Materiały źródłowe

• #1 Mechanisms of hepatotoxicity – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11812920/

  This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. […] Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.

• #2 Hepatotoxicity – Wikipedia

  https://en.wikipedia.org/wiki/Hepatotoxicity

  Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. […] The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. acetaminophen, paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. […] Chemicals that cause liver injury are called hepatotoxins. […] Many chemicals damage mitochondria, an intracellular organelle that produces energy. Its dysfunction releases excessive amount of oxidants that, in turn, injure hepatic cells. Activation of some enzymes in the cytochrome P-450 system such as CYP2E1 also lead to oxidative stress.

• #3 Hepatotoxicity – Wikipedia

  https://en.wikipedia.org/wiki/Hepatotoxicity

  Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. […] Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via portal veins that bring drugs and xenobiotics in near-undiluted form. […] The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.

• #4 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms. […] After absorption into the systemic circulation and distribution throughout the body: localization of toxicity in distinct tissues. […] Mechanism of Liver Damage Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and then spleen via portal veins which bring drugs and xenobiotics in concentrated form. Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside liver. This promotes further liver damage. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process. Many chemicals damage mitochondria, an intracellular organelle that produce energy. Its dysfunction releases excessive amount of oxidants which in turn injures hepatic cells. Non-parenchymal cells such as Kupffer cells, fat storing stellate cells and leukocytes (i.e. neutrophil and monocyte) also have role in the mechanism.

• #5 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  The pathophysiologic mechanisms of hepatotoxicity are still being explored and include both hepatocellular and extracellular mechanisms. The following are some of the mechanisms that have been described: […] Disruption of the hepatocyte: Covalent binding of the drug to intracellular proteins can cause a decrease in ATP levels, leading to actin disruption. Disassembly of actin fibrils at the surface of the hepatocyte causes blebs and rupture of the membrane. […] Disruption of the transport proteins: Drugs that affect transport proteins at the canalicular membrane can interrupt bile flow. Loss of villous processes and interruption of transport pumps such as multidrug resistance-associated protein 3 prevent the excretion of bilirubin, causing cholestasis. […] Cytolytic T-cell activation: Covalent binding of a drug to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response.

• #6 Toxic hepatitis in occupational exposure to solvents

  https://www.wjgnet.com/1007-9327/full/v18/i22/2756.htm

  The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. […] The principal alterations are: (1) Disruption of the hepatocyte; with a decrease in ATP levels. Disassembly of actin fibrils at the surface of the hepatocyte with blistering and rupture of the membrane; (2) Disruption of the transport proteins; toxins may affect transport proteins at the canalicular membrane and can interrupt bile flow. It also detects interruption of transport pumps; (3) Cytolytic T-cell activation: the covalent binding of a toxin to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response; (4) Apoptosis of hepatocytes; activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death; and (5) Bile duct injury; toxic metabolites excreted in bile may cause injury to the bile duct epithelium. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress.

• #7 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  The pathophysiologic mechanisms of hepatotoxicity are still being explored and include both hepatocellular and extracellular mechanisms. The following are some of the mechanisms that have been described: […] Disruption of the hepatocyte: Covalent binding of the drug to intracellular proteins can cause a decrease in ATP levels, leading to actin disruption. Disassembly of actin fibrils at the surface of the hepatocyte causes blebs and rupture of the membrane. […] Disruption of the transport proteins: Drugs that affect transport proteins at the canalicular membrane can interrupt bile flow. Loss of villous processes and interruption of transport pumps such as multidrug resistance-associated protein 3 prevent the excretion of bilirubin, causing cholestasis. […] Cytolytic T-cell activation: Covalent binding of a drug to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response.

• #8 Toxic hepatitis in occupational exposure to solvents

  https://www.wjgnet.com/1007-9327/full/v18/i22/2756.htm

  The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. […] The principal alterations are: (1) Disruption of the hepatocyte; with a decrease in ATP levels. Disassembly of actin fibrils at the surface of the hepatocyte with blistering and rupture of the membrane; (2) Disruption of the transport proteins; toxins may affect transport proteins at the canalicular membrane and can interrupt bile flow. It also detects interruption of transport pumps; (3) Cytolytic T-cell activation: the covalent binding of a toxin to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response; (4) Apoptosis of hepatocytes; activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death; and (5) Bile duct injury; toxic metabolites excreted in bile may cause injury to the bile duct epithelium. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress.

• #9 Biochemical and cellular mechanisms of toxic liver injury – PubMed

  https://pubmed.ncbi.nlm.nih.gov/12016545/

  The pathogenesis of drug- or toxin-induced liver injury usually involves the participation of toxic metabolites that either elicit an immune response or directly affect the biochemistry of the cell. […] The clinical appearance of hepatitis is then a consequence of cell death mediated by either the extrinsic immune system (e.g., cytotoxic T cells) or intracellular stress. […] Intracellular stress can lead to apoptotic or necrotic cell death, depending on the extent of mitochondrial involvement and the balance of factors that activate and inhibit the Bcl 2 family of proteins and the caspases. […] Drug metabolites can undergo or promote a variety of chemical reactions, including covalent binding, depletion of reduced glutathione, or oxidative stress with consequent effects on proteins, lipids, and DNA.

• #10 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  Apoptosis of hepatocytes: Activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death. […] Mitochondrial disruption: Certain drugs inhibit mitochondrial function by a dual effect on both beta-oxidation energy production by inhibiting the synthesis of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, resulting in decreased ATP production. […] Bile duct injury: Toxic metabolites excreted in bile may cause injury to the bile duct epithelium.

• #11 Hepatotoxicity – Wikipedia

  https://en.wikipedia.org/wiki/Hepatotoxicity

  Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. […] Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via portal veins that bring drugs and xenobiotics in near-undiluted form. […] The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.

• #12 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms. […] After absorption into the systemic circulation and distribution throughout the body: localization of toxicity in distinct tissues. […] Mechanism of Liver Damage Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and then spleen via portal veins which bring drugs and xenobiotics in concentrated form. Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside liver. This promotes further liver damage. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process. Many chemicals damage mitochondria, an intracellular organelle that produce energy. Its dysfunction releases excessive amount of oxidants which in turn injures hepatic cells. Non-parenchymal cells such as Kupffer cells, fat storing stellate cells and leukocytes (i.e. neutrophil and monocyte) also have role in the mechanism.

• #13 Mechanisms of hepatotoxicity – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11812920/

  This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. […] Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.

• #14 Mechanisms of hepatotoxicity – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11812920/

  This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. […] Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.

• #15 Hepatotoxicity – Wikipedia

  https://en.wikipedia.org/wiki/Hepatotoxicity

  Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. […] Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via portal veins that bring drugs and xenobiotics in near-undiluted form. […] The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.

• #16 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  Acetaminophen:- (Paracetamol, also known by the brand name Tylenol and Panadol) is usually well tolerated in prescribed dose but overdose is the most common cause of drug induced liver disease and acute liver failure worldwide. Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease. […] Acetaminophen Mechanism of Toxicity APAP is metabolized in the liver By glucuronidation and sulfation At therapeutic doses 4% converted by the cytochrome P450 into the reactive toxic intermediate N-acetyl-p-benzoquinoneimine (NAPQI) NAPQI becomes nontoxic when it binds to glutathione. […] Acetaminophen Mechanism of Toxicity APAP overdose occurs due to CYP enzyme induction Glutathione depletion Inhibition of glucuronidation If any of the previous actions occur NAPQI is no longer able to bind to glutathione Instead, NAPQI reacts with the cysteine group of hepatocellular proteins Leads to the loss of cell function and cell death. […] General Effects of Toxicity The classic effect is hepatotoxicity, can lead to jaundice and increased liver enzymes in the blood Liver failure can result in encephalopathy, confusion, coma and ultimately leading to death.

• #17 Mechanisms of hepatotoxicity – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11812920/

  This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. […] Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.

• #18 Hepatotoxicity by Drugs | IntechOpen

  https://www.intechopen.com/chapters/57809

  The drug metabolites generated in the liver through biotransformation can cause hepatic damage because formation of toxic or reactive substances such as electrophilic chemicals or free radicals, and thus an unchain a variety of chemical reactions may happen. […] These mechanisms can either generate necrosis or apoptosis or both. […] Mitochondrial dysfunction: may be generated by the disruption of -oxidation of lipids and oxidative energy production within the hepatocytes. […] Immune response: is attributed to the formation of new antigens, this give origin to the idiosyncratic hepatotoxicity. […] Oxidative stress: is produced by ATP depletion accompanied by increase in intracellular calcium concentration, it can generate necrosis. […] Lipid peroxidation: is generated by the interaction between free radicals and fatty acids in membrane, the subsequent reaction may produce electrophilic metabolites generating DNA damage.

