1428:
40:
661:
303:
750:; six of them metabolize 90% of drugs. 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 most drugs) in phase 1. Three important characteristics of the P-450 system have roles in drug-induced toxicity:
434:
1461:, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.
1240:
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 by which phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid
1435:
This remains a challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established,
196:
More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the
1444:
involves a scoring system that 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
1125:
is associated with infiltration of inflammatory cells. There can be three types of drug-induced hepatitis. (A) viral hepatitis is the most common, where histological features are similar to acute viral hepatitis. (B) in focal or non-specific hepatitis, scattered foci of cell necrosis may accompany
874:
Many substances can influence the P-450 enzyme mechanism. Drugs interact with the enzyme family in several ways. 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
262:
hepatotoxicity in susceptible individuals, which is not related to dose and has a variable latency period. This type of injury does not have a clear dose-response nor temporal relationship, and most often does not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of
333:
also plays a role in inducing toxicity. 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 the liver is quite variable from person to person and is often
1436:
but might be difficult, especially when idiosyncratic reaction is suspected. 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
1469:
An elevation in serum bilirubin level of more than 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
889:
Some drugs may share the same P-450 specificity and thus competitively block their biotransformation. This may lead to accumulation of drugs metabolized by the enzyme. This type of drug interaction may also reduce the rate of generation of toxic metabolites.
764:) in P-450 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.
382:
are so named due to their effect on the carbohydrate mechanism. They promote glycogen storage in the liver. An enlarged liver is a rare side-effect of long-term steroid use in children. The classical effect of prolonged use both in adult and
366:
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. Aspirin and
3601:
672:) to make them suitable for elimination. This involves chemical transformations to (a) reduce fat solubility and (b) to change biological activity. Although almost all tissues in the body have some ability to metabolize chemicals,
726:
and many other rare chemical reactions. These processes tend to increase water solubility of the drug and can generate metabolites that are more chemically active and/or potentially toxic. Most of phase 2 reactions take place in
710:. Phase 1 reaction is generally speaking to prepare a drug for phase 2. However, many compounds can be metabolized by phase 2 directly or be excreted without any phase 2 reactions occurring. Phase 1 reaction involves
1321:
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.
609:, 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
1699:
Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, et al. (December 2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States".
1060:
level more than twice ULN, or (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular (predominantly initial
399:
Isoniazide (INH) is one of the most commonly used drugs 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.
313:
also known as acetaminophen, and by the brand names of
Tylenol and Panadol, is usually well-tolerated in prescribed dose, but overdose is the most common cause of drug-induced liver disease and
1437:
1179:
Liver injury leads to impairment of bile flow and cases are predominated by itching and jaundice. Histology may show inflammation (cholestatic hepatitis) or it can be bland (without any
244:(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
161:
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.
1393:
Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, angiosarcoma, and liver adenomas are the ones usually reported.
371:
are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin.
875:
usually occurs immediately. On the other hand, inducers increase P-450 activity by increasing enzyme production, or, in the case of CYP2E1, preventing degradation in the
664:
Drug metabolism in liver: transferases are: glutathione, sulfate, acetate, glucoronic acid. P-450 is cytochrome P-450. Different pathways are shown for Drugs A, B and C.
334:
thought to be lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher levels predicting a worse prognosis. Administration of
598:, 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
746:, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is not a single enzyme, but rather consists of a closely related family of 50
2695:"Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways"
696:
substances (e.g., drugs, alcohol). The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.
288:
has been associated with hepatic toxicity, including some fatalities; however, such effects appear to be limited to doses taken over a period longer than 7 days.
2490:
602:
that bring drugs and xenobiotics in near-undiluted form. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process.
1474:). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or
2520:
Schoental R (April 1959). "Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, lasiocarpine and retrorsine".
1457:
In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In
325:-benzoquinone imine (NAPQI)) produced by cytochrome P-450 enzymes in the liver. In normal circumstances, this metabolite is detoxified by conjugating with
2334:
Sarich TC, Adams SP, Petricca G, Wright JM (1999). "Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor".
329:
in phase 2 reaction. In an overdose, a large amount of NAPQI is generated, which overwhelms the detoxification process and leads to liver cell damage.
1923:
Banankhah PS, Garnick KA, Greenblatt DJ (October 2016). "Ketoconazole-Associated Liver Injury in Drug-Drug
Interaction Studies in Healthy Volunteers".
1183:
inflammation). On rare occasions, it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (
760:
Each of the P-450 proteins is unique and accounts (to some extent) for the variation in drug metabolism between individuals. Genetic variations (
594:
Drugs continue to be taken off the market due to late discovery of hepatotoxicity. Due to its unique metabolism and close relationship with the
2361:
Schläppi B (1985). "The lack of hepatotoxicity in the rat with the new and reversible MAO-A inhibitor moclobemide in contrast to iproniazid".
3077:
3016:
2991:
1986:
1758:
1683:
1571:
2458:
231:
are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic). Type A drug reaction accounts for 80% of all toxicities.
1440:/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage.
451:, which occur in some plants, can be toxic. Green tea extract is a growing cause of liver failure due to its inclusion in more products.
1068:(initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed types of injuries are often encountered.
1445:
between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in
1404:
1195:
2186:
O'Grady JG, Alexander GJ, Hayllar KM, Williams R (August 1989). "Early indicators of prognosis in fulminant hepatic failure".
173:), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g.,
3093:
2939:
Patel T, Roberts LR, Jones BA, Gores GJ (1998). "Dysregulation of apoptosis as a mechanism of liver disease: an overview".
338:, a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. Those that develop
3037:
Lynch T, Price A (2007). "The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects".
158:
caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
3639:
3535:
Shah RR (November 1999). "Drug-induced hepatotoxicity: pharmacokinetic perspectives and strategies for risk reduction".
2500:
1874:
Dixit VA, Bharatam PV (July 2011). "Toxic metabolite formation from
Troglitazone (TGZ): new insights from a DFT study".
1184:
673:
189:, through pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called
3205:
Bénichou C (September 1990). "Criteria of drug-induced liver disorders. Report of an international consensus meeting".
2579:
255:
2644:"Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation"
3659:
1286:
355:
2904:
Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ (2002). "Mechanisms of hepatotoxicity".
3616:
1639:
Greenhough S, Hay DC (2012). "Stem Cell-Based
Toxicity Screening: Recent Advances in Hepatocyte Generation".
3439:"Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry"
80:
278:
has caused a number of cases of idiosyncratic liver injury, ranging everywhere from asymptomatic to fatal.
