Hepatotoxicity

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Alternative names
Toxic liver disease

Toxin induced liver disease
Drug induced liver disease
Drug induced liver damage
Hepatogenous poisoning

Subordinate terms
Toxic hepatitis

Toxin induced hepatitis
Drug induced hepatitis
Drug-induced hepatic necrosis
Drug induced hepatic fibrosis
Drug induced hepatic granuloma
Toxic liver disease with hepatitis
Toxic liver disease with cholestasis

Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. 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 and sometime even when introduced within therapeutic ranges may injure the organ. Other chemical agents such as those used in laboratories and industries, natural chemicals (e.g. microcystins) and herbal remedies can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.

More than 900 drugs have been implicated in causing liver injury[1] and it is the most common reason for a drug to be withdrawn from the market. Chemicals often cause subclinical injury to liver which manifests only as abnormal liver enzyme tests. Drug induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.[2][3]

Contents

Drug metabolism in liver

Image:Hepatic drug metabolism.svg
Drug metabolism in liver: transferases are : glutathione, sulfate, acetate, glucoronic acid. P-450 is cytochrome P-450 enzymes. 3 different pathways are depicted for Drugs A, B and C.

The human body identifies almost all drugs as foreign substances (i.e. xenobiotics) and subjects them to various chemical processes (i.e. metabolism) to make them suitable for elimination. This involves chemical transformations to (a) reduce fat solubility and (b) to change biological activity. Although almost all tissue in the body have some ability to metabolize chemicals, smooth endoplasmic reticulum in liver is the principal "metabolic clearing house" for both endogenous chemicals (e.g., cholesterol, steroid hormones, fatty acids, and proteins), and exogenous substances (e.g. drugs).[4] The central role played by liver in the clearance and transformation of chemicals also makes it susceptible to drug induced injury.

Drug metabolism is usually divided into two phases: phase 1 and phase 2. Phase 1 reaction is thought to prepare a drug for phase 2. However many compounds can be metabolised by phase 2 directly. Phase 1 reaction involves oxidation, reduction, hydrolysis, hydration and many other rare chemical reactions. These processes tend to increase water solubility of the drug and can generate metabolites which are more chemically active and potentially toxic. Most of phase 2 reactions take place in cytosol and involve conjugation with endogenous compounds via transferase enzymes. Chemically active phase 1 products are rendered relatively inert and suitable for elimination by this step.

A group of enzymes located in the endoplasmic reticulum, known as cytochrome P-450, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is the terminal oxidase component of an electron transport chain. It is not a single enzyme, rather consists of a family of closely related 50 isoforms, six of them metabolize 90% of drugs.[5][6] There is a tremendous diversity of individual P-450 gene products and this heterogeneity allows the liver to perform oxidation on a vast array of chemicals (including almost all drugs) in phase 1. Three important characteristics of the P450 system have roles in drug induced toxicity:

1. Genetic diversity:

Each of the P-450 proteins is unique and accounts to some extent for the variation in drug metabolism between individuals. Genetic variations (polymorphism) in CYP450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal doses. Such polymorphism is also responsible for variable drug response among patients of differing ethnic backgrounds.

Cytochrome P-450 enzyme induction and inhibition[6][7][8]
Potent inducers Potent inhibitors Substrates
Rifampicin, Carbamazepine,
Phenobarbital, Phenytoin,
(St John's wort), 		Amiodarone, cimetidine,
ciprofloxacin, fluconazole,
fluoxetine, erythromycin,
isoniazid, diltiazem 		Caffeine, clozapine,
omeprazole, losartan,
theophylline
2. Change in enzyme activity:

Many substances can influence P-450 enzyme mechanism. Drugs interact with the enzyme family in several ways.[9] Drugs that modify Cytochrome P-450 enzyme are referred to as either inhibitors or inducers. Enzyme inhibitors block the metabolic activity of one or several P-450 enzymes. This effect usually occurs immediately. On the other hand inducers increase P-450 activity by increasing its synthesis. Depending on inducing drug's half life, there is usually a delay before enzyme activity increases.[6]

3. Competitive inhibition:

Some drugs may share the same P-450 specificity and thus competitively block their bio transformation. This may lead to accumulation of drugs metabolised by the enzyme. This type of drug interaction may also reduce the rate of generation of toxic substrate.

Mechanism of liver damage

Factors influencing
drug induced hepatotoxicity[10]
  • Age
  • Ethnicity and race
  • Gender
  • Nutritional status
  • underlying liver disease
  • Renal function
  • Pregnancy
  • Duration and dosage of drug
  • Enzyme induction
  • Drug- drug interaction

Drugs continue to be taken off the market due to late discovery of hepatotoxicity. Due to its unique metabolism and close relationship with gastro-intestinal tract, liver is susceptible to injury from drugs and other substances. 75% of blood coming to liver arrives directly from gastrointestinal organs and spleen via portal veins which brings drugs and xenobiotics in concentrated form. 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. Activation of some enzymes in the cytochrome P-450 system such as CYP2E1 also lead to oxidative stress.[11] Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside liver. This promotes further liver damage.[12] Non-parenchymal cells such as Kupffer cells, fat storing stellate cells and leukocytes (i.e. neutrophil and monocyte) also have role in the mechanism.