• #19 Hepatotoxicity – Wikipedia

  https://en.wikipedia.org/wiki/Hepatotoxicity

  Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. […] Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via portal veins that bring drugs and xenobiotics in near-undiluted form. […] The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.

• #20 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms. […] After absorption into the systemic circulation and distribution throughout the body: localization of toxicity in distinct tissues. […] Mechanism of Liver Damage Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and then spleen via portal veins which bring drugs and xenobiotics in concentrated form. Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside liver. This promotes further liver damage. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process. Many chemicals damage mitochondria, an intracellular organelle that produce energy. Its dysfunction releases excessive amount of oxidants which in turn injures hepatic cells. Non-parenchymal cells such as Kupffer cells, fat storing stellate cells and leukocytes (i.e. neutrophil and monocyte) also have role in the mechanism.

• #21 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms. […] After absorption into the systemic circulation and distribution throughout the body: localization of toxicity in distinct tissues. […] Mechanism of Liver Damage Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and then spleen via portal veins which bring drugs and xenobiotics in concentrated form. Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside liver. This promotes further liver damage. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process. Many chemicals damage mitochondria, an intracellular organelle that produce energy. Its dysfunction releases excessive amount of oxidants which in turn injures hepatic cells. Non-parenchymal cells such as Kupffer cells, fat storing stellate cells and leukocytes (i.e. neutrophil and monocyte) also have role in the mechanism.

• #22 Mechanisms of hepatotoxicity – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11812920/

  This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. […] Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.

• #23

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  The diagnosis of hepatitis (acute, chronic, etc.) is only possible with histology of the liver. […] In an acute hepatitis all of the enzymes are usually definitely elevated. […] Very extensive liver cell necrosis is called fulminant hepatitis. It leads to the development of hepatic encephalopathy, DIC, jaundice, and hypoglycaemia. […] Acute hepatitis is characterized by liver necrosis and the accompanying inflammation. The necrosis is usually a liquefying necrosis with collapse of the reticular framework. […] Infection with canine adenovirus-1 is usually characterized by confluent and bridging necrosis in the centrilobular zone and by the presence of intranuclear inclusions in hepatocytes and Kupffer’s cells. […] Acute hepatitis may also be caused by various toxins, such as mushroom toxins (Amanitum), blue-green algae toxins (Cyanophyceae) or dose-dependent drug toxicity (acetaminophen in dogs and cats).

• #24 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  The pathophysiologic mechanisms of hepatotoxicity are still being explored and include both hepatocellular and extracellular mechanisms. The following are some of the mechanisms that have been described: […] Disruption of the hepatocyte: Covalent binding of the drug to intracellular proteins can cause a decrease in ATP levels, leading to actin disruption. Disassembly of actin fibrils at the surface of the hepatocyte causes blebs and rupture of the membrane. […] Disruption of the transport proteins: Drugs that affect transport proteins at the canalicular membrane can interrupt bile flow. Loss of villous processes and interruption of transport pumps such as multidrug resistance-associated protein 3 prevent the excretion of bilirubin, causing cholestasis. […] Cytolytic T-cell activation: Covalent binding of a drug to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response.

• #25 Toxic hepatitis in occupational exposure to solvents

  https://www.wjgnet.com/1007-9327/full/v18/i22/2756.htm

  The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. […] The principal alterations are: (1) Disruption of the hepatocyte; with a decrease in ATP levels. Disassembly of actin fibrils at the surface of the hepatocyte with blistering and rupture of the membrane; (2) Disruption of the transport proteins; toxins may affect transport proteins at the canalicular membrane and can interrupt bile flow. It also detects interruption of transport pumps; (3) Cytolytic T-cell activation: the covalent binding of a toxin to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response; (4) Apoptosis of hepatocytes; activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death; and (5) Bile duct injury; toxic metabolites excreted in bile may cause injury to the bile duct epithelium. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress.

• #26 Biochemical and cellular mechanisms of toxic liver injury – PubMed

  https://pubmed.ncbi.nlm.nih.gov/12016545/

  The pathogenesis of drug- or toxin-induced liver injury usually involves the participation of toxic metabolites that either elicit an immune response or directly affect the biochemistry of the cell. […] The clinical appearance of hepatitis is then a consequence of cell death mediated by either the extrinsic immune system (e.g., cytotoxic T cells) or intracellular stress. […] Intracellular stress can lead to apoptotic or necrotic cell death, depending on the extent of mitochondrial involvement and the balance of factors that activate and inhibit the Bcl 2 family of proteins and the caspases. […] Drug metabolites can undergo or promote a variety of chemical reactions, including covalent binding, depletion of reduced glutathione, or oxidative stress with consequent effects on proteins, lipids, and DNA.

• #27 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  Apoptosis of hepatocytes: Activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death. […] Mitochondrial disruption: Certain drugs inhibit mitochondrial function by a dual effect on both beta-oxidation energy production by inhibiting the synthesis of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, resulting in decreased ATP production. […] Bile duct injury: Toxic metabolites excreted in bile may cause injury to the bile duct epithelium.

• #28 Toxic hepatitis in occupational exposure to solvents

  https://www.wjgnet.com/1007-9327/full/v18/i22/2756.htm

  The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. […] The principal alterations are: (1) Disruption of the hepatocyte; with a decrease in ATP levels. Disassembly of actin fibrils at the surface of the hepatocyte with blistering and rupture of the membrane; (2) Disruption of the transport proteins; toxins may affect transport proteins at the canalicular membrane and can interrupt bile flow. It also detects interruption of transport pumps; (3) Cytolytic T-cell activation: the covalent binding of a toxin to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response; (4) Apoptosis of hepatocytes; activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death; and (5) Bile duct injury; toxic metabolites excreted in bile may cause injury to the bile duct epithelium. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress.

• #29 Biochemical and cellular mechanisms of toxic liver injury – PubMed

  https://pubmed.ncbi.nlm.nih.gov/12016545/

  The pathogenesis of drug- or toxin-induced liver injury usually involves the participation of toxic metabolites that either elicit an immune response or directly affect the biochemistry of the cell. […] The clinical appearance of hepatitis is then a consequence of cell death mediated by either the extrinsic immune system (e.g., cytotoxic T cells) or intracellular stress. […] Intracellular stress can lead to apoptotic or necrotic cell death, depending on the extent of mitochondrial involvement and the balance of factors that activate and inhibit the Bcl 2 family of proteins and the caspases. […] Drug metabolites can undergo or promote a variety of chemical reactions, including covalent binding, depletion of reduced glutathione, or oxidative stress with consequent effects on proteins, lipids, and DNA.

• #30 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  Apoptosis of hepatocytes: Activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death. […] Mitochondrial disruption: Certain drugs inhibit mitochondrial function by a dual effect on both beta-oxidation energy production by inhibiting the synthesis of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, resulting in decreased ATP production. […] Bile duct injury: Toxic metabolites excreted in bile may cause injury to the bile duct epithelium.

• #31 Toxic hepatitis in occupational exposure to solvents

  https://www.wjgnet.com/1007-9327/full/v18/i22/2756.htm

  The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. […] The principal alterations are: (1) Disruption of the hepatocyte; with a decrease in ATP levels. Disassembly of actin fibrils at the surface of the hepatocyte with blistering and rupture of the membrane; (2) Disruption of the transport proteins; toxins may affect transport proteins at the canalicular membrane and can interrupt bile flow. It also detects interruption of transport pumps; (3) Cytolytic T-cell activation: the covalent binding of a toxin to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response; (4) Apoptosis of hepatocytes; activation of the apoptotic pathways by the tumor necrosis factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results in programmed cell death; and (5) Bile duct injury; toxic metabolites excreted in bile may cause injury to the bile duct epithelium. […] The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress.