3068:
Concise Guide to Drug
Interaction Principles for Medical Practice: Cytochrome P450s, Ugts, P-Glycoproteins
1479:
1458:
1024:
1006:
761:
595:
492:
488:
448:
1242:
1367:
715:
637:
297:
228:
3247:"Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists"
2787:
McRae CA, Agarwal K, Mutimer D, Bassendine MF (May 2002). "Hepatitis associated with
Chinese herbs".
2693:
Zhou P, Gross S, Liu JH, Yu BY, Feng LL, Nolta J, Sharma V, Piwnica-Worms D, Qiu SX (December 2010).
1379:
1131:
1110:
1092:
1072:
1057:
1045:
936:
920:
806:
532:
480:
249:
210:
1490:
The following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity:
263:
several drugs from market even after rigorous clinical testing as part of the FDA approval process;
3664:
3654:
1978:
1296:
1096:
1061:
1053:
1041:
599:
468:
339:
314:
241:
217:
2423:
Kothari UC (February 1960). "Toxic and other side effects of nardil phenelzine sulphate W-1544A".
39:
3517:
3468:
3419:
3370:
3321:
3149:
2964:
2886:
2769:
2624:
2595:"ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury"
2301:
2252:
2119:
2076:
1948:
1856:
1725:
1656:
723:
508:
504:
2822:
Furukawa M, Kasajima S, Nakamura Y, Shouzushima M, Nagatani N, Takinishi A, et al. (2010).
2744:
Pak E, Esrason KT, Wu VH (June 2004). "Hepatotoxicity of herbal remedies: an emerging dilemma".
2465:
1536:
1257:
1750:
1744:
1427:
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3411:
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3073:
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2537:
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2405:
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2343:
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1982:
1940:
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1813:
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1717:
1679:
1621:
1567:
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472:
166:
67:
3245:
Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI (2007).
1713:
1478:) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high
3499:
3450:
3401:
3352:
3305:
3268:
3258:
3214:
3179:
3131:
2948:
2913:
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2835:
2796:
2753:
2716:
2706:
2665:
2655:
2606:
2529:
2432:
2397:
2283:
2234:
2195:
2158:
2150:
2103:
2060:
2023:
2015:
1970:
1932:
1883:
1840:
1803:
1795:
1709:
1648:
1611:
1603:
1531:
1475:
1408:
1373:
1199:
990:
743:
202:
72:
1052:) are often used to indicate liver damage. Liver injury is defined as a rise in either (a)
425:
has been associated with abnormal liver tests. Toxic effects can develop from antibiotics.
248:
overdose, this type of injury occurs shortly after some threshold for toxicity is reached.
2491:"Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Pyrrolizidine Alkaloids"
2094:
Riordan SM, Williams R (2002). "Alcohol exposure and paracetamol-induced hepatotoxicity".
1563:
1557:
699:
496:
306:
Paracetomol (3D structure) overdose is the most common cause of drug-induced liver disease
216:
Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all
3562:
1971:
668:
The human body subjects most, but not all, compounds to various chemical processes (i.e.
317:
worldwide. Damage to the liver is not due to the drug itself but to a toxic metabolite (
2051:
James LP, Mayeux PR, Hinson JA (December 2003). "Acetaminophen-induced hepatotoxicity".
660:
3273:
3246:
3136:
3119:
3066:
2721:
2694:
2670:
2643:
2388:
Cook GC, Sherlock S (January 1965). "Jaundice And Its
Relation To Therapeutic Agents".
2163:
2138:
2028:
2003:
1808:
1783:
1616:
1591:
1400:
1302:
1227:
1223:
994:
536:
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379:
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302:
174:
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2401:
1909:
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821:
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268:
155:
89:
3423:
3153:
2968:
2890:
2593:
Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ (July 2014).
2305:
2256:
1860:
1729:
1660:
201:-derived hepatocyte-like cells, that are capable of detecting toxicity early in the
3521:
3472:
3374:
3325:
2628:
2495:
2080:
1515:
1491:
1446:
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1213:
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1037:
1002:
866:
834:
633:
606:
512:
351:
330:
285:
264:
197:
need for toxicity prediction models (e.g. DTI), and drug screening assays, such as
2223:"Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects"
2123:
271:(Trovan) are two prime examples of idiosyncratic hepatotoxins pulled from market.
237:
or toxins that have a pharmacological (type A) hepatotoxicity are those that have
59:
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3309:
3097:
1471:
1329:
1209:
1180:
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973:
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681:
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326:
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245:
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162:
48:
2865:"Hepatoprotective activity of Clearliv a polyherbal formulation in Wistar rats"
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1234:
1203:
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1016:
852:
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839:
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408:
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85:
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3513:
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3415:
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2925:
2849:
2808:
2765:
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2620:
2565:
2541:
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2409:
2347:
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2172:
2115:
2072:
2064:
2037:
2019:
1944:
1895:
1721:
1625:
3226:
3145:
2984:
2960:
2560:. National Institute of Diabetes and Digestive and Kidney Diseases. 2012.
2436:
2374:
2297:
2207:
1817:
342:
can still recover spontaneously, but may require transplantation if poor
2711:
2611:
2594:
1852:
1519:
1387:
1084:
861:
848:
689:
649:
3593:
3183:
2555:
2824:"Toxic hepatitis induced by show-wu-pian, a Chinese herbal preparation"
1652:
1607:
1412:
1341:
1253:
1156:
1075:
patterns of liver injury from drug-induced damage are discussed below.
747:
728:
528:
500:
476:
252:
is commonly used to induce acute type A liver injury in animal models.
186:
3504:
3487:
3455:
3438:
3357:
3340:
3072:. Washington, DC: American Psychiatric Association. pp. 167–396.
1887:
1782:
Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK (April 1998).
3605:
3488:"Outcome and prognostic markers in severe drug-induced liver disease"
1936:
739:
610:
55:
3120:"Update: clinically significant cytochrome P-450 drug interactions"
3296:
Arundel C, Lewis JH (2007). "Drug-induced liver disease in 2006".
1426:
985:
981:
676:
in the liver is the principal "metabolic clearing house" for both
659:
460:
437:
432:
301:
234:
147:
52:
3170:
Mumoli N, Cei M, Cosimi A (2006). "Drug-related hepatotoxicity".
2642:
Kim YJ, Choi MS, Park YB, Kim SR, Lee MK, Jung UJ (August 2013).
1087:
where the injury is largely confined to a particular zone of the
1056:
level more than three times of upper limit of normal (ULN), (b)
484:
412:
275:
182:
2863:
Kumar EP, Kumar A, Parasuraman S, Rajan VR, Emerson SF (2013).
433:
735:
enzymes. Phase 1 are typically more suitable for elimination.
2982:
Blumenthal D, Brunton L, Parker K, Lazo JS, Buxton I (2006).