Adverse drug Reactions

Adverse drug reactions are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic).[13]Type A drug reaction accounts for 80% of all toxicities.[14]

Drugs or toxins that have a pharmacological (type A) hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity such as directly damaging liver tissue or blocking a metabolic process. As in the case of Acetaminophen overdose, this type of injury occurs shortly after some threshold for toxicity is reached.

Idiosyncratic (type B) injury occurs without warning; when agents cause non-predictable hepatotoxicity in susceptible individuals which is not related to dose and has variable latency period.[15] This type of injury does not have a clear dose-response or temporal relationship, and most often do not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of several drugs from market even after rigorous clinical testing as part of the FDA approval process; Troglitazone (Rezulin®) and trovafloxacin (Trovan®) are two prime examples of idiosyncratic hepatotoxins.

Patterns of injury

Patterns of drug-induced liver disease
Type of injury: Hepatocellular CholestaticMixed
ALT ≥ Twofold rise Normal≥ Twofold rise
ALP Normal ≥ Twofold rise≥ Twofold rise
ALT: ALP ratio High, ≥5 Low, ≤22-5
Examples[16] Acetaminophen
Allopurinol
Amiodarone
HAART
NSAID		Anabolic steroid
Chlorpromazine
Clopidogrel
Erythromycin
Hormonal contraception		Amitryptyline,
Enalapril
Carbamazepine
Sulphonamide
Phenytoin

Chemicals produce a wide variety of clinical and pathological hepatic injury. Biochemical markers (i.e. alanine transferase, alkaline phosphatase and bilirubin) are often used to indicate liver damage. Liver injury is defined as rise in either (a) ALT level more than three times of upper limit of normal (ULN), (b) ALP level more than twice ULN, or (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP.[17][16] Liver damage is further characterized into hepatocellular (predominantly initial Alanine transferase elevation) and cholestatic (initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed type of injuries are often encountered.

Specific histo-pathological patterns of liver injury from drug induced damage are discussed below.

Zonal Necrosis

This is the commonest 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 very high level of ALT and severe disturbance of liver function leading to acute liver failure.

Causes:
Acetaminophen, carbon tetrachloride

Hepatitis

In this pattern hepatocellular necrosis is associated with infiltration of inflammatory cells. There can be three types of drug induced hepatitis. (A) viral hepatitis type picture is the commonest, where histological features are similar to acute viral hepatitis. (B) in the focal or non specific hepatitis scattered foci of cell necrosis may accompany lymphocytic infiltrate. (C) chronic hepatitis type is very similar to autoimmune hepatitis clinically, serologically as well as histologically.

Causes:
(a) Viral hepatitis like: Halothane, Isoniazid, Phenytoin
(b) Focal hepatitis: Aspirin
(c) Chronic hepatitis: Methyldopa, Diclofenac

Cholestasis

Liver injury leads to impairment of bile flow and clinical picture is predominated by itching and jaundice. Histology may show inflammation (cholestatic hepatitis) or it can be bland without any parenchymal inflammation. In rare occasions it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (Vanishing duct syndrome).

Causes:
(a) Bland: Oral contraceptive pills, anabolic steroid, Androgens
(b) Inflammatory: Allopurinol, Co-amoxiclav, Carbamazepine
(c) Ductal: Chlorpromazine, flucloxacillin

Steatosis

Hepatotoxicity may manifest as triglyceride accumulation which leads to either small droplet (microvesicular) or large droplet (macrovesicular) fatty liver. There is a separate type of steatosis where phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid metabolism defects (e.g. Tay-Sachs disease)

Causes:
(a) Microvesicuilar: Aspirin (Reye's syndrome), Ketoprofen, Tetracycline
(b) Macrovesicular: Acetamenophen, methotrexate
(c) Phospholipidosis: Amiodarone, Total parenteral nutrition

Granuloma

Drug induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. More than 50 drugs have been implicated.

Causes:
Allopurinol, Phenytoin, Isoniazid, Quinine, Penicillin, Quinidine

Vascular lesions

They result from injury to the vascular endothelium.

Causes:
Venoocclusive disease: Chemotherapeutic agents, bush tea
Peliosis hepatis: anabolic steroid
Hepatic vein thrombosis: Oral contraceptives

Neoplasm

Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, angiosarcoma and liver adenomas are the ones usually reported.

Causes:
Vinyl chloride, Combined oral contraceptive pill,Anabolic steroid, Arsenic, Thorotrast

Clinical assessment

Image:Aseessement of hepatotoxicity.svg
Algorithm for suspected drug induced hepatic toxicity

This remains a major challenge in clinical practice due to lack of reliable markers.[18] Many other conditions lead to similar clinical as well as pathological picture. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected.[19] Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established dose dependent pharmacological hepatotoxicity is easier to spot. Several clinical scales such as CIOMS/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. CIOMS/RUCAM scale involves a scoring system which categorizes the suspicion into "definite or highly probable" (score > 8), “probable” (score 6-8), “possible” (score 3-5), “unlikely” (score 1-2) and “excluded” (score ≤ 0). In clinical practice physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity ( e.g. cholestatic damage in amoxycillin-clauvonic acid ).[18]

Treatment and prognosis

In most cases liver function will return to normality if offending drug is stopped early. However in acetamenophen toxicity initial insult can be fatal. In most instances supportive treatment is all that is required. However in fulminant hepatic failure from drug induced hepatotoxicity may require liver transplantation. In the past glucocorticoides in allergic features and ursodeoxycholic acid in cholestatic pictures had been used, but there is no good evidence to support their effectiveness.