• #32 Drug-Induced Hepatotoxicity: Overview, Metabolism of Drugs, Clinical and Pathological Manifestations of Drug-Induced Liver Disease

  https://emedicine.medscape.com/article/169814-overview

  The pathophysiologic mechanisms of hepatotoxicity are still being explored and include both hepatocellular and extracellular mechanisms. The following are some of the mechanisms that have been described: […] Disruption of the hepatocyte: Covalent binding of the drug to intracellular proteins can cause a decrease in ATP levels, leading to actin disruption. Disassembly of actin fibrils at the surface of the hepatocyte causes blebs and rupture of the membrane. […] Disruption of the transport proteins: Drugs that affect transport proteins at the canalicular membrane can interrupt bile flow. Loss of villous processes and interruption of transport pumps such as multidrug resistance-associated protein 3 prevent the excretion of bilirubin, causing cholestasis. […] Cytolytic T-cell activation: Covalent binding of a drug to the P-450 enzyme acts as an immunogen, activating T cells and cytokines and stimulating a multifaceted immune response.

• #33 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  Acetaminophen:- (Paracetamol, also known by the brand name Tylenol and Panadol) is usually well tolerated in prescribed dose but overdose is the most common cause of drug induced liver disease and acute liver failure worldwide. Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease. […] Acetaminophen Mechanism of Toxicity APAP is metabolized in the liver By glucuronidation and sulfation At therapeutic doses 4% converted by the cytochrome P450 into the reactive toxic intermediate N-acetyl-p-benzoquinoneimine (NAPQI) NAPQI becomes nontoxic when it binds to glutathione. […] Acetaminophen Mechanism of Toxicity APAP overdose occurs due to CYP enzyme induction Glutathione depletion Inhibition of glucuronidation If any of the previous actions occur NAPQI is no longer able to bind to glutathione Instead, NAPQI reacts with the cysteine group of hepatocellular proteins Leads to the loss of cell function and cell death. […] General Effects of Toxicity The classic effect is hepatotoxicity, can lead to jaundice and increased liver enzymes in the blood Liver failure can result in encephalopathy, confusion, coma and ultimately leading to death.

• #34 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  Acetaminophen:- (Paracetamol, also known by the brand name Tylenol and Panadol) is usually well tolerated in prescribed dose but overdose is the most common cause of drug induced liver disease and acute liver failure worldwide. Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease. […] Acetaminophen Mechanism of Toxicity APAP is metabolized in the liver By glucuronidation and sulfation At therapeutic doses 4% converted by the cytochrome P450 into the reactive toxic intermediate N-acetyl-p-benzoquinoneimine (NAPQI) NAPQI becomes nontoxic when it binds to glutathione. […] Acetaminophen Mechanism of Toxicity APAP overdose occurs due to CYP enzyme induction Glutathione depletion Inhibition of glucuronidation If any of the previous actions occur NAPQI is no longer able to bind to glutathione Instead, NAPQI reacts with the cysteine group of hepatocellular proteins Leads to the loss of cell function and cell death. […] General Effects of Toxicity The classic effect is hepatotoxicity, can lead to jaundice and increased liver enzymes in the blood Liver failure can result in encephalopathy, confusion, coma and ultimately leading to death.

• #35 Mechanisms of Hepatotoxicity | PPT

  https://www.slideshare.net/slideshow/mechanisms-of-hepatotoxicity/76647473

  Acetaminophen:- (Paracetamol, also known by the brand name Tylenol and Panadol) is usually well tolerated in prescribed dose but overdose is the most common cause of drug induced liver disease and acute liver failure worldwide. Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease. […] Acetaminophen Mechanism of Toxicity APAP is metabolized in the liver By glucuronidation and sulfation At therapeutic doses 4% converted by the cytochrome P450 into the reactive toxic intermediate N-acetyl-p-benzoquinoneimine (NAPQI) NAPQI becomes nontoxic when it binds to glutathione. […] Acetaminophen Mechanism of Toxicity APAP overdose occurs due to CYP enzyme induction Glutathione depletion Inhibition of glucuronidation If any of the previous actions occur NAPQI is no longer able to bind to glutathione Instead, NAPQI reacts with the cysteine group of hepatocellular proteins Leads to the loss of cell function and cell death. […] General Effects of Toxicity The classic effect is hepatotoxicity, can lead to jaundice and increased liver enzymes in the blood Liver failure can result in encephalopathy, confusion, coma and ultimately leading to death.

• #36 Hepatotoxicity by Drugs | IntechOpen

  https://www.intechopen.com/chapters/57809

  Hepatotoxicity is the injury or liver damage caused by exposure to drugs; it is an adverse drug reaction that may be uncommon but serious. […] The hepatic injury can be classified into hepatocellular, cholestatic and mixed, caused by increase in alanine aminotransferase and alkaline phosphatase than upper limit of normal. […] There are two types of hepatotoxicity: intrinsic reaction which is dose-dependent and predictable (less common) and idiosyncratic reaction which is not dose-dependent and not predictable (more common). […] The underlying mechanism of the idiosyncratic reaction may be a genetic polymorphism of the cytochrome P450 (CYP450) system, responsible for the drugs hepatic biotransformation. […] The hepatocytes, cholangiocytes, Kupffer cells, ductal and endothelial cells are involved in the mechanisms by which drugs cause hepatotoxicity; having direct effects on cellular organelles such as mitochondria, endoplasmic reticulum, cytoskeleton, microtubules or nucleus.

• #37 Hepatotoxicity by Drugs | IntechOpen

  https://www.intechopen.com/chapters/57809

  Hepatotoxicity is the injury or liver damage caused by exposure to drugs; it is an adverse drug reaction that may be uncommon but serious. […] The hepatic injury can be classified into hepatocellular, cholestatic and mixed, caused by increase in alanine aminotransferase and alkaline phosphatase than upper limit of normal. […] There are two types of hepatotoxicity: intrinsic reaction which is dose-dependent and predictable (less common) and idiosyncratic reaction which is not dose-dependent and not predictable (more common). […] The underlying mechanism of the idiosyncratic reaction may be a genetic polymorphism of the cytochrome P450 (CYP450) system, responsible for the drugs hepatic biotransformation. […] The hepatocytes, cholangiocytes, Kupffer cells, ductal and endothelial cells are involved in the mechanisms by which drugs cause hepatotoxicity; having direct effects on cellular organelles such as mitochondria, endoplasmic reticulum, cytoskeleton, microtubules or nucleus.

• #38 Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues

  https://atm.amegroups.org/article/view/49630/html

  In conclusion, most of the mechanistic steps leading to idiosyncratic DILI remain unclear. […] The aim of this article is to analyze unresolved basic issues of mechanistic steps in idiosyncratic DILI. Special attention is given to immune aspects in connection with the gut microbiome and the hepatic cytochrome P450 (CYP). […] Compelling evidence exists that for most idiosyncratic DILI cases the hepatic immune system plays a prominent pathogenetic role. […] Although it is likely that most idiosyncratic DILI is immune mediated, the details of how a drug induces an immune response leading to DILI are unknown and likely different for different drugs. […] There is a large amount of circumstantial evidence for the involvement of reactive metabolites in the mechanism of idiosyncratic DILI; however, it is very difficult to prove that a specific reactive metabolite is responsible for human idiosyncratic DILI caused by a specific drug.

• #39 Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues

  https://atm.amegroups.org/article/view/49630/html

  In conclusion, most of the mechanistic steps leading to idiosyncratic DILI remain unclear. […] The aim of this article is to analyze unresolved basic issues of mechanistic steps in idiosyncratic DILI. Special attention is given to immune aspects in connection with the gut microbiome and the hepatic cytochrome P450 (CYP). […] Compelling evidence exists that for most idiosyncratic DILI cases the hepatic immune system plays a prominent pathogenetic role. […] Although it is likely that most idiosyncratic DILI is immune mediated, the details of how a drug induces an immune response leading to DILI are unknown and likely different for different drugs. […] There is a large amount of circumstantial evidence for the involvement of reactive metabolites in the mechanism of idiosyncratic DILI; however, it is very difficult to prove that a specific reactive metabolite is responsible for human idiosyncratic DILI caused by a specific drug.

• #40

  https://www.ijcrimedicine.com/archive/2015-archive/100004Z09MS2015-sterling/100004Z09MS2015-sterling-full-text.php

  Dietary and weight loss supplements have been shown to cause acute hepatitis through toxic liver injury. […] Over the last decade, research has demonstrated that dietary and weight-loss supplements are capable of causing acute hepatitis secondary to drug induced liver injury (DILI). […] This case offers new insight into the conceptualization of AIH and the ability of weight-loss supplements to act as precipitants of both acute and chronic hepatitis. […] The hepatotoxic components of these agents most likely to cause injury are Cambogia, Camellia sinensis and Chromium, which are found in several other weight-loss aids on the market such as thermo cut and Garcinia extreme. […] Although the acute presentation, history of substance use and histologic features are consistent with drug toxicity, the patient’s serologic studies and biopsy results also suggest drug-induced autoimmune hepatitis as an additional diagnosis.