2272:"Hepatomegaly following short-term high-dose steroid therapy"
879:. There is usually a delay before enzyme activity increases.
51:. Other causes were excluded with extensive investigations.
3635:
447:
containing mushrooms, kava, and aflatoxin producing molds.
2319:
Alpers DH, Sabesin SM (1982). Schiff L, Schiff ER (eds.).
258:(type B) injury occurs without warning, when agents cause
1592:"A simple model to solve a complex drug toxicity problem"
3437:
Andrade RJ, Lucena MI, Kaplowitz N, et al. (2006).
1083:
This is the most common type of drug-induced liver cell
1130:
infiltration. (C) chronic hepatitis is very similar to
1360:
These result from injury to the vascular endothelium.
731:
and involve conjugation with endogenous compounds via
209:
injury to the liver, which manifests only as abnormal
1562:. New York: Lang Medical Books/McGraw-Hill. pp.
1559:
Current diagnosis & treatment in gastroenterology
1431:
Algorithm for suspected drug-induced hepatic toxicity
3583:
1964:
1962:
1095:
and severe disturbance of liver function leading to
3587:
1831:Zimmerman HJ (1978). "Drug-induced liver disease".
79:
66:
29:
24:
3065:
1036:Chemicals produce a wide variety of clinical and
2004:"Acetaminophen hepatotoxicity: NO to the rescue"
3240:
3238:
3236:
3165:
3163:
3032:
3030:
3028:
2323:. Philadelphia: JB Lippincott. pp. 813–45.
2221:Manov I, Motanis H, Frumin I, Iancu TC (2006).
1134:clinically, serologically, and histologically.
742:located in the endoplasmic reticulum, known as
2580:"Liver Damage from Supplements is on the Rise"
1585:
1583:
185:, though the causal mechanism is unknown, and
3064:Oesterheld JR, Cozza KL, Armstrong S (2003).
3011:. Cheltenham, UK: Nelson Thornes Publishers.
1977:. Edinburgh: Churchill Livingstone. pp.
1749:. Oxford : Oxford University Press. pp.
1676:GI/Liver Secrets: with STUDENT CONSULT Access
1556:Friedman SE, Grendell JH, McQuaid KR (2003).
8:
165:) and sometimes even when introduced within
3390:"Anticoagulants and transaminase elevation"
3584:
1091:. It may manifest as a very high level of
1040:hepatic injury. Biochemical markers (e.g.
773:
628:. This promotes further liver damage. Non-
38:
21:
3503:
3454:
3405:
3356:
3272:
3262:
3135:
2880:
2839:
2720:
2710:
2669:
2659:
2610:
2287:
2238:
2162:
2027:
1807:
1615:
613:also lead to oxidative stress. Injury to
16:Liver damage caused by a drug or chemical
2869:Archives of Medicine and Health Sciences
1714:10.7326/0003-4819-137-12-200212170-00007
3007:Skett, Paul; Gibson, G. Gordon (2001).
1548:
154:(DILI) is a cause of acute and chronic
900:Patterns of drug-induced liver disease
96:
652:) also have a role in the mechanism.
7:
2270:Iancu TC, Shiloh H, Dembo L (1986).
2139:"Paracetamol, alcohol and the liver"
702:is usually divided into two phases:
421:, are associated with liver damage.
362:Nonsteroidal anti-inflammatory drugs
120:Toxic liver disease with cholestasis
3178:(20): 2191–3, author reply 2191–3.
1370:: Chemotherapeutic agents, bush tea
3137:10.1002/j.1875-9114.1998.tb03830.x
1746:Textbook of adverse drug reactions
118:Toxic liver disease with hepatitis
14:
3407:10.1161/CIRCULATIONAHA.105.603100
407:There are also cases where other
2841:10.2169/internalmedicine.49.3509
2801:10.1097/00042737-200205000-00015
2289:10.1097/00005176-198601000-00008
2240:10.1111/j.1745-7254.2006.00278.x
2155:10.1046/j.1365-2125.2000.00167.x
1845:10.2165/00003495-197816010-00002
1405:combined oral contraceptive pill
403:Other hydrazine derivative drugs
106:Drug-induced liver injury (DILI)
3009:Introduction to drug metabolism
2276:J. Pediatr. Gastroenterol. Nutr
1969:Keeffe EB, Friedman LM (2004).
914:
911:
908:
905:
782:
779:
776:
549:
205:process. Chemicals often cause
3537:Adverse Drug React Toxicol Rev
3486:Björnsson E, Olsson R (2005).
3388:Arora N, Goldhaber SZ (2006).
621:cells lead to accumulation of
411:derivative drugs, such as the
181:(two prominent examples being
116:Drug-induced hepatic granuloma
1:
2464:. Davis. 2017. Archived from
2402:10.1016/s0140-6736(65)90969-4
2002:Wallace JL (September 2004).
769:2. Change in enzyme activity:
114:Drug-induced hepatic fibrosis
112:Drug-induced hepatic necrosis
3640:National Library of Medicine
3310:10.1097/MOG.0b013e3280b17dfb
3219:10.1016/0168-8278(90)90124-a
2986:. McGraw-Hill Professional.
2501:Food and Drug Administration
2200:10.1016/0016-5085(89)90081-4
674:smooth endoplasmic reticulum
552:drug-induced hepatotoxicity
47:Drug-induced hepatitis with
3563:Drug-Induced Hepatotoxicity
2789:Eur J Gastroenterol Hepatol
1678:. Saint Louis: C.V. Mosby.
580:Duration and dosage of drug
503:. Chinese herbal remedies:
126:Toxin-induced liver disease
3681:
3339:Reuben A (February 2004).
2758:10.1177/152692480401400203
2137:Prescott LF (April 2000).
1973:Handbook of liver diseases
1447:amoxycillin-clauvonic acid
1287:total parenteral nutrition
1241:metabolism defects (e.g.,
884:3. Competitive inhibition:
295:
163:acetaminophen, paracetamol
146:) implies chemical-driven
128:Drug-induced liver disease
3298:Curr. Opin. Gastroenterol
3039:American Family Physician
2108:10.1080/13556210220120424
1800:10.1136/bmj.316.7140.1295
152:Drug-induced liver injury
130:Drug-induced liver damage
46:
37:
2882:10.4103/2321-4848.123023
2661:10.3748/wjg.v19.i29.4689
1784:"Adverse drug reactions"
1196:Oral contraceptive pills
656:Drug metabolism in liver
586:Drug-to-drug interaction
571:Underlying liver disease
2918:10.1093/toxsci/65.2.166
2605:(7): 950–66, quiz 967.
2534:10.1002/path.1700770220
2336:J. Pharmacol. Exp. Ther
1590:Dixit VA (March 2019).