An elevation in serum bilirubin level of more that 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (Hy's Law).[20][21] This is due to the fact that it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or Gilbert syndrome) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high AST.[22][23]

Drugs withdrawn for hepatotoxicity

Troglitazone, bromfenac, trovafloxacin, ebrotidine, nimesulide, nefazodone and ximelagatran.[18][24]

Specific drug or toxin

Acetaminophen

Image:Paracetamol-rod-povray.png
Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease

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.[10] Damage to the liver is not due to the drug itself but to a toxic metabolite (N-acetyl-p-benzoquinone imine NAPQI) which is produced by cytochrome P450 enzymes in the liver.[25] In normal circumstances this metabolite is detoxified by conjugating with glutathione in phase 2 reaction. In overdose large amount of NAPQI is generated which overwhelm the detoxification process and lead to damage to liver cells. Nitric oxide also plays role in inducing toxicity.[26] The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote etc. The dose toxic to liver is quite variable and is lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher level predicting worse prognosis. Administration of Acetylcysteine can limit the severity of the liver damage by capturing the toxic NAPQI. Those who develop acute liver failure can still recover spontaneously, but may require transplantation if poor prognostic signs such as encephalopathy or coagulopathy is present (see King's College Criteria).

Nonsteroidal anti-inflammatory drugs

Although individual analgesics rarely induce liver damage, due to their widespread use NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. Both dose dependent and idiosyncratic reactions have been documented.[27] Aspirin and phenylbutazone are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin.

Glucocorticoids

Glucocorticoids are so named due to their effect on carbohydrate mechanism. they promote glycogen storage in liver. Enlarged liver is a rare side effect of long term steroid use in children.[28] The classical effect of prolonged use both in adult and paediatric population is steatosis.[29]

Isoniazid

Isoniazide (INH) is one of the most commonly used drug for tuberculosis; it is associated with mild elevation of liver enzymes in up to 20% of patients and severe hepatotoxicity in 1-2% of patients.[30]

Natural products

Example: Amanita mushroom, particularly the destroying angels, aflatoxins

Industrial toxin

Example: Arsenic, Carbon tetraChloride, Vinyl Chloride

Herbal and alternative remedies

Ackee fruit, Bajiaolian, Camphor, Copaltra, Cycasin, Kava, Pyrrolizidine alkaloids, Horse chestnut leaf, Valerian, Comfrey (often used in herbal tea)[31]

  • Chinese herbal remedies:
Jin Bu Huan, Ma-huan, Sho-wu-pian
Amanita muscaria (fly agaric).JPG