• #41

  https://www.ijcrimedicine.com/archive/2015-archive/100004Z09MS2015-sterling/100004Z09MS2015-sterling-full-text.php

  This patient’s clinical and pathological diagnoses suggest that both acute toxic hepatitis and an acute presentation of autoimmune hepatitis were present. […] Given this patient’s dual diagnosis of acute hepatitis and autoimmune hepatitis, it is important to consider the long-term and chronic effects that dietary supplements can have. […] There is much to be learned regarding the mechanism by which a subset of herbal and dietary supplements can induce autoimmune hepatitis. […] This case highlights the variability in which such a disease process comes to clinical attention. […] In recent years, research has found weight loss supplements to cause severe hepatic toxicity.

• #42

  https://www.ijcrimedicine.com/archive/2015-archive/100004Z09MS2015-sterling/100004Z09MS2015-sterling-full-text.php

  This patient’s clinical and pathological diagnoses suggest that both acute toxic hepatitis and an acute presentation of autoimmune hepatitis were present. […] Given this patient’s dual diagnosis of acute hepatitis and autoimmune hepatitis, it is important to consider the long-term and chronic effects that dietary supplements can have. […] There is much to be learned regarding the mechanism by which a subset of herbal and dietary supplements can induce autoimmune hepatitis. […] This case highlights the variability in which such a disease process comes to clinical attention. […] In recent years, research has found weight loss supplements to cause severe hepatic toxicity.

• #43

  https://www.xiahepublishing.com/2310-8819/JCTH-2013-00015

  The following pathogenetic model has been proposed: in a genetically predisposed host, defined environmental agent(s) catalyze(s) and trigger a series of T cell-mediated immune events directed at hepatic cellular antigens, resulting in unfettered inflammation, which ultimately culminates in fibrotic transformation of the liver, aberrant regeneration, and cirrhosis. […] A major contributor to AIH pathogenesis is the failure of immunoregulation as a result of diminished function and sheer number of Tregs, with consequent massive recruitment of inflammatory effector cells, which inflict hepatic injury. […] Tregs express unique markers including the interleukin-2R (IL-2R) chain (CD25), the glucocorticoid induced tumor necrosis factor receptor (GITR), CD62L, CTLA-4, and forkhead/winged helix transcription factor (FOXP3) as well as CD39, an ectonucleotidase responsible for extracellular nucleotide phosphohydrolysis, culminating in the production of immunosuppressive adenosine and regulated purinergic signaling.

• #44

  https://www.xiahepublishing.com/2310-8819/JCTH-2013-00015

  The following pathogenetic model has been proposed: in a genetically predisposed host, defined environmental agent(s) catalyze(s) and trigger a series of T cell-mediated immune events directed at hepatic cellular antigens, resulting in unfettered inflammation, which ultimately culminates in fibrotic transformation of the liver, aberrant regeneration, and cirrhosis. […] A major contributor to AIH pathogenesis is the failure of immunoregulation as a result of diminished function and sheer number of Tregs, with consequent massive recruitment of inflammatory effector cells, which inflict hepatic injury. […] Tregs express unique markers including the interleukin-2R (IL-2R) chain (CD25), the glucocorticoid induced tumor necrosis factor receptor (GITR), CD62L, CTLA-4, and forkhead/winged helix transcription factor (FOXP3) as well as CD39, an ectonucleotidase responsible for extracellular nucleotide phosphohydrolysis, culminating in the production of immunosuppressive adenosine and regulated purinergic signaling.

• #45 Hepatitis: What It Is, Symptoms, Transmission & Treatments

  https://my.clevelandclinic.org/health/diseases/hepatitis

  Toxic hepatitis can be acute or chronic. […] This is hepatitis you can get from exposure to chemicals. Alcohol-induced hepatitis and drug-induced hepatitis are other types of toxic hepatitis. […] Many things can cause hepatitis. So can exposure to toxins like alcohol, drugs including medications and chemicals.

• #46

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  The diagnosis of hepatitis (acute, chronic, etc.) is only possible with histology of the liver. […] In an acute hepatitis all of the enzymes are usually definitely elevated. […] Very extensive liver cell necrosis is called fulminant hepatitis. It leads to the development of hepatic encephalopathy, DIC, jaundice, and hypoglycaemia. […] Acute hepatitis is characterized by liver necrosis and the accompanying inflammation. The necrosis is usually a liquefying necrosis with collapse of the reticular framework. […] Infection with canine adenovirus-1 is usually characterized by confluent and bridging necrosis in the centrilobular zone and by the presence of intranuclear inclusions in hepatocytes and Kupffer’s cells. […] Acute hepatitis may also be caused by various toxins, such as mushroom toxins (Amanitum), blue-green algae toxins (Cyanophyceae) or dose-dependent drug toxicity (acetaminophen in dogs and cats).

• #47

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  The diagnosis of hepatitis (acute, chronic, etc.) is only possible with histology of the liver. […] In an acute hepatitis all of the enzymes are usually definitely elevated. […] Very extensive liver cell necrosis is called fulminant hepatitis. It leads to the development of hepatic encephalopathy, DIC, jaundice, and hypoglycaemia. […] Acute hepatitis is characterized by liver necrosis and the accompanying inflammation. The necrosis is usually a liquefying necrosis with collapse of the reticular framework. […] Infection with canine adenovirus-1 is usually characterized by confluent and bridging necrosis in the centrilobular zone and by the presence of intranuclear inclusions in hepatocytes and Kupffer’s cells. […] Acute hepatitis may also be caused by various toxins, such as mushroom toxins (Amanitum), blue-green algae toxins (Cyanophyceae) or dose-dependent drug toxicity (acetaminophen in dogs and cats).

• #48

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  Chronic hepatitis is characterized by periportal fibrosis, infiltration of lymphocytes and plasma cells, and periportal liver cell apoptosis or necrosis. […] The limiting plate, which is the layer of cells dividing the portal tracts from the liver parenchyma, may become disrupted with expansion of the inflammatory reaction from portal areas into the parenchyma. […] Chronic hepatitis may be a chronic extension of acute hepatitis, but in most cases the first presentation of signs is in the chronic stage. […] The gradually progressive liver cell necrosis may cause a continuing elevation of all liver enzymes and the bile acids. […] The increased copper concentration in the liver can be confirmed after 1 year of age; before that age some dogs with the disease have not yet stored sufficient copper to distinguish them from normal animals.

• #49

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  Chronic hepatitis is characterized by periportal fibrosis, infiltration of lymphocytes and plasma cells, and periportal liver cell apoptosis or necrosis. […] The limiting plate, which is the layer of cells dividing the portal tracts from the liver parenchyma, may become disrupted with expansion of the inflammatory reaction from portal areas into the parenchyma. […] Chronic hepatitis may be a chronic extension of acute hepatitis, but in most cases the first presentation of signs is in the chronic stage. […] The gradually progressive liver cell necrosis may cause a continuing elevation of all liver enzymes and the bile acids. […] The increased copper concentration in the liver can be confirmed after 1 year of age; before that age some dogs with the disease have not yet stored sufficient copper to distinguish them from normal animals.

• #50 Toxic hepatitis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/toxic-hepatitis/symptoms-causes/syc-20352202

  Toxic hepatitis is an inflammation of your liver in reaction to certain substances to which you’re exposed. Toxic hepatitis can be caused by alcohol, chemicals, drugs or nutritional supplements. […] Toxic hepatitis occurs when your liver develops inflammation because of exposure to a toxic substance. Toxic hepatitis may also develop when you take too much of a prescription or over-the-counter medication. […] The liver normally removes and breaks down most drugs and chemicals from your bloodstream. Breaking down toxins creates byproducts that can damage the liver. Although the liver has a great capacity for regeneration, constant exposure to toxic substances can cause serious, sometimes irreversible harm. […] The inflammation associated with toxic hepatitis can lead to liver damage and scarring. Over time, this scarring, called cirrhosis, makes it difficult for your liver to do its job. Eventually cirrhosis leads to liver failure. The only treatment for chronic liver failure is to replace your liver with a healthy one from a donor (liver transplant).