1380:Hepatic vein thrombosis
1268:(especially if expired)
1185:vanishing duct syndrome
1161:(c) Chronic hepatitis:
1123:hepatocellular necrosis
605:Many chemicals damage
489:pyrrolizidine alkaloids
449:Pyrrolizidine alkaloids
356:King's College Criteria
132:Hepatogenous poisoning
108:Toxin-induced hepatitis
3264:10.3748/wjg.v13.i3.329
3251:World J. Gastroenterol
2953:10.1055/s-2007-1007147
2065:10.1124/dmd.31.12.1499
2020:10.1038/sj.bjp.0705781
1910:"Ketoconazole Tablets"
1459:acetaminophen toxicity
1432:
1281:(c) Phospholipidosis:
1007:Hormonal contraception
665:
596:gastrointestinal tract
440:
307:
229:Adverse drug reactions
110:Drug-induced hepatitis
3638:at the United States
3118:Michalets EL (1998).
2648:World J Gastroenterol
2437:10.1176/ajp.116.8.746
2363:Arzneimittelforschung
2321:Diseases of the liver
1430:
1382:: Oral contraceptives
1368:Venoocclusive disease
1155:(b) Focal hepatitis:
1141:(a) Viral hepatitis:
755:1. Genetic diversity:
684:, steroid hormones,
663:
636:, collagen-producing
436:
305:
298:Paracetamol poisoning
2712:10.1096/fj.10-163311
2612:10.1038/ajg.2014.131
1297:nucleoside analogues
1271:(b) Macrovesicular:
1252:(a) Microvesicular:
1132:autoimmune hepatitis
1111:carbon tetrachloride
1046:alkaline phosphatase
550:Factors influencing
533:carbon tetrachloride
455:Alternative remedies
250:Carbon tetrachloride
242:dose-response curves
218:acute liver failures
3184:10.1056/NEJMc060733
2471:on October 27, 2017
2227:Acta Pharmacol. Sin
2143:Br J Clin Pharmacol
1674:McNally PF (2006).
1376:: Anabolic steroids
1097:acute liver failure
1062:Alanine transferase
1042:alanine transferase
902:
340:acute liver failure
315:acute liver failure
124:Toxic liver disease
2599:Am J Gastroenterol
2522:J Pathol Bacteriol
1653:10.1007/BF03256896
1608:10.1039/c8tx00261d
1433:
1208:(b) Inflammatory:
1073:histo-pathological
898:
894:Patterns of injury
666:
568:Nutritional status
562:Ethnicity and race
459:Examples include:
441:
308:
211:liver enzyme tests
167:therapeutic ranges
3660:Diseases of liver
3631:
3630:
3505:10.1002/hep.20800
3456:10.1002/hep.21424
3358:10.1002/hep.20081
3079:978-1-58562-111-8
3018:978-0-7487-6011-4
2993:978-0-07-146804-6
2053:Drug Metab Dispos
1988:978-0-443-06633-7
1888:10.1021/tx200110h
1760:978-0-19-261479-7
1743:Davies D (1985).
1685:978-1-56053-618-5
1573:978-0-8385-1551-8
1442:CIOMS/RUCAM scale
1243:Tay–Sachs disease
1121:In this pattern,
1034:
1033:
872:
871:
780:Potent inhibitors
680:chemicals (e.g.,
592:
591:
527:Examples include
443:Examples include
137:
136:
95:
94:
19:Medical condition
3672:
3585:
3570:
3559:
3553:
3552:
3532:
3526:
3525:
3507:
3483:
3477:
3476:
3458:
3434:
3428:
3427:
3409:
3400:(15): e698–702.
3385:
3379:
3378:
3360:
3336:
3330:
3329:
3293:
3287:
3286:
3276:
3266:
3242:
3231:
3230:
3202:
3196:
3195:
3167:
3158:
3157:
3139:
3115:
3109:
3108:
3106:
3105:
3096:. Archived from
3090:
3084:
3083:
3071:
3061:
3055:
3054:
3034:
3023:
3022:
3004:
2998:
2997:
2979:
2973:
2972:
2941:Semin. Liver Dis
2936:
2930:
2929:
2901:
2895:
2894:
2884:
2860:
2854:
2853:
2843:
2819:
2813:
2812:
2784:
2778:
2777:
2741:
2735:
2734:
2724:
2714:
2690:
2684:
2683:
2673:
2663:
2654:(29): 4689–701.
2639:
2633:
2632:
2614:
2590:
2584:
2583:
2576:
2570:
2569:
2552:
2546:
2545:
2517:
2511:
2510:
2508:
2507:
2499:. United States
2487:
2481:
2480:
2478:
2476:
2470:
2463:
2455:
2449:
2448:
2420:
2414:
2413:
2385:
2379:
2378:
2358:
2352:
2351:
2331:
2325:
2324:
2316:
2310:
2309:
2291:
2267:
2261:
2260:
2242:
2218:
2212:
2211:
2188:Gastroenterology
2183:
2177:
2176:
2166:
2134:
2128:
2127:
2091:
2085:
2084:
2059:(12): 1499–506.
2048:
2042:
2041:
2031:
1999:
1993:
1992:
1976:
1966:
1957:
1956:
1937:10.1002/jcph.711
1931:(10): 1196–202.
1925:J Clin Pharmacol
1920:
1914:
1913:
1906:
1900:
1899:
1876:Chem Res Toxicol
1871:
1865:
1864:
1828:
1822:
1821:
1811:
1794:(7140): 1295–8.
1779:
1773:
1772:
1740:
1734:
1733:
1696:
1690:
1689:
1671:
1665:
1664:
1636:
1630:
1629:
1619:
1587:
1578:
1577:
1553:
1532:Hepatoprotection
1476:Gilbert syndrome
1409:anabolic steroid
1374:Peliosis hepatis
1356:Vascular lesions
1200:anabolic steroid
991:Anabolic steroid
903:
897:
774:
744:cytochrome P-450
626:inside the liver
583:Enzyme induction
547:
546:
523:Industrial toxin
429:Natural products
354:is present (see
281:Oral use of the
203:drug development
144:hepatic toxicity
97:
73:Gastroenterology
42:
22:
3680:
3679:
3675:
3674:
3673:
3671:
3670:
3669:
3645:
3644:
3632:
3627:
3626:
3596:
3582:
3576:
3574:
3573:
3560:
3556:
3534:
3533:
3529:
3485:
3484:
3480:
3436:
3435:
3431:
3387:
3386:
3382:
3338:
3337:
3333:
3295:
3294:
3290:
3244:
3243:
3234:
3204:
3203:
3199:
3172:N. Engl. J. Med
3169:
3168:
3161:
3124:Pharmacotherapy
3117:
3116:
3112:
3103:
3101:
3092:
3091:
3087:
3080:
3063:
3062:
3058:
3036:
3035:
3026:
3019:
3006:
3005:
3001:
2994:
2981:
2980:
2976:
2938:
2937:
2933:
2903:
2902:
2898:
2862:
2861:
2857:
2834:(15): 1537–40.