Fly agaric (Amanita muscaria) is one of the natural products toxic to the liver

Horse chestnut leaf.jpg

Horse chestnut leaf

Akee.jpg

Ackee fruit

Saint johns wart flowers.jpg

Saint John's wart Induces Cytochrome P-450 enzyme

See also

References

  1. ↑ {{ #if: Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. }} }} }}{{ #if: Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: 2003 | {{ #if: | ({{{month}}} 2003) | (2003) }} }} }}{{ #if: Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} Current diagnosis & treatment in gastroenterology] | Current diagnosis & treatment in gastroenterology }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: Lang Medical Books/McGraw-Hill | {{#if: | , | . }}{{ #if: New York | New York: }}Lang Medical Books/McGraw-Hill }}{{ #if: p664-679 | , p664-679 }}{{ #if: | . DOI:[1] }}{{ #if: | . {{{id}}} }}{{ #if: 0-8385-1551-7 | . ISBN 0-8385-1551-7 }}{{ #if: | . OCLC [2] }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  2. ↑ {{ #if: McNally, Peter F. | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | McNally, Peter F. }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | McNally, Peter F. }} }} }}{{ #if: McNally, Peter F. | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: | {{ #if: | ({{{month}}} ) | () }} }} }}{{ #if: McNally, Peter F. | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} GI/Liver Secrets: with STUDENT CONSULT Access] | GI/Liver Secrets: with STUDENT CONSULT Access }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: C.V. Mosby | {{#if: | , | . }}{{ #if: Saint Louis | Saint Louis: }}C.V. Mosby }}{{ #if: | , }}{{ #if: | . DOI:[3] }}{{ #if: | . {{{id}}} }}{{ #if: 1-56053-618-7 | . ISBN 1-56053-618-7 }}{{ #if: | . OCLC [4] }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  3. ↑ {{#if:Ostapowicz G, Fontana RJ, Schiødt FV, et al |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Ostapowicz G, Fontana RJ, Schiødt FV, et al }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Ostapowicz G, Fontana RJ, Schiødt FV, et al }} }} }}{{#if:Ostapowicz G, Fontana RJ, Schiødt FV, et al |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2002 |{{#if: | ({{{month}}} 2002) | (2002) }} }} }}{{#if:Ostapowicz G, Fontana RJ, Schiødt FV, et al | . }}{{#if:Ostapowicz G, Fontana RJ, Schiødt FV, et al2002 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States] |Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Ann. Intern. Med. |. Ann. Intern. Med. }}{{#if:137 | 137 }}{{#if:12 | (12) }}{{#if:947–54 |: 947–54 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[5] }}{{#if: |. ISSN {{{issn}}} }}{{#if:12484709 |. PMID 12484709 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  4. ↑ {{ #if: Donald Blumenthal; Laurence Brunton; Keith Parker; Lazo, John S.; Iain Buxton | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Donald Blumenthal; Laurence Brunton; Keith Parker; Lazo, John S.; Iain Buxton }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Donald Blumenthal; Laurence Brunton; Keith Parker; Lazo, John S.; Iain Buxton }} }} }}{{ #if: Donald Blumenthal; Laurence Brunton; Keith Parker; Lazo, John S.; Iain Buxton | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: | {{ #if: | ({{{month}}} ) | () }} }} }}{{ #if: Donald Blumenthal; Laurence Brunton; Keith Parker; Lazo, John S.; Iain Buxton | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} Goodman and Gilman's Pharmacological Basis of Therapeutics Digital Edition] | Goodman and Gilman's Pharmacological Basis of Therapeutics Digital Edition }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: McGraw-Hill Professional | {{#if: | , | . }}{{ #if: | : }}McGraw-Hill Professional }}{{ #if: | , }}{{ #if: | . DOI:[6] }}{{ #if: | . {{{id}}} }}{{ #if: 0-07-146804-8 | . ISBN 0-07-146804-8 }}{{ #if: | . OCLC [7] }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  5. ↑ {{ #if: Skett, Paul; Gibson, G. Gordon | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Skett, Paul; Gibson, G. Gordon }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Skett, Paul; Gibson, G. Gordon }} }} }}{{ #if: Skett, Paul; Gibson, G. Gordon | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: 2001 | {{ #if: | ({{{month}}} 2001) | (2001) }} }} }}{{ #if: Skett, Paul; Gibson, G. Gordon | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} Introduction to drug metabolism] | Introduction to drug metabolism }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: Nelson Thornes Publishers | {{#if: | , | . }}{{ #if: Cheltenham, UK | Cheltenham, UK: }}Nelson Thornes Publishers }}{{ #if: | , }}{{ #if: | . DOI:[8] }}{{ #if: | . {{{id}}} }}{{ #if: 0-7487-6011-3 | . ISBN 0-7487-6011-3 }}{{ #if: | . OCLC [9] }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  6. ↑ 6.0 6.1 6.2 {{#if:Lynch T, Price A |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Lynch T, Price A }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Lynch T, Price A }} }} }}{{#if:Lynch T, Price A |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2007 |{{#if: | ({{{month}}} 2007) | (2007) }} }} }}{{#if:Lynch T, Price A | . }}{{#if:Lynch T, Price A2007 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects] |The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:American family physician |. American family physician }}{{#if:76 | 76 }}{{#if:3 | (3) }}{{#if:391–6 |: 391–6 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[10] }}{{#if: |. ISSN {{{issn}}} }}{{#if:17708140 |. PMID 17708140 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  7. ↑ {{ #if: Jessica R. Oesterheld; Kelly L. Cozza; Armstrong, Scott | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Jessica R. Oesterheld; Kelly L. Cozza; Armstrong, Scott }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Jessica R. Oesterheld; Kelly L. Cozza; Armstrong, Scott }} }} }}{{ #if: Jessica R. Oesterheld; Kelly L. Cozza; Armstrong, Scott | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: | {{ #if: | ({{{month}}} ) | () }} }} }}{{ #if: Jessica R. Oesterheld; Kelly L. Cozza; Armstrong, Scott | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, Ugts, P-Glycoproteins] | Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, Ugts, P-Glycoproteins }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: American Psychiatric Association | {{#if: | , | . }}{{ #if: Washington, DC | Washington, DC: }}American Psychiatric Association }}{{ #if: 167-396 | , 167-396 }}{{ #if: | . DOI:[11] }}{{ #if: | . {{{id}}} }}{{ #if: 1-58562-111-0 | . ISBN 1-58562-111-0 }}{{ #if: | . OCLC [12] }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  8. ↑ {{