• #51 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  You may develop liver toxicity if you take too much acetaminophen (Tylenol), an over-the-counter pain reliever. […] Taking too much vitamin A (more than 40,000 IU daily) can cause vitamin A liver toxicity. […] Toxic hepatitis can lead to acute liver damage (cirrhosis) and chronic liver failure. If you develop liver failure, you may need liver transplantation. […] Toxic hepatitis treatment depends on the extent of damage to your liver. […] In many instances, toxic hepatitis is curable. Your liver can replace damaged cells over time, reversing the damage that occurred. […] Toxic hepatitis recovery time depends on: […] If damage is mild to moderate, your liver may take a few weeks or months to replace the damaged cells and heal. […] To help prevent toxic hepatitis: […] You can help keep your liver healthy by making healthy lifestyle changes. […] Talk to your healthcare provider about the causes of liver toxicity and how you can improve your liver’s health.

• #52

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  Chronic hepatitis is characterized by periportal fibrosis, infiltration of lymphocytes and plasma cells, and periportal liver cell apoptosis or necrosis. […] The limiting plate, which is the layer of cells dividing the portal tracts from the liver parenchyma, may become disrupted with expansion of the inflammatory reaction from portal areas into the parenchyma. […] Chronic hepatitis may be a chronic extension of acute hepatitis, but in most cases the first presentation of signs is in the chronic stage. […] The gradually progressive liver cell necrosis may cause a continuing elevation of all liver enzymes and the bile acids. […] The increased copper concentration in the liver can be confirmed after 1 year of age; before that age some dogs with the disease have not yet stored sufficient copper to distinguish them from normal animals.

• #53

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  Oxidative damage to cell organelles causes cell death followed by an inflammatory reaction when. […] A chronic persistent hepatitis develops and the general reaction of the liver is loss of regenerative capacity and formation of fibrous tissue. […] This is a diffuse fibrosis with pericellular fibrosis around all hepatocytes. […] The progression is usually much more rapid than the regular form of chronic hepatitis; the course of this disease takes weeks rather than months.

• #54 Hepatotoxicity – Wikiwand

  http://www.wikiwand.com/en/Hepatotoxicity

  Chemicals produce a wide variety of clinical and pathological hepatic injury. Liver injury is defined as a rise in either ALT level more than three times of upper limit of normal (ULN), ALP level more than twice ULN, or total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular and cholestatic types. Specific histo-pathological patterns of liver injury from drug-induced damage are discussed below. This is the most common type of drug-induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule. It may manifest as a very high level of ALT and severe disturbance of liver function leading to acute liver failure. In this pattern, hepatocellular necrosis is associated with infiltration of inflammatory cells. Liver injury leads to impairment of bile flow and cases are predominated by itching and jaundice. Hepatotoxicity may manifest as triglyceride accumulation, which leads to either small-droplet or large-droplet fatty liver. Drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. These result from injury to the vascular endothelium. Neoplasms have been described with prolonged exposure to some medications or toxins.

• #55 Hepatotoxicity – Wikiwand

  http://www.wikiwand.com/en/Hepatotoxicity

  Chemicals produce a wide variety of clinical and pathological hepatic injury. Liver injury is defined as a rise in either ALT level more than three times of upper limit of normal (ULN), ALP level more than twice ULN, or total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular and cholestatic types. Specific histo-pathological patterns of liver injury from drug-induced damage are discussed below. This is the most common type of drug-induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule. It may manifest as a very high level of ALT and severe disturbance of liver function leading to acute liver failure. In this pattern, hepatocellular necrosis is associated with infiltration of inflammatory cells. Liver injury leads to impairment of bile flow and cases are predominated by itching and jaundice. Hepatotoxicity may manifest as triglyceride accumulation, which leads to either small-droplet or large-droplet fatty liver. Drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. These result from injury to the vascular endothelium. Neoplasms have been described with prolonged exposure to some medications or toxins.

• #56 Pathology Outlines – Drug / toxin induced hepatitis (DILI)-general

  https://www.pathologyoutlines.com/topic/liverdrugtoxingeneral.html

  Liver injury associated with exposure to certain drugs or toxins […] Underlying mechanisms include direct / indirect toxicity, aberrant metabolism producing toxic metabolites and immune mediated hypersensitivity […] Diagnosis is based on the likelihood of DILI: time to onset, time to recovery, clinicopathological phenotype, exclusion of other causes, potentially offensive drug / toxin being a known cause of liver injury, and response to re-exposure […] Very wide range of clinical and pathological presentations can result; the time of onset after drug exposure varies from hours to months […] Clinical manifestations range from asymptomatic deranged liver function to fulminant hepatic failure and death […] Diagnosis is based on likelihood of DILI […] R value = [serum alanine aminotransferase (ALT) / upper limit of normal (ULN)] / [serum alkaline phosphatase (ALP) / ULN]

• #57 Pathology Outlines – Drug / toxin induced hepatitis (DILI)-general

  https://www.pathologyoutlines.com/topic/liverdrugtoxingeneral.html

  Hepatocellular injury: R value ≥ 5 or ALT elevation ≥ 5 fold above ULN […] Cholestatic injury: R value ≤ 2 or ALP elevation ≥ 2 fold above ULN […] Mixed injury: R value between 2 and 5 […] 5 – 20% may develop chronic DILI […] DILI severity grading (U.S. Drug Induced Liver Injury Network) […] Score 1 (mild): elevated ALT or ALP but total bilirubin < 2.5 mg/dL and international normalized ratio (INR) < 1.5 [...] Score 2 (moderate): elevated ALT or ALP and total bilirubin ≥ 2.5 mg/dL or INR ≥ 1.5 [...] Score 3 (moderate - severe): elevated ALT, ALP, total bilirubin or INR and hospitalization or ongoing hospitalization is prolonged because of a DILI episode [...] Score 4 (severe): elevated ALT or ALP and total bilirubin ≥ 2.5 mg/dL and at least 1 of the following: Liver failure (INR > 1.5, ascites or encephalopathy)

• #58 Pathology Outlines – Drug / toxin induced hepatitis (DILI)-general

  https://www.pathologyoutlines.com/topic/liverdrugtoxingeneral.html

  Hepatocellular injury: R value ≥ 5 or ALT elevation ≥ 5 fold above ULN […] Cholestatic injury: R value ≤ 2 or ALP elevation ≥ 2 fold above ULN […] Mixed injury: R value between 2 and 5 […] 5 – 20% may develop chronic DILI […] DILI severity grading (U.S. Drug Induced Liver Injury Network) […] Score 1 (mild): elevated ALT or ALP but total bilirubin < 2.5 mg/dL and international normalized ratio (INR) < 1.5 [...] Score 2 (moderate): elevated ALT or ALP and total bilirubin ≥ 2.5 mg/dL or INR ≥ 1.5 [...] Score 3 (moderate - severe): elevated ALT, ALP, total bilirubin or INR and hospitalization or ongoing hospitalization is prolonged because of a DILI episode [...] Score 4 (severe): elevated ALT or ALP and total bilirubin ≥ 2.5 mg/dL and at least 1 of the following: Liver failure (INR > 1.5, ascites or encephalopathy)

• #59 Pathology Outlines – Drug / toxin induced hepatitis (DILI)-general

  https://www.pathologyoutlines.com/topic/liverdrugtoxingeneral.html

  Hepatocellular injury: R value ≥ 5 or ALT elevation ≥ 5 fold above ULN […] Cholestatic injury: R value ≤ 2 or ALP elevation ≥ 2 fold above ULN […] Mixed injury: R value between 2 and 5 […] 5 – 20% may develop chronic DILI […] DILI severity grading (U.S. Drug Induced Liver Injury Network) […] Score 1 (mild): elevated ALT or ALP but total bilirubin < 2.5 mg/dL and international normalized ratio (INR) < 1.5 [...] Score 2 (moderate): elevated ALT or ALP and total bilirubin ≥ 2.5 mg/dL or INR ≥ 1.5 [...] Score 3 (moderate - severe): elevated ALT, ALP, total bilirubin or INR and hospitalization or ongoing hospitalization is prolonged because of a DILI episode [...] Score 4 (severe): elevated ALT or ALP and total bilirubin ≥ 2.5 mg/dL and at least 1 of the following: Liver failure (INR > 1.5, ascites or encephalopathy)

• #60 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  Toxic hepatitis refers to inflammation of the liver due to medication or exposure to toxic chemicals, drugs, pollutants and nutritional supplements. In some cases, toxic hepatitis develops within hours or days of exposure to a toxin. It also known as Drug Induced Liver Injury (DILI) […] Drug-induced liver injury has an estimated incidence of 10- 15 per 10,000 to 100,000 persons exposed to prescription medications. It accounts for approximately 10 percent of all cases of acute hepatitis and it is the most common cause of acute liver failure in the United States […] More than 900 drugs, toxins, and herbs have been reported to cause liver injury, and drugs account for 20-40% of all instances of fulminant hepatic failure. Approximately 75% of the idiosyncratic drug reactions result in liver transplantation or death.