2821:
2820:
2816:
2786:
2785:
2781:
2746:Prog Transplant
2743:
2742:
2738:
2705:(12): 4722–32.
2692:
2691:
2687:
2641:
2640:
2636:
2592:
2591:
2587:
2578:
2577:
2573:
2554:
2553:
2549:
2519:
2518:
2514:
2505:
2503:
2489:
2488:
2484:
2474:
2472:
2468:
2461:
2457:
2456:
2452:
2425:Am J Psychiatry
2422:
2421:
2417:
2396:(7378): 175–9.
2387:
2386:
2382:
2360:
2359:
2355:
2333:
2332:
2328:
2318:
2317:
2313:
2269:
2268:
2264:
2220:
2219:
2215:
2185:
2184:
2180:
2136:
2135:
2131:
2093:
2092:
2088:
2050:
2049:
2045:
2001:
2000:
1996:
1989:
1968:
1967:
1960:
1922:
1921:
1917:
1908:
1907:
1903:
1873:
1872:
1868:
1830:
1829:
1825:
1781:
1780:
1776:
1761:
1742:
1741:
1737:
1698:
1697:
1693:
1686:
1673:
1672:
1668:
1638:
1637:
1633:
1589:
1588:
1581:
1574:
1555:
1554:
1550:
1545:
1537:Reye's syndrome
1528:
1488:
1486:Drugs withdrawn
1467:
1455:
1425:
1391:
1358:
1319:
1258:Reye's syndrome
1238:
1177:
1119:
1103:Causes include:
1081:
1064:elevation) and
1027:
1023:
1019:
1015:
1005:
1001:
997:
993:
984:
980:
976:
972:
952:ALT: ALP ratio
947:≥ Twofold rise
931:≥ Twofold rise
906:Type of injury:
896:
865:
856:
838:
829:
820:
805:
796:
777:Potent inducers
700:Drug metabolism
658:
551:
545:
525:
457:
431:
405:
397:
380:Glucocorticoids
377:
375:Glucocorticoids
364:
300:
294:
260:non-predictable
226:
179:herbal remedies
131:
129:
127:
125:
123:
122:Toxic hepatitis
121:
119:
117:
115:
113:
111:
109:
107:
20:
17:
12:
11:
5:
3678:
3676:
3668:
3667:
3662:
3657:
3647:
3646:
3643:
3642:
3629:
3628:
3625:
3624:
3613:
3597:
3592:
3591:
3589:
3588:Classification
3581:
3580:External links
3578:
3572:
3571:
3554:
3543:(4): 181–233.
3527:
3478:
3429:
3380:
3331:
3288:
3232:
3197:
3159:
3110:
3085:
3078:
3056:
3024:
3017:
2999:
2992:
2974:
2931:
2896:
2855:
2814:
2779:
2736:
2685:
2634:
2585:
2582:. 19 May 2017.
2571:
2547:
2512:
2482:
2450:
2415:
2380:
2353:
2342:(2): 695–702.
2326:
2311:
2262:
2213:
2178:
2149:(4): 291–301.
2129:
2102:(2): 191–206.
2086:
2043:
2008:Br J Pharmacol
1994:
1987:
1958:
1915:
1901:
1882:(7): 1113–22.
1866:
1823:
1774:
1759:
1735:
1708:(12): 947–54.
1702:Ann Intern Med
1691:
1684:
1666:
1631:
1602:(2): 157–171.
1579:
1572:
1547:
1546:
1544:
1541:
1540:
1539:
1534:
1527:
1524:
1487:
1484:
1466:
1463:
1454:
1451:
1424:
1421:
1420:
1419:
1401:Vinyl chloride
1398:
1390:
1385:
1384:
1383:
1377:
1371:
1365:
1357:
1354:
1353:
1352:
1327:
1318:
1313:
1312:
1311:
1307:(f) Hormonal:
1305:
1303:Corticosteroid
1299:
1289:
1279:
1269:
1250:
1237:
1232:
1231:
1230:
1228:flucloxacillin
1224:Chlorpromazine
1220:
1206:
1192:
1176:
1171:
1170:
1169:
1159:
1153:
1139:
1118:
1115:
1114:
1113:
1104:
1080:
1079:Zonal Necrosis
1077:
1032:
1031:
1009:
995:Chlorpromazine
988:
967:
963:
962:
959:
956:
953:
949:
948:
945:
944:≥ Twofold rise
942:
939:
933:
932:
929:
926:
925:≥ Twofold rise
923:
917:
916:
913:
910:
909:Hepatocellular
907:
895:
892:
887:
886:
870:
869:
846:
810:
807:St John's wort
785:
784:
781:
778:
772:
771:
758:
757:
657:
654:
638:stellate cells
632:cells such as
590:
589:
588:
587:
584:
581:
578:
575:
574:Renal function
572:
569:
566:
563:
560:
554:
553:
544:
541:
537:vinyl chloride
524:
521:
493:Horse chestnut
456:
453:
445:alpha-Amanitin
430:
427:
416:antidepressant
404:
401:
396:
393:
387:population is
376:
373:
369:phenylbutazone
363:
360:
348:encephalopathy
346:signs such as
336:Acetylcysteine
296:Main article:
293:
290:
267:(Rezulin) and
225:
222:
175:alpha-amanitin
140:Hepatotoxicity
135:
134:
102:
101:
93:
92:
83:
77:
76:
70:
64:
63:
44:
43:
35:
34:
33:see below list
31:
27:
26:
25:Hepatotoxicity
18:
15:
13:
10:
9:
6:
4:
3:
2:
3677:
3666:
3663:
3661:
3658:
3656:
3653:
3652:
3650:
3641:
3637:
3634:
3633:
3623:
3619:
3618:
3614:
3612:
3608:
3607:
3603:
3599:
3598:
3595:
3590:
3586:
3579:
3577:
3569:
3565:
3564:
3558:
3555:
3550:
3546:
3542:
3538:
3531:
3528:
3523:
3519:
3515:
3511:
3506:
3501:
3497:
3493:
3489:
3482:
3479:
3474:
3470:
3466:
3462:
3457:
3452:
3449:(6): 1581–8.
