and organs, after TISSUE HARVESTING, to HOSPITALS for processing and transplantation.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Liver Glycogen: Glycogen stored in the liver. (Dorland, 28th ed)Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein.Protoporphyria, Erythropoietic: An autosomal dominant porphyria that is due to a deficiency of FERROCHELATASE (heme synthetase) in both the LIVER and the BONE MARROW, the last enzyme in the 8-enzyme biosynthetic pathway of HEME. Clinical features include mainly neurological symptoms, rarely cutaneous lesions, and elevated levels of protoporphyrin and COPROPORPHYRINS in the feces.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Living Donors: Non-cadaveric providers of organs for transplant to related or non-related recipients.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Biliary Tract Diseases: Diseases in any part of the BILIARY TRACT including the BILE DUCTS and the GALLBLADDER.Biliary Atresia: Progressive destruction or the absence of all or part of the extrahepatic BILE DUCTS, resulting in the complete obstruction of BILE flow. Usually, biliary atresia is found in infants and accounts for one third of the neonatal cholestatic JAUNDICE.Elasticity Imaging Techniques: Non-invasive imaging methods based on the mechanical response of an object to a vibrational or impulsive force. It is used for determining the viscoelastic properties of tissue, and thereby differentiating soft from hard inclusions in tissue such as microcalcifications, and some cancer lesions. Most techniques use ultrasound to create the images - eliciting the response with an ultrasonic radiation force and/or recording displacements of the tissue by Doppler ultrasonography.Hemochromatosis: A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)Hepatolenticular Degeneration: A rare autosomal recessive disease characterized by the deposition of copper in the BRAIN; LIVER; CORNEA; and other organs. It is caused by defects in the ATP7B gene encoding copper-transporting ATPase 2 (EC 22.214.171.124), also known as the Wilson disease protein. The overload of copper inevitably leads to progressive liver and neurological dysfunction such as LIVER CIRRHOSIS; TREMOR; ATAXIA and intellectual deterioration. Hepatic dysfunction may precede neurologic dysfunction by several years.Hepatorenal Syndrome: Functional KIDNEY FAILURE in patients with liver disease, usually LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL), and in the absence of intrinsic renal disease or kidney abnormality. It is characterized by intense renal vasculature constriction, reduced renal blood flow, OLIGURIA, and sodium retention.Cholagogues and Choleretics: Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Alcoholism: A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Cytochrome P-450 CYP2E1: An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.Liver Diseases, Parasitic: Liver diseases caused by infections with PARASITES, such as tapeworms (CESTODA) and flukes (TREMATODA).Keratin-18: A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.Hepatitis B Surface Antigens: Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.Transaminases: A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.alpha-Fetoproteins: The first alpha-globulins to appear in mammalian sera during FETAL DEVELOPMENT and the dominant serum proteins in early embryonic life.Esophageal and Gastric Varices: Dilated blood vessels in the ESOPHAGUS or GASTRIC FUNDUS that shunt blood from the portal circulation (PORTAL SYSTEM) to the systemic venous circulation. Often they are observed in individuals with portal hypertension (HYPERTENSION, PORTAL).Hepatitis A: INFLAMMATION of the LIVER in humans caused by a member of the HEPATOVIRUS genus, HUMAN HEPATITIS A VIRUS. It can be transmitted through fecal contamination of food or water.Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.Bile Ducts, Intrahepatic: Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Choline Deficiency: A condition produced by a deficiency of CHOLINE in animals. Choline is known as a lipotropic agent because it has been shown to promote the transport of excess fat from the liver under certain conditions in laboratory animals. Combined deficiency of choline (included in the B vitamin complex) and all other methyl group donors causes liver cirrhosis in some animals. Unlike compounds normally considered as vitamins, choline does not serve as a cofactor in enzymatic reactions. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Hepatitis B Antigens: Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.TriglyceridesRats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Jaundice: A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Tissue Donors: Individuals supplying living tissue, organs, cells, blood or blood components for transfer or transplantation to histocompatible recipients.Carbon Tetrachloride PoisoningCytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Organ Size: The measurement of an organ in volume, mass, or heaviness.Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Biliary Tract: The BILE DUCTS and the GALLBLADDER.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Kinetics: The rate dynamics in chemical or physical systems.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system.Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Iron Overload: An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. (From Churchill's Illustrated Medical Dictionary, 1989)Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Hepatitis Antibodies: Immunoglobulins raised by any form of viral hepatitis; some of these antibodies are used to diagnose the specific kind of hepatitis.DNA Virus InfectionsMice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 126.96.36.199.