    1. if: {{#if: http://medicine.iupui.edu/flockhart/table.htm | {{#if: P450 Table |1}}}}
    ||You must specify title = and url = when using {{cite web}}. {{#if: ||}} }}{{
    1. if:
    | {{#if: {{#if: | {{#if: |1}}}} ||You must specify archiveurl = and archivedate = when using {{cite web}}. {{#if: ||}} }} }}{{#if: | {{#if: | [[{{{authorlink}}}|{{#if: | {{{last}}}{{#if: | , {{{first}}} }} | {{{author}}} }}]] | {{#if: | {{{last}}}{{#if: | , {{{first}}} }} | {{{author}}} }} }} }}{{#if: | {{#if: | ; {{{coauthors}}} }} }}{{#if: | {{#if: | ({{#ifeq:{{#time:Y-m-d|{{{date}}}}}|{{{date}}}|[[{{{date}}}]]|{{{date}}}}}) | {{#if: | {{#if: | ({{{month}}} {{{year}}}) | ({{{year}}}) }} }} |}} }}{{#if: | . }}{{ #if: | {{{editor}}}: }}{{#if: | {{#if: | {{#if: P450 Table | [{{{archiveurl}}} P450 Table] }}}} | {{#if: http://medicine.iupui.edu/flockhart/table.htm | {{#if: P450 Table | P450 Table }}}} }}{{#if: | () }}{{#if: | ({{{language}}}) }}{{#if: | . ' }}{{#if: | {{{pages}}} }}{{#if: | . {{{publisher}}}{{#if: | | {{#if: || }} }} }}{{#if: ||{{#if: | ({{#ifeq:{{#time:Y-m-d|{{{date}}}}}|{{{date}}}|[[{{{date}}}]]|{{{date}}}}}) | {{#if: | {{#if: | ({{{month}}} {{{year}}}) | ({{{year}}}) }} }} }} }}.{{#if: | Archived from the original on [[{{{archivedate}}}]]. }}{{#if: | DOI:{{{doi}}}. }}{{#if: 2007-09-29 | Retrieved on 2007-09-29{{#if: | , [[{{{accessyear}}}]] }}. }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}}. }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}}. }}{{#if: |  “{{{quote}}}” }}
  9. ↑ {{#if:Michalets EL |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Michalets EL }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Michalets EL }} }} }}{{#if:Michalets EL |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1998 |{{#if: | ({{{month}}} 1998) | (1998) }} }} }}{{#if:Michalets EL | . }}{{#if:Michalets EL1998 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Update: clinically significant cytochrome P-450 drug interactions] |Update: clinically significant cytochrome P-450 drug interactions }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Pharmacotherapy |. Pharmacotherapy }}{{#if:18 | 18 }}{{#if:1 | (1) }}{{#if:84–112 |: 84–112 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[13] }}{{#if: |. ISSN {{{issn}}} }}{{#if:9469685 |. PMID 9469685 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  10. ↑ 10.0 10.1 {{ #if: Keeffe, Emmet B; Friedman, Lawrence M. | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Keeffe, Emmet B; Friedman, Lawrence M. }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Keeffe, Emmet B; Friedman, Lawrence M. }} }} }}{{ #if: Keeffe, Emmet B; Friedman, Lawrence M. | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: 2004 | {{ #if: | ({{{month}}} 2004) | (2004) }} }} }}{{ #if: Keeffe, Emmet B; Friedman, Lawrence M. | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} Handbook of liver diseases] | Handbook of liver diseases }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: Churchill Livingstone | {{#if: | , | . }}{{ #if: Edinburgh | Edinburgh: }}Churchill Livingstone }}{{ #if: 104-123 | , 104-123 }}{{ #if: | . DOI:[14] }}{{ #if: | . {{{id}}} }}{{ #if: 0-443-06633-7 | . ISBN 0-443-06633-7 }}{{ #if: | . OCLC [15] }}{{ #if: | {{ #if: 2007-09-07 | . Retrieved on 2007-09-07 | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  11. ↑ {{#if:Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ }} }} }}{{#if:Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2002 |{{#if: | ({{{month}}} 2002) | (2002) }} }} }}{{#if:Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ | . }}{{#if:Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ2002 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Mechanisms of hepatotoxicity] |Mechanisms of hepatotoxicity }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Toxicol. Sci. |. Toxicol. Sci. }}{{#if:65 | 65 }}{{#if:2 | (2) }}{{#if:166–76 |: 166–76 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[16] }}{{#if: |. ISSN {{{issn}}} }}{{#if:11812920 |. PMID 11812920 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  12. ↑ {{#if:Patel T, Roberts LR, Jones BA, Gores GJ |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Patel T, Roberts LR, Jones BA, Gores GJ }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Patel T, Roberts LR, Jones BA, Gores GJ }} }} }}{{#if:Patel T, Roberts LR, Jones BA, Gores GJ |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1998 |{{#if: | ({{{month}}} 1998) | (1998) }} }} }}{{#if:Patel T, Roberts LR, Jones BA, Gores GJ | . }}{{#if:Patel T, Roberts LR, Jones BA, Gores GJ1998 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Dysregulation of apoptosis as a mechanism of liver disease: an overview] |Dysregulation of apoptosis as a mechanism of liver disease: an overview }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Semin. Liver Dis. |. Semin. Liver Dis. }}{{#if:18 | 18 }}{{#if:2 | (2) }}{{#if:105–14 |: 105–14 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[17] }}{{#if: |. ISSN {{{issn}}} }}{{#if:9606808 |. PMID 9606808 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  13. ↑ {{ #if: Davies, D. | {{ #if: | [[{{{authorlink}}}|{{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Davies, D. }}]] | {{ #if: | {{{last}}}{{ #if: | , {{{first}}} }} | Davies, D. }} }} }}{{ #if: Davies, D. | {{ #if: | ; {{{coauthors}}} }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: | ({{{date}}}) | {{ #if: 1985 | {{ #if: | ({{{month}}} 1985) | (1985) }} }} }}{{ #if: Davies, D. | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [{{{url}}} Textbook of adverse drug reactions] | Textbook of adverse drug reactions }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: Oxford University Press | {{#if: | , | . }}{{ #if: Oxford [Oxfordshire] | Oxford [Oxfordshire]: }}Oxford University Press }}{{ #if: 18-45 | , 18-45 }}{{ #if: | . DOI:[18] }}{{ #if: | . {{{id}}} }}{{ #if: 0-19-261479-7 | . ISBN 0-19-261479-7 }}{{ #if: 12558288 | . OCLC 12558288 }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  14. ↑ {{#if:Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK }} }} }}{{#if:Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1998 |{{#if: | ({{{month}}} 1998) | (1998) }} }} }}{{#if:Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK | . }}{{#if:Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK1998 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Adverse drug reactions] |Adverse drug reactions }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:BMJ |. BMJ }}{{#if:316 | 316 }}{{#if:7140 | (7140) }}{{#if:1295–8 |: 1295–8 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[19] }}{{#if: |. ISSN {{{issn}}} }}{{#if:9554902 |. PMID 9554902 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  15. ↑ {{#if:Zimmerman HJ |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Zimmerman HJ }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Zimmerman HJ }} }} }}{{#if:Zimmerman HJ |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1978 |{{#if: | ({{{month}}} 1978) | (1978) }} }} }}{{#if:Zimmerman HJ | . }}{{#if:Zimmerman HJ1978 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Drug-induced liver disease.] |Drug-induced liver disease. }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Drugs |. Drugs }}{{#if:16 | 16 }}{{#if:1 | (1) }}{{#if:25-45 |: 25-45 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[20] }}{{#if: |. ISSN {{{issn}}} }}{{#if:352664 |. PMID 352664 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  16. ↑ 16.0 16.1 {{#if:Mumoli N, Cei M, Cosimi A |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Mumoli N, Cei M, Cosimi A }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Mumoli N, Cei M, Cosimi A }} }} }}{{#if:Mumoli N, Cei M, Cosimi A |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2006 |{{#if: | ({{{month}}} 2006) | (2006) }} }} }}{{#if:Mumoli N, Cei M, Cosimi A | . }}{{#if:Mumoli N, Cei M, Cosimi A2006 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Drug-related hepatotoxicity] |Drug-related hepatotoxicity }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:N. Engl. J. Med. |. N. Engl. J. Med. }}{{#if:354 | 354 }}{{#if:20 | (20) }}{{#if:2191-3; author reply 2191-3 |: 2191-3; author reply 2191-3 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[21] }}{{#if: |. ISSN {{{issn}}} }}{{#if:16710915 |. PMID 16710915 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  17. ↑ {{#if:Bénichou C |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Bénichou C }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Bénichou C }} }} }}{{#if:Bénichou C |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1990 |{{#if: | ({{{month}}} 1990) | (1990) }} }} }}{{#if:Bénichou C | . }}{{#if:Bénichou C1990 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Criteria of drug-induced liver disorders. Report of an international consensus meeting] |Criteria of drug-induced liver disorders. Report of an international consensus meeting }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:J. Hepatol. |. J. Hepatol. }}{{#if:11 | 11 }}{{#if:2 | (2) }}{{#if:272–6 |: 272–6 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[22] }}{{#if: |. ISSN {{{issn}}} }}{{#if:2254635 |. PMID 2254635 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  18. ↑ 18.0 18.1 18.2 {{#if:Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI }} }} }}{{#if:Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2007 |{{#if: | ({{{month}}} 2007) | (2007) }} }} }}{{#if:Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI | . }}{{#if:Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI2007 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if:http://www.wjgnet.com/1007-9327/13/329.asp |Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists |Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:World J. Gastroenterol. |. World J. Gastroenterol. }}{{#if:13 | 13 }}{{#if:3 | (3) }}{{#if:329–40 |: 329–40 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[23] }}{{#if: |. ISSN {{{issn}}} }}{{#if:17230599 |. PMID 17230599 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  19. ↑ {{#if:Arundel C, Lewis JH |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Arundel C, Lewis JH }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Arundel C, Lewis JH }} }} }}{{#if:Arundel C, Lewis JH |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2007 |{{#if: | ({{{month}}} 2007) | (2007) }} }} }}{{#if:Arundel C, Lewis JH | . }}{{#if:Arundel C, Lewis JH2007 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Drug-induced liver disease in 2006] |Drug-induced liver disease in 2006 }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Curr. Opin. Gastroenterol. |. Curr. Opin. Gastroenterol. }}{{#if:23 | 23 }}{{#if:3 | (3) }}{{#if:244–54 |: 244–54 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1097/MOG.0b013e3280b17dfb |. doi:10.1097/MOG.0b013e3280b17dfb }}{{#if: |. ISSN {{{issn}}} }}{{#if:17414839 |. PMID 17414839 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  20. ↑ {{#if:Reuben A |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Reuben A }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Reuben A }} }} }}{{#if:Reuben A |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2004 |{{#if: | ({{{month}}} 2004) | (2004) }} }} }}{{#if:Reuben A | . }}{{#if:Reuben A2004 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Hy's law] |Hy's law }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Hepatology |. Hepatology }}{{#if:39 | 39 }}{{#if:2 | (2) }}{{#if:574–8 |: 574–8 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1002/hep.20081 |. doi:10.1002/hep.20081 }}{{#if: |. ISSN {{{issn}}} }}{{#if:14768020 |. PMID 14768020 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  21. ↑ {{#if:Arora N, Goldhaber SZ |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Arora N, Goldhaber SZ }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Arora N, Goldhaber SZ }} }} }}{{#if:Arora N, Goldhaber SZ |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2006 |{{#if: | ({{{month}}} 2006) | (2006) }} }} }}{{#if:Arora N, Goldhaber SZ | . }}{{#if:Arora N, Goldhaber SZ2006 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Anticoagulants and transaminase elevation] |Anticoagulants and transaminase elevation }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Circulation |. Circulation }}{{#if:113 | 113 }}{{#if:15 | (15) }}{{#if:e698–702 |: e698–702 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1161/CIRCULATIONAHA.105.603100 |. doi:10.1161/CIRCULATIONAHA.105.603100 }}{{#if: |. ISSN {{{issn}}} }}{{#if:16618822 |. PMID 16618822 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  22. ↑ {{#if:Andrade RJ, Lucena MI, Kaplowitz N, et al |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Andrade RJ, Lucena MI, Kaplowitz N, et al }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Andrade RJ, Lucena MI, Kaplowitz N, et al }} }} }}{{#if:Andrade RJ, Lucena MI, Kaplowitz N, et al |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2006 |{{#if: | ({{{month}}} 2006) | (2006) }} }} }}{{#if:Andrade RJ, Lucena MI, Kaplowitz N, et al | . }}{{#if:Andrade RJ, Lucena MI, Kaplowitz N, et al2006 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry] |Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Hepatology |. Hepatology }}{{#if:44 | 44 }}{{#if:6 | (6) }}{{#if:1581–8 |: 1581–8 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1002/hep.21424 |. doi:10.1002/hep.21424 }}{{#if: |. ISSN {{{issn}}} }}{{#if:17133470 |. PMID 17133470 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  23. ↑ {{#if:Björnsson E, Olsson R |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Björnsson E, Olsson R }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Björnsson E, Olsson R }} }} }}{{#if:Björnsson E, Olsson R |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2005 |{{#if: | ({{{month}}} 2005) | (2005) }} }} }}{{#if:Björnsson E, Olsson R | . }}{{#if:Björnsson E, Olsson R2005 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Outcome and prognostic markers in severe drug-induced liver disease] |Outcome and prognostic markers in severe drug-induced liver disease }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Hepatology |. Hepatology }}{{#if:42 | 42 }}{{#if:2 | (2) }}{{#if:481–9 |: 481–9 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1002/hep.20800 |. doi:10.1002/hep.20800 }}{{#if: |. ISSN {{{issn}}} }}{{#if:16025496 |. PMID 16025496 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  24. ↑ {{#if:Shah RR |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Shah RR }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Shah RR }} }} }}{{#if:Shah RR |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1999 |{{#if: | ({{{month}}} 1999) | (1999) }} }} }}{{#if:Shah RR | . }}{{#if:Shah RR1999 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Drug-induced hepatotoxicity: pharmacokinetic perspectives and strategies for risk reduction] |Drug-induced hepatotoxicity: pharmacokinetic perspectives and strategies for risk reduction }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Adverse drug reactions and toxicological reviews |. Adverse drug reactions and toxicological reviews }}{{#if:18 | 18 }}{{#if:4 | (4) }}{{#if:181–233 |: 181–233 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[24] }}{{#if: |. ISSN {{{issn}}} }}{{#if:10687025 |. PMID 10687025 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  25. ↑ {{#if:Wallace JL |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Wallace JL }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Wallace JL }} }} }}{{#if:Wallace JL |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2004 |{{#if: | ({{{month}}} 2004) | (2004) }} }} }}{{#if:Wallace JL | . }}{{#if:Wallace JL2004 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Acetaminophen hepatotoxicity: NO to the rescue] |Acetaminophen hepatotoxicity: NO to the rescue }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Br. J. Pharmacol. |. Br. J. Pharmacol. }}{{#if:143 | 143 }}{{#if:1 | (1) }}{{#if:1–2 |: 1–2 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1038/sj.bjp.0705781 |. doi:10.1038/sj.bjp.0705781 }}{{#if: |. ISSN {{{issn}}} }}{{#if:15345657 |. PMID 15345657 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  26. ↑ {{#if:James LP, Mayeux PR, Hinson JA |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |James LP, Mayeux PR, Hinson JA }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |James LP, Mayeux PR, Hinson JA }} }} }}{{#if:James LP, Mayeux PR, Hinson JA |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2003 |{{#if: | ({{{month}}} 2003) | (2003) }} }} }}{{#if:James LP, Mayeux PR, Hinson JA | . }}{{#if:James LP, Mayeux PR, Hinson JA2003 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Acetaminophen-induced hepatotoxicity] |Acetaminophen-induced hepatotoxicity }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Drug Metab. Dispos. |. Drug Metab. Dispos. }}{{#if:31 | 31 }}{{#if:12 | (12) }}{{#if:1499–506 |: 1499–506 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1124/dmd.31.12.1499 |. doi:10.1124/dmd.31.12.1499 }}{{#if: |. ISSN {{{issn}}} }}{{#if:14625346 |. PMID 14625346 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  27. ↑ {{#if:Manov I, Motanis H, Frumin I, Iancu TC |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Manov I, Motanis H, Frumin I, Iancu TC }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Manov I, Motanis H, Frumin I, Iancu TC }} }} }}{{#if:Manov I, Motanis H, Frumin I, Iancu TC |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2006 |{{#if: | ({{{month}}} 2006) | (2006) }} }} }}{{#if:Manov I, Motanis H, Frumin I, Iancu TC | . }}{{#if:Manov I, Motanis H, Frumin I, Iancu TC2006 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects] |Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Acta Pharmacol. Sin. |. Acta Pharmacol. Sin. }}{{#if:27 | 27 }}{{#if:3 | (3) }}{{#if:259–72 |: 259–72 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[25] }}{{#if: |. ISSN {{{issn}}} }}{{#if:16490160 |. PMID 16490160 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  28. ↑ {{#if:Iancu TC, Shiloh H, Dembo L |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Iancu TC, Shiloh H, Dembo L }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Iancu TC, Shiloh H, Dembo L }} }} }}{{#if:Iancu TC, Shiloh H, Dembo L |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1986 |{{#if: | ({{{month}}} 1986) | (1986) }} }} }}{{#if:Iancu TC, Shiloh H, Dembo L | . }}{{#if:Iancu TC, Shiloh H, Dembo L1986 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Hepatomegaly following short-term high-dose steroid therapy] |Hepatomegaly following short-term high-dose steroid therapy }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:J. Pediatr. Gastroenterol. Nutr. |. J. Pediatr. Gastroenterol. Nutr. }}{{#if:5 | 5 }}{{#if:1 | (1) }}{{#if:41–6 |: 41–6 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[26] }}{{#if: |. ISSN {{{issn}}} }}{{#if:3944744 |. PMID 3944744 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  29. ↑ {{ #if: Alpers DH | {{ #if: | [[|{{ #if: Alpers DH | Alpers DH{{ #if: Sabesin SM | , Sabesin SM }} | {{{author}}} }}]] | {{ #if: Alpers DH | Alpers DH{{ #if: Sabesin SM | , Sabesin SM }} | {{{author}}} }} }} }}{{ #if: Alpers DH | {{ #if: Schiff L, Schiff ER, editors. | ; Schiff L, Schiff ER, editors. }} }}{{ #if: | [{{{origdate}}}] | {{ #if: | {{ #if: | [{{{origmonth}}} {{{origyear}}}] | [{{{origyear}}}] }} }} }}{{ #if: 1982 | (1982) | {{ #if: | {{ #if: | ({{{month}}} {{{year}}}) | ({{{year}}}) }} }} }}{{ #if: Alpers DH | . }}{{ #if: | "{{ #if: | [{{{chapterurl}}} {{{chapter}}}] | {{{chapter}}} }}",}}{{ #if: | in {{{editor}}}: }} {{ #if: | [ Diseases of the liver] | Diseases of the liver }}{{ #if: | ({{{format}}}) }}{{ #if: | , {{{others}}} }}{{ #if: | , {{{edition}}} }}{{ #if: | , {{{series}}} }}{{ #if: | (in {{{language}}}) }}{{ #if: JB Lippincott | {{#if: | , | . }}{{ #if: Philadelphia | Philadelphia: }}JB Lippincott }}{{ #if: 813-45 | , 813-45 }}{{ #if: | . DOI:[27] }}{{ #if: | . }}{{ #if: | . ISBN }}{{ #if: | . OCLC {{{oclc}}} }}{{ #if: | {{ #if: | . Retrieved on [[{{{accessdate}}}]] | {{ #if: | . Retrieved {{ #if: | on [[{{{accessmonth}}} {{{accessyear}}}]] | during [[{{{accessyear}}}]] }}}} }} }}.{{ #if: |  “{{{quote}}}” }} 
  30. ↑ {{#if:Sarich TC, Adams SP, Petricca G, Wright JM |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Sarich TC, Adams SP, Petricca G, Wright JM }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Sarich TC, Adams SP, Petricca G, Wright JM }} }} }}{{#if:Sarich TC, Adams SP, Petricca G, Wright JM |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1999 |{{#if: | ({{{month}}} 1999) | (1999) }} }} }}{{#if:Sarich TC, Adams SP, Petricca G, Wright JM | . }}{{#if:Sarich TC, Adams SP, Petricca G, Wright JM1999 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor] |Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:J. Pharmacol. Exp. Ther. |. J. Pharmacol. Exp. Ther. }}{{#if:289 | 289 }}{{#if:2 | (2) }}{{#if:695–702 |: 695–702 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[28] }}{{#if: |. ISSN {{{issn}}} }}{{#if:10215642 |. PMID 10215642 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  31. ↑ {{#if:Pak E, Esrason KT, Wu VH |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Pak E, Esrason KT, Wu VH }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Pak E, Esrason KT, Wu VH }} }} }}{{#if:Pak E, Esrason KT, Wu VH |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2004 |{{#if: | ({{{month}}} 2004) | (2004) }} }} }}{{#if:Pak E, Esrason KT, Wu VH | . }}{{#if:Pak E, Esrason KT, Wu VH2004 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Hepatotoxicity of herbal remedies: an emerging dilemma] |Hepatotoxicity of herbal remedies: an emerging dilemma }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Progress in transplantation (Aliso Viejo, Calif.) |. Progress in transplantation (Aliso Viejo, Calif.) }}{{#if:14 | 14 }}{{#if:2 | (2) }}{{#if:91–6 |: 91–6 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[29] }}{{#if: |. ISSN {{{issn}}} }}{{#if:15264453 |. PMID 15264453 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
pl:Hepatotoksyczność

pt:Hepatotoxicidade ru:Гепатотоксичность

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