3448:
3444:
3440:
3433:
3430:
3425:
3421:
3417:
3413:
3408:
3403:
3399:
3395:
3391:
3384:
3381:
3376:
3372:
3368:
3364:
3359:
3354:
3350:
3346:
3342:
3335:
3332:
3327:
3323:
3319:
3315:
3311:
3307:
3304:(3): 244–54.
3303:
3299:
3292:
3289:
3284:
3280:
3275:
3270:
3265:
3260:
3257:(3): 329–40.
3256:
3252:
3248:
3241:
3239:
3237:
3233:
3228:
3224:
3220:
3216:
3212:
3208:
3201:
3198:
3193:
3189:
3185:
3181:
3177:
3173:
3166:
3164:
3160:
3155:
3151:
3147:
3143:
3138:
3133:
3130:(1): 84–112.
3129:
3125:
3121:
3114:
3111:
3100:on 2007-10-10
3099:
3095:
3089:
3086:
3081:
3075:
3070:
3069:
3060:
3057:
3052:
3048:
3044:
3040:
3033:
3031:
3029:
3025:
3020:
3014:
3010:
3003:
3000:
2995:
2989:
2985:
2978:
2975:
2970:
2966:
2962:
2958:
2954:
2950:
2947:(2): 105–14.
2946:
2942:
2935:
2932:
2927:
2923:
2919:
2915:
2912:(2): 166–76.
2911:
2907:
2900:
2897:
2892:
2888:
2883:
2878:
2874:
2870:
2866:
2859:
2856:
2851:
2847:
2842:
2837:
2833:
2829:
2825:
2818:
2815:
2810:
2806:
2802:
2798:
2795:(5): 559–62.
2794:
2790:
2783:
2780:
2775:
2771:
2767:
2763:
2759:
2755:
2751:
2747:
2740:
2737:
2732:
2728:
2723:
2718:
2713:
2708:
2704:
2700:
2696:
2689:
2686:
2681:
2677:
2672:
2667:
2662:
2657:
2653:
2649:
2645:
2638:
2635:
2630:
2626:
2622:
2618:
2613:
2608:
2604:
2600:
2596:
2589:
2586:
2581:
2575:
2572:
2567:
2563:
2559:
2558:
2551:
2548:
2543:
2539:
2535:
2531:
2528:(2): 485–95.
2527:
2523:
2516:
2513:
2502:
2498:
2497:
2492:
2486:
2483:
2467:
2460:
2459:"Amoxicillin"
2454:
2451:
2446:
2442:
2438:
2434:
2430:
2426:
2419:
2416:
2411:
2407:
2403:
2399:
2395:
2391:
2384:
2381:
2376:
2372:
2368:
2364:
2357:
2354:
2349:
2345:
2341:
2337:
2330:
2327:
2322:
2315:
2312:
2307:
2303:
2299:
2295:
2290:
2285:
2281:
2277:
2273:
2266:
2263:
2258:
2254:
2250:
2246:
2241:
2236:
2233:(3): 259–72.
2232:
2228:
2224:
2217:
2214:
2209:
2205:
2201:
2197:
2194:(2): 439–45.
2193:
2189:
2182:
2179:
2174:
2170:
2165:
2160:
2156:
2152:
2148:
2144:
2140:
2133:
2130:
2125:
2121:
2117:
2113:
2109:
2105:
2101:
2097:
2090:
2087:
2082:
2078:
2074:
2070:
2066:
2062:
2058:
2054:
2047:
2044:
2039:
2035:
2030:
2025:
2021:
2017:
2013:
2009:
2005:
1998:
1995:
1990:
1984:
1980:
1975:
1974:
1965:
1963:
1959:
1954:
1950:
1946:
1942:
1938:
1934:
1930:
1926:
1919:
1916:
1911:
1905:
1902:
1897:
1893:
1889:
1885:
1881:
1877:
1870:
1867:
1862:
1858:
1854:
1850:
1846:
1842:
1838:
1834:
1827:
1824:
1819:
1815:
1810:
1805:
1801:
1797:
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1542:
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1535:
1533:
1530:
1529:
1525:
1523:
1521:
1517:
1513:
1509:
1505:
1501:
1500:trovafloxacin
1497:
1493:
1485:
1483:
1481:
1477:
1473:
1464:
1462:
1460:
1452:
1450:
1448:
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1306:
1304:
1300:
1298:
1294:
1290:
1288:
1284:
1280:
1278:
1274:
1273:Acetaminophen
1270:
1267:
1263:
1259:
1255:
1251:
1248:
1247:
1246:
1244:
1236:
1233:
1229:
1225:
1221:
1219:
1218:carbamazepine
1215:
1211:
1207:
1205:
1201:
1197:
1193:
1190:
1189:
1188:
1186:
1182:
1175:
1172:
1168:
1164:
1160:
1158:
1154:
1152:
1148:
1144:
1140:
1137:
1136:
1135:
1133:
1129:
1124:
1116:
1112:
1108:
1105:
1102:
1101:
1100:
1098:
1094:
1090:
1086:
1078:
1076:
1074:
1069:
1067:
1063:
1059:
1055:
1051:
1047:
1043:
1039:
1030:
1026:
1022:
1021:Carbamazepine
1018:
1013:
1012:Amitriptyline
1010:
1008:
1004:
1000:
996:
992:
989:
987:
983:
979:
975:
971:
970:Acetaminophen
968:
965:
964:
960:
957:
954:
951:
950:
946:
943:
940:
938:
935:
934:
930:
927:
924:
922:
919:
918:
904:
901:
893:
891:
885:
882:
881:
880:
878:
868:
863:
859:
854:
850:
847:
845:
841:
836:
832:
827:
823:
822:Ciprofloxacin
818:
814:
811:
808:
803:
799:
798:Phenobarbital
794:
793:Carbamazepine
790:
787:
786:
775:
770:
767:
766:
765:
763:
756:
753:
752:
751:
749:
745:
741:
736:
734:
730:
725:
721:
717:
713:
709:
705:
701:
697:
695:
691:
687:
683:
679:
675:
671:
662:
655:
653:
651:
647:
643:
639:
635:
634:Kupffer cells
631:
627:
624:
620:
616:
612:
608:
603:
601:
597:
585:
582:
579:
576:
573:
570:
567:
564:
561:
558:
557:
556:
555:
548:
542:
540:
538:
534:
530:
522:
520:
518:
514:
510:
506:
502:
498:
494:
490:
486:
482:
478:
474:
470:
466:
462:
454:
452:
450:
446:
439:
435:
428:
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424:
420:
417:
414:
410:
402:
400:
394:
392:
390:
386:
381:
374:
372:
370:
361:
359:
357:
353:
349:
345:
341:
337:
332:
328:
324:
320:
316:
312:
304:
299:
291:
289:
287:
284:
279:
277:
272:
270:
269:trovafloxacin
266:
261:
257:
256:Idiosyncratic
253:
251:
247:
243:
240:
236:
232:
230:
223:
221:
219:
214:
212:
208:
204:
200:
194:
192:
188:
184:
180:
176:
172:
168:
164:
159:
157:
156:liver disease
153:
149:
145:
141:
133:
104:
103:
99:
98:
91:
90:liver failure
87:
84:
82:
81:Complications
78:
74:
71:
69:
65:
61:
60:H&E stain
57:
54:
50:
45:
41:
36:
32:
28:
23:
3615:
3600:
3575:
3561:
3557:
3540:
3536:
3530:
3498:(2): 481–9.