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Metabolic Syndrome X: A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas).Alcohol Drinking: Behaviors associated with the ingesting of alcoholic beverages, including social drinking.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Silymarin: A mixture of flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum. It consists primarily of silybin and its isomers, silicristin and silidianin. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent.Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Alcohol Abstinence: Non-consumption of ALCOHOLIC BEVERAGES.Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Lipogenesis: De novo fat synthesis in the body. This includes the synthetic processes of FATTY ACIDS and subsequent TRIGLYCERIDES in the LIVER and the ADIPOSE TISSUE. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements.Platelet Count: The number of PLATELETS per unit volume in a sample of venous BLOOD.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Diet: Regular course of eating and drinking adopted by a person or animal.GalactosamineThioacetamide: A crystalline compound used as a laboratory reagent in place of HYDROGEN SULFIDE. It is a potent hepatocarcinogen.Hepatitis D, Chronic: INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS in conjunction with HEPATITIS B VIRUS and lasting six months or more.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols.Rats, Inbred F344Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Keratin-8: A type II keratin found associated with KERATIN-18 in simple, or predominately single layered, internal epithelia.Siderosis: A form of pneumoconiosis resulting from inhalation of iron in the mining dust or welding fumes.ROC Curve: A graphic means for assessing the ability of a screening test to discriminate between healthy and diseased persons; may also be used in other studies, e.g., distinguishing stimuli responses as to a faint stimuli or nonstimuli.Serum Albumin: A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Recurrence: The return of a sign, symptom, or disease after a remission.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.Portacaval Shunt, Surgical: Surgical portasystemic shunt between the portal vein and inferior vena cava.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Egypt: A country in northern Africa, bordering the Mediterranean Sea, between Libya and the Gaza Strip, and the Red Sea north of Sudan, and includes the Asian Sinai Peninsula Its capital is Cairo.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Albumins: Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Risk Assessment: The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)Diet, High-Fat: Consumption of excessive DIETARY FATS.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.Biopsy, Needle: Removal and examination of tissue obtained through a transdermal needle inserted into the specific region, organ, or tissue being analyzed.Cholangitis: Inflammation of the biliary ductal system (BILE DUCTS); intrahepatic, extrahepatic, or both.Prothrombin Time: Clotting time of PLASMA recalcified in the presence of excess TISSUE THROMBOPLASTIN. Factors measured are FIBRINOGEN; PROTHROMBIN; FACTOR V; FACTOR VII; and FACTOR X. It is used for monitoring anticoagulant therapy with COUMARINS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Bacterial Translocation: The passage of viable bacteria from the GASTROINTESTINAL TRACT to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the INTESTINAL MUCOSA resulting in increased intestinal permeability. Bacterial translocation from the lung to the circulation is also possible and sometimes accompanies MECHANICAL VENTILATION.Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.Hyperbilirubinemia: A condition characterized by an abnormal increase of BILIRUBIN in the blood, which may result in JAUNDICE. Bilirubin, a breakdown product of HEME, is normally excreted in the BILE or further catabolized before excretion in the urine.Flaviviridae: A family of RNA viruses, many of which cause disease in humans and domestic animals. There are three genera FLAVIVIRUS; PESTIVIRUS; and HEPACIVIRUS, as well as several unassigned species.Alagille Syndrome: A multisystem disorder that is characterized by aplasia of intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC), and malformations in the cardiovascular system, the eyes, the vertebral column, and the facies. Major clinical features include JAUNDICE, and congenital heart disease with peripheral PULMONARY STENOSIS. Alagille syndrome may result from heterogeneous gene mutations, including mutations in JAG1 on CHROMOSOME 20 (Type 1) and NOTCH2 on CHROMOSOME 1 (Type 2).Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Adenoma, Liver Cell: A benign epithelial tumor of the LIVER.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Gastrointestinal Hemorrhage: Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.Blood Coagulation Disorders: Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.Hepatitis C Antibodies: Antibodies to the HEPATITIS C ANTIGENS including antibodies to envelope, core, and non-structural proteins.Bile Duct Diseases: Diseases in any part of the ductal system of the BILIARY TRACT from the smallest BILE CANALICULI to the largest COMMON BILE DUCT.Acute Disease: Disease having a short and relatively severe course.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Hepatitis B Antibodies: Antibodies to the HEPATITIS B ANTIGENS, including antibodies to the surface (Australia) and core of the Dane particle and those to the "e" antigens.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.