• #61 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  Toxic hepatitis refers to inflammation of the liver due to medication or exposure to toxic chemicals, drugs, pollutants and nutritional supplements. In some cases, toxic hepatitis develops within hours or days of exposure to a toxin. It also known as Drug Induced Liver Injury (DILI) […] Drug-induced liver injury has an estimated incidence of 10- 15 per 10,000 to 100,000 persons exposed to prescription medications. It accounts for approximately 10 percent of all cases of acute hepatitis and it is the most common cause of acute liver failure in the United States […] More than 900 drugs, toxins, and herbs have been reported to cause liver injury, and drugs account for 20-40% of all instances of fulminant hepatic failure. Approximately 75% of the idiosyncratic drug reactions result in liver transplantation or death.

• #62 Drug-induced toxic hepatitis associated with the combination of quetiapine and fluphenazine: A case report | European Journal of Psychiatry

  https://www.elsevier.es/en-revista-european-journal-psychiatry-431-articulo-drug-induced-toxic-hepatitis-associated-with-S0213616317300368

  Toxic hepatitis is an inflammation of the liver that occurs in response to various substances, such as alcohol, drugs and various chemicals. […] Toxic hepatitis can permanently damage the liver, and in some cases can lead to liver failure. […] More than 1000 drugs have showed toxic effects on the liver, of which 16% are neuropsychiatric drugs. […] Hepatic toxicity in our patient probably was caused by the combination of quetiapine and fluphenazine. […] After the discontinuation of quetiapine and fluphenazine a mild decrease in liver transaminases was observed. […] The mechanism of hepatic damage remains not fully understood. […] Diagnosing toxic hepatitis is mainly based on the coincidence of treatment initiation and symptom development, and the exclusion of other possible causes. […] We therefore advocate regularly monitoring laboratory values in order to prevent toxic liver damage. […] We consider that it is important to monitor patients for liver damage due to the cumulative toxic effects of combination drug treatment.

• #63 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  Toxic hepatitis is an inflammatory condition caused by ingestion or inhalation of certain substances Dry cleaning, fluid, Glue, Insecticides pesticides, Poisonous mushrooms, Rat poison, Tylenol, Aspirin, Thorazine, INH, Valium and Alcohol. […] When taken in overdose, acetaminophen becomes bioactivated to a toxic intermediate known as N-acetyl-p- benzoquinone imine (NAPQI). Reyes syndrome is an aggressive form of toxic hepatitis often associated with aspirin use in children. Valproate toxicity can also present in this pattern In advanced stages of Reyes syndrome, many patients develop intracranial hypertension that can be life threatening and refractory to therapy. […] Patients experience periods of symptomatic hepatitis followed by periods of convalescence, only to repeat the experience months later. It is a progressive disease with a high mortality rate and is more common in females than males.

• #64 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  Toxic hepatitis, or liver toxicity, is liver swelling (inflammation) that results from contact with a harmful substance (toxin), whether you: […] Liver inflammation can also occur if you take too much of certain medications or drink too much alcohol. Over time, inflammation causes permanent liver damage. […] Exposure to certain chemicals or medications can cause toxic hepatitis symptoms to develop. Symptoms may develop soon after exposure, or they may develop over weeks or months. […] Some causes of toxic hepatitis include: […] This type of toxic hepatitis results from medications or supplements. Certain medications or dietary supplements may cause this drug-induced liver injury, including: […] Drinking too much alcohol can cause alcohol-induced hepatitis. If you experience alcohol use disorder, it’s important to talk to a healthcare provider.

• #65 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  Toxic hepatitis, or liver toxicity, is liver swelling (inflammation) that results from contact with a harmful substance (toxin), whether you: […] Liver inflammation can also occur if you take too much of certain medications or drink too much alcohol. Over time, inflammation causes permanent liver damage. […] Exposure to certain chemicals or medications can cause toxic hepatitis symptoms to develop. Symptoms may develop soon after exposure, or they may develop over weeks or months. […] Some causes of toxic hepatitis include: […] This type of toxic hepatitis results from medications or supplements. Certain medications or dietary supplements may cause this drug-induced liver injury, including: […] Drinking too much alcohol can cause alcohol-induced hepatitis. If you experience alcohol use disorder, it’s important to talk to a healthcare provider.

• #66 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  Toxic hepatitis is an inflammatory condition caused by ingestion or inhalation of certain substances Dry cleaning, fluid, Glue, Insecticides pesticides, Poisonous mushrooms, Rat poison, Tylenol, Aspirin, Thorazine, INH, Valium and Alcohol. […] When taken in overdose, acetaminophen becomes bioactivated to a toxic intermediate known as N-acetyl-p- benzoquinone imine (NAPQI). Reyes syndrome is an aggressive form of toxic hepatitis often associated with aspirin use in children. Valproate toxicity can also present in this pattern In advanced stages of Reyes syndrome, many patients develop intracranial hypertension that can be life threatening and refractory to therapy. […] Patients experience periods of symptomatic hepatitis followed by periods of convalescence, only to repeat the experience months later. It is a progressive disease with a high mortality rate and is more common in females than males.

• #67 Liver: toxic hepatitis in Dogs (Canis) | Vetlexicon

  https://www.vetlexicon.com/canis/gastrohepatology/articles/liver-toxic-hepatitis/

  Cause: ingestion of plant toxins, chemicals, therapeutic agents, insect envenomation. […] Pathophysiology: Overwhelming hepatic insult functional reserve capacity exceeded failure to perform diverse metabolic functions clinical signs. […] Hepatic functional reserve large 70% damage before capacity exhausted peri-acinar zonal necrosis, infiltration of inflammatory cells due to toxins, living agents and metabolic disease will cause massive damage. […] Local and systemic release of cytokines and other pro-inflammatory mediators pyrexia, anorexia, depression. […] Decreased production of clotting factors bleeding tendency. […] Inflammation of biliary system partial obstruction to biliary flow icterus. […] Inadequate bile delivery to intestine impairment of fat digestion diarrhea. […] Failure to maintain euglycemia hypoglycemia.

• #68 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1125597

  To report upon a case of toxic hepatitis in a worker exposed to chloroform. […] The blood tests revealed acute toxic hepatitis. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis could be excluded. […] The authors presume that this patient’s liver injury was related to an interaction of chloroform toxicity and a predisposition to autoimmune hepatitis. The rapid improvement of the clinical symptoms and the progressive normalization of the liver function tests once the chloroform exposure eliminated supports the diagnosis.

• #69 Liver: toxic hepatitis in Dogs (Canis) | Vetlexicon

  https://www.vetlexicon.com/canis/gastrohepatology/articles/liver-toxic-hepatitis/

  Cause: ingestion of plant toxins, chemicals, therapeutic agents, insect envenomation. […] Pathophysiology: Overwhelming hepatic insult functional reserve capacity exceeded failure to perform diverse metabolic functions clinical signs. […] Hepatic functional reserve large 70% damage before capacity exhausted peri-acinar zonal necrosis, infiltration of inflammatory cells due to toxins, living agents and metabolic disease will cause massive damage. […] Local and systemic release of cytokines and other pro-inflammatory mediators pyrexia, anorexia, depression. […] Decreased production of clotting factors bleeding tendency. […] Inflammation of biliary system partial obstruction to biliary flow icterus. […] Inadequate bile delivery to intestine impairment of fat digestion diarrhea. […] Failure to maintain euglycemia hypoglycemia.

• #70 Drug-Induced Liver Injury: Twenty Five Cases of Acute Hepatitis Following Ingestion of Polygonum multiflorum Thunb

  https://www.gutnliver.org/journal/view.html?volume=5&number=4&spage=493

  Background/Aims: Complementary medicines, including herbal preparations and nutritional supplements, are widely used without prescriptions. As a result, there has been growing interest in the risk of hepatotoxicity with these agents. It is difficult to determine causal relationships between these herbal preparations and hepatotoxicity. We report on 25 patients diagnosed with toxic hepatitis following ingestion of Polygonum multiflorum Thunb. […] In our cases, we found that P. multiflorum Thunb could be hepatotoxic and could lead to severe drug-induced liver injury, and even death. […] Drug induced liver injury (DILI) is an adverse drug reaction associated with commonly used drugs, mostly nonsteroidal anti-inflammatory drugs, paracetamol, and antimicrobial agents. […] DILI associated with herbal preparations is not uncommon in Western and Asian societies.