3495:
3491:
3481:
3446:
3442:
3432:
3397:
3393:
3383:
3351:(2): 574–8.
3348:
3344:
3334:
3301:
3297:
3291:
3254:
3250:
3213:(2): 272–6.
3210:
3206:
3200:
3175:
3171:
3127:
3123:
3113:
3102:. Retrieved
3098:the original
3094:"P450 Table"
3088:
3067:
3059:
3045:(3): 391–6.
3042:
3038:
3008:
3002:
2983:
2977:
2944:
2940:
2934:
2909:
2906:Toxicol. Sci
2905:
2899:
2875:(2): 120–5.
2872:
2868:
2858:
2831:
2827:
2817:
2792:
2788:
2782:
2749:
2745:
2739:
2702:
2698:
2688:
2651:
2647:
2637:
2602:
2598:
2588:
2574:
2556:
2550:
2525:
2521:
2515:
2504:. Retrieved
2496:Bad Bug Book
2494:
2485:
2473:. Retrieved
2466:the original
2453:
2431:(8): 746–7.
2428:
2424:
2418:
2393:
2389:
2383:
2369:(5): 800–3.
2366:
2362:
2356:
2339:
2335:
2329:
2320:
2314:
2279:
2275:
2265:
2230:
2226:
2216:
2191:
2187:
2181:
2146:
2142:
2132:
2099:
2095:
2089:
2056:
2052:
2046:
2011:
2007:
1997:
1972:
1928:
1924:
1918:
1904:
1879:
1875:
1869:
1839:(1): 25–45.
1836:
1832:
1826:
1791:
1787:
1777:
1745:
1738:
1705:
1701:
1694:
1675:
1669:
1647:(2): 85–89.
1644:
1640:
1634:
1599:
1595:
1558:
1551:
1516:ximelagatran
1492:Troglitazone
1489:
1468:
1456:
1434:
1392:
1359:
1320:
1277:methotrexate
1266:tetracycline
1239:
1222:(c) Ductal:
1214:co-amoxiclav
1178:
1120:
1089:liver lobule
1082:
1070:
1038:pathological
1035:
1003:Erythromycin
899:
888:
883:
873:
867:Theophylline
835:Erythromycin
768:
762:polymorphism
759:
754:
737:
707:
703:
698:
667:
607:mitochondria
604:
600:portal veins
593:
526:
513:Shou Wu Pian
458:
442:
406:
398:
378:
365:
352:coagulopathy
331:Nitric oxide
322:
318:
309:
286:ketoconazole
280:
273:
265:Troglitazone
259:
254:
238:
233:
227:
215:
195:
191:hepatotoxins
160:
151:
143:
139:
138:
105:
75:, Toxicology
3394:Circulation
2752:(2): 91–6.
2282:(1): 41–6.
2096:Addict Biol
1596:Toxicol Res
1330:Allopurinol
1210:Allopurinol
1194:(a) Bland:
1181:parenchymal
1174:Cholestasis
1128:lymphocytic
1107:Paracetamol
1066:cholestatic
1025:Sulfonamide
999:Clopidogrel
974:Allopurinol
912:Cholestatic
826:Fluconazole
783:Substrates
738:A group of
733:transferase
686:fatty acids
682:cholesterol
630:parenchymal
517:Bai Xian Pi
505:Jin Bu Huan
461:Ackee fruit
438:Ackee fruit
327:glutathione
311:Paracetamol
292:Paracetamol
246:paracetamol
239:predictable
207:subclinical
49:granulomata
30:Other names
3665:Hepatology
3655:Toxicology
3649:Categories
3492:Hepatology
3443:Hepatology
3345:Hepatology
3341:"Hy's law"
3104:2007-09-29
2828:Intern Med
2506:2009-07-11
2014:(1): 1–2.
1543:References
1512:nefazodone
1508:nimesulide
1504:ebrotidine
1417:thorotrast
1346:penicillin
1283:Amiodarone
1262:ketoprofen
1167:diclofenac
1163:Methyldopa
978:Amiodarone
877:proteasome
858:Omeprazole
831:Fluoxetine
817:Cimetidine
813:Amiodarone
789:Rifampicin
720:hydrolysis
678:endogenous
670:metabolism
646:neutrophil
642:leukocytes
615:hepatocyte
465:Bajiaolian
423:Phenelzine
419:iproniazid
385:paediatric
344:prognostic
283:antifungal
3568:eMedicine
3207:J Hepatol
2774:208042609
2475:March 24,
1953:206060985
1641:Pharm Med
1496:bromfenac
1465:Prognosis
1453:Treatment
1423:Diagnosis
1350:quinidine
1338:isoniazid
1334:phenytoin
1316:Granuloma
1309:Tamoxifen
1293:Antiviral
1235:Steatosis
1204:androgens
1151:phenytoin
1147:isoniazid
1143:Halothane
1117:Hepatitis
1071:Specific
1050:bilirubin
1029:Phenytoin
1017:Enalapril
966:Examples
853:Clozapine
844:Diltiazem
840:Isoniazid
802:Phenytoin
724:hydration
716:reduction
712:oxidation
694:exogenous
623:bile acid
619:bile duct
577:Pregnancy
543:Mechanism
409:hydrazine
395:Isoniazid
389:steatosis
274:The herb
199:stem cell
171:halothane
100:Synonyms
86:Cirrhosis
68:Specialty
3636:LiverTox
3549:10687025
3514:16025496
3465:17133470
3424:32207352
3416:16618822
3367:14768020
3318:17414839
3283:17230599
3192:16710915
3154:18552904
3051:17708140
2969:28395693
2926:11812920
2891:98429527
2850:20686286
2809:11984156
2766:15264453
2731:20696856
2680:23922466
2621:24935270
2566:31643176
2557:GreenTea
2542:13642195
2445:14411298
2410:14238042
2348:10215642
2306:35749798
2257:26874901
2249:16490160
2173:10759684
2116:12006215
2073:14625346
2038:15345657
1945:26829173
1896:21657230
1861:45207777
1769:12558288
1730:11390513
1722:12484709
1661:15893493
1626:30997019
1526:See also
1520:pemoline
1472:Hy's Law
1388:Neoplasm
1085:necrosis
955:High, ≥5
862:Losartan
849:Caffeine
748:isoforms
690:proteins
650:monocyte
497:Valerian
495:leaves,
487:leaves,
481:Garcinia
473:Copaltra
321:-acetyl-
150:damage.