• #71

  https://www.ijcrimedicine.com/archive/2015-archive/100004Z09MS2015-sterling/100004Z09MS2015-sterling-full-text.php

  Dietary and weight loss supplements have been shown to cause acute hepatitis through toxic liver injury. […] Over the last decade, research has demonstrated that dietary and weight-loss supplements are capable of causing acute hepatitis secondary to drug induced liver injury (DILI). […] This case offers new insight into the conceptualization of AIH and the ability of weight-loss supplements to act as precipitants of both acute and chronic hepatitis. […] The hepatotoxic components of these agents most likely to cause injury are Cambogia, Camellia sinensis and Chromium, which are found in several other weight-loss aids on the market such as thermo cut and Garcinia extreme. […] Although the acute presentation, history of substance use and histologic features are consistent with drug toxicity, the patient’s serologic studies and biopsy results also suggest drug-induced autoimmune hepatitis as an additional diagnosis.

• #72 Drug-Induced Liver Injury: Twenty Five Cases of Acute Hepatitis Following Ingestion of Polygonum multiflorum Thunb

  https://www.gutnliver.org/journal/view.html?volume=5&number=4&spage=493

  Background/Aims: Complementary medicines, including herbal preparations and nutritional supplements, are widely used without prescriptions. As a result, there has been growing interest in the risk of hepatotoxicity with these agents. It is difficult to determine causal relationships between these herbal preparations and hepatotoxicity. We report on 25 patients diagnosed with toxic hepatitis following ingestion of Polygonum multiflorum Thunb. […] In our cases, we found that P. multiflorum Thunb could be hepatotoxic and could lead to severe drug-induced liver injury, and even death. […] Drug induced liver injury (DILI) is an adverse drug reaction associated with commonly used drugs, mostly nonsteroidal anti-inflammatory drugs, paracetamol, and antimicrobial agents. […] DILI associated with herbal preparations is not uncommon in Western and Asian societies.

• #73 Drug-Induced Liver Injury: Twenty Five Cases of Acute Hepatitis Following Ingestion of Polygonum multiflorum Thunb

  https://www.gutnliver.org/journal/view.html?volume=5&number=4&spage=493

  The main constituents of Shou-Wu-Pain are polyphenols and anthraquinones – the latter is metabolized into anthrones and absorbed in the gastrointestinal tract, which can induce liver damage. […] To date, there are 6 case reports of P. multiflorum Thunb-induced hepatotoxicity although the mechanism of P. multiflorum Thunb-induced hepatotoxicity is still unclear. […] The type of liver injury on the basis of laboratory findings at the time of diagnosis was hepatocellular in 18 patients. The histological findings were consistent with toxic hepatitis in 7 out of 9 individuals in whom liver biopsy was performed, with the exception of 2 patients whose specimen demonstrated toxic hepatitis mixed with alcoholic hepatitis. […] Given that liver injury was dose-independent and the time interval from P. multiflorum Thunb intake to clinical manifestation was short in some patients, there might be different opinions about their diagnosis. But, authors presume that the mechanism of P. multiflorum Thunb-induced liver injury is idiosyncratic liver injury even though we cannot assure you that our anticipation is absolutely true owing to the lack of data.

• #74 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  You may develop liver toxicity if you take too much acetaminophen (Tylenol), an over-the-counter pain reliever. […] Taking too much vitamin A (more than 40,000 IU daily) can cause vitamin A liver toxicity. […] Toxic hepatitis can lead to acute liver damage (cirrhosis) and chronic liver failure. If you develop liver failure, you may need liver transplantation. […] Toxic hepatitis treatment depends on the extent of damage to your liver. […] In many instances, toxic hepatitis is curable. Your liver can replace damaged cells over time, reversing the damage that occurred. […] Toxic hepatitis recovery time depends on: […] If damage is mild to moderate, your liver may take a few weeks or months to replace the damaged cells and heal. […] To help prevent toxic hepatitis: […] You can help keep your liver healthy by making healthy lifestyle changes. […] Talk to your healthcare provider about the causes of liver toxicity and how you can improve your liver’s health.

• #75 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  Toxic hepatitis, or liver toxicity, is liver swelling (inflammation) that results from contact with a harmful substance (toxin), whether you: […] Liver inflammation can also occur if you take too much of certain medications or drink too much alcohol. Over time, inflammation causes permanent liver damage. […] Exposure to certain chemicals or medications can cause toxic hepatitis symptoms to develop. Symptoms may develop soon after exposure, or they may develop over weeks or months. […] Some causes of toxic hepatitis include: […] This type of toxic hepatitis results from medications or supplements. Certain medications or dietary supplements may cause this drug-induced liver injury, including: […] Drinking too much alcohol can cause alcohol-induced hepatitis. If you experience alcohol use disorder, it’s important to talk to a healthcare provider.

• #76 Hepatitis: What It Is, Symptoms, Transmission & Treatments

  https://my.clevelandclinic.org/health/diseases/hepatitis

  Toxic hepatitis can be acute or chronic. […] This is hepatitis you can get from exposure to chemicals. Alcohol-induced hepatitis and drug-induced hepatitis are other types of toxic hepatitis. […] Many things can cause hepatitis. So can exposure to toxins like alcohol, drugs including medications and chemicals.

• #77 Drug-induced toxic hepatitis associated with the combination of quetiapine and fluphenazine: A case report | European Journal of Psychiatry

  https://www.elsevier.es/en-revista-european-journal-psychiatry-431-articulo-drug-induced-toxic-hepatitis-associated-with-S0213616317300368

  Toxic hepatitis is an inflammation of the liver that occurs in response to various substances, such as alcohol, drugs and various chemicals. […] Toxic hepatitis can permanently damage the liver, and in some cases can lead to liver failure. […] More than 1000 drugs have showed toxic effects on the liver, of which 16% are neuropsychiatric drugs. […] Hepatic toxicity in our patient probably was caused by the combination of quetiapine and fluphenazine. […] After the discontinuation of quetiapine and fluphenazine a mild decrease in liver transaminases was observed. […] The mechanism of hepatic damage remains not fully understood. […] Diagnosing toxic hepatitis is mainly based on the coincidence of treatment initiation and symptom development, and the exclusion of other possible causes. […] We therefore advocate regularly monitoring laboratory values in order to prevent toxic liver damage. […] We consider that it is important to monitor patients for liver damage due to the cumulative toxic effects of combination drug treatment.

• #78

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=5124413&pid=11343

  The diagnosis of hepatitis (acute, chronic, etc.) is only possible with histology of the liver. […] In an acute hepatitis all of the enzymes are usually definitely elevated. […] Very extensive liver cell necrosis is called fulminant hepatitis. It leads to the development of hepatic encephalopathy, DIC, jaundice, and hypoglycaemia. […] Acute hepatitis is characterized by liver necrosis and the accompanying inflammation. The necrosis is usually a liquefying necrosis with collapse of the reticular framework. […] Infection with canine adenovirus-1 is usually characterized by confluent and bridging necrosis in the centrilobular zone and by the presence of intranuclear inclusions in hepatocytes and Kupffer’s cells. […] Acute hepatitis may also be caused by various toxins, such as mushroom toxins (Amanitum), blue-green algae toxins (Cyanophyceae) or dose-dependent drug toxicity (acetaminophen in dogs and cats).

• #79 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1125597

  To report upon a case of toxic hepatitis in a worker exposed to chloroform. […] The blood tests revealed acute toxic hepatitis. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis could be excluded. […] The authors presume that this patient’s liver injury was related to an interaction of chloroform toxicity and a predisposition to autoimmune hepatitis. The rapid improvement of the clinical symptoms and the progressive normalization of the liver function tests once the chloroform exposure eliminated supports the diagnosis.

• #80 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1125597

  To report upon a case of toxic hepatitis in a worker exposed to chloroform. […] The blood tests revealed acute toxic hepatitis. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis could be excluded. […] The authors presume that this patient’s liver injury was related to an interaction of chloroform toxicity and a predisposition to autoimmune hepatitis. The rapid improvement of the clinical symptoms and the progressive normalization of the liver function tests once the chloroform exposure eliminated supports the diagnosis.

• #81 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1125597

  To report upon a case of toxic hepatitis in a worker exposed to chloroform. […] The blood tests revealed acute toxic hepatitis. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis could be excluded. […] The authors presume that this patient’s liver injury was related to an interaction of chloroform toxicity and a predisposition to autoimmune hepatitis. The rapid improvement of the clinical symptoms and the progressive normalization of the liver function tests once the chloroform exposure eliminated supports the diagnosis.

• #82 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  The first and most important step in treating toxic hepatitis is to identify and eliminate the substance that is causing the problem, such as medications, herbs or alcohol. […] Early recognition of drug-induced liver reactions is essential to minimizing injury. […] No specific treatment is indicated for drug-induced hepatic disease. Treatment is largely supportive and based on symptomatology. The first step is to discontinue the suspected drug. Specific therapy against drug-induced liver injury is limited to the use of N-acetylcysteine in the early phases of acetaminophen toxicity. […] Urgent liver transplantation should be considered for patients with life-threatening liver damage caused by a medication, herb or nutritional supplement.

• #83 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  The first and most important step in treating toxic hepatitis is to identify and eliminate the substance that is causing the problem, such as medications, herbs or alcohol. […] Early recognition of drug-induced liver reactions is essential to minimizing injury. […] No specific treatment is indicated for drug-induced hepatic disease. Treatment is largely supportive and based on symptomatology. The first step is to discontinue the suspected drug. Specific therapy against drug-induced liver injury is limited to the use of N-acetylcysteine in the early phases of acetaminophen toxicity. […] Urgent liver transplantation should be considered for patients with life-threatening liver damage caused by a medication, herb or nutritional supplement.

• #84 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  The first and most important step in treating toxic hepatitis is to identify and eliminate the substance that is causing the problem, such as medications, herbs or alcohol. […] Early recognition of drug-induced liver reactions is essential to minimizing injury. […] No specific treatment is indicated for drug-induced hepatic disease. Treatment is largely supportive and based on symptomatology. The first step is to discontinue the suspected drug. Specific therapy against drug-induced liver injury is limited to the use of N-acetylcysteine in the early phases of acetaminophen toxicity. […] Urgent liver transplantation should be considered for patients with life-threatening liver damage caused by a medication, herb or nutritional supplement.

• #85 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  The first and most important step in treating toxic hepatitis is to identify and eliminate the substance that is causing the problem, such as medications, herbs or alcohol. […] Early recognition of drug-induced liver reactions is essential to minimizing injury. […] No specific treatment is indicated for drug-induced hepatic disease. Treatment is largely supportive and based on symptomatology. The first step is to discontinue the suspected drug. Specific therapy against drug-induced liver injury is limited to the use of N-acetylcysteine in the early phases of acetaminophen toxicity. […] Urgent liver transplantation should be considered for patients with life-threatening liver damage caused by a medication, herb or nutritional supplement.

• #86 Toxic hepatitis | PPT

  https://www.slideshare.net/slideshow/toxic-hepatitis-149284884/149284884

  The first and most important step in treating toxic hepatitis is to identify and eliminate the substance that is causing the problem, such as medications, herbs or alcohol. […] Early recognition of drug-induced liver reactions is essential to minimizing injury. […] No specific treatment is indicated for drug-induced hepatic disease. Treatment is largely supportive and based on symptomatology. The first step is to discontinue the suspected drug. Specific therapy against drug-induced liver injury is limited to the use of N-acetylcysteine in the early phases of acetaminophen toxicity. […] Urgent liver transplantation should be considered for patients with life-threatening liver damage caused by a medication, herb or nutritional supplement.

• #87 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  You may develop liver toxicity if you take too much acetaminophen (Tylenol), an over-the-counter pain reliever. […] Taking too much vitamin A (more than 40,000 IU daily) can cause vitamin A liver toxicity. […] Toxic hepatitis can lead to acute liver damage (cirrhosis) and chronic liver failure. If you develop liver failure, you may need liver transplantation. […] Toxic hepatitis treatment depends on the extent of damage to your liver. […] In many instances, toxic hepatitis is curable. Your liver can replace damaged cells over time, reversing the damage that occurred. […] Toxic hepatitis recovery time depends on: […] If damage is mild to moderate, your liver may take a few weeks or months to replace the damaged cells and heal. […] To help prevent toxic hepatitis: […] You can help keep your liver healthy by making healthy lifestyle changes. […] Talk to your healthcare provider about the causes of liver toxicity and how you can improve your liver’s health.

• #88 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  You may develop liver toxicity if you take too much acetaminophen (Tylenol), an over-the-counter pain reliever. […] Taking too much vitamin A (more than 40,000 IU daily) can cause vitamin A liver toxicity. […] Toxic hepatitis can lead to acute liver damage (cirrhosis) and chronic liver failure. If you develop liver failure, you may need liver transplantation. […] Toxic hepatitis treatment depends on the extent of damage to your liver. […] In many instances, toxic hepatitis is curable. Your liver can replace damaged cells over time, reversing the damage that occurred. […] Toxic hepatitis recovery time depends on: […] If damage is mild to moderate, your liver may take a few weeks or months to replace the damaged cells and heal. […] To help prevent toxic hepatitis: […] You can help keep your liver healthy by making healthy lifestyle changes. […] Talk to your healthcare provider about the causes of liver toxicity and how you can improve your liver’s health.

• #89 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  You may develop liver toxicity if you take too much acetaminophen (Tylenol), an over-the-counter pain reliever. […] Taking too much vitamin A (more than 40,000 IU daily) can cause vitamin A liver toxicity. […] Toxic hepatitis can lead to acute liver damage (cirrhosis) and chronic liver failure. If you develop liver failure, you may need liver transplantation. […] Toxic hepatitis treatment depends on the extent of damage to your liver. […] In many instances, toxic hepatitis is curable. Your liver can replace damaged cells over time, reversing the damage that occurred. […] Toxic hepatitis recovery time depends on: […] If damage is mild to moderate, your liver may take a few weeks or months to replace the damaged cells and heal. […] To help prevent toxic hepatitis: […] You can help keep your liver healthy by making healthy lifestyle changes. […] Talk to your healthcare provider about the causes of liver toxicity and how you can improve your liver’s health.

• #90 Toxic Hepatitis (Liver Toxicity): Symptoms, Causes & Treatments

  https://my.clevelandclinic.org/health/diseases/17915-toxic-hepatitis

  You may develop liver toxicity if you take too much acetaminophen (Tylenol), an over-the-counter pain reliever. […] Taking too much vitamin A (more than 40,000 IU daily) can cause vitamin A liver toxicity. […] Toxic hepatitis can lead to acute liver damage (cirrhosis) and chronic liver failure. If you develop liver failure, you may need liver transplantation. […] Toxic hepatitis treatment depends on the extent of damage to your liver. […] In many instances, toxic hepatitis is curable. Your liver can replace damaged cells over time, reversing the damage that occurred. […] Toxic hepatitis recovery time depends on: […] If damage is mild to moderate, your liver may take a few weeks or months to replace the damaged cells and heal. […] To help prevent toxic hepatitis: […] You can help keep your liver healthy by making healthy lifestyle changes. […] Talk to your healthcare provider about the causes of liver toxicity and how you can improve your liver’s health.

• #91 Drug-induced toxic hepatitis associated with the combination of quetiapine and fluphenazine: A case report | European Journal of Psychiatry

  https://www.elsevier.es/en-revista-european-journal-psychiatry-431-articulo-drug-induced-toxic-hepatitis-associated-with-S0213616317300368

  Toxic hepatitis is an inflammation of the liver that occurs in response to various substances, such as alcohol, drugs and various chemicals. […] Toxic hepatitis can permanently damage the liver, and in some cases can lead to liver failure. […] More than 1000 drugs have showed toxic effects on the liver, of which 16% are neuropsychiatric drugs. […] Hepatic toxicity in our patient probably was caused by the combination of quetiapine and fluphenazine. […] After the discontinuation of quetiapine and fluphenazine a mild decrease in liver transaminases was observed. […] The mechanism of hepatic damage remains not fully understood. […] Diagnosing toxic hepatitis is mainly based on the coincidence of treatment initiation and symptom development, and the exclusion of other possible causes. […] We therefore advocate regularly monitoring laboratory values in order to prevent toxic liver damage. […] We consider that it is important to monitor patients for liver damage due to the cumulative toxic effects of combination drug treatment.

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