3622:D056486
3522:2742529
3473:9067701
3375:5916660
3326:5842491
3274:4065885
3227:2254635
3146:9469685
2961:9606808
2722:2992378
2699:FASEB J
2671:3732841
2629:2417493
2375:4026902
2298:3944744
2208:2490426
2164:2014937
2081:1556558
2029:1575258
1818:9554902
1809:1113033
1617:6417485
1564:664–679
1413:arsenic
1397:Causes:
1364:Causes:
1342:quinine
1326:Causes:
1254:Aspirin
1249:Causes:
1191:Causes:
1157:Aspirin
1138:Causes:
958:Low, ≤2
740:enzymes
729:cytosol
708:phase 2
704:phase 1
529:arsenic
509:Ephedra
501:Comfrey
477:Cycasin
469:Camphor
187:comfrey
177:), and
3547:
3520:
3512:
3471:
3463:
3422:
3414:
3373:
3365:
3324:
3316:
3281:
3271:
3225:
3190:
3152:
3144:
3076:
3049:
3015:
2990:
2967:
2959:
2924:
2889:
2848:
2807:
2772:
2764:
2729:
2719:
2678:
2668:
2627:
2619:
2564:
2540:
2443:
2408:
2390:Lancet
2373:
2346:
2304:
2296:
2255:
2247:
2206:
2171:
2161:
2124:370682
2122:
2114:
2079:
2071:
2036:
2026:
1985:
1981:–123.
1951:
1943:
1894:
1859:
1853:352664
1851:
1816:
1806:
1767:
1757:
1728:
1720:
1682:
1659:
1624:
1614:
1570:
941:Normal
928:Normal
915:Mixed
692:) and
644:(i.e.
640:, and
611:CYP2E1
565:Gender
535:, and
224:Causes
169:(e.g.
142:(from
56:biopsy
3611:K71.0
3518:S2CID
3469:S2CID
3420:S2CID
3371:S2CID
3322:S2CID
3150:S2CID
2965:S2CID
2887:S2CID
2770:S2CID
2625:S2CID
2469:(PDF)
2462:(PDF)
2302:S2CID
2253:S2CID
2120:S2CID
2077:S2CID
1949:S2CID
1857:S2CID
1833:Drugs
1751:18–45
1726:S2CID
1657:S2CID
1438:CIOMS
986:NSAID
982:HAART
235:Drugs
148:liver
53:Liver
3617:MeSH
3545:PMID
3510:PMID
3461:PMID
3412:PMID
3363:PMID
3314:PMID
3279:PMID
3223:PMID
3188:PMID
3142:PMID
3074:ISBN
3047:PMID
3013:ISBN
2988:ISBN
2957:PMID
2922:PMID
2846:PMID
2805:PMID
2762:PMID
2727:PMID
2676:PMID
2617:PMID
2562:PMID
2538:PMID
2477:2017
2441:PMID
2406:PMID
2371:PMID
2344:PMID
2294:PMID
2245:PMID
2204:PMID
2169:PMID
2112:PMID
2069:PMID
2034:PMID
1983:ISBN
1941:PMID
1892:PMID
1849:PMID
1814:PMID
1765:OCLC
1755:ISBN
1718:PMID
1680:ISBN
1622:PMID
1568:ISBN
1518:and
1301:(e)
1291:(d)
1048:and
961:2–5
706:and
648:and
617:and
485:Kava
413:MAOI
276:kava
183:kava
3602:ICD
3566:at
3500:doi
3451:doi
3402:doi
3398:113
3353:doi
3306:doi
3269:PMC
3259:doi
3215:doi
3180:doi
3176:354
3132:doi
2949:doi
2914:doi
2877:doi
2836:doi
2797:doi
2754:doi
2717:PMC
2707:doi
2666:PMC
2656:doi
2607:doi
2603:109
2530:doi
2433:doi
2429:116
2398:doi
2340:289
2284:doi
2235:doi
2196:doi
2159:PMC
2151:doi
2104:doi
2061:doi
2024:PMC
2016:doi
2012:143
1979:104
1933:doi
1884:doi
1841:doi
1804:PMC
1796:doi
1792:316
1788:BMJ
1710:doi
1706:137
1649:doi
1612:PMC
1604:doi
1480:AST
1449:).
1260:),
1187:).
1093:ALT
1058:ALP
1054:ALT
937:ALP
921:ALT
559:Age
358:).
350:or
3651::
3620::
3609::
3606:10
3541:18
3539:.
3516:.
3508:.
3496:42
3494:.
3490:.
3467:.
3459:.
3447:44
3445:.
3441:.
3418:.
3410:.
3396:.
3392:.
3369:.
3361:.
3349:39
3347:.
3343:.
3320:.
3312:.
3302:23
3300:.
3277:.
3267:.
3255:13
3253:.
3249:.
3235:^
3221:.
3211:11
3209:.
3186:.
3174:.
3162:^
3148:.
3140:.
3128:18
3126:.
3122:.
3043:76
3041:.
3027:^
2963:.
2955:.
2945:18
2943:.
2920:.
2910:65
2908:.
2885:.
2871:.
2867:.
2844:.
2832:49
2830:.
2826:.
2803:.
2793:14
2791:.
2768:.
2760:.
2750:14
2748:.
2725:.
2715:.
2703:24
2701:.
2697:.
2674:.
2664:.
2652:19
2650:.
2646:.
2623:.
2615:.
2601:.
2597:.
2536:.
2526:77
2524:.
2493:.
2439:.
2427:.
2404:.
2392:.
2367:35
2365:.
2338:.
2300:.
2292:.
2278:.
2274:.
2251:.
2243:.
2231:27
2229:.
2225:.
2202:.
2192:97
2190:.
2167:.
2157:.
2147:49
2145:.
2141:.
2118:.
2110:.
2098:.
2075:.
2067:.
2057:31
2055:.
2032:.
2022:.
2010:.
2006:.
1961:^
1947:.
1939:.
1929:56
1927:.
1890:.
1880:24
1878:.
1855:.
1847:.
1837:16
1835:.
1812:.
1802:.
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1786:.
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1407:,
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1099:.
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860:,
851:,
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88:,
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3604:-
3594:D
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